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["Candidate_ID","Source_id","Source_Type","Compound_Type","Compound_Name","Synonyms","Molecular_Formula","SMILES","Description","cas_number","Molecular_Weight","Indication","Pharmacodynamics","MOA","Targets","Inclusion_Criteria"]
[1,"DB00002","approved","biotech","Cetuximab",{"$nulls":3},"Cetuximab is a recombinant chimeric human/mouse IgG1 monoclonal antibody that competitively binds to epidermal growth factor receptor (EGFR) and competitively inhibits the binding of epidermal growth factor (EGF). EGFR is a member of the ErbB family of receptor tyrosine kinases found in both normal and tumour cells; it is responsible for regulating epithelial tissue development and homeostasis. EGFR has been implicated in various types of cancer, as it is often overexpressed in malignant cells  and EGFR overexpression has been linked to more advanced disease and poor prognosis. EGFR is often mutated in certain types of cancer and serves as a driver of tumorigenesis. _In vitro_, cetuximab was shown to mediate anti-tumour effects in numerous cancer cell lines and human tumour xenografts.\r\n\r\nApproved by the FDA in February 2004 under the brand name ERBITUX, cetuximab is used for the treatment of head and neck cancer and metastatic, KRAS wild-type colorectal cancer, and metastatic colorectal cancer with a BRAF V600E mutation. It has also been investigated in advanced colorectal cancer, EGFR-expressing non-small cell lung cancer (NSCLC), and unresectable squamous cell skin cancer. Cetuximab is administered via intravenous infusion and is used as monotherapy or in combination with other chemotherapies, including platinum agents, radiation therapy, , , and .","205923-56-4",null,"Cetuximab indicated for the treatment of locally or regionally advanced squamous cell carcinoma of the head and neck in combination with radiation therapy. It is indicated for treating a recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck in combination with platinum-based therapy with fluorouracil. It is indicated for recurrent or metastatic squamous cell carcinoma of the head and neck progressing after platinum-based therapy.\r\n\r\nCetuximab is also indicated for K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer as determined by an FDA-approved test in combination with FOLFIRI, a chemotherapy combination that includes , , and ; in combination with irinotecan in patients who are refractory to irinotecan-based chemotherapy; or as monotherapy in patients who have failed oxaliplatin- and irinotecan-based chemotherapy or who are intolerant to irinotecan.\r\n\r\nAdditionally, cetuximab is also indicated for metastatic colorectal cancer that is BRAF V600E mutation-positive (as determined by an FDA-approved test) in combination with  but only after prior therapy.\r\n\r\nCetuximab is not indicated for the treatment of Ras-mutant colorectal cancer or when the results of the Ras mutation tests are unknown.","Cetuximab is an anticancer agent that works by inhibiting the growth and survival of epidermal growth factor receptor (EGFR)-expressing tumour cells with high specificity and higher affinity than epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-α), which are natural ligands of EGFR. Cetuximab works by inhibiting the growth and survival of EGFR-positive tumours. _In vitro_, it promotes antibody-dependent cellular cytotoxicity (ADCC) against certain human tumour types. On the contrary, cetuximab does not exert its anti-tumour effects on human tumour xenografts lacking EGFR expression.\r\n\r\nCetuximab potentiates the cytotoxic effects of chemotherapeutics and radiation therapy when used in combination. In human tumour xenograft models in mice, cetuximab and irinotecan synergistically inhibited the growth of orthotopic anaplastic thyroid carcinoma xenografts _in vitro_ and _in vivo_. Cetuximab potentiated the _in vitro_ anti-proliferative and pro-apoptotic effect of irinotecan and achieved 93% _in vivo_ inhibition of tumour growth when combined with irinotecan, compared to 77% and 79% inhibition when cetuximab and irinotecan were used alone, respectively.","The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein and a type I receptor tyrosine kinase expressed on both normal and malignant cells. It has been investigated as a therapeutic target for anticancer treatment, as it is often upregulated in cancer types, including head and neck, colon, and rectal cancers. When activated by its ligand, EGFR undergoes a conformational change and dimerization to form homodimers or heterodimers with another member of the ErbB family of receptors. Dimerization of EGFR activates the intracellular tyrosine kinase region of EGFR and promotes autophosphorylation, initiating a series of downstream signalling cascades, including cell differentiation, proliferation, migration, angiogenesis, and apoptosis. This EGFR signalling pathway is often dysregulated in cancer cells, leading to aberrant cell growth and enhanced cell survival.\r\n\r\nCetuximab is a monoclonal antibody that binds specifically to the EGFR on both normal and tumour cells to competitively inhibit the binding of epidermal growth factor (EGF) and other ligands that are produced by normal and tumour tissue epithelial cells. Upon binding to domain III of EGFR - which is the binding site for its growth factor ligands - cetuximab prevents the receptor from adopting an extended conformation and thereby inhibits EGFR activation, as well as phosphorylation and activation of receptor-associated kinases (MAPK, PI3K/Akt, Jak/Stat). Inhibition of the EGFR signalling pathway ultimately leads to inhibition of cell cycle progression, cell survival pathways, and tumour cell motility and invasion. Cetuximab also induces cell apoptosis and decreases matrix metalloproteinase and vascular endothelial growth factor (VEGF) production. _In vitro_, cetuximab was shown to inhibit tumour angiogenesis. Binding of cetuximab to EGFR also results in internalization of the antibody-receptor complex, leading to an overall downregulation of EGFR expression.\r\n\r\nK-ras is a small G-protein downstream of EGFR that plays an important role in promoting the EGFR signalling cascade: in some malignant cells, K-ras can acquire activating mutations in exon 2  and thus be continuously active regardless of EGFR regulation. Since mutant Ras proteins can isolate the pathway from the effect of EGFR, K-Ras mutations can render EGFR inhibitors like cetuximab ineffective in exerting anti-tumour effects. Cetuximab is thus only limited in its use for K-Ras wild-type, EGFR-expressing cancers.","Epidermal growth factor receptor binder; Low affinity immunoglobulin gamma Fc region receptor III-B binder; Complement C1q subcomponent subunit A binder; Complement C1q subcomponent subunit B binder; Complement C1q subcomponent subunit C binder; Low affinity immunoglobulin gamma Fc region receptor III-A binder; High affinity immunoglobulin gamma Fc receptor I binder; Low affinity immunoglobulin gamma Fc region receptor II-a binder","Therapeutic strategy associated"]
[2,"DB00003","approved","biotech","Dornase alfa","Deoxyribonuclease (human clone 18-1 protein moiety); Dornase alfa; Dornase alfa, recombinant; Dornase alpha; Recombinant deoxyribonuclease (DNAse)",null,null,"Dornase alfa is a biosynthetic form of human deoxyribunuclease I (DNase I) enzyme. It is produced in genetically modified Chinese hamster ovary (CHO) cells using recombinant DNA technology. The 260-amino acid sequence of dornase alfa is identical to the endogenous human enzyme. Dornase alfa cleaves extracellular DNA to 5´-phosphodinucleotide and 5´-phosphooligonucleotide end products without affecting intracellular DNA. In individuals with cystic fibrosis, extracellular DNA, which is an extremely viscous anion, is released by degenerating leukocytes that accumulate during inflammatory responses to infections. Enzymatic breakdown of this extracellular DNA appears to reduce sputum viscosity and viscoelasticity.","143831-71-4",null,"Used as adjunct therapy in the treatment of cystic fibrosis.","Cystic fibrosis (CF) is a disease characterized by the retention of viscous purulent secretions in the airways. These thick secretions contribute both to reduced pulmonary function and to frequent pulmonary infection. Purulent pulmonary secretions of individuals with cystic fibrosis contain very high concentrations of extracellular DNA released by degenerating leukocytes that accumulate in response to these infections. Dornase alfa hydrolyzes the DNA in sputum of CF patients and reduces sputum viscosity and viscoelasticity. The enzyme does not appear to affect sputum in the absence of an inflammatory response to infection, nor does it affect the sputum of healthy individuals.","Dornase alfa is a biosynthetic form of human DNase I. The enzyme is involved in endonucleolytic cleavage of extracellular DNA to 5´-phosphodinucleotide and 5´-phosphooligonucleotide end products. It has no effect on intracellular DNA. Optimal activity is dependent on the presence of divalent cations such as calcium and magnesium. Extracellular DNA is a viscous anionic polymer and its breakdown appears to improve the viscosity and viscoelasticity of purulent sputum of individuals with CF, thus reducing airflow obstruction. Dornase alfa does not seem to have any effect on non-purulent sputum.","DNA","Therapeutic strategy associated"]
[3,"DB00005","approved; investigational","biotech","Etanercept","Etanercept; etanercept-szzs; etanercept-ykro; Recombinant human TNF; rhu TNFR:Fc; rhu-TNFR:Fc; TNFR-Immunoadhesin",null,null,"Dimeric fusion protein consisting of the extracellular ligand-binding portion of the human 75 kilodalton (p75) tumor necrosis factor receptor (TNFR) linked to the Fc portion of human IgG1. The Fc component of etanercept contains the CH2 domain, the CH3 domain and hinge region, but not the CH1 domain of IgG1. Etanercept is produced by recombinant DNA technology in a Chinese hamster ovary (CHO) mammalian cell expression system. It consists of 934 amino acids. It is used to treat or manage a variety of inflammatory conditions including rheumatoid arthritis (RA), ankylosing spondylitis (AS), and juvenile idiopathic poly-articular arthritis (JIA).","185243-69-0",null,"Etanercept is indicated for the treatment of moderately to severely active rheumatoid arthritis in adults and in chronic moderate to severe plaque psoriasis in patients 4 years of age and older. It is also used to manage signs and symptoms of polyarticular idiopathic arthritis in those aged 2 years and older. Etanercept is also used to manage the symptoms of psoriatic arthritis and ankylosing spondylitis.","Etanercept binds specifically to tumor necrosis factor (TNF) and thereby modulates biological processes that are induced or regulated by TNF. Such processes or molecules affected include the level of adhesion molecules expressed, as well as serum levels of cytokines and matrix metalloproteinases.","There are two distinct receptors for TNF (TNFRs), a 55 kilodalton protein (p55) and a 75 kilodalton protein (p75). The biological activity of TNF is dependent upon binding to either cell surface receptor (p75 or p55). Etanercept is a dimeric soluble form of the p75 TNF receptor that can bind to two TNF molecules, thereby effectively removing them from circulation. Notably, etancerpt is only capable of binding to the active trimeric form of TNF as its binding site is located in the cleft between subunits.TNF is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Increased levels of TNF are found in tissues and fluids of those with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and plaque psoriasis.","Tumor necrosis factor antibody; High affinity immunoglobulin gamma Fc receptor I ligand; Low affinity immunoglobulin gamma Fc region receptor II-a ligand; Low affinity immunoglobulin gamma Fc region receptor II-b ligand; Low affinity immunoglobulin gamma Fc region receptor II-c ligand; Low affinity immunoglobulin gamma Fc region receptor III-A ligand; Low affinity immunoglobulin gamma Fc region receptor III-B ligand; Lymphotoxin-alpha antibody; Complement component 1q (C1q) ligand","Therapeutic strategy associated"]
[4,"DB00009","approved","biotech","Alteplase","Alteplase; Alteplase (genetical recombination); Alteplase, recombinant; Alteplase,recombinant; Plasminogen activator (human tissue-type protein moiety); rt-PA; t-PA; t-plasminogen activator; Tissue plasminogen activator; Tissue plasminogen activator alteplase; Tissue plasminogen activator, recombinant; tPA",null,null,"Human tissue plasminogen activator, purified, glycosylated, 527 residues purified from CHO cells","105857-23-6",null,"For management of acute myocardial infarction, acute ischemic stroke and for lysis of acute pulmonary emboli.","Alteplase binds to fibrin in a thrombus and converts the entrapped plasminogen to plasmin. It also produces limited conversion of plasminogen in the absence of fibrin.","Alteplase binds to fibrin rich clots via the fibronectin finger-like domain and the Kringle 2 domain. The protease domain then cleaves the Arg/Val bond in plasminogen to form plasmin. Plasmin in turn degrades the fibrin matrix of the thrombus, thereby exerting its thrombolytic action.","Plasminogen activator; Fibrinogen alpha chain; Urokinase plasminogen activator surface receptor; Plasminogen activator inhibitor 1","Indication associated"]
[5,"DB00015","approved; investigational","biotech","Reteplase","Human t-PA (residues 1-3 and 176-527); Reteplase; Reteplase, recombinant; Reteplase,recombinant",null,null,"Human tissue plasminogen activator, purified, glycosylated, 355 residues purified from CHO cells. Retavase is considered a \"third-generation\" thrombolytic agent, genetically engineered to retain and delete certain portions of human tPA. Retavase is a deletion mutein of human tPA formed by deleting various amino acids present in endogenous human tPA. Retavase contains 355 of the 527 amino acids of native human tPA (amino acids 1-3 and 176-527), and retains the activity-related kringle-2 and serine protease domains of human tPA. Three domains are deleted from retavase - kringle-1, finger, and epidermal growth factor (EGF).","133652-38-7",null,"For lysis of acute pulmonary emboli, intracoronary emboli, and management of myocardial infarction.","Reteplase cleaves the Arg/Val bond in plasminogen to form plasmin. Plasmin in turn degrades the fibrin matrix of the thrombus, thereby exerting its thrombolytic action. This helps eliminate blood clots or arterial blockages that cause myocardial infarction.","Reteplase binds to fibrin rich clots via the fibronectin finger-like domain and the Kringle 2 domain. The protease domain then cleaves the Arg/Val bond in plasminogen to form plasmin. Plasmin in turn degrades the fibrin matrix of the thrombus, thereby exerting its thrombolytic action.","Plasminogen activator; Fibrinogen alpha chain; Plasminogen activator inhibitor 1","Indication associated"]
[6,"DB00016","approved","biotech","Erythropoietin","E.P.O.; Epoetin alfa; Epoetin alfa rDNA; Epoetin alfa-epbx; Epoetin alfa, recombinant; Epoetin beta; Epoetin beta rDNA; Epoetin epsilon; Epoetin gamma; Epoetin gamma rDNA; Epoetin kappa; Epoetin omega; Epoetin theta; Erythropoiesis stimulating factor; Erythropoietin (human, recombinant); Erythropoietin (recombinant human); ESF; SH-polypeptide-72",null,null,"Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow . Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures . It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market . The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product . Epoetin alfa formulations can be administered intravenously or subcutaneously.","11096-26-7",null,"Indicated in adult and paediatric patients for the: \r\n\r\n- treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis.\r\n- treatment of anemia due to zidovudine in patients with HIV-infection. \r\n- treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy.\r\n- reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery.","Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks . Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly . \r\n\r\nEpoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks . Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy .","Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways . The affinity (Kd) of EPO for its receptor on human cells is ∼100 to 200 pM . Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins . The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x . The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C-γ1 .","Erythropoietin receptor agonist","Therapeutic strategy associated"]
[7,"DB00017","approved; investigational","biotech","Salmon calcitonin","Calcitonin (Salmon Synthetic); Calcitonin salmon; Calcitonin salmon recombinant; Calcitonin-salmon; Calcitonin, salmon; Recombinant salmon calcitonin; Salmon calcitonin",null,null,"Synthetic peptide, 32 residues long formulated as a nasal spray.","47931-85-1",null,"Used in the treatment of symptomatic Paget's disease for patients unresponsive to alternate treatments or intolerant to such treatments. In addition, it is used in emergency situations when serum calcium levels must be decreased quickly until the underlying condition is identified. It can also be added to existing therapeutic regimens for hypercalcemia such as intravenous fluids and furosemide, oral phosphate or corticosteroids, or other agents. Calcitonin can be used in patients with azotemia and cases where intravenous fluids would be contraindicated due to limited cardiac reserves. Also for the treatment of post-menopausal osteoporosis in women more than 5 years post-menopause.","Calcitonin inhibits bone resorption by osteoclasts (bone remodeling cells) and promotes bone formation by osteoblasts. This leads to a net increase in bone mass and a reduction in plasma calcium levels. It also promotes the renal excretion of ions such as calcium, phosphate, sodium, magnesium, and potassium by decreasing tubular reabsorption. In consequence, there is an increase in the jejunal secretion of water, sodium, potassium, and chloride.","Calcitonin binds to the calcitonin receptor (found primarily in osteoclasts) which then enhances the production of vitamin D producing enzymes (25-hydroxyvitamine D-24-hydroxylase), leading to greater calcium retention and enhanced bone density. Binding of calcitonin to its receptor also activates adenylyl cyclase and the phosphatidyl-inositol-calcium pathway.","Calcitonin receptor agonist","Indication associated"]
[8,"DB00022","approved","biotech","Peginterferon alfa-2b","Peginterferon alfa-2b",null,null,"Peginterferon alfa-2b is a form of recombinant interferon used as part of combination therapy to treat chronic Hepatitis C, an infectious liver disease caused by infection with Hepatitis C Virus (HCV). HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients . Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) resulting in less use of Peginterferon alfa-2b. Peginterferon alfa-2b is derived from the alfa-2b moeity of recombinant human interferon and acts by binding to human type 1 interferon receptors. Activation and dimerization of this receptor induces the body's innate antiviral response by activating the janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Use of Peginterferon alfa-2b is associated with a wide range of severe adverse effects including the aggravation and development of endocrine and autoimmune disorders, retinopathies, cardiovascular and neuropsychiatric complications, and increased risk of hepatic decompensation in patients with cirrhosis. The use of Peginterferon alfa-2b has largely declined since newer interferon-free antiviral therapies have been developed.\r\n\r\nIn a joint recommendation published in 2016, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) no longer recommend Peginterferon alfa-2b for the treatment of Hepatitis C . Peginterferon alfa-2b was used alongside  with the intent to cure, or achieve a sustained virologic response (SVR), after 48 weeks of therapy. SVR and eradication of HCV infection is associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of Hepatocellular Carcinoma, and reduced all-cause mortality .\r\n\r\nPeginterferon alfa-2b is available as a variable dose injectable product (tradename Pegintron) used for the treatment of chronic Hepatitis C. Approved in 2001 by the FDA, Pegintron is indicated for the treatment of HCV with  or other antiviral drugs . When combined together, Peginterferon alfa-2b and  have been shown to achieve a SVR between 41% for genotype 1 and 75% for genotypes 2-6 after 48 weeks of treatment.","215647-85-1",null,"Peginterferon alfa-2b is indicated for the treatment of HCV in combination with  and a NS3/4A protease inhibitor for genotype 1 or without a NS3/4A protease inhibitor for genotypes 2-6 . May be used as a monotherapy in patients with contraindications to or significant intolerance to other anti-viral therapies.\r","Peginterferon alfa-2b inhibits viral replication in infected cells, suppresses cell proliferation, induces apoptosis, and exerts an anti-angiogenic effect . Exerts immunomodulatory effects such as enhancement of the phagocytic activity of macrophages, activation of NK cells, stimulation of cytotoxic T-lymphocytes, and the upregulation of the Th1 T-helper cell subset. Also increases concentrations of effector proteins such as serum neopterin and 2'5' oligoadenylate synthetase, raises body temperature, and causes reversible decreases in leukocyte and platelet counts.","Peginterferon alfa-2b is derived from recombinant human interferon's alfa-2b moeity . It binds to and activates human type 1 interferon receptors causing them to dimerize. This activates the JAK/STAT pathway. Activation of the JAK/STAT pathway increases expression of multiple genes in multiple tissues involved in the innate antiviral response. Peginterferon alfa-2b may also acitvate the nuclear factor κB pathway.","Interferon alpha/beta receptor 1 agonist; Interferon alpha/beta receptor 2 agonist","Therapeutic strategy associated"]
[9,"DB00026","approved","biotech","Anakinra","Anakinra; IL-1RA; Interleukin-1 receptor antagonist anakinra",null,null,"Anakinra is a recombinant, nonglycosylated human interleukin-1 receptor antagonist (IL-1Ra). The difference between anakinra and the native human IL-1Ra is that anakinra has an extra methionine residue at the amino terminus. It is manufactured by using the E. coli expression system. Anakinra is composed of 153 amino acid residues. FDA approved on November 14, 2001 for the treatment of rheumatoid arthritis.","143090-92-0",null,"For the treatment of adult rheumatoid arthritis and treatment of Neonatal-Onset Multisystem Inflammatory Disease (NOMID).","Used to treat rheumatoid arthritis, Anakinra blocks the biologic activity of IL-1 by competitively inhibiting IL-1 binding to the interleukin-1 type I receptor (IL-1RI), which is expressed in a wide variety of tissues and organs. IL-1 production is induced in response to inflammatory stimuli and mediates various physiologic responses including inflammatory and immunological responses. Patients with rheumatoid arthritis have elevated levels of IL-1. The levels of the naturally occurring IL-1Ra in synovium and synovial fluid from rheumatoid arthritis (RA) patients are not sufficient to compete with the elevated amount of locally produced IL-1. Increasing the levels of IL-1Ra by artificial means reduces the negative effects (cartilage degradation, bone resorption) of IL-1.","Anakinra binds competitively to the Interleukin-1 type I receptor (IL-1RI), thereby inhibiting the action of elevated levels IL-1 which normally can lead to cartilage degradation and bone resorption.","Interleukin-1 receptor type 1 antagonist","Therapeutic strategy associated"]
[10,"DB00028","approved; investigational","biotech","Human immunoglobulin G","Human IGG; Human immunoglobulin G; Human normal immunoglobulin; Immune globulin (human); Immune globulin human; Immunoglobulin (human); Immunoglobulin G (human); Immunoglobulin G, human; IVIg",null,null,"Intravenous immunoglobulin (IVIg) is a mixture of IgG1 and other antibodies derived from healthy human plasma via Cohn fractionation. The purification process includes cold alcohol fractionation, polyethylene glycol precipitation, and ion exchange chromatography. IVIg contains the same distribution of IgG antibody subclasses as is found in the general human population. IgG subclasses are fully represented in the following proportions: 70.3% IgG1, 24.7% IgG2, 3.1% IgG3, and 1.9% IgG4. IVIg is used in the treatment of immunodeficiencies, as well as autoimmune and inflammatory disorders.","308067-58-5",null,"IVIg is used in the treatment of immunodeficiencies, as well as autoimmune and inflammatory disorders. These indications includes idiopathic thrombocytopenic purpura, Kawasaki disease, hypogammaglobulinemia, B cell chronic lymphocytic leukemia, bone marrow transplant complications, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP), multiple sclerosis, rheumatoid arthritis, myesthenia gravis, Wiskott–Aldrich syndrome and inflammatory skin diseases.","Used as a replacement therapy in inherited humoral immunodeficiency disorders such as severe combined immunodeficiency syndrome, x-linked agammaglobulinemia, and Wiskott-Aldrich Syndrome. The immunoglobulins target, bind and kill bacterial cells as well as viral particles. IgG is the monomeric immunoglobulin of which there are four subclasses (IgG1, IgG2, IgG3 and IgG4) in differing abundances (66%, 23%, 7% and 4%). IgAs represent about 15% of the immunoglobulins in the blood. These target inhaled or ingested pathogens.","IVIg interacts with a number of different components of the immune system, including cytokines, complement, Fc receptors and several cell surface immunocompetent molecules. IVIg also impacts different effector cells of the immune system (B and T lymphocytes, dendritic cells, etc.) and regulates a wide range of genes. Its main mechanism of actions are believed to be Fc-dependent and F(ab')2-dependent. IVIg competitively blocks gamma Fc receptors, preventing the binding and ingestion of phagocytes and suppressing platelet depletion. IVIg contains a number of different antobodies, which prevent infection by attaching to the surface of invading pathogens and aiding in their disposal before they can infect cells. Antibodies remove pathogens via complement activation, agglutination or precipitation, pathogen receptor blocking, macrophage “tagging” or neutralization (via binding) of pathogen toxins. Intact IVIg and F(ab′)2 fragments of IVIg can also neutralize the activity of various autoantibodies. By triggering the production of interleukin-1 receptor antagonist, IVIg modulates of the production of cytokines and cytokine antagonists. It also prevents the generation of the C5b-9 membrane attack complex and subsequent complement-mediated tissue damage by binding active complement components.","High affinity immunoglobulin gamma Fc receptor I antagonist; High affinity immunoglobulin gamma Fc receptor IB antagonist; Low affinity immunoglobulin gamma Fc region receptor II-a antagonist; Low affinity immunoglobulin gamma Fc region receptor II-b antagonist; Low affinity immunoglobulin gamma Fc region receptor II-c antagonist; Low affinity immunoglobulin gamma Fc region receptor III-A antagonist; Low affinity immunoglobulin gamma Fc region receptor III-B antagonist; Complement C3 binder; Complement C4-A binder; Complement C4-B binder; Complement C5 binder","Indication associated"]
[11,"DB00029","approved","biotech","Anistreplase","Anisoylated plasminogen streptokinase activator complex; Anistreplase; APSAC",null,null,"Human tissue plasminogen activator, purified, glycosylated, 527 residues purified from CHO cells. Eminase is a lyophilized (freeze-dried) formulation of anistreplase, the p-anisoyl derivative of the primary Lys-plasminogen-streptokinase activator complex (a complex of Lys-plasminogen and streptokinase). A p-anisoyl group is chemically conjugated to a complex of bacterial-derived streptokinase and human Plasma-derived Lys-plasminogen proteins.","81669-57-0",null,"For lysis of acute pulmonary emboli, intracoronary emboli and management of myocardial infarction","Anistreplase cleaves the Arg/Val bond in plasminogen to form plasmin. Plasmin in turn degrades the fibrin matrix of the thrombus, thereby exerting its thrombolytic action. This helps eliminate blood clots or arterial blockages that cause myocardial infarction.","Anistreplase cleaves the Arg/Val bond in plasminogen to form plasmin. This in turn leads to the degradation of blood clots.","Plasminogen activator; Fibrinogen alpha chain; Plasminogen activator inhibitor 1","Indication associated"]
[12,"DB00031","approved","biotech","Tenecteplase","Tenecteplase; TNK-tPA",null,null,"Tenecteplase is a tissue plasminogen activator (tPA) developed from modifications of natural human tPA complementary DNA (cDNA). It is a 527 amino acid with a substitution of threonine 103 with asparagine and substitution of asparagine 117 with glutamine within the kringle 1 domain, and a tetra-alanine substitution at amino acids 296-299 in the protease domain.","191588-94-0",null,"For treatment of myocardial infarction and lysis of intracoronary emboli","Tenecteplase is a fibrin-specific tissue-plasminogen activator. It binds to fibrin rich clots and cleaves the Arg/Val bond in plasminogen to form plasmin. Plasmin in turn degrades the fibrin matrix of the thrombus, thereby exerting its thrombolytic action. This helps eliminate blood clots or arterial blockages that cause myocardial infarction.","Tenecteplase binds to fibrin rich clots via the fibronectin finger-like domain and the Kringle 2 domain. The protease domain then cleaves the Arg/Val bond in plasminogen to form plasmin. Plasmin in turn degrades the fibrin matrix of the thrombus, thereby exerting its thrombolytic action.","Plasminogen activator; Fibrinogen alpha chain; Urokinase plasminogen activator surface receptor; Plasminogen activator inhibitor 1; Plasminogen activator inhibitor 2; Tetranectin; Keratin, type II cytoskeletal 8; Annexin A2; Calreticulin; Calnexin; Prolow-density lipoprotein receptor-related protein 1","Indication associated"]
[13,"DB00035","approved","small molecule","Desmopressin","1-(3-mercaptopropionic acid)-8-D-arginine-vasopressin; 1-deamino-8-D-arginine vasopressin; 1-desamino-8-D-arginine vasopressin; dDAVP; Desmopressin","C46H64N14O12S2","NC(=O)CC[C@@H]1NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)CCSSC[C@H](NC(=O)[C@H](CC(N)=O)NC1=O)C(=O)N1CCC[C@H]1C(=O)N[C@H](CCCNC(N)=N)C(=O)NCC(N)=O","Desmopressin (dDAVP), a synthetic analogue of 8-arginine vasopressin (ADH), is an antidiuretic peptide drug modified by deamination of 1-cysteine and substitution of 8-L-arginine by 8-D-arginine. ADH is an endogenous pituitary hormone that has a crucial role in the control of the water content in the body. Upon release from the stimulation of increased plasma osmolarity or decreased circulating blood volume, ADH mainly acts on the cells of the distal part of the nephron and the collecting tubules in the kidney . The hormone interacts with V1, V2 or V3 receptors with differing signal cascade systems.\r\n\r\nDesmopressin displays enhanced antidiuretic potency, fewer pressor effects due to V2-selective actions, and a prolonged half-life and duration of action compared to endogenous ADH . It has been employed clinically since 1972 and is available in various formulations including intranasal solution, intravenous solution, oral tablet and oral lyophilisate . Desmopressin is indicated for the treatment of polyuric conditions including primary nocturnal enuresis, nocturia, and diabetes insipidus. It was also newly approved for the treatment of mild classical hemophilia and von Willebrand's disease for minor surgeries. The active ingredient in most formulations is desmopressin acetate. Nocdurna, or desmopressin acetate, was approved by the FDA on June 21st, 2018 for the treatment of nocturia due to nocturnal polyuria in adults. It is available as a sublingual tablet.","16679-58-6","1069.22","- Indicated for the treatment of nocturia due to nocturnal polyuria in adults who awaken at least 2 times per night to void (intranasal). \r\n\r\n- Indicated as antidiuretic replacement therapy in the management of central cranial diabetes insipidus and for management of the temporary polyuria and polydipsia following head trauma or surgery in the pituitary region (intranasal/parenteral).\r\n\r\n- Indicated for patients with hemophilia A with factor VIII coagulant activity levels greater than 5% or mild to moderate classic von Willebrand's Disease (Type I) with factor VIII levels greater than 5% during surgical procedures and postoperatively to maintain hemostasis (parenteral).","By mimicking the actions of endogenous ADH, desmopressin acts as a selective agonist of V2 receptors expressed in the renal collecting duct (CD) to increase water re-absorption and reduce urine production. Desmopressin has been shown to be more potent than ADH in increasing plasma levels of factor VIII activity in patients with hemophilia and von Willebrand's disease Type I . Desmopressin demonstrates markedly diminished pressor activity. Desmopressin administered intranasally has an antidiuretic effect about one-tenth that of an equivalent dose administered by injection .","Upon binding of desmopressin to V2 receptors in the basolateral membrane of the cells of the distal tubule and collecting ducts of the nephron, adenylyl cyclase is stimulated. The resulting intracellular cascades in the collecting duct lead to increased rate of insertion of water channels, called aquaporins, into the lumenal membrane and enhanced the permeability of the membrane to water .","Vasopressin V2 receptor agonist; Vasopressin V1a receptor; Vasopressin V1b receptor","Indication associated"]
[14,"DB00043","approved; investigational","biotech","Omalizumab","Omalizumab",null,null,"Omalizumab, manufactured by _Genentech_, was first FDA approved in 2003 to treat adults and children 12 years of age and older with moderate to severe persistent allergic asthma which is not controlled by inhaled steroids . Since its U.S. approval, more than 200,000 patients older than 12 with allergic asthma have been treated .  In September 2018, a new prefilled syringe formulation of this drug was approved by the FDA .","242138-07-4",null,"This drug is an anti-IgE antibody indicated for:\r\n\r\n1. Moderate to severe persistent asthma in patients 6 years of age and older\r\nwith a positive skin test or in vitro reactivity to a perennial aeroallergen and symptoms that are inadequately controlled with inhaled corticosteroids \r\n\r\n2. Chronic idiopathic urticaria in adults and adolescents 12 years of age and older who remain symptomatic despite H1 antihistamine treatment","Omalizumab is a recombinant, humanized, monoclonal antibody against human immunoglobulin E (IgE) which treats the symptoms of asthma and chronic idiopathic urticaria by limiting the allergic response , .  It inhibits the binding of IgE to receptors on mast cells and basophils, blocking the IgE-mediated secretion of inflammatory mediators from these cells .\r\n\r\nMast cell activation and the release of mediators, in response to allergen exposure and IgE, results in a cascade of events. This cascade culminates in the activation of B-lymphocytes, T-lymphocytes, eosinophils, fibroblasts, smooth muscle cells, and the endothelium. This cellular interaction, as well as the release of cytokines, chemokines and growth factors and inflammatory remodeling of the airway results in chronic asthma .\r\n\r\nAfter 4 weeks of use of this medication in patients with chronic urticaria, it was found that rescue medication use was reduced significantly and quality of life improved .","When an environmental allergen first enters the body, is taken up by antigen-presenting cells (APCs). It is then processed, and presented to T and B immune cells. This is followed by the activation of B-lymphocyte and production of allergen-specific IgE. This IgE is then released by plasma cells (converted B lymphocytes) and is therefore available to bind to IgE receptors on several other cells .\r\n\r\nIgE binds to high-affinity (Fc€RI) and low-affinity (Fc€RII) receptors on multiple cells of the immune system. Following subsequent antigen exposure, cross-linking of the antigen occurs by several Fc€RI-bound IgE molecules on the surface of both basophils and mast cells. This leads to the activation of mast cells and histamine release, producing a wheal and other symptoms of urticaria .\r\n\r\nThe following are explanations of the mechanism of action for both indications of this drug:\r\n\r\n**Asthma**\r\n\r\nOmalizumab inhibits the binding of IgE to the high-affinity IgE receptor (FcεRI) on the surface of both mast cells and basophils. The reduction in surface-bound IgE on FcεRI-bearing cells limits the degree of release of mediators of the typical allergic response. Treatment with omalizumab also reduces the number of FcεRI receptors on basophils in atopic patients .\r\n\r\nOmalizumab binds to free IgE with a higher affinity than IgE itself binds to the high-affinity Fc€RI receptors found on basophils. Therefore, it decreases the availability of free IgE for binding . Omalizumab by itself does not bind to the Fc€RI receptors, nor does the drug bind to receptor-bound IgE. These binding characteristics allow omalizumab to neutralize the typical IgE-mediated responses without causing the degranulation of basophils or cross-linking with basophil-bound IgE .\r\n\r\n**Chronic Idiopathic Urticaria**\r\nOmalizumab binds to IgE and decreases free IgE levels. Subsequently, IgE receptors (FcεRI) on cells are down-regulated. The mechanism by which these effects of omalizumab result in an improvement of CIU symptoms is unclear.","High affinity immunoglobulin epsilon receptor subunit alpha inhibitor; High affinity immunoglobulin epsilon receptor subunit beta inhibitor","Therapeutic strategy associated"]
[15,"DB00046","approved","biotech","Insulin lispro","Insulin lispro; Insulin lispro (genetical recombination); Insulin lispro (rDNA origin); Insulin lispro protamine; Insulin lispro protamine recombinant; Insulin lispro recombinant; insulin lispro-aabc; Insulin,lispro,human/rDNA; Insulin,lispro,protamine/rDNA",null,null,"Insulin lispro is a rapid-acting form of insulin used for the treatment of hyperglycemia caused by Type 1 and Type 2 Diabetes. Insulin is prescribed for the management of diabetes mellitus to mimic the activity of endogenously produced human insulin, a peptide hormone produced by beta cells of the pancreas that promotes glucose metabolism. Insulin is released from the pancreas following a meal to promote the uptake of glucose from the blood into internal organs and tissues such as the liver, fat cells, and skeletal muscle. Absorption of glucose into cells allows for its transformation into glycogen or fat for storage. Insulin also inhibits hepatic glucose production, enhances protein synthesis, and inhibits lipolysis and proteolysis among many other functions.\r\n\r\nInsulin is an important treatment in the management of Type 1 Diabetes (T1D) which is caused by an autoimmune reaction that destroys the beta cells of the pancreas, resulting in the body not being able to produce the insulin needed to manage circulating blood sugar levels. As a result, people with T1D rely primarily on exogenous forms of insulin, such as insulin lispro, to lower glucose levels in the blood. Insulin is also used in the treatment of Type 2 Diabetes (T2D), another form of diabetes mellitus that is a slowly progressing metabolic disorder caused by a combination of genetic and lifestyle factors that promote chronically elevated blood sugar levels. Without treatment or improvement in non-pharmacological measures such as diet and exercise to lower blood glucose, high blood sugar eventually cause cellular resistance to endogenous insulin, and in the long term, damage to pancreatic islet cells. Insulin is typically prescribed later in the course of T2D, after several oral medications such as , , or  have been tried, and when sufficient damage has been caused to pancreatic cells that the body is no longer able to produce insulin on its own. \r\n\r\nMarketed as the brand name product Humalog, insulin lispro begins to exert its effects within 15 minutes of subcutaneous administration, while peak levels occur 30 to 90 minutes after administration. Due to its duration of action of around 5 hours, Humalog is considered \"bolus insulin\" as it provides high levels of insulin in a short period of time to mimic the release of endogenous insulin from the pancreas after meals. Bolus insulin is often combined with once daily, long-acting \"basal insulin\" such as , , or  to provide low concentrations of background insulin that can keep blood sugar stable between meals or overnight. Use of basal and bolus insulin together is intended to mimic the pancreas' production of endogenous insulin, with a goal of avoiding any periods of hypoglycemia.\r\n\r\nInsulin lispro is produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli and was the first commercially available insulin analog. Formerly called LYSPRO from the chemical nomenclature , insulin lispro differs from human insulin in that the amino acid proline at position B28 is replaced by lysine and the lysine in position B29 is replaced by proline. These biochemical changes result in a reduced tendency for self-association resulting in dissolution to a dimer and then to a monomer that is absorbed more rapidly after subcutaneous injection compared to endogenous human insulin. \r\n\r\nWithout an adequate supply of insulin to promote absorption of glucose from the bloodstream, blood sugar levels can climb to dangerously high levels and can result in symptoms such as fatigue, headache, blurred vision, and increased thirst. If left untreated, the body starts to break down fat, instead of glucose, for energy which results in a build-up of ketone acids in the blood and a syndrome called ketoacidosis, which is a life-threatening medical emergency. In the long term, elevated blood sugar levels increase the risk of heart attack, stroke, and diabetic neuropathy.","133107-64-9",null,"Insulin lispro is indicated to improve glycemic control in adults and children with diabetes mellitus.","Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, a basal level of insulin is supplemented with insulin spikes following meals. Increased insulin secretion following meals is responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin lispro is a rapid-acting insulin analogue used to mimic postprandial insulin spikes in diabetic individuals. The onset of action of insulin lispro is 10-15 minutes. Its activity peaks 60 minutes following subcutaneous injection and its duration of action is 4-5 hours. Compared to regular human insulin, insulin lispro  has a more rapid onset of action and a shorter duration of action. Insulin lispro is also shown to be equipotent to human insulin on a molar basis.","Insulin lispro binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism and catabolism. In humans, insulin is stored in the form of hexamers; however, only insulin monomers are able to interact with IR. Reversal of the proline and lysine residues at positions B28 and B29 of native insulin eliminates hydrophobic interactions and weakens some of the hydrogen bonds that contribute to the stability of the insulin dimers that comprise insulin hexamers. Hexamers of insulin lispro are produced in the presence of zinc and <i>m</i>-cresol. These weakly associated hexamers quickly dissociate upon subcutaneous injection and are absorbed as monomers through vascular endothelial cells. These properties give insulin lispro its fast-acting properties.","Insulin receptor agonist; Insulin-like growth factor 1 receptor activator","Indication associated"]
[16,"DB00049","approved; investigational","biotech","Rasburicase","Rasburicase; Urate oxidase",null,null,"Rasburicase is a recombinant urate-oxidase enzyme produced by a genetically modified <i>Saccharomyces cerevisiae</i> strain. The cDNA coding for rasburicase was cloned from a strain of _Aspergillus flavus_.","134774-45-1",null,"For treatment of hyperuricemia, reduces elevated plasma uric acid levels (from chemotherapy)","Drugs used to treat lympohoid leukemia, non-Hodgkin's lymphoma and acute myelogenous leukemia often lead to the accumulation of toxic plasma levels of purine metabolites (i.e. uric acid). The injection of rasburicase reduces levels of uric acid and mitigates the toxic effects of chemotherapy induced tumor lysis.","Rasburicase catalyzes enzymatic oxidation of uric acid into an inactive and soluble metabolite (allantoin).","Uric acid metabolizer","Indication associated"]
[17,"DB00051","approved; experimental","biotech","Adalimumab","Adalimumab; Adalimumab (genetical recombination); adalimumab-adaz; adalimumab-adbm; adalimumab-afzb; adalimumab-atto; adalimumab-bwwd; adalimumab-fkjp",null,null,"Adalimumab is a subcutaneously administered biological disease modifier for the treatment of rheumatoid arthritis and other chronic debilitating diseases mediated by tumor necrosis factor , . It was originally launched by Abbvie in the U.S. and approved in 2002 by the FDA . This drug is frequently known as _Humira_. It is produced by recombinant DNA technology using a mammalian cell expression system. This drug is available in a prefilled syringe form and convenient pen form for subcutaneous self-administered doses . A new biosimilar to adalimumab, named _adalimumab-adaz_, was approved by the FDA on October 31, 2018. This biosimilar is known as _Hyrimoz_, and is a trademark of Novartis AG .","331731-18-1",null,"The following are conditions for which adalimumab has been indicated , , , , , . \r\n\r\nRheumatoid Arthritis (Moderate to Severe)\r\n\r\nJuvenile Idiopathic Arthritis (Moderately to Severely Active)\r\n\r\nPsoriatic Arthritis (Active)\r\n\r\nAnkylosing Spondylitis (Active)\r\n\r\nCrohn’s Disease (Moderately to Severely Active)\r\n\r\nUlcerative Colitis (Moderately to Severely Active)\r\n\r\nPlaque Psoriasis (Moderate to Severe Chronic)\r\n\r\nNon-infectious Intermediate, Posterior and Panuveitis\r\n\r\nHidradenitis Suppurativa (Moderate to Severe)\r\n\r\nPyoderma Gangrenosum (off-label)\r","After treatment with adalimumab, a decrease in levels of acute phase reactant proteins of inflammation (C­ reactive protein  and erythrocyte sedimentation rate ) and serum cytokines (IL-6) was measured compared to baseline in patients diagnosed with rheumatoid arthritis. A decrease in CRP levels was also observed in patients diagnosed with Crohn’s disease. Serum levels of matrix metalloproteinases (MMP-1 and MMP-3) that lead to the tissue remodeling responsible for cartilage destruction were also found to be decreased after administration of adalimumab , .  A reduction in signs and symptoms of disease, the induction of a clinical response, an inhibition of structural damage, and improvements in physical function in adult and pediatric patients with various inflammatory conditions have been demonstrated , , .","Adalimumab binds with specificity to tumor necrosis factor-alpha (TNF-alpha) ,  and inhibits its interaction with the p55 and p75 cell surface TNF receptors. Adalimumab also lyses surface tumor necrosis factor expressing cells in vitro when in the presence of complement. Adalimumab does not bind or inactivate lymphotoxin (Tumor necrosis factor-beta). TNF is a naturally occurring cytokine that plays a role in normal inflammatory and immune responses . Increased levels of TNF are found in the joint synovial fluid of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis patients, and play an imperative role in pathologic inflammation and the joint destruction that are major complications of these diseases. Increased levels of TNF are also measured in psoriasis plaques. In plaque psoriasis, treatment with adalimumab may decrease the epidermal thickness and inflammatory cell infiltration. The relationship between these pharmacodynamics and the mechanism(s) by which adalimumab achieves its clinical effects is not known. Additionally, adalimumab alters biological responses that are induced/regulated by TNF, including changes in the levels of adhesion molecules responsible for leukocyte migration during inflammation (ELAM-1, VCAM-1, and ICAM-1 with an IC50 of 1-2 X 10-10M) .","Tumor necrosis factor antibody","Therapeutic strategy associated"]
[18,"DB00054","approved","biotech","Abciximab","Abciximab; Abciximab (genetical recombination); c7E3",null,null,"Abciximab is a Fab fragment of the chimeric human-murine monoclonal antibody 7E3. Abciximab binds to the glycoprotein (GP) IIb/IIIa receptor of human platelets and inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules. It also binds to vitronectin (αvβ3) receptor found on platelets and vessel wall endothelial and smooth muscle cells.","143653-53-6",null,"Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting.","Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes.","Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion.","Integrin beta-3 antagonist; Integrin alpha-IIb antagonist; Low affinity immunoglobulin gamma Fc region receptor II-a; Low affinity immunoglobulin gamma Fc region receptor II-b; Vitronectin","Therapeutic strategy associated"]
[19,"DB00063","approved; investigational","biotech","Eptifibatide","Eptifibatide; Integrelin; Intrifiban",null,null,"Synthetic cyclic hexapeptide that binds to platelet receptor glycoprotein and inhibits platelet aggregation. Derived from venom of the Southeastern pygmy rattlesnake (Sistrurus miliarus barbouri), eptifibatide is a cyclic heptapeptide that belongs to the class of arginin-glycin-aspartat-mimetics.","188627-80-7",null,"For treatment of myocardial infarction and acute coronary syndrome.","Eptifibatide is an anti-coagulant that selectively and reversibly blocks the platelet glycoprotein IIb/IIIa receptor.","Eptifibatide inhibits platelet aggregation by reversibly binding to the platelet receptor glycoprotein (GP) IIb/IIIa of human platelets, thus preventing the binding of fibrinogen, von Willebrand factor, and other adhesive ligands. Inhibition of platelet aggregation occurs in a dose- and concentration-dependent manner.","Integrin beta-3","Therapeutic strategy associated"]
[20,"DB00065","approved","biotech","Infliximab","Infliximab; Infliximab (genetical recombination); Infliximab-abda; Infliximab-axxq; Infliximab-dyyb; Infliximab-qbtx",null,null,"Infliximab is a tumor necrosis factor (TNF-alpha or TNF-α) blocker and a chimeric monoclonal IgG1 antibody composed of human constant (75%) and murine variable (25%) regions . Infliximab is produced by a recombinant cell line cultured by continuous perfusion. Tumor necrosis factor-alpha (TNF-α) is a key proinflammatory cytokine involved in chronic inflammatory diseases . Its hyperactivity and enhanced signalling pathways can be observed in inflammatory diseases where it activates further pro-inflammatory cascades. By binding to both the soluble subunit and the membrane-bound precursor of TNF-α , infliximab disrupts the interaction of TNF-α with its receptors and may also cause lysis of cells that produce TNF-α .\r\n\r\nInfliximab was first approved by the FDA in 1998 under the market name Remicade as an intravenous injection. It is indicated for the treatment of various inflammatory disorders such as adult or pediatric Chron's disease, adult or pediatric ulcerative colitis, rheumatoid arthritis in combination with methotrexate, ankylosing spondyliti, psoriatic arthritis, and plaque psoriasis . In clinical trials, multiple infusions of infliximab displayed in a reduction of signs and symptoms of inflammatory diseases and induction of remission in patients who have had an inadequate response to alternative first-line therapies for that disorder . \r\n\r\nThere are currently two biosilimars of infliximab available in the US market that demonstrate a high degree of similarity to the reference product, Remicade. They are approved for all eligible indications of the reference product. Inflectra, a first biosimilar drug product, was approved in 2016. In December 2017, Ixifi, a second biosimilar that was developed by Pfizer, was granted approval by the FDA.","170277-31-3",null,"* Indicated for reducing signs and symptoms and inducing and maintaining clinical remission in adult or pediatric (≥ 6 years of age) patients with moderately to severely active **Crohn’s disease** who have had an inadequate response to conventional therapy\r\n* Indicated for reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing **Crohn’s disease**. \r\n* Indicated for reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in adult or pediatric (≥ 6 years of age) patients with moderately to severely active **ulcerative colitis** who have had an inadequate response to conventional therapy. \r\n* Indicated for, in combination with methotrexate, reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active **rheumatoid arthritis**. \r\n* Indicated for reducing signs and symptoms in patients with active **ankylosing spondylitis**. \r\n* Indicated for reducing signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function in patients with **psoriatic arthritis**. \r\n* Indicated for the treatment of adult patients with chronic severe (i.e., extensive and/or disabling) **plaque psoriasis** who are candidates for systemic therapy and when other systemic therapies are medically less appropriate.","Infliximab disrupts the activation of pro-inflammaory cascade signalling. Infliximab has shown to reduce infiltration of inflammatory cells into sites of inflammation. It also attenautes the expression of molecules mediating cellular adhesion {including E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)}, chemoattraction {.","Infliximab is a IgG1κ monoclonal antibody that binds to soluble and transmembrane forms of TNF-α with high affinity to disrupt the pro-inflammatory cascade signalling. Binding of the antibody to TNF-α prevents TNF-α from interacting with its receptors. Infliximab does not neutralize TNF-β (lymphotoxin-α), a related cytokine that utilizes the same receptors as TNF-α . Blocked actions of TNF-α further leads to downregulation of local and systemic pro-inflammatory cytokines (i.e. IL-1, IL-6), reduction of lymphocyte and leukocyte migration to sites of inflammation, induction of apoptosis of TNF-producing cells (i.e. activated monocytes and T lymphocytes), increased levels of nuclear factor-κB inhibitor, and reduction of reduction of endothelial adhesion molecules and acute phase proteins . Its inhibitory actions on TNF-α was demonstrated in human fibroblasts, endothelial cells, neutrophils, B and Tlymphocytes and epithelial cells . Infliximab also atteunates the production of tissue degrading enzymes synthesized by synoviocytes and/or chondrocytes. According to a transgenic mice study that developed polyarthritis due to consitutive levels of human TNF-α, infliximab decreased synovitis and joint erosions in collagen-induced arthritis and allows eroded joints to heal .","Tumor necrosis factor inhibitor","Therapeutic strategy associated"]
[21,"DB00071","approved","biotech","Insulin pork","Insulin (pork); Insulin porcine; Insulin purified porcine; Insulin purified pork; Insulin, porcine; Insulin, regular, pork; Porcine insulin",null,null,"Insulin isolated from pig pancreas. Composed of alpha and beta chains, processed from pro-insulin. Forms a hexameric structure.","12584-58-6",null,"For the treatment of type I and II diabetes mellitus.","Insulin is used in the treatment of type I and type II diabetes. The primary activity of insulin is the regulation of glucose metabolism. In muscle and other tissues (except the brain), insulin causes rapid transport of glucose and amino acids intracellularly. It also promotes anabolism, and inhibits protein catabolism. In the liver, insulin promotes the uptake and storage of glucose in the form of glycogen, inhibits gluconeogenesis, and promotes the conversion of excess glucose into fat.","Insulin binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor is able to autophosphorylate and phosphorylate numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. These activated proteins, in turn, lead to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC) which play a critical role in metabolism.","Insulin receptor binder; Insulin-like growth factor 1 receptor","Indication associated"]
[22,"DB00073","approved","biotech","Rituximab","Rituximab; rituximab-abbs; rituximab-arrx; rituximab-pvvr",null,null,"Rituximab is a genetically engineered chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes. The antibody is an IgG1 kappa immunoglobulin containing murine light and heavy-chain variable region sequences and human constant region sequences , . It was originally approved by the U.S. FDA in 1997 as a single agent to treat patients with B-cell Non-Hodgkin's Lymphoma (NHL) , however, has now been approved for a variety of conditions . On November 28, 2018, the US FDA approved _Truxima_, the first biosimilar to Rituxan (Rituximab) .","174722-31-7",null,"Rituximab is indicated in the following conditions :\r\n\r\nNon–Hodgkin’s Lymphoma (NHL)\r\n\r\nChronic Lymphocytic Leukemia (CLL)\r\n\r\nRheumatoid Arthritis (RA) in combination with methotrexate in adult patients with moderately-to severely-active RA\r\n\r\nGranulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) and Microscopic Polyangiitis (MPA)\r\n\r\nModerate to severe Pemphigus Vulgaris (PV) in adult patients\r\n\r\nThe biosimilar (approved in November 2018), _Truxima_, is indicated For the treatment of adult patients with CD20-positive, B-cell non-Hodgkin’s lymphoma (NHL) to be used as a single agent or in combination with chemotherapy .\r\n\r\nIn September 2019, the rituximab injection was approved along with glucocorticoids to manage granulomatosis with polyangiitis (GPA) in addition to microscopic polyangiitis (MPA) in children of at least 2 years of age .","Rituximab binds to the CD20 antigen, which is predominantly expressed on mature B cells and on >90% of B-cell non-Hodgkin's lymphomas . The antibody leads to selective killing of B-cells. The following are the pharmacodynamic outcomes for various conditions, including non- Hodgkin's Lymphoma :\r\n\r\n**Non-Hodgkin’s Lymphoma (NHL)**\r\nIn Non-Hodgkin's Lymphoma patients, the administration of rituximab led to the depletion of circulating and tissue-based B cells. Among 166 patients in Study 1, circulating CD19-positive B cells were depleted within the first three weeks, showing sustained depletion for up to 6-9 months post-treatment in 83% of treated patients. B-cell recovery began at approximately 6 months and median B-cell levels returned to normal by 12 months following the completion of treatment . There were sustained and statistically significant decreases in serum IgM and IgG levels measured from 5-11 months following rituximab administration; 14% of patients showed IgM and/or IgG serum levels below the normal range .\r\n\r\n**Rheumatoid Arthritis**\r\nIn rheumatoid arthritis (RA) patients, treatment with rituximab induced the depletion of peripheral B lymphocytes, with the majority of patients showing near-complete depletion (CD19 counts below the lower limit of quantification, 20 c-lls/μl) within 2 weeks after the first dose of rituximab. The majority of treated patients showed peripheral B-cell depletion, sustained for a minimum of 6 months. A small percentage of patients (~4%) had peripheral B-cell depletion that was sustained for more than 3 years after one course of treatment. Total serum immunoglobulin levels, IgM, IgG, and IgA were decreased at 6 months with the greatest change observed in IgM. At Week 24 of the first cycle of rituximab treatment, small percentages of patients experienced decreases in IgM (10%), IgG (2.8%), and IgA (0.8%) levels below the lower limit of normal (LLN). When rituximab was administered to RA patients during repeated rituximab treatment, 23.3%, 5.5%, and 0.5% of patients experienced decreases in IgM, IgG, and IgA concentrations below LLN at any time after receiving rituximab, respectively. The clinical consequences of decreases in immunoglobulin levels in RA patients treated with rituximab are not clear at this time. Treatment with rituximab in patients with RA was associated with a decreased level of several biologic markers of inflammation such as interleukin-6 (IL-6), C-reactive protein (CRP), serum amyloid protein (SAA), S100 A8/S100 A9 heterodimer complex (S100 A8/9), anti-citrullinated peptide (anti-CCP), and RF  and was found to decrease disease symptoms .\r\n\r\n**Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) and Microscopic Polyangiitis**\r\nIn GPA and MPA patients, peripheral blood CD19 B-cells were depleted to less than 10 cells/μl after the first two infusions of rituximab and remained at the same level in most (84%) patients through Month 6 of the treatment. By Month 12, most patients (81%) demonstrated signs of B-cell return with counts >10 cells/μL. By Month 18, the majority of patients (87%) had counts >10 cells/μL .","Rituximab is a monoclonal antibody that targets the CD20 antigen, which is expressed on the surface of pre-B and mature B-lymphocytes , , , . After binding to CD20, rituximab mediates B-cell lysis (or breakdown). The possible mechanisms of cell lysis include complement dependent cytotoxicity (CDC) and antibody dependent cell-mediated cytotoxicity (ADCC) .\r\n\r\nRituximab belongs to the immunoglobulin G1 (IgG1) sub-class, consisting of a murine variable region (Fab region) and a human constant region (Fc region). The Fab region has variable sections that define a specific target antigen, allowing the antibody to attract and secure its exclusive antigen, specifically the binding of rituximab (IgG1) to CD20 on pre-B and mature B lymphocytes. The Fc region is the tail end of the antibody that communicates with cell surface receptors to activate the immune system, in this case, a sequence of events leading to the depletion of circulating B lymphocytes by complement-dependent cell lysis, antibody-dependent cellular cytotoxicity, as well as apoptosis .\r\n\r\nIn regards to the mechanism of action in rheumatoid arthritis, B cells are thought to play a role in the pathogenesis of rheumatoid arthritis (RA) and the associated condition of chronic synovitis. B cells may act at various sites in the autoimmune/inflammatory process, including through production of rheumatoid factor (RF) and other autoantibodies, antigen presentation, T-cell activation, and/or the production of proinflammatory cytokines .  The administration of rituximab in this condition has been shown to result in significant clinical and symptomatic improvements , .","B-lymphocyte antigen CD20 antibody","Therapeutic strategy associated"]
[23,"DB00080","approved; investigational","small molecule","Daptomycin","Daptomycin","C72H101N17O26","CCCCCCCCCC(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H]1[C@@H](C)OC(=O)[C@H](CC(=O)C2=CC=CC=C2N)NC(=O)[C@@H](NC(=O)[C@@H](CO)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCCN)NC(=O)CNC1=O)[C@H](C)CC(O)=O","Daptomycin is a cyclic lipopeptide antibacterial agent with a broad spectrum of activity against Gram-positive bacteria, including methicillin-susceptible and -resistant _Staphylococcus aureus_ (MSSA/MRSA) and vancomycin-resistant Enterococci (VRE). Chemically, daptomycin comprises 13 amino acids, including several non-standard and D-amino acids, with the C-terminal 10 amino acids forming an ester-linked ring and the N-terminal tryptophan covalently bonded to decanoic acid. Daptomycin was first discovered in the early 1980s by researchers at Eli Lilly in soil samples from Mount Ararat in Turkey. Early work on developing daptomycin was abandoned due to observed myopathy but was resumed in 1997 when Cubist Pharmaceuticals Inc. licensed daptomycin; it was found that a once-daily dosing scheme reduced side effects while retaining efficacy.\r\n\r\nDaptomycin was approved by the FDA on September 12, 2003, and is marketed under the name CUBICIN® by Cubist Pharmaceuticals LLC (Merck & Co.).","103060-53-3","1620.693","Daptomycin is indicated for the treatment of complicated skin and skin structure infections (cSSSI) in patients one year of age and older. It is also indicated for the treatment of _Staphylococcus aureus_ bloodstream infections (bacteremia) in patients one year of age and older, including in adult patients with right-sided infective endocarditis.\r\n\r\nDaptomycin is not indicated for the treatment of pneumonia or left-sided infective endocarditis due to _S. aureus_. Use is not recommended in pediatric patients younger than one year of age due to the risk of potential effects on muscular, neuromuscular, and/or nervous systems (either peripheral and/or\r\ncentral).\r\n\r\nAs with all antibacterial drugs, it is strongly suggested to perform sufficient testing before treatment initiation in order to confirm an infection caused by susceptible bacteria. Failure to do so may result in suboptimal treatment, treatment failure, and the development of drug-resistant bacteria.","Daptomycin is a cyclic lipopeptide antibacterial agent produced as a fermentation product by the soil microbe _Streptomyces roseosporus_. The daptomycin core consists of 13 amino acids, including three D-amino acids, ornithine, 3-methyl-glutamic acid, and kynurenine, with the C-terminal 10 amino acids forming an ester-linked ring and the N-terminal tryptophan covalently bonded to decanoic acid. Daptomycin is active against aerobic Gram-positive bacteria, including clinically relevant strains such as methicillin-susceptible and -resistant _Staphylococcus aureus_ (MSSA/MRSA), vancomycin-resistant _S. aureus_, vancomycin-resistant Enterococci (VRE),  _Staphylococcus_ spp., _Streptococcus_ spp., _Clostridiodes difficile_, _Clostridium perfringens_, _Finegoldia magna_, and _Propionibacterium acnes_, among others. Although daptomycin is active against _Streptococcus pneumoniae_ _in vitro_, it is inhibited by lung surfactant, and hence is not effective for the treatment of pneumonia or other similar lung infections. Daptomycin exhibits rapid concentration-dependent bactericidal activity _in vitro_, which correlates best with the ratio of the area under the concentration-time curve to the minimum inhibitory concentration (AUC/MIC) in animal models of infection. \r\n\r\nLike other antibacterial agents, daptomycin carries a risk of severe hypersensitivity reactions, including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). There have been reports of myopathy, rhabdomyolysis, and increased creatine phosphokinase (CPK) levels in patients taking daptomycin, which increased when daptomycin was given more than once per day. Patients should be monitored for CPK levels and, in those with renal impairment, renal function, at least once per week and should consider temporarily suspending the use of HMG-CoA reductase inhibitors. Daptomycin should not be administered more than once per day. Severe adverse reactions such as tubulointerstitial nephritis and peripheral neuropathy have been reported, which may require treatment discontinuation. Based on animal studies, patients less than one year of age may experience serious muscular, neuromuscular, and nervous system effects; daptomycin is not recommended for use in patients under one year of age. Patients undergoing daptomycin treatment may experience eosinophilic pneumonia and _Clostridioides difficile_-associated diarrhea, both of which may require the cessation of antibacterial treatment and initiation of symptomatic/supportive measures. Persisting or relapsing _S. aureus_ bacteremia and endocarditis should be investigated for sequestered foci of infection and the possibility of daptomycin resistance; the dose or treatment regimen may require adjusting. Patients with moderate to severe renal impairment (creatine clearance < 50 mL/min) experienced reduced clinical benefit from daptomycin treatment based on limited data. Clinically relevant daptomycin plasma concentrations have significantly affected prothrombin time and International Normalized Ratio (INR) measurements. As with all antibiotics, daptomycin use may promote the overgrowth of non-susceptible organisms and the development of resistant organisms; daptomycin use should be limited to cases where it is proven or strongly suspected that an infection is caused by susceptible bacteria.","The mechanism of action of daptomycin remains poorly understood. Studies have suggested a direct inhibition of cell membrane/cell wall constituent biosynthesis, including peptidoglycan, uridine diphosphate-N-acid, acetyl-L-alanine, and lipoteichoic acid (LTA). However, no convincing evidence has been presented for any of these models, and an effect on LTA biosynthesis has been ruled out by other studies in _S. aureus_ and _E. faecalis_.\r\n\r\nIt is well understood that free daptomycin (apo-daptomycin) is a trianion at physiological pH, which binds Ca<sup>2+</sup> in a 1:1 stoichiometric ratio to become a monoanion, which is thought to rely primarily on the Asp(7), Asp(9), and L-3MeGlu12 residues that form a DXDG motif. Calcium-binding facilitates daptomycin's insertion into bacterial membranes preferentially due to their high content of the acidic phospholipids phosphatidylglycerol (PG) and cardiolipin (CL), wherein it is proposed that daptomycin can bind two calcium equivalents and form oligomers. PG is recognized as the main membrane requirement for daptomycin activity; daptomycin preferentially localizes in PG-rich membrane domains, and mutations affecting PG prevalence are linked to daptomycin resistance. Calcium-dependent membrane binding is the generally accepted mechanism of action for daptomycin, but the precise downstream effects are unclear, and numerous models have been proposed.\r\n\r\nOne mechanism proposes that the daptomycin membrane binding alters membrane fluidity, causing dissociation of cell wall biosynthetic enzymes such as the lipid II synthase MurG and the phospholipid synthase PlsX. This is consistent with the observed effects of daptomycin on cell shape in various bacteria at concentrations at or above the minimum inhibitory concentration (MIC). Aberrant cell morphology is also consistent with the observed localization of daptomycin at the division septa and a hypothesized role in inhibiting cell division. A recent study suggested the formation of tripartite complexes containing calcium-bound daptomycin, PG, and various undecaprenyl-coupled cell envelope precursors, which subsequently include lipid II. This complex is proposed to inhibit cell division, lead to the dispersion of cell wall biosynthetic machinery, and eventually cause lysis of the membrane bilayer at the septum causing cell death.\r\n\r\nAnother popular model is based on early observations that daptomycin, in a calcium-dependent manner, caused potassium ion leakage and loss of membrane potential in treated bacterial cells. Although this lead some to suggest that daptomycin could bind PG to form oligomeric pores in the bacterial membrane, no cell lysis was observed in _S. aureus_ or _E. faecalis_, and the daptomycin-induced ion conduction is inconsistent with pore formation. Rather, it has been proposed that daptomycin forms calcium-dependent dimeric complexes in fixed ratios of Dap<sub>2</sub>Ca<sub>3</sub>PG<sub>2</sub>, which can act as transient ionophores. The observed loss of membrane potential is suggested to result in a non-specific loss of gradient-dependent nutrient transport, ATP production, and biosynthesis, leading to cell death.\r\n\r\nNotably, these models are not strictly mutually exclusive and are supported to varying extents by observed resistance mutations. The strict requirement for PG for daptomycin bactericidal action is supported by mutations in _mprF_, _cls2_, _pgsA_, and the _dlt_ operon in _S. aureus_, _cls_ in various enterococci, and _pgsA_, PG synthase, and the _dlt_ operon in _E. faecium_, all of which alter the bacterial membrane composition and specifically the PG content of bacterial membranes. Other noted mutations in various regulatory systems that control membrane homeostasis also support the cell membrane as the site of daptomycin action. Curiously, in _E. faecalis_, the most commonly observed form of daptomycin resistance is characterized by abnormal division septa, which supports the cell division-based mechanism of daptomycin action.","Cytoplasmic membrane incorporation into and destabilization","Indication associated"]
[24,"DB00081","approved; investigational","biotech","Tositumomab","Tositumomab",null,null,"Murine IgG2a lambda monoclonal antibody against CD20 antigen (2 heavy chains of 451 residues, 2 lambda chains of 220 residues). It is produced in an antibiotic-free culture of mammalian cells. It can be covalently linked to Iodine 131 (a radioactive isotope of iodine).","208921-02-2",null,"For treatment of non-Hodgkin's lymphoma (CD20 positive, follicular)","Tositumomab binds to the CD20 antigen, which is predominantly expressed on mature B cells and on >90% of B-cell non-Hodgkin's lympohomas. The antibody leads to selective killing of B-cells.","Binds to the CD20 antigen which is found on mature B lymphocytes. The antibody binding appears to induce apoptosis, complement-dependent cytotoxicity and cell death through ionizing radiation.","B-lymphocyte antigen CD20 antibody; Low affinity immunoglobulin gamma Fc region receptor II-b","Therapeutic strategy associated"]
[25,"DB00083","approved; investigational","biotech","Botulinum toxin type A","AbobotulinumtoxinA; Botulinum A neurotoxin; Botulinum antitoxin type A; Botulinum toxin A; Botulinum toxin type A; BTX-A; EvabotulinumtoxinA; IncobotulinumtoxinA; OnabotulinumtoxinA; Prabotulinumtoxin A",null,null,"In 2002, botulinum toxin A, also known as onabotulinumtoxinA or Botox, was the first type A botulism toxin to be introduced into the market for cosmetic use. With a wide variety of applications and favourable safety profile, Botulinum toxin A injection is a minimally invasive and promising treatment for cosmetic imperfections, muscle spasms, and other conditions. A popular use for Botox is the treatment of facial wrinkles and lines, however, there are many uses for the botulinum toxin A in the treatment of dystonia, incontinence, migraine, blepharospasm, and hyperhidrosis.","93384-43-1",null,"Botulinum toxin A is indicated for a variety of conditions, depending on the preparations. Cosmetically, it is used for the treatment of facial fine lines and wrinkles, specifically for upper facial rhytides, including forehead, lateral canthus, and glabellar lines.\r\n\r\nIn addition to the above indications, botulinum toxin A is used for the following conditions: treatment of adults with symptomatic overactive bladder with or without incontinence,  treatment of incontinence in adult patients who are not candidates for anticholinergic therapy, treatment of Neurogenic Detrusor Overactivity (NDO) in patients over 5 years who cannot undergo anticholinergic therapy.  Botulinum toxin A is indicated for the prevention of chronic migraines, for the treatment of muscle spasms, cervical dystonia, axillary hyperhidrosis, strabismus, and disorders of the 7th cranial nerve.\r\n\r\nOff-label, botulinum toxin A is used for a variety of conditions such as temporomandibular joint (TMJ) disorders and myofascial pain, neurogenic thoracic outlet syndrome, epicondylitis, post-stroke pain, post-herpetic neuralgia, diabetic neuropathy, trigeminal neuralgia, neuropathic pain, spinal cord injury, and bladder pain.","Botulinum toxin A inhibits the release of acetylcholine, relieving muscle contraction and spasm associated with many conditions, such as incontinence and dystonia. Cosmetically, botulinum toxin A paralyses muscles in the face to temporarily treat wrinkles. The maximum effects of muscle paralysis occur four to seven days after a dose.  When injected at therapeutic doses, botulinum toxin A causes partial chemical denervation of muscle tissue, causing local reduction of muscle activity. Muscle atrophy may result, axonal sprouting may begin, and extrajunctional acetylcholine receptors can be formed. Reinnervation of the muscle may occur, reversing muscle denervation caused by botulinum toxin A.","Botulinum toxin is a 150-kDa molecular weight protein consisting of a light chain (50 kDa) and heavy chain (100 kDa) linked by a single disulfide bond. The crystal structure reveals 3 lobes - the light chain, the amino-terminal portion of the heavy chain, and the carboxyl-terminal portion of the heavy chain.\r\n\r\nBotulinum toxin type A blocks neuromuscular transmission on motor or sympathetic nerve terminals, inhibiting the release of acetylcholine. Botulinum toxins have actions on various regions: the neuromuscular junction, autonomic ganglia, and both postganglionic sympathetic and parasympathetic nerve endings. The heavy chain of the toxin binds selectively  at the presynaptic surface of cholinergic neurons in an irreversible fashion. After binding, the toxin-receptor complex is transported into the cell by endocytosis. The disulfide bond between the two chains is cleaved and the botulism toxin enters the cytoplasm. The light chain specifically interacts with SNAP-25 in the nerve terminals to block binding of acetylcholine vesicles with the cell membrane.  SNAP-25 is required for successful binding and release of acetylcholine from vesicles in nerve endings.","Synaptosomal-associated protein 25 inhibitor; Rho-related GTP-binding protein RhoB inhibitor","Indication associated"]
[26,"DB00086","approved; investigational","biotech","Streptokinase","Streptococcal fibrinolysin; Streptokinase",null,null,"Streptokinase, is a sterile, purified preparation of a bacterial protein elaborated by group C (beta) -hemolytic streptococci.","9002-01-1",null,"For the treatment of acute evolving transmural myocardial infarction, pulmonary embolism, deep vein thrombosis, arterial thrombosis or emolism and occlusion of arteriovenous cannulae","Streptokinase creates an active complex which promotes the cleavage of the Arg/Val bond in plasminogen to form the proteolytic enzyme plasmin. Plasmin in turn degrades the fibrin matrix of the thrombus, thereby exerting its thrombolytic action. This helps eliminate blood clots or arterial blockages that cause myocardial infarction.","Plasminogen is an inactive molecule that becomes activated to plasmin when the Arg/Val bond is cleaved. Plasmin breaks down fibrin clots created by the blood clotting cascade. Streptokinase forms a highly specific 1:1 enzymatic complex with plasminogen which converts inactive plasminogen molecules into active plasmin. Plasmin degrades fibrin clots as well as fibrinogen and other plasma proteins. This in turn leads to the degradation of blood clots.","Plasminogen activator; Proteinase-activated receptor 1 activator","Indication associated"]
[27,"DB00091","approved; investigational; vet_approved","small molecule","Cyclosporine","Ciclosporin; CsA; CyA; Cyclosporin; Cyclosporin A; Cyclosporine","C62H111N11O12","CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\\C=C\\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O)C(C)C","Cyclosporine is a calcineurin inhibitor known for its immunomodulatory properties that prevent organ transplant rejection and treat various inflammatory and autoimmune conditions. It is isolated from the fungus _Beauveria nivea_. Initially manufactured by Sandoz and approved for use by the FDA in 1983, cyclosporine is now available in various products by Novartis (previously known as Sandoz).","59865-13-3","1202.635","Cyclosporine is approved for a variety of conditions. Firstly, it is approved for the prophylaxis of organ rejection in allogeneic kidney, liver, and heart transplants. It is also used to prevent bone marrow transplant rejection. For the above indications, cyclosporine can be used in conjunction with azathioprine and corticosteroids. Finally, cyclosporine can be used in patients who have chronic transplant rejection and have received previous immunosuppressive therapy and to prevent or treat graft-versus-host disease (GVHD).\r\n\r\nSecondly, cyclosporine is used for the treatment of patients with severe active rheumatoid arthritis (RA) when they no longer respond to methotrexate alone. It can be used for the treatment of adult non-immunocompromised patients with severe, recalcitrant, plaque psoriasis that have failed to respond to at least one systemic therapy or when systemic therapies are not tolerated or contraindicated. The ophthalmic solution of cyclosporine is indicated to increase tear production in patients suffering from keratoconjunctivitis sicca. In addition, cyclosporine is approved for the treatment of steroid dependent and steroid-resistant nephrotic syndrome due to glomerular diseases which may include minimal change nephropathy, focal and segmental glomerulosclerosis or membranous glomerulonephritis.\r\n\r\nA cyclosporine ophthalmic emulsion is indicated in the treatment of vernal keratoconjunctivitis in adults and children.\r\n\r\nOff-label, cyclosporine is commonly used for the treatment of various autoimmune and inflammatory conditions such as atopic dermatitis, blistering disorders, ulcerative colitis, juvenile rheumatoid arthritis, uveitis, connective tissue diseases, as well as idiopathic thrombocytopenic purpura.","Cyclosporine exerts potent immunosuppressive actions on T cells, thereby prolonging survival following organ and bone marrow transplants. This drug prevents and controls serious immune-mediated reactions including allograft rejection,  graft versus host disease, and inflammatory autoimmune disease.\r\n\r\nSome notable effects of cyclosporine are hypertrichosis, gingival hyperplasia, and hyperlipidemia. There is also some debate about this drug causing nephrotoxicity.\r","Cyclosporine is a calcineurin inhibitor that inhibits T cell activation. Its binding to the receptor cyclophilin-1 inside cells produces a complex known as cyclosporine-cyclophilin. This complex subsequently inhibits calcineurin, which in turn stops the dephosphorylation as well as the activation of the nuclear factor of activated T cells (NF-AT) that normally cause inflammatory reactions.  NF-AT is a transcription factor that promotes the production of cytokines such as IL-2, IL-4, interferon-gamma and TNF-alpha, all of which are involved in the inflammatory process. Specifically, the inhibition of IL-2, which is necessary for T cell activation or proliferation, is believed to be responsible for cyclosporine's  immunosuppressive actions. In addition to the above, the inhibition of NF-AT leads to lower levels of other factors associated with T helper cell function and thymocyte development.","Calcium signal-modulating cyclophilin ligand binder; Calcineurin subunit B type 2 inhibitor; Peptidyl-prolyl cis-trans isomerase A inhibitor&binder; Peptidyl-prolyl cis-trans isomerase F, mitochondrial binder","Therapeutic strategy associated"]
[28,"DB00098","approved","biotech","Antithymocyte immunoglobulin (rabbit)","Anti-human thymocyte immunoglobulin, rabbit; Anti-T-lymphocyte immune globulin, rabbit; Anti-thymocyte globulin (rabbit); Anti-thymocyte globulin rabbit; Antithymocyte immunoglobulin; Lapine T-lymphocyte immune globulin; Rabbit anti-human thymocyte globulin; Rabbit anti-human thymocyte globulin (rATG); Rabbit anti-human thymocyte immunoglobulin; Rabbit anti-thymocyte immunoglobulin; Rabbit antithymocyte globulin; Rabbit ATG; rATG; Thymoglobulin; Thymoglobuline",null,null,"Rabbit anti-thymocyte globulin. Thymoglobulin is a polyclonal antibody that suppresses certain types of immune cells responsible for acute organ rejection in transplant patients. Thymoglobulin is a mixture of antibodies intended to bind to various cell surface antigens. The most common mode of action of Thymoglobulin is via selective depletion of T-cells.","308067-60-9",null,"For prevention of renal transplant rejection","Antithymocyte Globulin (ATG) is a concentrated anti-human T-lymphocyte immunoglobulin preparation derived from rabbits after immunization with a T-lympoblast cell line. ATG is an immunosuppressive product for the prevention and treatment of acute rejection following organ transplantation. ATG reduces the host immune response against tissue transplants or organ allografts.","Binds to multiple, T-cell specific antigens leading to T-lymphocyte cell death via complement mediated cytotoxicity or apoptosis.","T-cell surface glycoprotein CD1a inhibitor; Major histocompatibility complex class I-related gene protein antagonist; Integrin alpha-L; T-lymphocyte activation antigen CD86 binder; Low affinity immunoglobulin gamma Fc region receptor II-b; T-cell surface glycoprotein CD4; Integrin beta-1; Integrin alpha-V; Integrin beta-3","Therapeutic strategy associated"]
[29,"DB00102","approved; investigational","biotech","Becaplermin","Becaplermin; PDGF-2; PDGF-BB; PDGFB; Platelet-derived growth factor BB, recombinant; Platelet-derived growth factor beta polypeptide; Recombinant platelet-derived growth factor BB; rhPDGF-BB; rPDGF-BB; SH-POLYPEPTIDE-59",null,null,"Becaplermin is produced by recombinant DNA technology by insertion of the gene for the B chain of platelet derived growth factor (PDGF) into the yeast, Saccharomyces cerevisiae. Becaplermin has a molecular weight of approximately 25 KD and is a homodimer composed of two identical polypeptide chains that are bound together by disulfide bonds.","165101-51-9",null,"For topical treatment of skin ulcers (from diabetes)","Used for the topical treatment of skin ulcers, Regranex has a biological activity similar to that of endogenous platelet-derived growth factor, which includes promoting the chemotactic recruitment and proliferation of cells involved in wound repair and enhancing the formation of granulation tissue.","Binds to the beta platelet-derived growth factor (PDGF) receptor, a tyrosine kinase receptor. PDGF is known to exist as a dimer, and activates its signaling pathway by a ligand induced receptor dimerization and autophosphorylation. PDGF receptors also contain many auto-phosphorylation sites, which serve to mediate binding of SH2 sites and subsequently signal corresponding pathways. There are five different isoforms of PDGF that activate through two different receptors (alpha and beta).","Platelet-derived growth factor receptor beta; Platelet-derived growth factor receptor alpha; Alpha-2-macroglobulin","Indication associated"]
[30,"DB00107","approved; vet_approved","biotech","Oxytocin","Oxytocin",null,null,"Sir Henry H. Dale first identified oxytocin and its uterine contractile properties in 1906. Like all other neurohypophysial hormones, oxytocin is composed of nine amino acids with a disulfide bridge between the Cys 1 and 6 residues. In the mid-1950s, synthetic oxytocin was successfully synthesized by a biochemist named Vincent du Vigneaud; he was later recognized with a Nobel prize for his work. Oxytocin continues to be an important tool in modern obstetrics to induce labor when indicated and to manage postpartum hemorrhage. It is estimated that labor induction with oxytocin is used in almost 10% of deliveries globally. \r\n\r\nIt should be noted that there are risks associated with oxytocin intervention during childbirth. Oxytocin should be used judiciously only when necessary and by experienced healthcare practitioners.\r\n\r\nAlthough most commonly linked to labor and delivery, oxytocin actually has broad peripheral and central effects. It plays an important role in pair bonding, social cognition and functioning, and even fear conditioning. Oxytocin also serves a role in metabolic homeostasis and cardiovascular regulation.","50-56-6",null,"Administration of exogenous oxytocin is indicated in the antepartum period to initiate or improve uterine contractions for vaginal delivery in situations where there is fetal or maternal concern. For example, It may be used to induce labor in cases of Rh sensitization, maternal diabetes, preeclampsia at or near term, and when delivery is indicated due to prematurely ruptured membranes. Importantly, oxytocin is not approved or indicated for elective induction of labor. Oxytocin may be used to reinforce labor in select cases of uterine inertia and as adjunctive therapy in the management of incomplete or inevitable abortion. In the postpartum period, oxytocin may be used to induced contractions in the 3rd stage of labor and to control postpartum bleeding or hemorrhage.","Oxytocin is a nonapeptide, pleiotropic hormone that exerts important physiological effects. It is most well known to stimulate parturition and lactation, but also has important physiological influences on metabolic and cardiovascular functions, sexual and maternal behaviour, pair bonding, social cognition, and fear conditioning. \r\n\r\nIt is worth noting that oxytocin receptors are not limited to the reproductive system but can be found in many peripheral tissues and in central nervous system structures including the brain stem and amygdala.","Oxytocin plays a vital role in labour and delivery. The hormone is produced in the hypothalamus and is secreted from the paraventricular nucleus to the posterior pituitary where it is stored. It is then released in pulses during childbirth to induce uterine contractions.\r\n\r\nThe concentration of oxytocin receptors on the myometrium increases significantly during pregnancy and reaches a peak in early labor. Activation of oxytocin receptors on the myometrium triggers a downstream cascade that leads to increased intracellular calcium in uterine myofibrils which strengthens and increases the frequency of uterine contractions.\r\n\r\nIn humans, most hormones are regulated by negative feedback; however, oxytocin is one of the few that is regulated by positive feedback. The head of the fetus pushing on the cervix signals the release of oxytocin from the posterior pituitary of the mother. Oxytocin then travels to the uterus where it stimulates uterine contractions. The elicited uterine contractions will then stimulate the release of increasing amounts of oxytocin. This positive feedback loop will continue until parturition.\r\n\r\nSince exogenously administered and endogenously secreted oxytocin result in the same effects on the female reproductive system, synthetic oxytocin may be used in specific instances during the antepartum and postpartum period to induce or improve uterine contractions.","Oxytocin receptor agonist","Indication associated"]
[31,"DB00108","approved; investigational","biotech","Natalizumab","Anti-alpha4 integrin; Anti-VLA4; Natalizumab",null,null,"Humanized IgG4k monoclonal antibody produced in murine myeloma cells. Natalizumab contains human framework regions and the complementarity-determining regions of a murine antibody that binds to a4-integrin. Natalizumab was voluntarily withdrawn from U.S. market because of risk of Progressive multifocal leukoencephalopathy (PML). It was returned to market July, 2006.","189261-10-7",null,"For treatment of multiple sclerosis.","In multiple sclerosis, lesions are believed to occur when activated inflammatory cells, including T-lymphocytes, cross the blood-brain barrier (BBB). Leukocyte migration across the BBB involves interaction between adhesion molecules on inflammatory cells, and their counter-receptors present on endothelial cells of the vessel wall. The clinical effect of natalizumab in multiple sclerosis may be a secondary result of its blockade of the molecular interaction of a 4b 1-integrin expressed by inflammatory cells with VCAM-1 on vascular endothelial cells, and with CS-1 and/or osteopontin expressed by parenchymal cells in the brain. α4-integrin is required for white blood cells to move into organs, therefore, natalizumab prevents these immune cells from crossing blood vessel walls to reach affected organs thereby decreasing inflamation.","Binds to the &alpha;4-subunit of &alpha;4b 1 and &alpha;4b 7 integrins expressed on the surface of all leukocytes except neutrophils, and inhibits the &alpha;4-mediated adhesion of leukocytes to their counter-receptor(s).","Integrin alpha-4 antibody; Low affinity immunoglobulin gamma Fc region receptor III-B; Intercellular adhesion molecule 1; High affinity immunoglobulin gamma Fc receptor I","Therapeutic strategy associated"]
[32,"DB00114","approved; investigational; nutraceutical","small molecule","Pyridoxal phosphate","3-hydroxy-2-methyl-5-((phosphonooxy)methyl)-4-pyridinecarboxaldehyde; 3-hydroxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde 5-phosphate; Codecarboxylase; PLP; Pyridoxal 5-monophosphoric acid ester; Pyridoxal 5-phosphate; Pyridoxal 5'-phosphate; Pyridoxal P; Pyridoxal phosphate anhydrous; Pyridoxal-5P; Pyridoxal-P","C8H10NO6P","CC1=NC=C(COP(O)(O)=O)C(C=O)=C1O","This is the active form of vitamin B6 serving as a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid. During transamination of amino acids, pyridoxal phosphate is transiently converted into pyridoxamine phosphate (pyridoxamine).","54-47-7","247.1419","For nutritional supplementation and for treating dietary shortage or imbalance.","The two major forms of vitamin B6 are pyridoxine and pyridoxamine. In the liver they are converted to pyridoxal phosphate (PLP) which is a cofactor in many reactions of amino acid metabolism. PLP also is necessary for the enzymatic reaction governing the release of glucose from glycogen. Pyroluria is one potential cause of vitamin B6 deficiency.","Pyridoxal Phosphate is a coenzyme of many enzymatic reactions. It is the active form of vitamin B6 which comprises three natural organic compounds, pyridoxal, pyridoxamine and pyridoxine. Pyridoxal phosphate acts as a coenzyme in all transamination reactions, and in some \r\noxylation and deamination reactions of amino acids. The aldehyde group of pyridoxal phosphate forms a Schiff-base linkage with the epsilon-amino group of a specific lysine group of the aminotransferase enzyme. The alpha-amino group of the amino acid substrate displaces the epsilon-amino group of the active-site lysine residue. The resulting aldimine becomes deprotonated to become a quinoid intermediate, which in turn accepts a proton at a different position to become a ketimine. Ketimine becomes hydrolyzed so that the amino group remains on the protein complex.","Alanine--glyoxylate aminotransferase 2, mitochondrial cofactor; Glutamate decarboxylase 1 cofactor; Cystathionine beta-synthase cofactor; Kynureninase cofactor; Serine hydroxymethyltransferase, cytosolic cofactor; Cysteine desulfurase, mitochondrial cofactor; Aspartate aminotransferase, cytoplasmic activator; Ornithine aminotransferase, mitochondrial cofactor; Ornithine decarboxylase cofactor; Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial cofactor; 4-aminobutyrate aminotransferase, mitochondrial inhibitor; Pyridoxine-5'-phosphate oxidase cofactor; Sphingosine-1-phosphate lyase 1 cofactor; Tyrosine aminotransferase cofactor; Kynurenine--oxoglutarate transaminase 1 cofactor; Glycogen phosphorylase, liver form cofactor; Serine palmitoyltransferase 2 cofactor; Cysteine sulfinic acid decarboxylase cofactor; Histidine decarboxylase cofactor; Arginine decarboxylase cofactor; L-serine dehydratase/L-threonine deaminase cofactor; 2-amino-3-ketobutyrate coenzyme A ligase, mitochondrial cofactor; Glycine dehydrogenase [decarboxylating], mitochondrial cofactor; Alanine aminotransferase 1 cofactor; Phosphoserine aminotransferase cofactor; 5-aminolevulinate synthase, nonspecific, mitochondrial cofactor; Serine--pyruvate aminotransferase cofactor; Pyridoxal phosphate phosphatase cofactor; Serine palmitoyltransferase 1 cofactor; Cystathionine gamma-lyase cofactor; Branched-chain-amino-acid aminotransferase, cytosolic cofactor; Branched-chain-amino-acid aminotransferase, mitochondrial cofactor; Proline synthase co-transcribed bacterial homolog protein binder; Aspartate aminotransferase, mitochondrial cofactor; Glycogen phosphorylase, brain form cofactor; Glycogen phosphorylase, muscle form cofactor; Aromatic-L-amino-acid decarboxylase cofactor; Aspartate aminotransferase cofactor; Serine hydroxymethyltransferase cofactor; Selenocysteine lyase variant cofactor; Phosphorylase cofactor; 5-aminolevulinate synthase cofactor; Glutamate decarboxylase 2 (Pancreatic islets and brain, 65kDa) cofactor; DDC protein cofactor; Kynurenine--oxoglutarate transaminase 3 cofactor; Glutamate decarboxylase-like protein 1 cofactor; Selenocysteine lyase cofactor; Immunoglobulin superfamily member 10 cofactor; 5-phosphohydroxy-L-lysine phospho-lyase cofactor; Glutamate decarboxylase 1 (Brain, 67kDa) cofactor; Serine hydroxymethyltransferase, mitochondrial cofactor; 5-aminolevulinate synthase, erythroid-specific, mitochondrial cofactor; Alanine aminotransferase 2 cofactor; Molybdenum cofactor sulfurase cofactor; Serine dehydratase-like cofactor; Hepatic peroxysomal alanine:glyoxylate aminotransferase cofactor; Serine racemase cofactor; O-phosphoseryl-tRNA(Sec) selenium transferase cofactor; Serine palmitoyltransferase 3 cofactor; Glutamic acid decarboxylase cofactor; Alanine-glyoxylate aminotransferase homolog cofactor","Indication associated"]
[33,"DB00116","nutraceutical","small molecule","Tetrahydrofolic acid","5,6,7,8-tetrahydrofolate; 5,6,7,8-tetrahydrofolic acid; Tetrahydrofolate","C19H23N7O6","NC1=NC(=O)C2=C(NCC(CNC3=CC=C(C=C3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)N2)N1","Tetrahydrofolic acid is a folic acid derivative that is produced from dihydrofolic acid after conversion by dihydrofolate reductase. It is converted into 5,10-methylenetetrahydrofolate by serine hydroxymethyltransferase. It is a soluble coenzyme in many reactions, especially in the metabolism of amino acids and nucleic acids.","135-16-0","445.4292","For nutritional supplementation, also for treating dietary shortage or imbalance.","Tetrahydrofolate is the main active metabolite of dietary folate. It is vital as a coenzyme in reactions involving transfers of single carbon groups. Tetrahydrofolate has a role in nucleic and amino acid synthesis. As nucleic and amino acid synthesis is affected by a deficiency of tetrahydrofolate, actively dividing and growing cells tend to be the first affected. Tetrahydrofolate is used to treat topical sprue and megaloblastic and macrocytic anemias, hematologic complications resulting from a deficiency in folic acid.","Tetrahydrofolate is transported across cells by receptor-mediated endocytosis where it is needed to maintain normal erythropoiesis, synthesize purine and thymidylate nucleic acids, interconvert amino acids, methylate tRNA, and generate and use formate.","C-1-tetrahydrofolate synthase, cytoplasmic cofactor; Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial cofactor; Aminomethyltransferase, mitochondrial cofactor; Cytosolic 10-formyltetrahydrofolate dehydrogenase cofactor; Methionine synthase cofactor; Formimidoyltransferase-cyclodeaminase cofactor; Bifunctional purine biosynthesis protein PURH cofactor; Serine hydroxymethyltransferase, cytosolic cofactor; Serine hydroxymethyltransferase, mitochondrial cofactor; Methylenetetrahydrofolate reductase cofactor; Serine hydroxymethyltransferase cofactor; Methionyl-tRNA formyltransferase, mitochondrial cofactor","Indication associated"]
[34,"DB00117","investigational; nutraceutical","small molecule","Histidine","(S)-4-(2-Amino-2-carboxyethyl)imidazole; (S)-a-Amino-1H-imidazole-4-propanoic acid; (S)-alpha-amino-1H-Imidazole-4-propanoic acid; (S)-alpha-Amino-1H-imidazole-4-propionic acid; (S)-α-amino-1H-Imidazole-4-propanoic acid; HIS; Histidine; L-(−)-histidine; L-Histidin; L-Histidine","C6H9N3O2","N[C@@H](CC1=CNC=N1)C(O)=O","An essential amino acid that is required for the production of histamine.","71-00-1","155.1546","The actions of supplemental L-histidine are entirely unclear. It may have some immunomodulatory as well as antioxidant activity. L-histidine may be indicated for use in some with rheumatoid arthritis. It is not indicated for treatment of anemia or uremia or for lowering serum cholesterol.","Is found abundantly in hemoglobin; has been used in the treatment of rheumatoid arthritis, allergic diseases, ulcers and anemia. A deficiency can cause poor hearing.","Since the actions of supplemental L-histidine are unclear, any postulated mechanism is entirely speculative. However, some facts are known about L-histidine and some of its metabolites, such as histamine and trans-urocanic acid, which suggest that supplemental L-histidine may one day be shown to have immunomodulatory and/or antioxidant activities. Low free histidine has been found in the serum of some rheumatoid arthritis patients. Serum concentrations of other amino acids have been found to be normal in these patients. L-histidine is an excellent chelating agent for such metals as copper, iron and zinc. Copper and iron participate in a reaction (Fenton reaction) that generates potent reactive oxygen species that could be destructive to tissues, including joints. <br/>L-histidine is the obligate precursor of histamine, which is produced via the decarboxylation of the amino acid. In experimental animals, tissue histamine levels increase as the amount of dietary L-histidine increases. It is likely that this would be the case in humans as well. Histamine is known to possess immunomodulatory and antioxidant activity. Suppressor T cells have H2 receptors, and histamine activates them. Promotion of suppressor T cell activity could be beneficial in rheumatoid arthritis. Further, histamine has been shown to down-regulate the production of reactive oxygen species in phagocytic cells, such as monocytes, by binding to the H2 receptors on these cells. Decreased reactive oxygen species production by phagocytes could play antioxidant, anti-inflammatory and immunomodulatory roles in such diseases as rheumatoid arthritis. <br/>This latter mechanism is the rationale for the use of histamine itself in several clinical trials studying histamine for the treatment of certain types of cancer and viral diseases. In these trials, down-regulation by histamine of reactive oxygen species formation appears to inhibit the suppression of natural killer (NK) cells and cytotoxic T lymphocytes, allowing these cells to be more effective in attacking cancer cells and virally infected cells.","Histidine decarboxylase; Histidine--tRNA ligase, cytoplasmic; Sodium-coupled neutral amino acid transporter 3; Histidine ammonia-lyase","Therapeutic strategy associated"]
[35,"DB00119","approved; investigational; nutraceutical","small molecule","Pyruvic acid","2-ketopropionic acid; 2-oxopropanoic acid; a-Ketopropionic acid; Acetylformic acid; alpha-ketopropionic acid; BTS; Pyroracemic acid; α-ketopropionic acid","C3H4O3","CC(=O)C(O)=O","An intermediate compound in the metabolism of carbohydrates, proteins, and fats. In thiamine deficiency, its oxidation is retarded and it accumulates in the tissues, especially in nervous structures. (From Stedman, 26th ed)","127-17-3","88.0621","For nutritional supplementation, also for treating dietary shortage or imbalance","Pyruvic acid or pyruvate is a key intermediate in the glycolytic and pyruvate dehydrogenase pathways, which are involved in biological energy production. Pyruvate is widely found in living organisms. It is not an essential nutrient since it can be synthesized in the cells of the body. Certain fruits and vegetables are rich in pyruvate. For example, an average-size red apple contains approximately 450 milligrams. Dark beer and red wine are also rich sources of pyruvate. Recent research suggests that pyruvate in high concentrations may have a role in cardiovascular therapy, as an inotropic agent. Supplements of this dietary substance may also have bariatric and ergogenic applications.","Pyruvate serves as a biological fuel by being converted to acetyl coenzyme A, which enters the tricarboxylic acid or Krebs cycle where it is metabolized to produce ATP aerobically. Energy can also be obtained anaerobically from pyruvate via its conversion to lactate. Pyruvate injections or perfusions increase contractile function of hearts when metabolizing glucose or fatty acids. This inotropic effect is striking in hearts stunned by ischemia/reperfusion. The inotropic effect of pyruvate requires intracoronary infusion. Among possible mechanisms for this effect are increased generation of ATP and an increase in ATP phosphorylation potential. Another is activation of pyruvate dehydrogenase, promoting its own oxidation by inhibiting pyruvate dehydrogenase kinase. Pyruvate dehydrogenase is inactivated in ischemia myocardium. Yet another is reduction of cytosolic inorganic phosphate concentration. Pyruvate, as an antioxidant, is known to scavenge such reactive oxygen species as hydrogen peroxide and lipid peroxides. Indirectly, supraphysiological levels of pyruvate may increase cellular reduced glutathione.","Monocarboxylate transporter 4; Monocarboxylate transporter 8; Alanine--glyoxylate aminotransferase 2, mitochondrial; Monocarboxylate transporter 6; Pyruvate kinase PKLR; Monocarboxylate transporter 7; Monocarboxylate transporter 2; Pyruvate dehydrogenase E1 component subunit beta, mitochondrial; Pyruvate kinase PKM; 4-aminobutyrate aminotransferase, mitochondrial inhibitor; Monocarboxylate transporter 5; Monocarboxylate transporter 3; Monocarboxylate transporter 1; Pyruvate carboxylase, mitochondrial","Indication associated"]
[36,"DB00120","approved; investigational; nutraceutical","small molecule","Phenylalanine","(S)-2-Amino-3-phenylpropionic acid; (S)-alpha-Amino-beta-phenylpropionic acid; 3-phenyl-L-alanine; beta-Phenyl-L-alanine; F; L-Phenylalanine; Phe; Phenylalanine; β-phenyl-L-alanine","C9H11NO2","N[C@@H](CC1=CC=CC=C1)C(O)=O","Phenylalanine is an essential aromatic amino acid that is a precursor of melanin, ,  (norepinephrine), and .","63-91-2","165.1891","L-phenylalanine may be helpful in some with depression. It may also be useful in the treatment of vitiligo. There is some evidence that L-phenylalanine may exacerbate tardive dyskinesia in some schizophrenic patients and in some who have used neuroleptic drugs.","Used by the brain to produce Norepinephrine, a chemical that transmits signals between nerve cells and the brain; keeps you awake and alert; reduces hunger pains; functions as an antidepressant and helps improve memory.","The supposed antidepressant effects of L-phenylalanine may be due to its role as a precursor in the synthesis of the neurotransmitters norepinephrine and dopamine. Elevated brain norepinephrine and dopamine levels are thought to be associated with antidepressant effects. <br/>The mechanism of L-phenylalanine's possible antivitiligo activity is not well understood. It is thought that L-phenylalanine may stimulate the production of melanin in the affected skin","Tyrosine aminotransferase; Large neutral amino acids transporter small subunit 2; Phenylalanine--tRNA ligase alpha subunit; Phenylalanine-4-hydroxylase; Phenylalanine--tRNA ligase, mitochondrial; Phenylalanine--tRNA ligase beta subunit; Tyrosine 3-monooxygenase binder","Indication associated"]
[37,"DB00121","approved; investigational; nutraceutical","small molecule","Biotin","(+)-cis-Hexahydro-2-oxo-1H-thieno[3,4]imidazole-4-valeric acid; (3aS,4S,6aR)-Hexahydro-2-oxo-1H-thieno[3,4-d]imidazole-4-valeric acid; 5-(2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanoic acid; Biotin; cis-(+)-Tetrahydro-2-oxothieno[3,4]imidazoline-4-valeric acid; cis-Hexahydro-2-oxo-1H-thieno(3,4)imidazole-4-valeric acid; cis-Tetrahydro-2-oxothieno(3,4-d)imidazoline-4-valeric acid; Coenzyme R; D-(+)-biotin; D-Biotin; Vitamin B7; Vitamin H","C10H16N2O3S","[H][C@]12CS[C@@H](CCCCC(O)=O)[C@@]1([H])NC(=O)N2","A water-soluble, enzyme co-factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.","58-85-5","244.311","For nutritional supplementation, also for treating dietary shortage or imbalance.","Biotin is a water-soluble B-complex vitamin which is composed of an ureido ring fused with a tetrahydrothiophene ring, which attaches a valeric acid substituent at one of its carbon atoms. Biotin is used in cell growth, the production of fatty acids, metabolism of fats, and amino acids. It plays a role in the Kreb cycle, which is the process in which energy is released from food. Biotin not only assists in various metabolic chemical conversions, but also helps with the transfer of carbon dioxide. Biotin is also helpful in maintaining a steady blood sugar level. Biotin is often recommended for strengthening hair and nails. Consequenty, it is found in many cosmetic and health products for the hair and skin. Biotin deficiency is a rare nutritional disorder caused by a deficiency of biotin. Initial symptoms of biotin deficiency include: Dry skin, Seborrheic dermatitis, Fungal infections, rashes including erythematous periorofacial macular rash, fine and brittle hair, and hair loss or total alopecia. If left untreated, neurological symptoms can develop, including mild depression, which may progress to profound lassitude and, eventually, to somnolence; changes in mental status, generalized muscular pains (myalgias), hyperesthesias and paresthesias. The treatment for biotin deficiency is to simply start taking some biotin supplements. A lack of biotin in infants will lead to a condition called seborrheic dermatitis or \"cradle cap\". Biotin deficiencies are extremely rare in adults but if it does occur, it will lead to anemia, depression, hair loss, high blood sugar levels, muscle pain, nausea, loss of appetite and inflamed mucous membranes.","Biotin is necessary for the proper functioning of enzymes that transport carboxyl units and fix carbon dioxide, and is required for various metabolic functions, including gluconeogenesis, lipogenesis, fatty acid biosynthesis, propionate metabolism, and catabolism of branched-chain amino acids.","Propionyl-CoA carboxylase beta chain, mitochondrial cofactor; Biotin--protein ligase substrate; Methylcrotonoyl-CoA carboxylase beta chain, mitochondrial cofactor; Acetyl-CoA carboxylase 2 cofactor; Methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial cofactor; Pyruvate carboxylase, mitochondrial cofactor; Propionyl-CoA carboxylase alpha chain, mitochondrial cofactor; Acetyl-CoA carboxylase 1 cofactor","Target associated"]
[38,"DB00125","investigational; nutraceutical","small molecule","Arginine","(2S)-2-amino-5-(carbamimidamido)pentanoic acid; (2S)-2-amino-5-guanidinopentanoic acid; (S)-2-amino-5-guanidinopentanoic acid; (S)-2-Amino-5-guanidinovaleric acid; Arg; Arginine; L-(+)-Arginine; L-Arg; L-arginine; R","C6H14N4O2","N[C@@H](CCCNC(N)=N)C(O)=O","An essential amino acid that is physiologically active in the L-form.","74-79-3","174.201","Used for nutritional supplementation, also for treating dietary shortage or imbalance.","Studies have shown that is has improved immune responses to bacteria, viruses and tumor cells; promotes wound healing and regeneration of the liver; causes the release of growth hormones; considered crucial for optimal muscle growth and tissue repair.","Many of supplemental L-arginine's activities, including its possible anti-atherogenic actions, may be accounted for by its role as the precursor to nitric oxide or NO. NO is produced by all tissues of the body and plays very important roles in the cardiovascular system, immune system and nervous system. NO is formed from L-arginine via the enzyme nitric oxide synthase or synthetase (NOS), and the effects of NO are mainly mediated by 3,'5' -cyclic guanylate or cyclic GMP. NO activates the enzyme guanylate cyclase, which catalyzes the synthesis of cyclic GMP from guanosine triphosphate or GTP. Cyclic GMP is converted to guanylic acid via the enzyme cyclic GMP phosphodiesterase. NOS is a heme-containing enzyme with some sequences similar to cytochrome P-450 reductase. Several isoforms of NOS exist, two of which are constitutive and one of which is inducible by immunological stimuli. The constitutive NOS found in the vascular endothelium is designated eNOS and that present in the brain, spinal cord and peripheral nervous system is designated nNOS. The form of NOS induced by immunological or inflammatory stimuli is known as iNOS. iNOS may be expressed constitutively in select tissues such as lung epithelium. All the nitric oxide synthases use NADPH (reduced nicotinamide adenine dinucleotide phosphate) and oxygen (O2) as cosubstrates, as well as the cofactors FAD (flavin adenine dinucleotide), FMN (flavin mononucleotide), tetrahydrobiopterin and heme. Interestingly, ascorbic acid appears to enhance NOS activity by increasing intracellular tetrahydrobiopterin. eNOS and nNOS synthesize NO in response to an increased concentration of calcium ions or in some cases in response to calcium-independent stimuli, such as shear stress. In vitro studies of NOS indicate that the Km of the enzyme for L-arginine is in the micromolar range. The concentration of L-arginine in endothelial cells, as well as in other cells, and in plasma is in the millimolar range. What this means is that, under physiological conditions, NOS is saturated with its L-arginine substrate. In other words, L-arginine would not be expected to be rate-limiting for the enzyme, and it would not appear that supraphysiological levels of L-arginine which could occur with oral supplementation of the amino acid^would make any difference with regard to NO production. The reaction would appear to have reached its maximum level. However, in vivo studies have demonstrated that, under certain conditions, e.g. hypercholesterolemia, supplemental L-arginine could enhance endothelial-dependent vasodilation and NO production.","Nitric oxide synthase, endothelial; Cationic amino acid transporter 3; Arginine decarboxylase; Argininosuccinate lyase; Nitric oxide synthase, inducible; High affinity cationic amino acid transporter 1; Arginase-2, mitochondrial; Cationic amino acid transporter 4; Argininosuccinate synthase","Therapeutic strategy associated"]
[39,"DB00127","experimental; nutraceutical","small molecule","Spermine","4,9-diaza-1,12-dodecanediamine; 4,9-diazadodecane-1,12-diamine; Musculamine; N,N'-Bis(3-aminopropyl)-1,4-butanediamine; Spermine","C10H26N4","NCCCNCCCCNCCCN","Spermine is a spermidine-derived biogenic polyamine found as a polycation at all pH values. Found in various tissues and organisms, it often acts as an essential growth factor in some bacterial species. Spermine is associated with nucleic acids, particularly in viruses, and is thought to stabilize the helical structure.","71-44-3","202.3402","For nutritional supplementation, also for treating dietary shortage or imbalance","Spermine is a polyamine. It is an organic molecule that is involved in cellular metabolism.","Spermine is derived from spermidine by spermine synthase. Spermine is a polyamine, a small organic cations that is absolutely required for eukaryotic cell growth. Spermine, is normally found in millimolar concentrations in the nucleus. Spermine functions directly as a free radical scavenger, and forms a variety of adducts that prevent oxidative damage to DNA. Oxidative damage to DNA by reactive oxygen species is a continual problem that cells must guard against to survive. Hence, spermine is a major natural intracellular compound capable of protecting DNA from free radical attack. Spermine is also implicated in the regulation of gene expression, the stabilization of chromatin, and the prevention of endonuclease-mediated DNA fragmentation.","Spermine synthase ligand; Spermine oxidase ligand; DNA binder; Ornithine decarboxylase product of; Extracellular calcium-sensing receptor; Beta-1 adrenergic receptor; Beta-2 adrenergic receptor","Indication associated"]
[40,"DB00129","approved; nutraceutical","small molecule","Ornithine","(S)-2,5-Diaminopentanoate; (S)-2,5-Diaminopentanoic acid; (S)-2,5-diaminovaleric acid; (S)-ornithine; (S)-α,δ-diaminovaleric acid; L-Ornithine; levo-ornithine; Ornithine","C5H12N2O2","NCCC[C@H](N)C(O)=O","Produced during the urea cycle, ornithine is an amino acid produced from the splitting off of urea from arginine. L-Ornithine allows for the disposal of excess nitrogen and acts as a precursor of citrulline and arginine.","70-26-8","132.161","Used for nutritional supplementation, also for treating dietary shortage or imbalance. It has been claimed that ornithine improves athletic performance, has anabolic effects, has wound-healing effects, and is immuno-enhancing.","A non-essential and nonprotein amino acid, ornithine is critical for the production of the body's proteins, enzymes and muscle tissue. Ornithine plays a central role in the urea cycle and is important for the disposal of excess nitrogen (ammonia). Ornithine is the starting point for the synthesis of many polyamines such as putrescine and spermine. Ornithine supplements are claimed to enhance the release of growth hormone and to burn excess body fat. Ornithine is necessary for proper immune function and good liver function.","L-Ornithine is metabolised to L-arginine. L-arginine stimulates the pituitary release of growth hormone. Burns or other injuries affect the state of L-arginine in tissues throughout the body. As De novo synthesis of L-arginine during these conditions is usually not sufficient for normal immune function, nor for normal protein synthesis, L-ornithine may have immunomodulatory and wound-healing activities under these conditions (by virtue of its metabolism to L-arginine).","Ornithine aminotransferase, mitochondrial; Ornithine carbamoyltransferase, mitochondrial; Arginase-1; Ornithine decarboxylase antizyme 1; High affinity cationic amino acid transporter 1; Low affinity cationic amino acid transporter 2; Mitochondrial ornithine transporter 2; Arginase-2, mitochondrial; Mitochondrial ornithine transporter 1; Glycine amidinotransferase, mitochondrial","Indication associated"]
[41,"DB00130","approved; investigational; nutraceutical","small molecule","L-Glutamine","(2S)-2-amino-4-carbamoylbutanoic acid; (2S)-2,5-diamino-5-oxopentanoic acid; (S)-2,5-diamino-5-oxopentanoic acid; Glutamic acid 5-amide; Glutamic acid amide; Glutamine; L-(+)-glutamine; L-2-aminoglutaramic acid; L-glutamic acid γ-amide; L-Glutamine; Levoglutamide; Q","C5H10N2O3","N[C@@H](CCC(N)=O)C(O)=O","A non-essential amino acid present abundantly throughout the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. An oral formulation of L-glutamine was approved by the FDA in July 2017 for use in sickle cell disease . This oral formulation is marketed under the tradename Endari by Emmaus Medical.","56-85-9","146.1445","Used for nutritional supplementation, also for treating dietary shortage or imbalance.\r\n\r\nUsed to reduce the acute complications of sickle cell disease in adult and pediatric patients 5 years of age and older .","Like other amino acids, glutamine is biochemically important as a constituent of proteins. Glutamine is also crucial in nitrogen metabolism. Ammonia (formed by nitrogen fixation) is assimilated into organic compounds by converting glutamic acid to glutamine. The enzyme which accomplishes this is called glutamine synthetase. Glutamine can then be used as a nitrogen donor in the biosynthesis of many compounds, including other amino acids, purines, and pyrimidines.\r\n\r\nL-glutamine improves nicotinamide adenine dinucleotide (NAD) redox potential .","Supplemental L-glutamine's possible immunomodulatory role may be accounted for in a number of ways. L-glutamine appears to play a major role in protecting the integrity of the gastrointestinal tract and, in particular, the large intestine. During catabolic states, the integrity of the intestinal mucosa may be compromised with consequent increased intestinal permeability and translocation of Gram-negative bacteria from the large intestine into the body. The demand for L-glutamine by the intestine, as well as by cells such as lymphocytes, appears to be much greater than that supplied by skeletal muscle, the major storage tissue for L-glutamine. L-glutamine is the preferred respiratory fuel for enterocytes, colonocytes and lymphocytes. Therefore, supplying supplemental L-glutamine under these conditions may do a number of things. For one, it may reverse the catabolic state by sparing skeletal muscle L-glutamine. It also may inhibit translocation of Gram-negative bacteria from the large intestine. L-glutamine helps maintain secretory IgA, which functions primarily by preventing the attachment of bacteria to mucosal cells. L-glutamine appears to be required to support the proliferation of mitogen-stimulated lymphocytes, as well as the production of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma). It is also required for the maintenance of lymphokine-activated killer cells (LAK). L-glutamine can enhance phagocytosis by neutrophils and monocytes. It can lead to an increased synthesis of glutathione in the intestine, which may also play a role in maintaining the integrity of the intestinal mucosa by ameliorating oxidative stress. The exact mechanism of the possible immunomodulatory action of supplemental L-glutamine, however, remains unclear. It is conceivable that the major effect of L-glutamine occurs at the level of the intestine. Perhaps enteral L-glutamine acts directly on intestine-associated lymphoid tissue and stimulates overall immune function by that mechanism, without passing beyond the splanchnic bed.\r\n\r\nThe exact mechanism of L-glutamine's effect on NAD redox potential is unknown but is thought to involve increased amounts of reduced glutathione made available by glutamine supplementation . This improvement in redox potential reduces the amount of oxidative damage which sickle red blood cells are more susceptible to. The reduction in cellular damage is thought to reduce chronic hemolysis and vaso-occlusive events.","CTP synthase 1 antagonist&substrate; Amidophosphoribosyltransferase substrate; Glutamine synthetase product of","Therapeutic strategy associated"]
[42,"DB00131","approved; investigational; nutraceutical","small molecule","Adenosine phosphate","5'-Adenosine monophosphate; 5'-Adenylic acid; 5'-AMP; 5'-O-Phosphonoadenosine; Adenosine 5'-(dihydrogen phosphate); Adenosine 5'-monophosphate; Adenosine 5'-phosphate; Adenosine monophosphate; Adenosine phosphate; Adenosine-5'-Monophosphate; Adenosine-5'-monophosphoric acid; Adenosine-5'P; Adenylate; Adenylic acid; Ado5'P; AMP; PAdo","C10H14N5O7P","NC1=C2N=CN([C@@H]3O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]3O)C2=NC=N1","Adenylic acid. Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2&#39;-, 3&#39;-, or 5&#39;-position.","61-19-8","347.2212","For nutritional supplementation, also for treating dietary shortage or imbalance","Adenosine monophosphate, also known as 5'-adenylic acid and abbreviated AMP, is a nucleotide that is found in RNA. It is an ester of phosphoric acid with the nucleoside adenosine. AMP consists of the phosphate group, the pentose sugar ribose, and the nucleobase adenine. AMP is used as a dietary supplement to boost immune activity, and is also used as a substitute sweetener to aid in the maintenance of a low-calorie diet.","Nucleotides such as Adenosine-5'-Monophosphate affect a number of immune functions, including the reversal of malnutrition and starvation-induced immunosuppression, the enhancement of T-cell maturation and function, the enhancement of natural killer cell activity, the improvement of delayed cutaneous hypersensitivity, helping resistance to such infectious agents as Staphylococcus aureus and Candida albicans, and finally the modulation of T-cell responses toward type 1 CD4 helper lymphocytes or Th1 cells. Studies have shown that mice fed a nucleotide-free diet have both impaired humoral and cellular immune responses. The addition of dietary nucleotides normalizes both types of responses. RNA, a delivery form of nucleotides, and ribonucleotides were used in these studies. The mechanism of the immune-enhancing activity of nucleic acids/nucleotides is not clear.","Cyclic AMP-responsive element-binding protein 1 activator; DNA component of; cAMP-specific 3',5'-cyclic phosphodiesterase 4B product of; Glycogen phosphorylase, liver form activator; 5'-AMP-activated protein kinase subunit beta-1 activator; Histidine triad nucleotide-binding protein 1 product of; cAMP-specific 3',5'-cyclic phosphodiesterase 4D product of; Acetyl-coenzyme A synthetase, cytoplasmic product of; 5'-AMP-activated protein kinase catalytic subunit alpha-1 activator; Adenylate cyclase type 1 product of; Long-chain-fatty-acid--CoA ligase 1 product of; Fructose-1,6-bisphosphatase 1 antagonist; Adenosine kinase product of; 5'-AMP-activated protein kinase activator","Target associated"]
[43,"DB00132","approved; investigational; nutraceutical","small molecule","alpha-Linolenic acid","(9,12,15)-linolenic acid; (9Z,12Z,15Z)-Octadecatrienoic acid; (Z,Z,Z)-9,12,15-octadecatrienoic acid; 9-cis,12-cis,15-cis-octadecatrienoic acid; 9,12,15-Octadecatrienoic acid; ALA; all-cis-9,12,15-Octadecatrienoic acid; alpha-Linolenic acid; cis-delta(9,12,15)-Octadecatrienoic acid; cis,cis,cis-9,12,15-Octadecatrienoic acid; Linolenic acid; α-linolenic acid","C18H30O2","CC\\C=C/C\\C=C/C\\C=C/CCCCCCCC(O)=O","Alpha-linolenic acid (ALA) is a polyunsaturated omega-3 fatty acid. It is a component of many common vegetable oils and is important to human nutrition.","463-40-1","278.4296","For nutritional supplementation and for treating dietary shortage or imbalance.","Alpha Linolenic Acid (ALA) is an 18-carbon polyunsaturated fatty acid with three double bonds. It is also called an omega-3 fatty acid, and is essential for all mammals. Alpha-linolenic acid (or omega 3 fatty acid) intake can decrease the risk of cardiovascular diseases by 1) preventing arrhythmias that can lead to sudden cardiac death, 2) decreasing the risk of thrombosis (blood clot formation) that can lead to heart attack or stroke, 3) decreasing serum triglyceride levels, 4) slowing the growth of atherosclerotic plaque, 5) improving vascular endothelial function, 6) lowering blood pressure slightly, and 7) decreasing inflammation. ALA deficiencies can lead to visual problems and sensory neuropathy. Scaly and hemorrhagic skin or scalp inflammations may also develop.","Alpha Linolenic Acid or ALA is considered an essential fatty acid because it is required for human health, but cannot be synthesized by humans. It is in fact  a plant-derived fatty acid. Humans can synthesize other omega-3 fatty acids from ALA, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA is a precursor of the series-3 prostaglandins, the series-5 leukotrienes and the series-3 thromboxanes. These eicosanoids have anti-inflammatory and anti-atherogenic properties. ALA metabolites may also inhibit the production of the pro-inflammatory eicosanoids, prostaglandin E2 (PGE2) and leukotriene B4 (LTB4), as well as the pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). Omega-3 fatty acids like ALA and its byproducts can modulate the expression of a number of genes, including those involved with fatty acid metabolism and inflammation. They regulate gene expression through their effects on the activity of transcription factors including NF-kappa B and members of the peroxisome proliferator-activated receptor (PPAR) family. Incorporation of ALA and its metabolites in cell membranes can affect membrane fluidity and may play a role in anti-inflammatory activity, inhibition of platelet aggregation and possibly in anti-proliferative actions of ALA. ALA is first metabolized by delta6 desaturease into steridonic acid.","Fatty acid desaturase 1 ligand; Fatty acid desaturase 2 ligand; Sodium/calcium exchanger 1; Transient receptor potential cation channel subfamily V member 1 inhibitor; Peroxisome proliferator-activated receptor alpha; Bile acid receptor agonist; Peroxisome proliferator-activated receptor delta; Peroxisome proliferator-activated receptor gamma; Retinoic acid receptor RXR-alpha; Elongation of very long chain fatty acids protein 2 substrate; Elongation of very long chain fatty acids protein 5 substrate","Therapeutic strategy associated"]
[44,"DB00134","approved; nutraceutical","small molecule","Methionine","(2S)-2-amino-4-(methylsulfanyl)butanoic acid; (S)-2-amino-4-(methylthio)butanoic acid; (S)-2-amino-4-(methylthio)butyric acid; (S)-methionine; L-(−)-methionine; L-a-Amino-g-methylthiobutyric acid; L-Methionine; L-α-amino-γ-methylmercaptobutyric acid; M; Met; Methionine","C5H11NO2S","CSCC[C@H](N)C(O)=O","A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals.","63-68-3","149.211","Used for protein synthesis including the formation of SAMe, L-homocysteine, L-cysteine, taurine, and sulfate.","L-Methionine is a principle supplier of sulfur which prevents disorders of the hair, skin and nails; helps lower cholesterol levels by increasing the liver's production of lecithin; reduces liver fat and protects the kidneys; a natural chelating agent for heavy metals; regulates the formation of ammonia and creates ammonia-free urine which reduces bladder irritation; influences hair follicles and promotes hair growth. L-methionine may protect against the toxic effects of hepatotoxins, such as acetaminophen. Methionine may have antioxidant activity.","The mechanism of the possible anti-hepatotoxic activity of L-methionine is not entirely clear. It is thought that metabolism of high doses of acetaminophen in the liver lead to decreased levels of hepatic glutathione and increased oxidative stress. L-methionine is a precursor to L-cysteine. L-cysteine itself may have antioxidant activity. L-cysteine is also a precursor to the antioxidant glutathione. Antioxidant activity of L-methionine and metabolites of L-methionine appear to account for its possible anti-hepatotoxic activity. Recent research suggests that methionine itself has free-radical scavenging activity by virtue of its sulfur, as well as its chelating ability.","Methionine synthase reductase product of; Methionine synthase product of; Methionine aminopeptidase 2 product of; Betaine--homocysteine S-methyltransferase 1 product of; S-methylmethionine--homocysteine S-methyltransferase BHMT2 product of","Therapeutic strategy associated"]
[45,"DB00137","approved; investigational; nutraceutical","small molecule","Lutein","Xanthophyll; Xantofyl","C40H56O2","C\\C(\\C=C\\C=C(/C)\\C=C\\[C@H]1C(C)=C[C@H](O)CC1(C)C)=C/C=C/C=C(\\C)/C=C/C=C(\\C)/C=C/C1=C(C)C[C@@H](O)CC1(C)C","Lutein is an xanthophyll and one of 600 known naturally occurring carotenoids. Lutein is synthesized only by plants and like other xanthophylls is found in high quantities in green leafy vegetables such as spinach, kale and yellow carrots. In green plants, xanthophylls act to modulate light energy and serve as non-photochemical quenching agents to deal with triplet chlorophyll (an excited form of chlorophyll), which is overproduced at very high light levels, during photosynthesis.","127-40-2","568.886","Xanthophylls are taken for nutritional supplementation, and also for treating dietary shortage or imbalance.","Lutein was found to be present in a concentrated area of the macula, a small area of the retina responsible for central vision. The hypothesis for the natural concentration is that lutein helps protect from oxidative stress and high-energy light. Several studies show that an increase in macula pigmentation decreases the risk for eye diseases such as Age-related Macular Degeneration (AMD).","Xanthophylls have antioxidant activity and react with active oxygen species, producing biologically active degradation products. They also can inhibit peroxidation of membrane phospholipids and reduce lipofuscin formation, both of which contribute to their antioxidant properties. Lutein is naturally present in the macula of the human retina. It filters out potentially phototoxic blue light and near-ultraviolet radiation from the macula. The protective effect is due in part, to the reactive oxygen species quenching ability of these carotenoids. Lutein is more stable to decomposition by pro-oxidants than are other carotenoids such as beta-carotene and lycopene. Lutein is abundant in the region surrounding the fovea, and lutein is the predominant pigment at the outermost periphery of the macula. Zeaxanthin, which is fully conjugated (lutein is not), may offer somewhat better protection than lutein against phototoxic damage caused by blue and near-ultraviolet light radiation. Lutein is one of only two carotenoids that have been identified in the human lens, may be protective against age-related increases in lens density and cataract formation. Again, the possible protection afforded by lutein may be accounted for, in part, by its reactive oxygen species scavenging abilities. Carotenoids also provide protection from cancer. One of the mechanisms of this is by increasing the expression of the protein connexin-43, thereby stimulating gap junctional communication and preventing unrestrained cell proliferation.",null,"Therapeutic strategy associated"]
[46,"DB00138","approved; nutraceutical","small molecule","Cystine","(R,R)-3,3'-dithiobis(2-aminopropanoic acid); Cystine; L-alpha-Diamino-beta-dithiolactic acid; L-Cystine; L-Dicysteine; β,β'-dithiodialanine","C6H12N2O4S2","N[C@@H](CSSC[C@H](N)C(O)=O)C(O)=O","A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine.","56-89-3","240.3","It has been claimed that L-cysteine has anti-inflammatory properties, that it can protect against various toxins, and that it might be helpful in osteoarthritis and rheumatoid arthritis. More research will have to be done before L-cysteine can be indicated for any of these conditions. Research to date has mostly been in animal models.","L-Cystine is a covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. Cystine is a chemical substance which naturally occurs as a deposit in the urine, and can form a calculus (hard mineral formation) when deposited in the kidney. The compound produced when two cysteine molecules linked by a disulfide (S-S) bond. Cystine is required for proper vitamin B6 utilization and is also helpful in the healing of burns and wounds, breaking down mucus deposits in illnesses such as bronchitis as well as cystic fibrosis. Cysteine also assists in the supply of insulin to the pancreas, which is needed for the assimilation of sugars and starches. It increases the level of glutathione in the lungs, liver, kidneys and bone marrow, and this may have an anti-aging effect on the body by reducing age-spots etc.","Certain conditions, e.g. an acetaminophen overdose, deplete hepatic glutathione and subject the tissues to oxidative stress resulting in loss of cellular integrity. L-Cystine serves as a major precursor for synthesis of glutathione.","Cystine/glutamate transporter; Cystinosin","Therapeutic strategy associated"]
[47,"DB00139","approved; nutraceutical","small molecule","Succinic acid","1,2-ethanedicarboxylic acid; Amber acid; Asuccin; Butanedioic acid; Butanedionic acid; Dihydrofumaric acid; Ethylenesuccinic acid; Spirit of amber; Succinic acid","C4H6O4","OC(=O)CCC(O)=O","A water-soluble, colorless crystal with an acid taste that is used as a chemical intermediate, in medicine, the manufacture of lacquers, and to make perfume esters. It is also used in foods as a sequestrant, buffer, and a neutralizing agent. (Hawley's Condensed Chemical Dictionary, 12th ed, p1099; McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed, p1851)","110-15-6","118.088","For nutritional supplementation, also for treating dietary shortage or imbalance",null,"Succinate is an essential component of the Krebs or citric acid cycle and serves an electron donor in the production of fumaric acid and FADH2. It also has been shown to be a good \"natural\" antibiotic because of its relative acidic or caustic nature (high concentrations can even cause burns). Succinate supplements have been shown to help reduce the effects of hangovers by activating the degradation of acetaldehyde - a toxic byproduct of alcohol metabolism - into CO2 and H2O through aerobic metabolism. Succinic acid has been shown to stimulate neural system recovery and bolster the immune system. Claims have also been made that it boosts awareness, concentration and reflexes.","Succinate receptor 1; Succinate-semialdehyde dehydrogenase, mitochondrial inhibitor","Indication associated"]
[48,"DB00141","approved; investigational; nutraceutical","small molecule","N-Acetylglucosamine","2-Acetamido-2-deoxy-D-glucose; aldehydo-N-acetyl-D-glucosamine; D-GlcNAc; N-Acetyl-D-glucosamine; N-Acetylchitosamine","C8H15NO6","[H]C(=O)[C@H](NC(C)=O)[C@@H](O)[C@H](O)[C@H](O)CO","The N-acetyl derivative of glucosamine.","7512-17-6","221.2078","For the treatment and prevention of osteoarthritis, by itself or in combination with chondroitin sulfate.",null,"The mechanism of action in relieving arthritic pain and in repair of cartilage is a matter of speculation. Biochemically, glucosamine is involved in glycoprotein metabolism. Glycoproteins, known as proteoglycans, form the ground substance in the extra-cellular matrix of connective tissue. Proteoglycans are polyanionic substances of high-molecular weight and contain many different types of heteropolysaccharide side-chains covalently linked to a polypeptide-chain backbone. These polysaccharides make up to 95% of the proteoglycan structure. In fact, chemically, proteoglycans resemble polysaccharides more than they do proteins. The polysaccharide groups in proteoglycans are called glycosaminoglycans (GAGs). GAGs include hyaluronic acid, chondroitin sulfate, dermatan sulfate, keratan sulfate, heparin and heparan sulfate. All of the GAGs contain derivatives of glucosamine or galactosamine. Glucosamine derivatives are found in hyaluronic acid, keratan sulfate and heparan sulfate. Chondroitin sulfate contains derivatives of galactosamine. The glucosamine-containing glycosaminoglycan hyaluronic acid is vital for the function of articular cartilage. GAG chains are fundamental components of aggrecan found in articular cartilage. Aggrecan confers upon articular cartilage shock-absorbing properties. It does this by providing cartilage with a swelling pressure that is restrained by the tensile forces of collagen fibers. This balance confers upon articular cartilage the deformable resilience vital to its function. In the early stages of degenerative joint disease, aggrecan biosynthesis is increased. However, in later stages, aggrecan synthesis is decreased, leading eventually to the loss of cartilage resiliency and to most of the symptoms that accompany osteoarthritis. During the progression of osteoarthritis, exogenous glucosamine may have a beneficial role. It is known that, in vitro, chondrocytes do synthesize more aggregan when the culture medium is supplemented with glucosamine. N-acetylglucosamine is found to be less effective in these in vitro studies. Glucosamine has also been found to have antioxidant activity and to be beneficial in animal models of experimental arthritis. The counter anion of the glucosamine salt (i.e. chloride or sulfate) is unlikely to play any role in the action or pharmacokinetics of glucosamine. Further, the sulfate in glucosamine sulfate supplements should not be confused with the glucosamine sulfate found in such GAGs as keratan sulfate and heparan sulfate. In the case of the supplement, sulfate is the anion of the salt. In the case of the above GAGs, sulfate is present as an ester. Also, there is no glucosamine sulfate in chondroitin sulfate (source: PDRhealth).","Beta-1,4-galactosyltransferase 1; Beta-1,4-galactosyltransferase 4; N-acetyl-D-glucosamine kinase; N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase; Alpha-N-acetylglucosaminidase activator; N-acylglucosamine 2-epimerase","Indication associated"]
[49,"DB00146","approved; nutraceutical","small molecule","Calcifediol","(3S,5Z,7E)-9,10-secocholesta-5,7,10-triene-3,25-diol; (3β,5Z,7E)-9,10-secocholesta-5,7,10(19)-triene-3,25-diol; (5Z,7E)-(3S)-9,10-secocholesta-5,7,10(19)-triene-3,25-diol; 25-hydroxycholecalciferol; 25-Hydroxyvitamin D3; Calcidiol; Calcifediol anhydrous","C27H44O2","C[C@H](CCCC(C)(C)O)[C@@]1([H])CC[C@@]2([H])\\C(CCC[C@]12C)=C\\C=C1\\C[C@@H](O)CCC1=C","The major circulating metabolite of vitamin D3 (cholecalciferol). It is produced in the liver and is the best indicator of the body's vitamin D stores. It is effective in the treatment of rickets and osteomalacia, both in azotemic and non-azotemic patients. Calcifediol also has mineralizing properties.","19356-17-3","400.6371","Used to treat vitamin D deficiency or insufficiency, refractory rickets (vitamin D resistant rickets), familial hypophosphatemia and hypoparathyroidism, and in the management of hypocalcemia and renal osteodystrophy in patients with chronic renal failure undergoing dialysis. Also used in conjunction with calcium in the management and prevention of primary or corticosteroid-induced osteoporosis.","Calcidiol is the precursor of vitamin D3. Vitamin D3 is a steroid hormone that has long been known for its important role in regulating body levels of calcium and phosphorus, in mineralization of bone, and for the assimilation of vitamin A. The classical manifestations of vitamin D deficiency is rickets, which is seen in children and results in bony deformaties including bowed long bones. Deficiency in adults leads to the disease osteomalacia. Both rickets and osteomalacia reflect impaired mineralization of newly synthesized bone matrix, and usually result from a combination of inadequate exposure to sunlight and decreased dietary intake of vitamin D. Common causes of vitamin D deficiency include genetic defects in the vitamin D receptor, severe liver or kidney disease, and insufficient exposure to sunlight. Vitamin D plays an important role in maintaining calcium balance and in the regulation of parathyroid hormone (PTH). It promotes renal reabsorption of calcium, increases intestinal absorption of calcium and phosphorus, and increases calcium and phosphorus mobilization from bone to plasma.","Calcidiol is transformed in the kidney by 25-hydroxyvitamin D3-1-(alpha)-hydroxylase to calcitriol, the active form of vitamin D3. Calcitriol binds to intracellular receptors that then function as transcription factors to modulate gene expression. Like the receptors for other steroid hormones and thyroid hormones, the vitamin D receptor has hormone-binding and DNA-binding domains. The vitamin D receptor forms a complex with another intracellular receptor, the retinoid-X receptor, and that heterodimer is what binds to DNA. In most cases studied, the effect is to activate transcription, but situations are also known in which vitamin D suppresses transcription. Calcitriol increases the serum calcium concentrations by: increasing GI absorption of phosphorus and calcium, increasing osteoclastic resorption, and increasing distal renal tubular reabsorption of calcium. Calcitriol appears to promote intestinal absorption of calcium through binding to the vitamin D receptor in the mucosal cytoplasm of the intestine. Subsequently, calcium is absorbed through formation of a calcium-binding protein.","Vitamin D3 receptor agonist","Indication associated"]
[50,"DB00147","experimental; nutraceutical","small molecule","Pyridoxal","2-methyl-3-hydroxy-4-formyl-5-hydroxymethylpyridine; 3-hydroxy-5-(hydroxymethyl)-2-methyl-4-pyridinecarboxaldehyde; 3-hydroxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde; 3-hydroxy-5-(hydroxymethyl)-2-methylpyridine-4-carboxaldehyde; Piridoxal; Pyridoxaldehyde","C8H9NO3","CC1=NC=C(CO)C(C=O)=C1O","The 4-carboxyaldehyde form of vitamin B 6 which is converted to pyridoxal phosphate which is a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid.","66-72-8","167.162","Pyridoxal is one of the natural forms available of vitamin B6, therefore, it is used for nutritional supplementation and for treating dietary shortage or imbalances.","Pyridoxal principally in the form of the coenzyme pyridoxal 5'-phosphate, is involved in a wide range of biochemical reactions, including the metabolism of amino acids and glycogen, the synthesis of nucleic acids, hemogloblin, sphingomyelin and other sphingolipids, and the synthesis of the neurotransmitters serotonin, dopamine, norepinephrine and gamma-aminobutyric acid (GABA).","Pyridoxal is the precursor to pyridoxal phosphate. Pyridoxal 5'-phosphate is involved in a wide range of biochemical reactions, including the metabolism of amino acids and glycogen, the synthesis of nucleic acids, hemogloblin, sphingomyelin and other sphingolipids, and the synthesis of the neurotransmitters serotonin, dopamine, norepinephrine and gamma-aminobutyric acid (GABA).","Pyridoxal kinase","Indication associated"]
[51,"DB00148","approved; investigational; nutraceutical","small molecule","Creatine","((amino(Imino)methyl)(methyl)amino)acetic acid; (alpha-Methylguanido)acetic acid; (N-methylcarbamimidamido)acetic acid; (α-methylguanido)acetic acid; alpha-Methylguanidino acetic acid; Creatin; Creatine; Kreatin; Methylglycocyamine; N-(aminoiminomethyl)-N-methylglycine; N-amidinosarcosine; N-carbamimidoyl-N-methylglycine; N-methyl-N-guanylglycine","C4H9N3O2","CN(CC(O)=O)C(N)=N","An amino acid derivative that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine.","57-00-1","131.1332","For nutritional supplementation, also for treating dietary shortage or imbalance.","Creatine is a essential, non-proteinaceous amino acid derivative found in all animals. It is synthesized in the kidney, liver, and pancreas from L-arginine, glycine and L-methionine. Following its biosynthesis, creatine is transported to the skeletal muscle, heart, brain and other tissues. Most of the creatine is metabolized in these tissues to phosphocreatine (creatine phosphate). Phosphocreatine is a major energy storage form in the body. Supplemental creatine may have an energy-generating action during anaerobic exercise and may also have neuroprotective and cardioprotective actions.","In the muscles, a fraction of the total creatine binds to phosphate - forming creatine phosphate. The reaction is catalysed by creatine kinase, and the result is phosphocreatine (PCr). Phosphocreatine binds with adenosine diphosphate to convert it back to ATP (adenosine triphosphate), an important cellular energy source for short term ATP needs prior to oxidative phosphorylation.","Creatine kinase M-type ligand; Creatine kinase U-type, mitochondrial ligand; Creatine kinase B-type ligand; Creatine kinase S-type, mitochondrial ligand; Sodium- and chloride-dependent creatine transporter 1; Guanidinoacetate N-methyltransferase product of","Indication associated"]
[52,"DB00150","approved; nutraceutical; withdrawn","small molecule","Tryptophan","(2S)-2-amino-3-(1H-indol-3-yl)propanoic acid; (S)-alpha-Amino-beta-(3-indolyl)-propionic acid; (S)-Tryptophan; (S)-α-amino-1H-indole-3-propanoic acid; L-(-)-Tryptophan; L-(−)-tryptophan; L-Tryptophan; L-β-3-indolylalanine; Trp; Tryptophan; W","C11H12N2O2","N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O","An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor of indole alkaloids in plants. It is a precursor of serotonin (hence its use as an antidepressant and sleep aid). It can be a precursor to niacin, albeit inefficiently, in mammals.","73-22-3","204.2252","Tryptophan may be useful in increasing serotonin production, promoting healthy sleep, managing depression by enhancing mental and emotional well-being, managing pain tolerance, and managing weight.","Tryptophan is critical for the production of the body's proteins, enzymes and muscle tissue. It is also essential for the production of niacin, the synthesis of the neurotransmitter serotonin and melatonin. Tryptophan supplements can be used as natural relaxants to help relieve insomnia. Tryptophan can also reduce anxiety and depression and has been shown to reduce the intensity of migraine headaches. Other promising indications include the relief of chronic pain, reduction of impulsivity or mania and the treatment of obsessive or compulsive disorders. Tryptophan also appears to help the immune system and can reduce the risk of cardiac spasms. Tryptophan deficiencies may lead to coronary artery spasms. Tryptophan is used as an essential nutrient in infant formulas and intravenous feeding. Tryptophan is marketed as a prescription drug (Tryptan) for those who do not seem to respond well to conventional antidepressants. It may also be used to treat those afflicted with seasonal affective disorder (a winter-onset depression). Tryptopan serves as the precursor for the synthesis of serotonin (5-hydroxytryptamine, 5-HT) and melatonin (N-acetyl-5-methoxytryptamine).","A number of important side reactions occur during the catabolism of tryptophan on the pathway to acetoacetate. The first enzyme of the catabolic pathway is an iron porphyrin oxygenase that opens the indole ring. The latter enzyme is highly inducible, its concentration rising almost 10-fold on a diet high in tryptophan. Kynurenine is the first key branch point intermediate in the pathway. Kynurenine undergoes deamniation in a standard transamination reaction yielding kynurenic acid. Kynurenic acid and metabolites have been shown to act as antiexcitotoxics and anticonvulsives. A second side branch reaction produces anthranilic acid plus alanine. Another equivalent of alanine is produced further along the main catabolic pathway, and it is the production of these alanine residues that allows tryptophan to be classified among the glucogenic and ketogenic amino acids. The second important branch point converts kynurenine into 2-amino-3-carboxymuconic semialdehyde, which has two fates. The main flow of carbon elements from this intermediate is to glutarate. An important side reaction in liver is a transamination and several rearrangements to produce limited amounts of nicotinic acid, which leads to production of a small amount of NAD<sup>+</sup> and NADP<sup>+</sup>.","Tryptophan--tRNA ligase, mitochondrial inhibitor; Tryptophan--tRNA ligase inhibitor; Tryptophan--tRNA ligase, cytoplasmic inhibitor","Indication associated"]
[53,"DB00152","approved; investigational; nutraceutical; vet_approved","small molecule","Thiamine","Aneurin; Antiberiberi factor; thiamine(1+); thiamine(1+) ion; Vitamin B1","C12H17N4OS","CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N","Thiamine or thiamin, also known as vitamin B1, is a colorless compound with the chemical formula C12H17N4OS. It is soluble in water and insoluble in alcohol. Thiamine decomposes if heated. Thiamine was first discovered by Umetaro Suzuki in Japan when researching how rice bran cured patients of Beriberi. Thiamine plays a key role in intracellular glucose metabolism and it is thought that thiamine inhibits the effect of glucose and insulin on arterial smooth muscle cell proliferation. Thiamine plays an important role in helping the body convert carbohydrates and fat into energy. It is essential for normal growth and development and helps to maintain proper functioning of the heart and the nervous and digestive systems. Thiamine cannot be stored in the body; however, once absorbed, the vitamin is concentrated in muscle tissue.","70-16-6","265.355","For the treatment of thiamine and niacin deficiency states, Korsakov's alcoholic psychosis, Wernicke-Korsakov syndrome, delirium, and peripheral neuritis.","Thiamine is a vitamin with antioxidant, erythropoietic, cognition-and mood-modulatory, antiatherosclerotic, putative ergogenic, and detoxification activities. Thiamine has been found to protect against lead-induced lipid peroxidation in rat liver and kidney. Thiamine deficiency results in selective neuronal death in animal models. The neuronal death is associated with increased free radical production, suggesting that oxidative stress may play an important early role in brain damage associated with thiamine deficiency. Thiamine plays a key role in intracellular glucose metabolism and it is thought that thiamine inhibits the effect of glucose and insulin on arterial smooth muscle cell proliferation. Inhibition of endothelial cell proliferation may also promote atherosclerosis. Endothelial cells in culture have been found to have a decreased proliferative rate and delayed migration in response to hyperglycemic conditions. Thiamine has been shown to inhibit this effect of glucose on endothelial cells.","It is thought that the mechanism of action of thiamine on endothelial cells is related to a reduction in intracellular protein glycation by redirecting the glycolytic flux. Thiamine is mainly the transport form of the vitamin, while the active forms are phosphorylated thiamine derivatives. Natural derivatives of thiamine phosphate, such as thiamine monophosphate (ThMP), thiamine diphosphate (ThDP), also sometimes called thiamine pyrophosphate (TPP), thiamine triphosphate (ThTP), and thiamine triphosphate (AThTP), that act as coenzymes in addition to their each unique biological functions.","Thiamin pyrophosphokinase 1 substrate","Therapeutic strategy associated"]
[54,"DB00154","investigational; nutraceutical","small molecule","Dihomo-gamma-linolenic acid","(8Z,11Z,14Z)-Icosatrienoic acid; (Z,Z,Z)-8,11,14-Eicosatrienoic acid; (Z,Z,Z)-8,11,14-Icosatrienoate; (Z,Z,Z)-8,11,14-Icosatrienoic acid; 20:3, n-6,9,12 all-cis; 8,11,14-Eicosatrienoic Acid; 8c,11c,14c-eicosatrienoic acid; all-cis-8,11,14-eicosatrienoic acid; all-cis-8,11,14-icosatrienoic acid; all-cis-eicosa-8,11,14-trienoic acid; all-cis-icosa-8,11,14-trienoic acid; C20:3, n-6,9,12 all-cis; cis,cis,cis-8,11,14-eicosatrienoic acid; DGLA; dihomo-γ-linolenic acid; eicosa-8Z,11Z,14Z-trienoic acid; gamma-Homolinolenic acid; Homo-gamma-linolenic acid","C20H34O2","CCCCC\\C=C/C\\C=C/C\\C=C/CCCCCCC(O)=O","A 20-carbon-chain fatty acid, unsaturated at positions 8, 11, and 14. It differs from arachidonic acid, 5,8,11,14-eicosatetraenoic acid, only at position 5.","1783-84-2","306.4828","For nutritional supplementation, also for treating dietary shortage or imbalance","Dihomo gamma-linolenic acid or DHLA is an n-6 (omega-6) polyunsaturated fatty acid. It is comprised of 20 carbon atoms and three double bonds. DHLA is a byproduct of the 18 carbon gamma-linolenic acid (GLA). DHLA is then converted into prostaglandin E1 (PGE1). PGE1 inhibits platelet aggregation and also exerts a vasodilatory effect.","DHLA (or DGLA) is a precursor in the synthesis of prostaglandin E1 (PGE1) as well as the series-3 prostaglandins. It also serves as a precursor in the synthesis of eicosapentaenoic acid (EPA). EPA is a precursor of the series-3 prostaglandins, the series-5 leukotrienes and the series-3 thromboxanes. These eicosanoids have anti-thrombogenic, anti-inflammatory and anti-atherogenic properties. PGE1 inhibits platelet aggregation and has a vasodilation action. DHLA has also been shown to reduce the production/activity of tumor necrosis factor alpha.","Prostaglandin G/H synthase 1 inhibitor; Prostaglandin G/H synthase 2","Therapeutic strategy associated"]
[55,"DB00157","approved; nutraceutical","small molecule","NADH","1,4-dihydronicotinamide adenine dinucleotide; DPNH; NAD reduced form; Nicotinamide adenine dinucleotide (reduced); Nicotinamide-adenine dinucleotide, reduced; Reduced nicotinamide adenine diphosphate; Reduced nicotinamide-adenine dinucleotide","C21H29N7O14P2","NC(=O)C1=CN(C=CC1)[C@@H]1O[C@H](CO[P@](O)(=O)O[P@](O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)N2C=NC3=C(N)N=CN=C23)[C@@H](O)[C@H]1O","NADH is the reduced form of NAD+, and NAD+ is the oxidized form of NADH, a coenzyme composed of ribosylnicotinamide 5'-diphosphate coupled to adenosine 5'-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). It forms NADP with the addition of a phosphate group to the 2' position of the adenosyl nucleotide through an ester linkage. (Dorland, 27th ed)","58-68-4","665.441","Some evidence suggests that NADH might be useful in treating Parkinson's disease, chronic fatigue syndrome, Alzheimer's disease and cardiovascular disease.","A coenzyme composed of ribosylnicotinamide 5'-diphosphate coupled to adenosine 5'-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). The action of supplemental NADH is unclear. Oral NADH supplementation has been used to combat simple fatigue as well as such mysterious and energy-sapping disorders as chronic fatigue syndrome and fibromyalgia. Researchers are also studying the value of NADH supplements for improving mental function in people with Alzheimer's disease, and minimizing physical disability and relieving depression in people with Parkinson's disease. Some healthy individuals also take NADH supplements orally to improve concentration and memory capacity, as well as to increase athletic endurance. However, to date there have been no published studies to indicate that using NADH is in any way effective or safe for these purposes.","NADH is synthesized by the body and thus is not an essential nutrient. It does require the essential nutrient nicotinamide for its synthesis, and its role in energy production is certainly an essential one. In addition to its role in the mitochondrial electron transport chain, NADH is produced in the cytosol. The mitochondrial membrane is impermeable to NADH, and this permeability barrier effectively separates the cytoplasmic from the mitochondrial NADH pools. However, cytoplasmic NADH can be used for biologic energy production. This occurs when the malate-aspartate shuttle introduces reducing equivalents from NADH in the cytosol to the electron transport chain of the mitochondria. This shuttle mainly occurs in the liver and heart.","UDP-glucose 6-dehydrogenase; Alcohol dehydrogenase 1A; Sorbitol dehydrogenase; Alcohol dehydrogenase 4; Alcohol dehydrogenase 1C; Alcohol dehydrogenase 1B; Alcohol dehydrogenase class 4 mu/sigma chain; Glycerol-3-phosphate dehydrogenase [NAD(+)], cytoplasmic; L-lactate dehydrogenase A-like 6A; Alcohol dehydrogenase class-3; Aldose reductase; 3-hydroxyacyl-CoA dehydrogenase type-2; Malate dehydrogenase, mitochondrial; L-lactate dehydrogenase A chain; NAD-dependent malic enzyme, mitochondrial; Peroxisomal multifunctional enzyme type 2; L-lactate dehydrogenase A-like 6B; L-lactate dehydrogenase C chain; L-lactate dehydrogenase B chain; Peroxisomal bifunctional enzyme; Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial; NADP-dependent malic enzyme, mitochondrial; D-beta-hydroxybutyrate dehydrogenase, mitochondrial; Malate dehydrogenase, cytoplasmic; 3-hydroxyisobutyrate dehydrogenase, mitochondrial; Testosterone 17-beta-dehydrogenase 3; 3-hydroxy-3-methylglutaryl-coenzyme A reductase; NADP-dependent malic enzyme; D-3-phosphoglycerate dehydrogenase; 3-keto-steroid reductase; Isocitrate dehydrogenase [NAD] subunit gamma, mitochondrial; Isocitrate dehydrogenase [NAD] subunit beta, mitochondrial; Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial; Estradiol 17-beta-dehydrogenase 1; Estradiol 17-beta-dehydrogenase 2; 11-cis retinol dehydrogenase; GDH/6PGL endoplasmic bifunctional protein; Estradiol 17-beta-dehydrogenase 8; Aldo-keto reductase family 1 member C4; Inosine-5'-monophosphate dehydrogenase 2; Aldo-keto reductase family 1 member C3; 15-hydroxyprostaglandin dehydrogenase [NAD(+)]; GDP-L-fucose synthase; Aldo-keto reductase family 1 member C1; Corticosteroid 11-beta-dehydrogenase isozyme 1; 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2; 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1; Inosine-5'-monophosphate dehydrogenase 1; Trifunctional enzyme subunit alpha, mitochondrial; Aldehyde dehydrogenase, mitochondrial; Corticosteroid 11-beta-dehydrogenase isozyme 2; Aldo-keto reductase family 1 member C2; Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating; Aldehyde dehydrogenase family 3 member B2; Methylmalonate-semialdehyde dehydrogenase [acylating], mitochondrial; Aldehyde dehydrogenase, dimeric NADP-preferring; Retinal dehydrogenase 1; Glyceraldehyde-3-phosphate dehydrogenase, testis-specific; 4-trimethylaminobutyraldehyde dehydrogenase; Aldehyde dehydrogenase family 1 member A3; Aldehyde dehydrogenase X, mitochondrial; Aldehyde dehydrogenase family 3 member B1; Glyceraldehyde-3-phosphate dehydrogenase; Retinal dehydrogenase 2; Fatty aldehyde dehydrogenase; Succinate-semialdehyde dehydrogenase, mitochondrial; Alpha-aminoadipic semialdehyde dehydrogenase; Flavin reductase (NADPH); Pyrroline-5-carboxylate reductase 2; Pyrroline-5-carboxylate reductase 1, mitochondrial; Glutamate dehydrogenase 1, mitochondrial; Pyruvate dehydrogenase E1 component subunit beta, mitochondrial; Pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial; Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial; Biliverdin reductase A; Short-chain specific acyl-CoA dehydrogenase, mitochondrial; Dihydrofolate reductase; 2-oxoglutarate dehydrogenase, mitochondrial; Glutamate dehydrogenase 2, mitochondrial; 7-dehydrocholesterol reductase; Ribosyldihydronicotinamide dehydrogenase [quinone]; NADH-ubiquinone oxidoreductase chain 2 binder; Alpha-aminoadipic semialdehyde synthase, mitochondrial; NADH-ubiquinone oxidoreductase chain 3 binder; NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial; C-1-tetrahydrofolate synthase, cytoplasmic; Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial; Delta-1-pyrroline-5-carboxylate dehydrogenase, mitochondrial; NADH-cytochrome b5 reductase 3; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11; NADH-ubiquinone oxidoreductase chain 4; Dihydropteridine reductase; NADH-ubiquinone oxidoreductase chain 1 binder; NAD(P) transhydrogenase, mitochondrial; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, mitochondrial; NADH-ubiquinone oxidoreductase chain 4L; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10, mitochondrial; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 7; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1; NADH-ubiquinone oxidoreductase chain 6; NADH-ubiquinone oxidoreductase chain 5; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 4; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 6; Acyl carrier protein, mitochondrial; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mitochondrial; NADH dehydrogenase [ubiquinone] 1 subunit C2; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 1; NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mitochondrial; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 7; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9; NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 5, mitochondrial; NADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrial; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6; NADH dehydrogenase [ubiquinone] flavoprotein 3, mitochondrial; Dihydrolipoyl dehydrogenase, mitochondrial; NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial; Glutathione reductase, mitochondrial; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12; NADH dehydrogenase [ubiquinone] iron-sulfur protein 5; NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial; NADH dehydrogenase [ubiquinone] flavoprotein 1, mitochondrial; NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13; Cysteine dioxygenase type 1; NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 4-like 2; NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, mitochondrial; Cytochrome P450 4A11; Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial; Aminomethyltransferase, mitochondrial; Methylsterol monooxygenase 1; Heme oxygenase 1; Heme oxygenase 2; Steroid 17-alpha-hydroxylase/17,20 lyase; Tyrosinase","Target associated"]
[56,"DB00159","approved; nutraceutical","small molecule","Icosapent","(5Z,8Z,11Z,14Z,17Z)-5,8,11,14,17-eicosapentaenoic acid; (5Z,8Z,11Z,14Z,17Z)-Eicosapentaenoate; (5Z,8Z,11Z,14Z,17Z)-Eicosapentaenoic acid; (5Z,8Z,11Z,14Z,17Z)-Icosapentaenoic acid; (all-Z)-5,8,11,14,17-eicosapentaenoic acid; 5,8,11,14,17-eicosapentaenoic acid; 5,8,11,14,17-Icosapentaenoic acid; all-cis-5,8,11,14,17-eicosapentaenoic acid; all-cis-5,8,11,14,17-icosapentaenoic acid; all-cis-icosa-5,8,11,14,17-pentaenoic acid; cis-5,8,11,14,17-eicosapentaenoic acid; cis-5,8,11,14,17-EPA; cis-delta(5,8,11,14,17)-Eicosapentaenoic acid; Eicosapentaenoic acid; EPA; Icosapent; Icosapentaenoic acid; Timnodonic acid","C20H30O2","CC\\C=C/C\\C=C/C\\C=C/C\\C=C/C\\C=C/CCCC(O)=O","Important polyunsaturated fatty acid found in fish oils. It serves as the precursor for the prostaglandin-3 and thromboxane-3 families. A diet rich in eicosapentaenoic acid lowers serum lipid concentration, reduces incidence of cardiovascular disorders, prevents platelet aggregation, and inhibits arachidonic acid conversion into the thromboxane-2 and prostaglandin-2 families.","10417-94-4","302.451","EPA can be used for lowering elevated triglycerides in those who are hyperglyceridemic. In addition, EPA may play a therapeutic role in patients with cystic fibrosis by reducing disease severity and may play a similar role in type 2 diabetics in slowing the progression of diabetic nephropathy.","Eicosanoids are chemical messengers derived from 20-carbon polyunsaturated fatty acids that play critical roles in immune and inflammatory responses. Both 20-carbon omega-6 fatty acids (arachidonic acid) and 20-carbon omega-3 fatty acids (EPA) can be found in cell membranes. During an inflammatory response, arachidonic acid and EPA are metabolized by enzymes known as cyclooxygenases and lipoxygenases to form eicosanoids. Increasing omega-3 fatty acid intake increases the EPA content of cell membranes and decreases the arachidonic acid content, resulting in higher proportions of eicosanoids derived from EPA. Physiologic responses to arachidonic acid-derived eicosanoids differ from responses to EPA-derived eicosanoids. In general, eicosanoids derived from EPA are less potent inducers of inflammation, blood vessel constriction, and clotting than eicosanoids derived from arachidonic acid.","The anti-inflammatory, antithrombotic and immunomodulatory actions of EPA is probably due to its role in eicosanoid physiology and biochemistry. Most eicosanoids are produced by the metabolism of omega-3 fatty acids, specifically, arachidonic acid. These eicosanoids, leukotriene B4 (LTB4) and thromboxane A2 (TXA2) stimulate leukocyte chemotaxis, platelet aggregation and vasoconstriction. They are thrombogenic and artherogenic. On the other hand, EPA is metabolized to leukotriene B5 (LTB5) and thromboxane A3 (TXA3), which are eicosanoids that promote vasodilation, inhibit platelet aggregation and leukocyte chemotaxis and are anti-artherogenic and anti-thrombotic. The triglyceride-lowering effect of EPA results from inhibition of lipogenesis and stimulation of fatty acid oxidation. Fatty acid oxidation of EPA occurs mainly in the mitochondria. EPA is a substrate for Prostaglandin-endoperoxide synthase 1 and 2. It also appears to affect the function and bind to the Carbohydrate responsive element binding protein (ChREBP) and to a fatty acid receptor (G-coupled receptor) known as GP40.","Prostaglandin G/H synthase 2 inhibitor; Prostaglandin G/H synthase 1 inhibitor; Peroxisome proliferator-activated receptor gamma agonist; Peroxisome proliferator-activated receptor delta agonist; Fatty acid desaturase 1 agonist; Long-chain-fatty-acid--CoA ligase 4 inducer; Free fatty acid receptor 1 agonist; Sodium/calcium exchanger 1 inhibitor; Transient receptor potential cation channel subfamily V member 1 inducer; Peroxisome proliferator-activated receptor alpha; Fatty acid-binding protein, brain agonist","Therapeutic strategy associated"]
[57,"DB00169","approved; nutraceutical","small molecule","Cholecalciferol","(+)-vitamin D3; (3β,5Z,7E)-9,10-secocholesta-5,7,10(19)-trien-3-ol; (5Z,7E)-(3S)-9,10-secocholesta-5,7,10(19)-trien-3-ol; Activated 7-dehydrocholesterol; Calciol; CC; Cholecalciferol; Colecalciferol; Oleovitamin D3; Vitamin D-3; Vitamin D3","C27H44O","CC(C)CCC[C@@H](C)[C@@]1([H])CC[C@@]2([H])\\C(CCC[C@]12C)=C\\C=C1\\C[C@@H](O)CCC1=C","Vitamin D, in general, is a secosteroid generated in the skin when 7-dehydrocholesterol located there interacts with ultraviolet irradiation - like that commonly found in sunlight . Both the endogenous form of vitamin D (that results from 7-dehydrocholesterol transformation), vitamin D3 (cholecalciferol), and the plant-derived form, vitamin D2 (ergocalciferol), are considered the main forms of vitamin d and are found in various types of food for daily intake . Structurally, ergocalciferol differs from cholecalciferol in that it possesses a double bond between C22 and C23 and has an additional methyl group at C24 . Finally, ergocalciferol is pharmacologically less potent than cholecalciferol, which makes vitamin D3 the preferred agent for medical use .\r\n\r\nAppropriate levels of vitamin D must be upheld in the body in order to maintain calcium and phosphorus levels in a healthy physiologic range to sustain a variety of metabolic functions, transcription regulation, and bone metabolism . However, studies are also ongoing to determine whether or not cholecalciferol may also play certain roles in cancer, autoimmune disorders, cardiovascular disease, and other medical conditions that may be associated with vitamin D deficiency .","67-97-0","384.6377","Cholecalciferol use is indicated for the treatment of specific medical conditions like refractory rickets (or vitamin D resistant rickets), hypoparathyroidism, and familial hypophosphatemia .\r\n\r\nConcurrently, as one of the most commonly utilized forms of vitamin D, cholecalciferol is also very frequently used as a supplement in individuals to maintain sufficient vitamin d levels in the body or to treat vitamin D deficiency, as well as various medical conditions that can be associated directly or indirectly with vitamin d insufficiency like osteoporosis and chronic kidney disease, among others .","The in vivo synthesis of the predominant two biologically active metabolites of vitamin D occurs in two steps. The first hydroxylation of vitamin D3 cholecalciferol (or D2) occurs in the liver to yield 25-hydroxyvitamin D while the second hydroxylation happens in the kidneys to give 1, 25-dihydroxyvitamin D . These vitamin D metabolites subsequently facilitate the active absorption of calcium and phosphorus in the small intestine, serving to increase serum calcium and phosphate levels sufficiently to allow bone mineralization . Conversely, these vitamin D metabolites also assist in mobilizing calcium and phosphate from bone and likely increase the reabsorption of calcium and perhaps also of phosphate via the renal tubules . There exists a period of 10 to 24 hours between the administration of cholecalciferol and the initiation of its action in the body due to the necessity of synthesis of the active vitamin D metabolites in the liver and kidneys . It is parathyroid hormone that is responsible for the regulation of such metabolism at the level of the kidneys .","Most individuals naturally generate adequate amounts of vitamin D through ordinary dietary intake of vitamin D (in some foods like eggs, fish, and cheese) and natural photochemical conversion of the vitamin D3 precursor 7-dehydrocholesterol in the skin via exposure to sunlight .\r\n\r\nConversely, vitamin D deficiency can often occur from a combination of insufficient exposure to sunlight, inadequate dietary intake of vitamin D, genetic defects with endogenous vitamin D receptor, or even severe liver or kidney disease . Such deficiency is known for resulting in conditions like rickets or osteomalacia, all of which reflect inadequate mineralization of bone, enhanced compensatory skeletal demineralization, resultant decreased calcium ion blood concentrations, and increases in the production and secretion of parathyroid hormone . Increases in parathyroid hormone stimulate the mobilization of skeletal calcium and the renal excretion of phosphorus . This enhanced mobilization of skeletal calcium leads towards porotic bone conditions .\r\n\r\nOrdinarily, while vitamin D3 is made naturally via photochemical processes in the skin, both itself and vitamin D2 can be found in various food and pharmaceutical sources as dietary supplements. The principal biological function of vitamin D is the maintenance of normal levels of serum calcium and phosphorus in the bloodstream by enhancing the efficacy of the small intestine to absorb these minerals from the diet . At the liver, vitamin D3 or D2 is hydroxylated to 25-hydroxyvitamin D and then finally to the primary active metabolite 1,25-dihydroxyvitamin D in the kidney via further hydroxylation . This final metabolite binds to endogenous vitamin d receptors, which results in a variety of regulatory roles - including maintaining  calcium balance, the regulation of parathyroid hormone, the promotion of the renal reabsorption of calcium, increased intestinal absorption of calcium and phosphorus, and increased calcium and phosphorus mobilization of calcium and phosphorus from bone to plasma to maintain balanced levels of each in bone and the plasma .\r\n\r\nIn particular, calcitriol interacts with vitamin D receptors in the small intestine to enhance the efficiency of intestinal calcium and phosphorous absorption from about 10-15% to 30-40% and 60% increased to 80%, respectively . Furthermore, calcitriol binds with vitamin D receptors in osteoblasts to stimulate a receptor activator of nuclear factor kB ligand (or RANKL) which subsequently interacts with receptor activator of nuclear factor kB (NFkB) on immature preosteoclasts, causing them to become mature bone-resorbing osteoclasts . Such mature osteoclasts ultimately function in removing calcium and phosphorus from bone to maintain blood calcium and phosphorus levels . Moreover, calcitriol also stimulates calcium reabsorption from the glomerular filtrate in the kidneys .\r\n\r\nAdditionally, it is believed that when calcitriol binds with nuclear vitamin D receptors, that this bound complex itself binds to retinoic acid X receptor (RXR) to generate a heterodimeric complex that consequently binds to specific nucleotide sequences in the DNA called vitamin D response elements . When bound, various transcription factors attach to this complex, resulting in either up or down-regulation of the associated gene's activity. It is thought that there may be as much as 200 to 2000 genes that possess vitamin D response elements or that are influenced indirectly to control a multitude of genes across the genome .  It is in this way that cholecalciferol is believed to function in regulating gene transcription associated with cancer risk, autoimmune disorders, and cardiovascular disease linked to vitamin D deficiency . In fact, there has been some research to suggest calcitriol may also be able to prevent malignancies by inducing cellular maturation and inducing apoptosis and inhibiting angiogenesis, exhibit anti-inflammatory effects by inhibiting foam cell formation and promoting angiogenesis in endothelial colony-forming cells in vitro, inhibit immune reactions by enhancing the transcription of endogenous antibiotics like cathelicidin and regulate the activity and differentiation of CD4+ T cells, amongst a variety of other proposed actions .","Vitamin D3 receptor agonist","Therapeutic strategy associated"]
[58,"DB00170","approved; nutraceutical","small molecule","Menadione","2-Methyl-1,4-Naphthalenedione; 2-Methyl-1,4-naphthochinon; 2-Methyl-1,4-naphthoquinone; Menadione; Vitamin K 3; Vitamin K3","C11H8O2","CC1=CC(=O)C2=CC=CC=C2C1=O","A synthetic naphthoquinone without the isoprenoid side chain and biological activity, but can be converted to active vitamin K2, menaquinone, after alkylation in vivo.","58-27-5","172.18","The primary known function of vitamin K is to assist in the normal clotting of blood, but it may also play a role in normal bone calcification.","Menadione (Vitamin K3) is a fat-soluble vitamin precursor that is converted into menaquinone in the liver. Vitamin K1 and K2 are the naturally occurring types of vitamin K. The former, which is also known as phylloquinone, is synthesized by plants and can be found in such foods as spinach, broccoli, lettuce, and soybeans. The latter, sometimes alternatively referred to as menaquinone, is primarily produced by bacteria in the anterior part of the gut and the intestines. Vitamin K3, on the other hand, is one of the many manmade versions of vitamin K. Also called menadione, this yellowish, synthetic crystalline substance is converted into the active form of the K2 vitamin inside of the animal body. While a vitamin K deficiency can be dangerous, especially to infants that may easily suffer from extensive hemorrhaging, an overdose can be as equally detrimental. Newborns that are administered too great a dosage of vitamin K3 can suffer from kernicterus, a form of severe brain damage that may produce decreased movement, loss of appetite, seizures, deafness, mental retardation, and even death. This condition is associated with an abnormally high concentration of bilirubin, a bile pigment, in the tissues of the brain, which can be caused by the presence of K3. For this reason, K3 is less often utilized medically than it was in former times.","Menadione (vitamin K3) is involved as a cofactor in the posttranslational gamma-carboxylation of glutamic acid residues of certain proteins in the body. These proteins include the vitamin K-dependent coagulation factors II (prothrombin), VII (proconvertin), IX (Christmas factor), X (Stuart factor), protein C, protein S, protein Zv and a growth-arrest-specific factor (Gas6). In contrast to the other vitamin K-dependent proteins in the blood coagulation cascade, protein C and protein S serve anticoagulant roles. The two vitamin K-dependent proteins found in bone are osteocalcin, also known as bone G1a (gamma-carboxyglutamate) protein or BGP, and the matrix G1a protein or MGP. Gamma-carboxylation is catalyzed by the vitamin K-dependent gamma-carboxylases. The reduced form of vitamin K, vitamin K hydroquinone, is the actual cofactor for the gamma-carboxylases. Proteins containing gamma-carboxyglutamate are called G1a proteins.","Vitamin K-dependent gamma-carboxylase cofactor; Vitamin K epoxide reductase complex subunit 1 cofactor; Vitamin K epoxide reductase complex subunit 1-like protein 1 cofactor; Prothrombin activator; Coagulation factor IX activator; Vitamin K-dependent protein C activator; Vitamin K-dependent protein S activator; Ribosyldihydronicotinamide dehydrogenase [quinone]; NAD(P)H dehydrogenase [quinone] 1; Osteocalcin agonist","Therapeutic strategy associated"]
[59,"DB00171","investigational; nutraceutical","small molecule","ATP","Adenosine 5'-triphosphate; Adenosine triphosphate; Adenosine-5'-triphosphate; ATP","C10H16N5O13P3","NC1=NC=NC2=C1N=CN2[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O","An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.","56-65-5","507.181","For nutritional supplementation, also for treating dietary shortage or imbalance","Adenosine triphosphate (ATP) is the nucleotide known in biochemistry as the \"molecular currency\" of intracellular energy transfer; that is, ATP is able to store and transport chemical energy within cells. ATP also plays an important role in the synthesis of nucleic acids. The total quantity of ATP in the human body is about 0.1 mole. The energy used by human cells requires the hydrolysis of 200 to 300 moles of ATP daily. This means that each ATP molecule is recycled 2000 to 3000 times during a single day. ATP cannot be stored, hence its consumption must closely follow its synthesis.","ATP is able to store and transport chemical energy within cells. ATP also plays an important role in the synthesis of nucleic acids. ATP can be produced by various cellular processes, most typically in mitochondria by oxidative phosphorylation under the catalytic influence of ATP synthase. The total quantity of ATP in the human body is about 0.1 mole. The energy used by human cells requires the hydrolysis of 200 to 300 moles of ATP daily. This means that each ATP molecule is recycled 2000 to 3000 times during a single day. ATP cannot be stored, hence its consumption must closely follow its synthesis.","Abelson tyrosine-protein kinase 2 inhibitor; P-glycoprotein 1; ATP-binding cassette sub-family G member 1; Canalicular multispecific organic anion transporter 1; ATP-binding cassette sub-family A member 1; Acetyl-coenzyme A synthetase, cytoplasmic; ALK tyrosine kinase receptor; NEDD8-activating enzyme E1 regulatory subunit; 5'-AMP-activated protein kinase catalytic subunit alpha-1; Serine/threonine-protein kinase A-Raf; Serine/threonine-protein kinase receptor R3; Long-chain-fatty-acid--CoA ligase 1; Cytosolic purine 5'-nucleotidase; ATPase ASNA1; ATP-binding cassette sub-family C member 9; RAC-alpha serine/threonine-protein kinase; Beta-adrenergic receptor kinase 1; Apoptotic protease-activating factor 1; Acetyl-coenzyme A synthetase 2-like, mitochondrial; Activin receptor type-1B; Activin receptor type-1; Bile salt export pump; Asparagine synthetase [glutamine-hydrolyzing]; Cyclin-dependent kinase 15; ADP/ATP translocase 1; ATP-binding cassette sub-family C member 8; Argininosuccinate synthase; AFG3-like protein 2; Beta-adrenergic receptor kinase 2; Anti-Muellerian hormone type-2 receptor; Activated CDC42 kinase 1; Tyrosine-protein kinase ABL1 inhibitor; Adenylate cyclase type 1; Multidrug resistance-associated protein 6; Multidrug resistance-associated protein 4; Multidrug resistance-associated protein 1; Cystic fibrosis transmembrane conductance regulator cofactor; Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform; Casein kinase II subunit alpha; Casein kinase II subunit beta; P2Y purinoceptor 11; Serine/threonine-protein phosphatase 5","Indication associated"]
[60,"DB00173","approved; nutraceutical","small molecule","Adenine","6-Aminopurine; Adenin; Adenine; Vitamin B4","C5H5N5","NC1=C2NC=NC2=NC=N1","A purine base and a fundamental unit of adenine nucleotides.","73-24-5","135.1267","For nutritional supplementation, also for treating dietary shortage or imbalance","Adenine (sometimes known as vitamin B4) combines with the sugar ribose to form adenosine, which in turn can be bonded with from one to three phosphoric acid units, yielding AMP, ADP and ATP . These adenine derivatives perform important functions in cellular metabolism. Adenine is one of four nitrogenous bases utilized in the synthesis of nucleic acids. A modified form of adenosine monophosphate (cyclic AMP) is an imporant secondary messenger in the propagation of many hormonal stimuli. Adenine is an integral part of the structure of many coenzymes. Adenosine (adenine with a ribose group) causes transient heart block in the AV node of the heart. In individuals suspected of suffering from a supraventricular tachycardia (SVT), adenosine is used to help identify the rhythm. Certain SVTs can be successfully terminated with adenosine.","Adenine forms adenosine, a nucleoside, when attached to ribose, and deoxyadenosine when attached to deoxyribose, and it forms adenosine triphosphate (ATP), which drives many cellular metabolic processes by transferring chemical energy between reactions.","Adenine phosphoribosyltransferase; 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase; Acetyl-CoA carboxylase 2; Low molecular weight phosphotyrosine protein phosphatase; Peroxisomal trans-2-enoyl-CoA reductase; A/G-specific adenine glycosylase; Nucleoside deoxyribosyltransferase-I; SRSF protein kinase 2; Holliday junction ATP-dependent DNA helicase RuvB; DNA; S-methyl-5'-thioadenosine phosphorylase; Nicotinate-nucleotide--dimethylbenzimidazole phosphoribosyltransferase","Target associated"]
[61,"DB00174","approved; investigational; nutraceutical","small molecule","Asparagine","(2S)-2-amino-3-carbamoylpropanoic acid; (2S)-2,4-diamino-4-oxobutanoic acid; (S)-2-amino-3-carbamoylpropanoic acid; (S)-Asparagine; 2-Aminosuccinamic acid; alpha-aminosuccinamic acid; Asn; Asparagine; Aspartamic acid; L-2-aminosuccinamic acid; L-Asparagine; L-aspartic acid beta-amide; L-aspartic acid β-amide; α-aminosuccinamic acid","C4H8N2O3","N[C@@H](CC(N)=O)C(O)=O","A non-essential amino acid that is involved in the metabolic control of cell functions in nerve and brain tissue. It is biosynthesized from aspartic acid and ammonia by asparagine synthetase. (From Concise Encyclopedia Biochemistry and Molecular Biology, 3rd ed)","70-47-3","132.1179","Used for nutritional supplementation, also for treating dietary shortage or imbalance.","A non-essential amino acid. Asparagine is critical for the production of the body's proteins, enzymes and muscle tissue. Supplements of this amino acid are claimed to balance nervous system function.","Asparagine, a non-essential amino acid is important in the metabolism of toxic ammonia in the body through the action of asparagine synthase which attaches ammonia to aspartic acid in an amidation reaction. Asparagine is also used as a structural component in many proteins.","Neutral amino acid transporter B(0); Isoaspartyl peptidase/L-asparaginase substrate; Probable asparagine--tRNA ligase, mitochondrial; Asparagine synthetase [glutamine-hydrolyzing]; Asparagine--tRNA ligase, cytoplasmic; Sodium-coupled neutral amino acid transporters inhibitor","Indication associated"]
[62,"DB00175","approved","small molecule","Pravastatin","(+)-(3R,5R)-3,5-dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2-methyl-8-{[(S)-2-methylbutyryl]oxy}-1,2,6,7,8,8a-hexahydro-1-naphthyl]heptanoic acid; Pravastatin; Pravastatin acid","C23H36O7","[H][C@]12[C@H](C[C@H](O)C=C1C=C[C@H](C)[C@@H]2CC[C@@H](O)C[C@@H](O)CC(O)=O)OC(=O)[C@@H](C)CC","Pravastatin is the 6-alpha-hydroxy acid form of . Pravastatin was firstly approved in 1991 becoming the second available statin in the United States. It was the first statin administered as the active form and not as a prodrug. This drug was developed by Sankyo Co. Ltd.; however, the first approved pravastatin product was developed by Bristol Myers Squibb and FDA approved in 1991.\r\n\r\nPravastatin is made through a fermentation process in which  is first obtained. The manufacturing process is followed by the hydrolysis of the lactone group and the biological hydroxylation with _Streptomyces carbophilus_ to introduce the allylic 6-alcohol group.","81093-37-0","424.5277","Pravastatin is indicated for primary prevention of coronary events hypercholesterolemic patients without clinical evidence of coronary heart disease. Its use includes the reduction of risk on myocardial infarction, undergoing myocardial revascularization procedures and cardiovascular mortality.\r\n\r\nAs well, pravastatin can be used as a secondary prevention agent for cardiovascular events in patients with clinically evident coronary heart disease. This indication includes the reduction of risk of total mortality by reducing coronary death, myocardial infarction, undergoing myocardial revascularization procedures, stroke, and stroke/transient ischemic attack as well as to slow the progression of coronary atherosclerosis.\r\n\r\nThe term cardiovascular events correspond to all the incidents that can produce damage to the heart muscle including the interruption of blood flow.\r\n\r\nAs adjunctive therapy to diet, pravastatin is used in:\r\n\r\n- Patients with primary hypercholesterolemia and mixed dyslipidemias including hyperlipidemia type IIa and IIb.\r\n- Patients with elevated serum triglycerides including type IV hyperlipidemia.\r\n- Patients with heterozygous familial hypercholesterolemia in patients over 8 years of age with low-density lipoprotein (LDL) cholesterol higher than 190 mg/dl after diet modifications or LDL levels higher than 160 mg/dl and familial history of premature cardiovascular diseases or at least two cardiovascular risk factors.\r\n\r\nIn patients that do not respond adequately to diet, pravastatin is used to treat patients with primary dysbetalipoproteinemia (type III hyperlipidemia). \r\n\r\nDyslipidemia is defined as an elevation of plasma cholesterol, triglycerides or both as well as to the presence of low levels of high-density lipoprotein. This condition represents an increased risk for the development of atherosclerosis.","The action of pravastatin on the 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase produces an increase in the expression of hepatic LDL receptors which in order decreases the plasma levels of LDL cholesterol.\r\n\r\nThe effect of pravastatin has been shown to significantly reduce the circulating total cholesterol, LDL cholesterol, and apolipoprotein B. As well, it modestly reduces very low-density-lipoproteins (VLDL) cholesterol and triglycerides while increasing the level of high-density lipoprotein (HDL) cholesterol and apolipoprotein A.\r\n\r\nIn clinical trials with patients with a history of myocardial infarction or angina with high total cholesterol, pravastatin decreased the level of total cholesterol by 18%, decreased of LDL by 27%, decreased of triglycerides by 6% and increased of high-density lipoprotein (HDL) by 4%. As well, there was reported a decrease in risk of death due to coronary disease of 24%. \r\n\r\nWhen coadministered with , pravastatin can reduce by 50% the levels of LDL and slow the progression of atherosclerosis and the risk of myocardial infarction and death.","Pravastatin is a specific inhibitor of the hepatic HMG-CoA reductase in humans. The inhibition of this enzyme produces a reduction in cholesterol biosynthesis as HMG-CoA reductase activity is an early-limiting step in cholesterol biosynthesis.\r\n\r\nThe inhibitory mechanism of action produces a reduction in cholesterol synthesis which in order has been observed to increase the number of LDL receptors on cell surfaces and an enhancement in receptor-mediated metabolism of LDL and clearance.\r\n\r\nOn the other hand, pravastatin-driven inhibition of LDL production inhibits hepatic synthesis of VLDL as the LDL is the precursor for these molecules.","3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor; Histone deacetylase 2 inhibitor","Target associated"]
[63,"DB00176","approved; investigational","small molecule","Fluvoxamine","Fluvoxamine","C15H21F3N2O2","COCCCC\\C(=N/OCCN)C1=CC=C(C=C1)C(F)(F)F","Fluvoxamine is an antidepressant which functions pharmacologically as a selective serotonin reuptake inhibitor. Though it is in the same class as other SSRI drugs, it is most often used to treat obsessive-compulsive disorder.\r\nFluvoxamine has been in use in clinical practice since 1983 and has a clinical trial database comprised of approximately 35,000 patients. It was launched in the US in December 1994 and in Japan in June 1999. As of the end of 1995, more than 10 million patients worldwide have been treated with fluvoxamine.","54739-18-3","318.34","Indicated predominantly for the management of depression and for Obsessive Compulsive Disorder (OCD) . Has also been used in the management of bulimia nervosa .","Fluvoxamine, an aralkylketone-derivative agent , is one of a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs) that differs structurally from other SSRIs . It is used to treat the depression associated with mood disorders. It is also used on occassion in the treatment of body dysmorphic disorder and anxiety . The antidepressant, antiobsessive-compulsive, and antibulimic actions of Fluvoxamine are presumed to be linked to its inhibition of CNS neuronal uptake of serotonin . <i>In vitro</i> studies show that Fluvoxamine is a potent and selective inhibitor of neuronal serotonin reuptake and has only very weak effects on norepinephrine and dopamine neuronal reuptake . Moreover, apart from binding to σ1 receptors , fluvoxamine has no significant affinity for adrenergic (alpha1, alpha2, beta), cholinergic, GABA, dopaminergic, histaminergic, serotonergic (5HT<sub>1A</sub>, 5HT<sub>1B</sub>, 5HT<sub>2</sub>), or benzodiazepine receptors; antagonism of such receptors has been hypothesized to be associated with various anticholinergic, sedative, and cardiovascular effects for other psychotropic drugs . Furthermore, some studies have demonstrated that the chronic administration of Fluvoxamine was found to downregulate brain norepinephrine receptors (as has been observed with other drugs effective in the treatment of major depressive disorder), while others suggest the opposite .","The exact mechanism of action of fluvoxamine has not been fully determined, but appears to be linked to its inhibition of CNS neuronal uptake of serotonin . Fluvoxamine blocks the reuptake of serotonin at the serotonin reuptake pump of the neuronal membrane, enhancing the actions of serotonin on 5HT<sub>1A</sub> autoreceptors . Studies have also demonstrated that fluvoxamine has virtually no affinity for α<sub>1</sub>- or α<sub>2</sub>-adrenergic, β-adrenergic, muscarinic, dopamine D<sub>2</sub>, histamine H<sub>1</sub>, GABA-benzodiazepine, opiate, 5-HT<sub>1</sub>, or 5-HT<sub>2</sub> receptors, despite having an affinity for binding to σ1 receptors .","Sodium-dependent serotonin transporter inhibitor; Potassium voltage-gated channel subfamily H member 2","Indication associated"]
[64,"DB00177","approved; investigational","small molecule","Valsartan","(S)-N-Valeryl-N-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]-methyl}-valine; N-(P-(O-1H-Tetrazol-5-ylphenyl)benzyl)-N-valeryl-L-valine; N-pentanoyl-N-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-L-valine; Valsartan","C24H29N5O3","CCCCC(=O)N(CC1=CC=C(C=C1)C1=CC=CC=C1C1=NNN=N1)[C@@H](C(C)C)C(O)=O","Valsartan belongs to the angiotensin II receptor blocker (ARB) family of drugs, which also includes , , , , and . ARBs selectively bind to angiotensin receptor 1 (AT1) and prevent the protein angiotensin II from binding and exerting its hypertensive effects, which include vasoconstriction, stimulation and synthesis of aldosterone and ADH, cardiac stimulation, and renal reabsorption of sodium, among others. Overall, valsartan's physiologic effects lead to reduced blood pressure, lower aldosterone levels, reduced cardiac activity, and increased excretion of sodium. \r\n\r\nValsartan also affects the renin-angiotensin aldosterone system (RAAS), which plays an important role in hemostasis and regulation of kidney, vascular, and cardiac functions. Pharmacological blockade of RAAS via  AT1 receptor blockade inhibits negative regulatory feedback within RAAS, which is a contributing factor to the pathogenesis and progression of cardiovascular disease, heart failure, and renal disease. In particular, heart failure is associated with chronic activation of RAAS, leading to inappropriate fluid retention, vasoconstriction, and ultimately a further decline in left ventricular function. ARBs have been shown to have a protective effect on the heart by improving cardiac function, reducing afterload, increasing cardiac output and preventing ventricular hypertrophy and remodelling. \r\n\r\nBy comparison, the angiotensin-converting enzyme inhibitor (ACEI) class of medications (which includes drugs such as , , and ) inhibit the conversion of angiotensin I to angiotensin II through inhibition of the ACE enzyme. However, this does not prevent the formation of all angiotensin II within the body. The angiotensin II receptor blocker (ARB) family of drugs unique in that it blocks all angiotensin II activity, regardless of where or how it was synthesized. \r\n\r\nValsartan is commonly used for the management of hypertension, heart failure, and Type 2 Diabetes-associated nephropathy, particularly in patients who are unable to tolerate ACE inhibitors. ARBs such as valsartan have been shown in a number of large-scale clinical outcomes trials to improve cardiovascular outcomes including reducing risk of myocardial infarction, stroke, the progression of heart failure, and hospitalization. Valsartan also slows the progression of diabetic nephropathy due to its renoprotective effects. Improvements in chronic kidney disease with valsartan include both clinically and statistically significant decreases in urinary albumin and protein excretion in patients diagnosed with type 2 diabetes and in nondiabetic patients diagnosed with chronic kidney disease.\r\n\r\nValsartan was initially approved in 1996 in Europe for the treatment of hypertension in adults. Shortly after, in 1997, this drug was approved in the United States. Valsartan is generally well-tolerated with a side-effect profile superior to that of other antihypertensive drugs.","137862-53-4","435.5188","Valsartan is indicated for the treatment of hypertension to reduce the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. It is also indicated for the treatment of heart failure (NYHA class II-IV) and for left ventricular dysfunction or failure after myocardial infarction when the use of an angiotensin-converting enzyme inhibitor (ACEI) is not appropriate.","Valsartan inhibits the pressor effects of angiotensin II with oral doses of 80 mg inhibiting the pressor effect by about 80% at peak with approximately 30% inhibition persisting for 24 hours. Removal of the negative feedback of angiotensin II causes a 2- to 3-fold rise in plasma renin and consequent rise in angiotensin II plasma concentration in hypertensive patients. Minimal decreases in plasma aldosterone were observed after administration of valsartan.\r\n\r\nIn multiple-dose studies in hypertensive patients, valsartan had no notable effects on total cholesterol, fasting triglycerides, fasting serum glucose, or uric acid.\r\n\r\n**Hypotension** \r\n\r\nExcessive hypotension was rarely seen (0.1%) in patients with uncomplicated hypertension treated with valsartan alone. In patients with an activated renin-angiotensin system, such as volume- and/or salt-depleted patients receiving high doses of diuretics, symptomatic hypotension may occur. This condition should be corrected prior to administration of valsartan, or the treatment should start under close medical supervision. \r\n\r\nCaution should be observed when initiating therapy in patients with heart failure. Patients with heart failure given valsartan commonly have some reduction in blood pressure, but discontinuation of therapy because of continuing symptomatic hypotension usually is not necessary when dosing instructions are followed. In controlled trials in heart failure patients, the incidence of hypotension in valsartan-treated patients was 5.5% compared to 1.8% in placebo-treated patients. \r\n\r\nIf excessive hypotension occurs, the patient should be placed in the supine position and, if necessary, given an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once the blood pressure has stabilized.\r\n\r\n\r\n**Impaired Renal Function**\r\n\r\nChanges in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system and by diuretics. Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion) may be at particular risk of developing acute renal failure on valsartan. Monitor renal function periodically in these patients. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on valsartan.\r\n\r\n\r\n**Hyperkalemia**\r\n\r\nSome patients with heart failure have developed increases in potassium. These effects are usually minor and transient, and they are more likely to occur in patients with pre-existing renal impairment. Dosage reduction and/or discontinuation of valsartan may be required.","Valsartan belongs to the angiotensin II receptor blocker (ARB) family of drugs, which selectively bind to angiotensin receptor 1 (AT1) and prevent angiotensin II from binding and exerting its hypertensive effects. These include vasoconstriction, stimulation and synthesis of aldosterone and ADH, cardiac stimulation, and renal reabsorption of sodium among others. Overall, valsartan's physiologic effects lead to reduced blood pressure, lower aldosterone levels, reduced cardiac activity, and increased excretion of sodium. \r\n\r\nValsartan also affects the renin-angiotensin aldosterone system (RAAS), which plays an important role in hemostasis and regulation of kidney, vascular, and cardiac functions. Pharmacological blockade of RAAS via  AT1 receptor blockade inhibits negative regulatory feedback within RAAS which is a contributing factor to the pathogenesis and progression of cardiovascular disease, heart failure, and renal disease. In particular, heart failure is associated with chronic activation of RAAS, leading to inappropriate fluid retention, vasoconstriction, and ultimately a further decline in left ventricular function. ARBs have been shown to have a protective effect on the heart by improving cardiac function, reducing afterload, increasing cardiac output and prevent ventricular hypertrophy.\r\n\r\nThe angiotensin-converting enzyme inhibitor (ACEI) class of medications (which includes drugs such as , , and ) inhibits the conversion of angiotensin I to angiotensin II by inhibiting the ACE enzyme but does not prevent the formation of all angiotensin II. ARB activity is unique in that it blocks all angiotensin II activity, regardless of where or how it was synthesized. \r\n\r\nValsartan is commonly used for the management of hypertension, heart failure, and type 2 diabetes-associated nephropathy, particularly in patients who are unable to tolerate ACE inhibitors. ARBs such as valsartan have been shown in a number of large-scale clinical outcomes trials to improve cardiovascular outcomes including reducing risk of myocardial infarction, stroke, the progression of heart failure, and hospitalization. Valsartan also slows the progression of diabetic nephropathy due to its renoprotective effects. Improvements in chronic kidney disease with valsartan include both clinically and statistically significant decreases in urinary albumin and protein excretion in patients diagnosed with type 2 diabetes and in nondiabetic patients diagnosed with chronic kidney disease.\r\n\r\nValsartan also binds to the AT2 receptor, however AT2 is not known to be associated with cardiovascular homeostasis like AT1. Valsartan has about 20,000-fold higher affinity for the AT1 receptor than for the AT2 receptor. The increased plasma levels of angiotensin II following AT1 receptor blockade with valsartan may stimulate the unblocked AT2 receptor.","Type-1 angiotensin II receptor antagonist","Therapeutic strategy associated"]
[65,"DB00178","approved","small molecule","Ramipril","(2S-(1(R*(R*)),2alpha,3abeta,6abeta))-1-(2-((1-(Ethoxycarbonyl)-3-phenylpropyl)amino)-1-oxopropyl)octahydrocyclopenta(b)pyrrole-2-carboxylic acid; Ramipril","C23H32N2O5","[H][C@@]12CCC[C@]1([H])N([C@@H](C2)C(O)=O)C(=O)[C@H](C)N[C@@H](CCC1=CC=CC=C1)C(=O)OCC","Ramipril is a prodrug belonging to the angiotensin-converting enzyme (ACE) inhibitor class of medications. It is metabolized to ramiprilat in the liver and, to a lesser extent, kidneys. Ramiprilat is a potent, competitive inhibitor of ACE, the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). Ramipril may be used in the treatment of hypertension, congestive heart failure, nephropathy, and to reduce the rate of death, myocardial infarction and stroke in individuals at high risk of cardiovascular events.","87333-19-5","416.5106","For the management of mild to severe hypertension. May be used to reduce cardiovascular mortality following myocardial infarction in hemodynamically stable individuals who develop clinical signs of congestive heart failure within a few days following myocardial infarction.  To reduce the rate of death, myocardial infarction and stroke in individuals at high risk of cardiovascular events. May be used to slow the progression of renal disease in individuals with hypertension, diabetes mellitus and microalubinuria or overt nephropathy.","Ramipril is an ACE inhibitor similar to benazepril, fosinopril and quinapril.  It is an inactive prodrug that is converted to ramiprilat in the liver, the main site of activation, and kidneys. Ramiprilat confers blood pressure lowing effects by antagonizing the effect of the RAAS. The RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from the granular cells of the juxtaglomerular apparatus in the kidneys. In the blood stream, renin cleaves circulating angiotensinogen to ATI, which is subsequently cleaved to ATII by ACE. ATII increases blood pressure using a number of mechanisms. First, it stimulates the secretion of aldosterone from the adrenal cortex. Aldosterone travels to the distal convoluted tubule (DCT) and collecting tubule of nephrons where it increases sodium and water reabsorption by increasing the number of sodium channels and sodium-potassium ATPases on cell membranes. Second, ATII stimulates the secretion of vasopressin (also known as antidiuretic hormone or ADH) from the posterior pituitary gland. ADH stimulates further water reabsorption from the kidneys via insertion of aquaporin-2 channels on the apical surface of cells of the DCT and collecting tubules. Third, ATII increases blood pressure through direct arterial vasoconstriction. Stimulation of the Type 1 ATII receptor on vascular smooth muscle cells leads to a cascade of events resulting in myocyte contraction and vasoconstriction. In addition to these major effects, ATII induces the thirst response via stimulation of hypothalamic neurons. ACE inhibitors inhibit the rapid conversion of ATI to ATII and antagonize RAAS-induced increases in blood pressure. ACE (also known as kininase II) is also involved in the enzymatic deactivation of bradykinin, a vasodilator. Inhibiting the deactivation of bradykinin increases bradykinin levels and may sustain the effects of ramiprilat by causing increased vasodilation and decreased blood pressure.","Ramipril inhibits the RAAS system by binding to and inhibiting ACE thereby preventing the conversion of angiotensin I to angiotensin II.  As plasma levels of angiotensin II fall, less activation of the G-protein coupled receptors angiotensin receptor I (AT<sub>1</sub>R) and angiotensin receptor II (AT<sub>2</sub>R) occurs. \r\n\r\nAT<sub>1</sub>R mediates vasoconstriction, inflammation, fibrosis, and oxidative stress through a variety of signaling pathways.  These include G<sub>q</sub> coupling to the inositol triphosphate pathway, activation of phospholipases C, A<sub>2</sub>, and D which contribute to eicosanoid production, activation of Ca<sup>2+</sup>-dependent and MAP kinases, G<sub>i</sub> and G<sub>12/13</sub>, and eventual activation of the Jak/STAT pathway leading to cell growth and production of extracellular matrix components. AT<sub>1</sub>R activation also leads to increased activity of membrane-bound NADH/NADPH oxidase which contributes to production of reactive oxygen species. Decreased activation of this receptor mediates the renoprotective, antihypertensive, and cardioprotective effects of ramipril by reducing inflammation and vasoconstriction.\r\n\r\nAT<sub>2</sub>R acts in opposition to the effects of AT<sub>1</sub>R by activating phosphotyrosine phosphatases which inhibit MAP kinases, inhibiting Ca<sup>2+</sup> channel opening, and stimulating cGMP and nitric oxide production leading to vasodilation.  These counteracting effects are shared by the Mas receptor which is activated by Ang(1-7), a subtype of angiotensin produced by plasma esterases from AngI or by ACE2 from AngII produced through a secondary pathway by tonin and cathepsin G. Ang(1-7) also activates AT<sub>2</sub>R although the bulk of its effect is mediated by MasR.\r\n\r\nACE is also responsible for the breakdown of bradykinin.  The resulting buildup of bradykinin due to ACE inhibition is thought to mediate the characteristic dry-cough as a side effect of ACE inhibitor medications.\r\n\r","Angiotensin-converting enzyme inhibitor; B1 bradykinin receptor","Therapeutic strategy associated"]
[66,"DB00180","approved; investigational","small molecule","Flunisolide","Flunisolide anhydrous","C24H31FO6","[H][C@@]12C[C@@]3([H])[C@]4([H])C[C@H](F)C5=CC(=O)C=C[C@]5(C)[C@@]4([H])[C@@H](O)C[C@]3(C)[C@@]1(OC(C)(C)O2)C(=O)CO","Flunisolide (marketed as AeroBid, Nasalide, Nasarel) is a corticosteroid with anti-inflammatory actions. It is often prescribed as treatment for allergic rhinitis and its principle mechanism of action involves activation of glucocorticoid receptors.","3385-03-3","434.4977","For the maintenance treatment of asthma as a prophylactic therapy.","Flunisolide is a synthetic corticosteroid. It is administered either as an oral metered-dose inhaler for the treatment of asthma or as a nasal spray for treating allergic rhinitis. Corticosteroids are naturally occurring hormones that prevent or suppress inflammation and immune responses. When given as an intranasal spray, flunisolide reduces watery nasal discharge (rhinorrhea), nasal congestion, postnasal drip, sneezing, and itching oat the back of the throat that are common allergic symptoms.","Flunisolide is a glucocorticoid receptor agonist. The antiinflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. The immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding. Flunisolide binds to plasma transcortin, and it becomes active when it is not bound to transcortin.","Glucocorticoid receptor agonist","Therapeutic strategy associated"]
[67,"DB00181","approved","small molecule","Baclofen","(+-)-Baclofen; 4-Amino-3-(4-chlorophenyl)butyric acid; Baclofen; beta-(4-Chlorophenyl)gaba; beta-(Aminomethyl)-4-chlorobenzenepropanoic acid; beta-(Aminomethyl)-p-chlorohydrocinnamic acid; beta-(p-Chlorophenyl)-gamma-aminobutyric acid; DL-4-Amino-3-p-chlorophenylbutanoic acid; DL-Baclofen; gamma-Amino-beta-(p-chlorophenyl)butyric acid","C10H12ClNO2","NCC(CC(O)=O)C1=CC=C(Cl)C=C1","Baclofen is a gamma-aminobutyric acid (GABA) agonist used as a skeletal muscle relaxant used for the relief of painful and uncomfortable muscle spasms caused by a variety of conditions. It is particularly useful in treating muscle spasticity associated with spinal cord injury.\r\n\r\nThis drug has recently been studied for the management of alcohol withdrawal, however, a conclusion has not been made regarding baclofen efficacy in this condition. \r\n\r\nThis drug was first approved by the FDA in 1992.","1134-47-0","213.661","Baclofen is indicated for the treatment of spasticity resulting from multiple sclerosis and is particularly useful for the relief of flexor spasms and concomitant pain, clonus, and muscular rigidity. It may also be of value in the treatment of patients with spinal cord injuries or diseases.\r\n\r\nBaclofen is also indicated as an intrathecal injection for the management of severe spasticity of cerebral or spinal original in patients 4 years of age and older. Patients who respond to bolus intrathecal doses of baclofen, and who require chronic therapy, can use an implantable intrathecal pump to administer baclofen via long-term infusion.","In neurological diseases associated with spasm of the skeletal muscles, the clinical effects of baclofen occur due to baclofen action on reflex muscle contractions and of significant relief from painful spasm, automatism, as well as clonus. Baclofen, when used as indicated, improves mobility, increasing levels of independence, and facilitates both passive and active physiotherapy. Baclofen also stimulates gastric acid secretion .\r\n\r\nGABA-B receptor activation by baclofen may produce protective neurological effects. Baclofen also possesses anti-inflammatory properties that may be of interest in the study of addiction treatment . Preclinical studies have shown that GABA-B receptors have roles in memory storage and retrieval, reward, motivation, mood, as well as anxiety. Neuroimaging studies in humans indicate that baclofen produces region-specific alterations in brain activity.","The exact mechanism of action of baclofen is not fully understood at this time , . Many studies indicate that baclofen is a GABA-B receptor agonist , , , , . Despite this, there is no conclusive evidence that the effects of baclofen on GABA systems are involved in the production of its clinical effects .   \r\n\r\nBaclofen is an effective and widely used antispastic agent with a spinal site of action. Its mechanism of action and pharmacological properties are different from the effects of other antispastic agents. In addition, baclofen has central sites of action, shown by its adverse event profile and general CNS depressant properties . GABA-B receptors interact with signal transduction pathways and neurotransmitter systems. Baclofen exerts an antinociceptive effect. The clinical significance of this warrants further research data for clarification. \r\n\r\nBaclofen depresses monosynaptic and polysynaptic reflex transmission, by various actions, and possibly including the stimulation of GABAβ-receptors. This stimulation results in the inhibition of excitatory neurotransmitter (glutamate and aspartate) release, which may normally contribute to pain and spasticity. Although baclofen is an analog of the inhibitory neurotransmitter gamma-amino-butyric acid (GABA), there are no conclusive data indicating GABA systems are involved in its clinical effects .","Gamma-aminobutyric acid type B receptor subunit 1 agonist; Gamma-aminobutyric acid type B receptor subunit 2 agonist","Therapeutic strategy associated"]
[68,"DB00182","approved; illicit; investigational","small molecule","Amphetamine","(+-)-alpha-Methylphenylethylamine; 1-phenyl-2-aminopropane; alpha-Methylbenzeneethaneamine; Amfetamine; Amphetamine; beta-Aminopropylbenzene; Desoxynorephedrine; rac-(2R)-1-phenylpropan-2-amine; rac-amphetamine; α-methylbenzeneethaneamine; α-methylphenethylamine; β-aminopropylbenzene; β-phenylisopropylamine","C9H13N","CC(N)CC1=CC=CC=C1","Amphetamine, a compound discovered over 100 years ago, is one of the more restricted controlled drugs. It was previously used for a large variety of conditions and this changed until this point where its use is highly restricted. Amphetamine, with the chemical formula alpha-methylphenethylamine, was discovered in 1910 and first synthesized by 1927. After being proven to reduce drug-induced anesthesia and produce arousal and insomnia, amphetamine racemic mix was registered by Smith, Kline and French in 1935. Amphetamine structure presents one chiral center and it exists in the form of dextro- and levo-isomers. The first product of Smith, Kline and French was approved by the FDA on 1976.\r\n\r\nDuring World War II, amphetamine was used to promote wakefulness in the soldiers. This use derived into a large overproduction of amphetamine and all the surplus after the war finalized ended up in the black market, producing the initiation of the illicit abuse.","300-62-9","135.2062","Amphetamine is indicated for the treatment of attention-deficit/hyperactivity disorders (ADHD) as well as for the treatment of central nervous system disorders such as narcolepsy. \r\n\r\nADHD is a complex disorder associated with the substantial heterogeneity in etiology, clinical presentation, and treatment outcome. ADHD comes from a complex interplay between interdependent genetic and non-genetic factors which cause complex mental disorders in children and teenagers.\r\n\r\nOn the other hand, narcolepsy is a chronic sleep disorder typically resenting during adolescence and characterized by excessive daytime sleepiness.\r\n\r\nAmphetamine is also being used nowadays off-label for the treatment of obesity, depression and chronic pain.","From its mechanism of action, it has been demonstrated that amphetamine augments the concentration of noradrenaline in the prefrontal cortex and dopamine in the striatum on a dose and time-dependent manner. The indistinct release of neurotransmitters which include adrenaline is known to produce cardiovascular side effects. \r\n\r\nThere are old reports of a cognitive enhancement related to the administration of amphetamine in which improvements in intelligence test scores were reported.\r\n\r\nIn ADHD, amphetamine has been largely showed to produce remarkable improvements in school performance, behavior, and demeanor. The effect was shown to be produced through both racemic forms and to this date, the use of racemic forms 3:1 (D:L) is very common. The therapeutic effect of amphetamine on serotonin does not seem to have a significant clinical effect on ADHD as observed on comparative studies with amphetamine and fenfluramine, a powerful serotonin releasing factor. However, the indirect effect on serotonin might have an effect on the depression and anxiety profile of ADHD.\r\n\r\nStudies regarding the illicit use of amphetamine in which heavy consumers were studied proved the generation of a paranoid state which flagged this drug as a psychiatric danger compound. This observation was supported by the continuous reports of misuse in patients under depression.","It is important to consider that amphetamine has a very similar structure to the catecholamine neurotransmitters mainly on the presence of a long planar conformation, the presence of an aromatic ring and nitrogen in the aryl side chain. Amphetamine, as well as other catecholamines, is taken into presynaptic nerve terminals by the association with two sodium ions and one chloride ion. The complex of the amphetamine with the ions is actively transported by monoamine reuptake transporters. As amphetamine acts competitively with the endogenous monoamines, the greater the number of amphetamines the more internalized amphetamine will be found.\r\n\r\nOnce inside the presynaptic terminal, amphetamine displaces other monoamines to be stored by VMAT2 which produces the pumping of the neurotransmitters into the synapse by a process called retro-transport. This process of release of neurotransmitters is approximately fourfold more potent in the d-isomer for the release of dopamine.\r\n\r\nThe mechanism of action of amphetamine is complemented by the inhibition of the reuptake and of monoamine oxidase which acts synergistically to produce a significant increase the monoamine concentration. This activity is not done as an inhibitor per se but more as a competitive substrate and thus, amphetamine is known to be a weak dopamine reuptake inhibitor, moderate noradrenaline reuptake inhibitor and very weak serotonin reuptake inhibitor. From this specific action, the l-isomer is known to be significantly less potent.\r\n\r\nLastly, amphetamine is known to be an inhibitor of the mitochondrial-bound enzyme MAO which is the catalytic enzyme in charge of degrading all the excess of neurotransmitters. This mechanism of action is often overpassed as amphetamine is a weak MAO inhibitor but this mechanism cannot be dismissed.","Synaptic vesicular amine transporter inhibitor; Sodium-dependent dopamine transporter negative modulator; Cocaine- and amphetamine-regulated transcript protein agonist; Trace amine-associated receptor 1 agonist; Sodium-dependent noradrenaline transporter agonist&substrate; Alpha adrenergic receptor agonist; Beta adrenergic receptor agonist; Dopamine D2 receptor binder; Amine oxidase [flavin-containing] B inhibitor; Sodium-dependent serotonin transporter binder; Monoamine oxidase inhibitor; vesicular monoamine transporter 2 (VMAT2)","Indication associated"]
[69,"DB00187","approved","small molecule","Esmolol","(±)-esmolol; (±)-methyl p-(2-hydroxy-3-(isopropylamino)propoxy)hydrocinnamate; 3-[4-(2-Hydroxy-3-isopropylamino-propoxy)-phenyl]-propionic acid methyl ester; Esmolol; Methyl 4-(2-hydroxy-3-((1-methylethyl)amino)propoxy)benzenepropanoate; methyl p-(2-hydroxy-3-(isopropylamino)propoxy)hydrocinnamate","C16H25NO4","COC(=O)CCC1=CC=C(OCC(O)CNC(C)C)C=C1","Esmolol, commonly marketed under the trade name Brevibloc, is a cardioselective beta-1 receptor blocker. It has a rapid onset but short duration of action without causing significant intrinsic sympathomimetic or membrane stabilizing activities at recommended therapeutic doses. It works by blocking beta-adrenergic receptors in the heart, which leads to decreased force and rate of heart contractions. Esmolol prevents the action of two naturally occurring substances: epinephrine and norepinephrine.","81147-92-4","295.374","For the rapid control of ventricular rate in patients with atrial fibrillation or atrial flutter in perioperative, postoperative, or other emergent circumstances where short term control of ventricular rate with a short-acting agent is desirable. Also used in noncompensatory sinus tachycardia where the rapid heart rate requires specific intervention.",null,"Similar to other beta-blockers, esmolol blocks the agonistic effect of the sympathetic neurotransmitters by competing for receptor binding sites. Because it predominantly blocks the beta-1 receptors in cardiac tissue, it is said to be cardioselective. In general, so-called cardioselective beta-blockers are relatively cardioselective; at lower doses they block beta-1 receptors only but begin to block beta-2 receptors as the dose increases. At therapeutic dosages, esmolol does not have intrinsic sympathomimetic activity (ISA) or membrane-stabilizing (quinidine-like) activity. Antiarrhythmic activity is due to blockade of adrenergic stimulation of cardiac pacemaker potentials. In the Vaughan Williams classification of antiarrhythmics, beta-blockers are considered to be class II agents.","Beta-1 adrenergic receptor antagonist","Indication associated"]
[70,"DB00188","approved; investigational","small molecule","Bortezomib","[(1R)-3-methyl-1-({(2S)-3-phenyl-2-[(pyrazin-2-ylcarbonyl)amino]propanoyl}amino)butyl]boronic acid; Bortezomib; N-[(1R)-1-(DIHYDROXYBORYL)-3-methylbutyl]-N-(pyrazin-2-ylcarbonyl)-L-phenylalaninamide","C19H25BN4O4","CC(C)C[C@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)C1=CN=CC=N1)B(O)O","Bortezomib is a dipeptide boronic acid derivative and proteasome inhibitor used to treat multiple myeloma and mantle cell lymphoma. The 26S proteasome is a protein complex that degrades ubiquitinated proteins in the ubiquitin-proteasome pathway: reversible inhibition of the 26S proteasome, leading to cell cycle arrest and apoptosis of cancer cells, is thought to be the main mechanism of action of bortezomib. However, multiple mechanisms may be involved in the anticancer activity of bortezomib.\r\n\r\nBortezomib was first synthesized in 1995. In May 2003, bortezomib became the first anticancer proteasome inhibitor that was approved by the FDA under the trade name VELCADE. Phase I, II, III, and IV clinical trials are undergoing to investigate the therapeutic efficacy of bortezomib in leukemia, myasthenia gravis, systemic lupus erythematosus, rheumatoid arthritis, and solid tumours.","179324-69-7","384.237","Bortezomib is indicated for the treatment of adult patients with multiple myeloma or mantle cell lymphoma.","Bortezomib works to target the ubiquitin-proteasome pathway, an essential molecular pathway that regulates intracellular concentrations of proteins and promotes protein degradation. The ubiquitin-proteasome pathway is often dysregulated in pathological conditions, leading to aberrant pathway signalling and the formation of malignant cells. In one study, patient-derived chronic lymphocytic leukemia (CLL) cells contained 3-fold higher levels of chymotrypsin-like proteasome activity than normal lymphocytes. By reversibly inhibiting proteasome, bortezomib prevents proteasome-mediated proteolysis. Bortezomib exerts a cytotoxic effect on various cancer cell types _in vitro_ and delays tumour growth _in vivo_ in nonclinical tumour models. Bortezomib inhibits the proteasome activity in a dose-dependent manner. In one pharmacodynamic study, more than 75% of proteasome inhibition was observed in whole blood samples within one hour after dosing of bortezomib.","The ubiquitin-proteasome pathway is a homeostatic proteolytic pathway for intracellular protein degradation: proteins marked with a poly-ubiquitin chain are degraded to small peptides and free ubiquitin by the proteasome, which is a large multimeric protease. Aberrant proteasome-dependent proteolysis, as seen in some malignancies, can lead to uncontrolled cell division, leading to tumorigenesis, cancer growth, and spread. \r\n\r\nBortezomib is a reversible inhibitor of the 26S proteasome, which is made up of a 20S core complexed with a 19S regulatory complex. Individual β-subunits allow specific catalytic action of the 20S core. In mammalian cells, bortezomib is a potent inhibitor of the proteasome’s chymotryptic-like activity, which is attributed to the β5-subunit of the 20S core particle. Bortezomib binds to the active site of the threonine hydroxyl group in the β5-subunit. A probing study showed bortezomib also binding to and inhibiting the β1-subunit, which mediates the caspase-like activity of the proteasome, and β1i-subunit, which is an altered subunit that is expressed to form immunoproteasomes in response to cell stress or inflammation. By inhibiting the proteasome-mediated degradation of key proteins that promote cell apoptosis, bortezomib induces a cell cycle arrest during the G2-M phase. It is believed that multiple mechanisms, other than proteasome inhibition, may be involved in the anticancer activity of bortezomib. The anticancer activity of bortezomib was largely associated with suppression of the NF-κB signalling pathway, resulting in the downregulation of anti-apoptotic target genes and expression of anti-apoptic proteins. This may be explained by bortezomib preventing uncontrolled degradation of IκB, which is an inhibitory protein of NF-κB. NOXA, which is a pro-apoptotic factor, induced by bortezomib selectively in cancer cells; thus, it is suggested to be another key mechanism of bortezomib.","Proteasome subunit beta type-5 inhibitor; Proteasome subunit beta type-1 inhibitor","Therapeutic strategy associated"]
[71,"DB00193","approved; investigational","small molecule","Tramadol","Tramadol","C16H25NO2","COC1=CC=CC(=C1)C1(O)CCCCC1CN(C)C","Tramadol is a centrally acting synthetic opioid analgesic and SNRI (serotonin/norepinephrine reuptake-inhibitor) that is structurally related to  and . Due to its good tolerability profile and multimodal mechanism of action, tramadol is generally considered a lower-risk opioid option for the treatment of moderate to severe pain. It is considered a Step 2 option on the World Health Organization's pain ladder and has about 1/10th of the potency of . \r\n\r\nTramadol differs from other traditional opioid medications in that it doesn't just act as a μ-opioid agonist, but also affects monoamines by modulating the effects of neurotransmitters involved in the modulation of pain such as serotonin and norepinpehrine which activate descending pain inhibitory pathways. Tramadol's effects on serotonin and norepinephrine mimic the effects of other SNRI antidepressants such as  and .\r\n\r\nTramadol exists as a racemic mixture consisting of two pharmacologically active enantiomers that both contribute to its analgesic property through different mechanisms and are also themselves metabolized into active metabolites: (+)-tramadol and its primary metabolite (+)-O-desmethyl-tramadol (M1) are agonists of the μ opioid receptor while (+)-tramadol inhibits serotonin reuptake and (-)-tramadol inhibits norepinephrine reuptake. These pathways are complementary and synergistic, improving tramadol's ability to modulate the perception of and response to pain. \r\n\r\nTramadol has also been shown to affect a number of other pain modulators within the central nervous system as well as non-neuronal inflammatory markers and immune mediators. Due to the broad spectrum of targets involved in pain and inflammation, it's not surprising that the evidence has shown that tramadol is effective for a number of pain types including neuropathic pain, post-operative pain, lower back pain, as well as pain associated with labour, osteoarthritis, fibromyalgia, and cancer. Due to its SNRI activity, tramadol also has anxiolytic, antidepressant, and anti-shivering effects which are all frequently found as comorbidities with pain.\r\n\r\nSimilar to other opioid medications, tramadol poses a risk for development of tolerance, dependence and abuse. If used in higher doses, or with other opioids, there is a dose-related risk of overdose, respiratory depression, and death. However, unlike other opioid medications, tramadol use also carries a risk of seizure and serotonin syndrome, particularly if used with other serotonergic medications.","27203-92-5","263.381","Tramadol is approved for the management of moderate to severe pain in adults.\r\n\r\nTramadol is also used off-label in the treatment of premature ejaculation.","Tramadol modulates the descending pain pathways within the central nervous system through the binding of parent and M1 metabolite to μ-opioid receptors and the weak inhibition of the reuptake of norepinephrine and serotonin. \r\n\r\nApart from analgesia, tramadol may produce a constellation of symptoms (including dizziness, somnolence, nausea, constipation, sweating and pruritus) similar to that of other opioids. \r\n\r\n**Central Nervous System**\r\n\r\nIn contrast to , tramadol has not been shown to cause histamine release. At therapeutic doses, tramadol has no effect on heart rate, left-ventricular function or cardiac index. Orthostatic hypotension has been observed.\r\n\r\nTramadol produces respiratory depression by direct action on brain stem respiratory centres. The respiratory depression involves both a reduction in the responsiveness of the brain stem centres to increases in CO2 tension and to electrical stimulation. \r\n\r\nTramadol depresses the cough reflex by a direct effect on the cough centre in the medulla. Antitussive effects may occur with doses lower than those usually required for analgesia.\r\n\r\nTramadol causes miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but\r\nare not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origin may produce\r\nsimilar findings). Marked mydriasis rather than miosis may be seen with hypoxia in the setting of\r\noxycodone overdose.\r\n\r\nSeizures have been reported in patients receiving tramadol within the recommended dosage range. Spontaneous post-marketing reports indicate that seizure risk is increased with doses of tramadol above the recommended range. Risk of convulsions may also increase in patients with epilepsy, those with a history of seizures\r\nor in patients with a recognized risk for seizure (such as head trauma, metabolic disorders,\r\nalcohol and drug withdrawal, CNS infections), or with concomitant use of other drugs known to reduce the seizure threshold.\r\n\r\nTramadol can cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs (e.g., anti-depressants, migraine medications). Treatment with the serotoninergic drug should be discontinued if such events (characterized by clusters of symptoms such as hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, mental status changes including confusion, irritability, extreme agitation progressing to delirium and coma) occur and supportive symptomatic treatment should be initiated. Tramadol should not be used in combination with MAO inhibitors or serotonin-precursors (such as L-tryptophan, oxitriptan) and should be used with caution in combination with other serotonergic drugs (triptans, certain tricyclic antidepressants, lithium, St. John’s Wort) due to the risk of serotonin syndrome.\r\n\r\n**Gastrointestinal Tract and Other Smooth Muscle**\r\n\r\nTramadol causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone may be increased to the point of spasm resulting in constipation. Other opioid-induced effects may include a reduction in gastric, biliary and pancreatic secretions, spasm of the sphincter of Oddi, and transient elevations in serum amylase.\r\n\r\n**Endocrine System**\r\n\r\nOpioids may influence the hypothalamic-pituitary-adrenal or -gonadal axes. Some changes that can be seen include an increase in serum prolactin and decreases in plasma cortisol and testosterone. Clinical signs and symptoms may be manifest from these hormonal changes.\r\n\r\nHyponatremia has been reported very rarely with the use of tramadol, usually in patients with predisposing risk factors, such as elderly patients and/or patients using concomitant medications that may cause hyponatremia (e.g., antidepressants, benzodiazepines, diuretics). In some reports, hyponatremia appeared to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and resolved with discontinuation of tramadol and appropriate treatment (e.g., fluid restriction). During tramadol treatment, monitoring for signs and symptoms of hyponatremia is recommended for patients with predisposing risk factors.\r\n\r\n**Cardiovascular**\r\n\r\nTramadol administration may result in severe hypotension in patients whose ability to maintain adequate blood pressure is compromised by reduced blood volume, or concurrent administration of drugs such as phenothiazines and other tranquillizers, sedative/hypnotics, tricyclic antidepressants or general anesthetics. These patients should be monitored for signs of hypotension after initiating or titrating the dose of tramadol.\r\n\r\n**QTc-Interval Prolongation**\r\n\r\nThe maximum placebo-adjusted mean change from baseline in the QTcF interval was 5.5 ms in the 400 mg/day treatment arm and 6.5 ms in the 600 mg/day mg treatment arm, both occurring at the 8h time point. Both treatment groups were within the 10 ms threshold for QT prolongation. Post-marketing experience with the use of tramadol containing products included rare reports of QT prolongation reported with an overdose. Particular care should be exercised when administering tramadol to patients who are suspected to be at an increased risk of experiencing torsade de pointes during treatment with a QTc-prolonging drug.\r\n\r\n**Abuse and Misuse**\r\n\r\nLike all opioids, tramadol has the potential for abuse and misuse, which can lead to overdose and death. Therefore, tramadol should be prescribed and handled with caution.\r\n\r\n**Dependence/Tolerance**\r\n\r\nPhysical dependence and tolerance reflect the neuroadaptation of the opioid receptors to chronic exposure to an opioid and are separate and distinct from abuse and addiction. Tolerance, as well as physical dependence, may develop upon repeated administration of opioids, and are not by themselves evidence of an addictive disorder or abuse. Patients on prolonged therapy should be tapered gradually from the drug if it is no longer required for pain control. Withdrawal symptoms may occur following abrupt discontinuation of therapy or upon administration of an opioid antagonist. Some of the symptoms that may be associated with abrupt withdrawal of an opioid analgesic include body aches, diarrhea, gooseflesh, loss of appetite, nausea, nervousness or restlessness, anxiety, runny nose, sneezing, tremors or shivering, stomach cramps, tachycardia, trouble with sleeping, unusual increase in sweating, palpitations, unexplained fever, weakness and yawning.","Tramadol is a centrally acting μ-opioid receptor agonist and SNRI (serotonin/norepinephrine reuptake-inhibitor) that is structurally related to  and . Tramadol binds weakly to κ- and δ-opioid receptors and to the μ-opioid receptor with 6000-fold less affinity than morphine.\r\n\r\nTramadol exists as a racemic mixture consisting of two pharmacologically active enantiomers that both contribute to its analgesic property through different mechanisms: (+)-tramadol and its primary metabolite (+)-O-desmethyl-tramadol (M1) are agonists of the μ opioid receptor while (+)-tramadol inhibits serotonin reuptake and (-)-tramadol inhibits norepinephrine reuptake. These pathways are complementary and synergistic, improving tramadol's ability to modulate the perception of and response to pain. \r\n\r\nIn animal models, M1 is up to 6 times more potent than tramadol in producing analgesia and 200 times more potent in μ-opioid binding. \r\n\r\nTramadol has also been shown to affect a number of pain modulators including alpha2-adrenoreceptors, neurokinin 1 receptors, the voltage-gated sodium channel type II alpha subunit, transient receptor potential cation channel subfamily V member 1 (TRPV1 - also known as the capsaicin receptor), muscarinic receptors (M1 and M3), N-methyl-D-aspartate receptor (also known as the NMDA receptor or glutamate receptor), Adenosine A1 receptors, and nicotinic acetylcholine receptor. \r\n\r\nIn addition to the above neuronal targets, tramadol has a number of effects on inflammatory and immune mediators involved in the pain response. This includes inhibitory effects on cytokines, prostaglandin E2 (PGE2), nuclear factor-κB, and glial cells as well as a change in the polarization state of M1 macrophages.","Mu-type opioid receptor agonist; Sodium-dependent noradrenaline transporter inhibitor; Sodium-dependent serotonin transporter inhibitor; 5-hydroxytryptamine receptor 2C antagonist; Kappa-type opioid receptor agonist; Delta-type opioid receptor agonist; Alpha-7 nicotinic cholinergic receptor subunit antagonist; Muscarinic acetylcholine receptor M3 antagonist; Muscarinic acetylcholine receptor M1 antagonist; Neurokinin 1 receptor inhibitor; Sodium channel protein type 2 subunit alpha inhibitor; Transient receptor potential cation channel subfamily V member 1 agonist; NMDA receptor inhibitor; Adenosine receptor A1 agonist; Alpha-2 adrenergic receptors inducer","Therapeutic strategy associated"]
[72,"DB00195","approved; investigational","small molecule","Betaxolol","1-(4-(2-(cyclopropylmethoxy)ethyl)phenoxy)-3-((1-methylethyl)amino)-2-propanol; 1-(isopropylamino)-3-[p-(cyclopropylmethoxyethyl)phenoxy]-2-propanol","C18H29NO3","CC(C)NCC(O)COC1=CC=C(CCOCC2CC2)C=C1","A cardioselective beta-1-adrenergic antagonist with no partial agonist activity.","63659-18-7","307.4278","For the management of hypertension.","Betaxolol is a competitive, beta(1)-selective (cardioselective) adrenergic antagonist. Betaxolol is used to treat hypertension, arrhythmias, coronary heart disease, glaucoma, and is also used to reduce non-fatal cardiac events in patients with heart failure. Activation of beta(1)-receptors (located mainly in the heart) by epinephrine increases the heart rate and the blood pressure, and the heart consumes more oxygen. Drugs such as betaxolol that block these receptors therefore have the reverse effect: they lower the heart rate and blood pressure and hence are used in conditions when the heart itself is deprived of oxygen. They are routinely prescribed in patients with ischemic heart disease. In addition, beta(1)-selective blockers prevent the release of renin, which is a hormone produced by the kidneys which leads to constriction of blood vessels. Betaxolol is lipophilic and exhibits no intrinsic sympathomimetic activity (ISA) or membrane stabilizing activity.","Betaxolol selectively blocks catecholamine stimulation of beta(1)-adrenergic receptors in the heart and vascular smooth muscle. This results in a reduction of heart rate, cardiac output, systolic and diastolic blood pressure, and possibly reflex orthostatic hypotension. Betaxolol can also competitively block beta(2)-adrenergic responses in the bronchial and vascular smooth muscles, causing bronchospasm.","Beta-1 adrenergic receptor antagonist; Beta-2 adrenergic receptor antagonist","Indication associated"]
[73,"DB00199","approved; investigational; vet_approved","small molecule","Erythromycin","3''-O-demethylerythromycin; Abomacetin; Erythromycin; Erythromycin A; Erythromycin C","C37H67NO13","CC[C@H]1OC(=O)[C@H](C)[C@@H](O[C@H]2C[C@@](C)(OC)[C@@H](O)[C@H](C)O2)[C@H](C)[C@@H](O[C@@H]2O[C@H](C)C[C@@H]([C@H]2O)N(C)C)[C@](C)(O)C[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@]1(C)O","Erythromycin is a bacteriostatic antibiotic drug produced by a strain of Saccharopolyspora erythraea (formerly Streptomyces erythraeus) and belongs to the macrolide group of antibiotics which consists of , ,  and others. It was originally discovered in 1952. Erythromycin is widely used for treating a variety of infections, including those caused by gram-positive and gram-negative bacteria. It is available for administration in various forms, including intravenous, topical, and eye drop preparations.","114-07-8","733.9268","\r\nErythromycin is indicated in the treatment of infections caused by susceptible strains of various bacteria. The indications for erythromycin have been summarized by body system below:\r\n\r\n**Respiratory infections**\r\n\r\nMild to moderate upper respiratory tract infections caused by Streptococcus pyogenes, Streptococcus pneumoniae, or Haemophilus influenzae (when used concomitantly with appropriate doses of sulfonamides) can be treated with erythromycin. Mild to moderate lower-respiratory tract infections due to susceptible strains of Streptococcus pneumoniae or Streptococcus pyogenes may also be treated. Erythromycin treats listeriosis caused by Listeria monocytogenes may also be treated with erythromycin.\r\nErythromycin is indicated to treat pertussis (whooping cough) caused by Bordetella pertussis. It is effective in eliminating the causative organism from the nasopharynx of infected individuals, rendering them noninfectious. Clinical studies suggest that erythromycin may aid in the prevention of pertussis infection for individuals who have been exposed to the bacteria. Respiratory tract infections due to Mycoplasma pneumoniae may also be treated with erythromycin.  Despite the fact that no controlled clinical efficacy studies have been conducted to this date, in vitro and certain preliminary clinical study results indicate that erythromycin may be an effective treatment in  Legionnaires’ Disease. Finally, erythromycin is indicated to treat diphtheria and other infections due to Corynebacterium diphtheriae, as an adjunct to antitoxin, to prevent carrier status and to eradicate the organism in existing carriers. In addition to the prevention of diphtheria, erythromycin can be used to prevent rheumatic fever in penicillin intolerant patients.\r\n \r\n\r\n**Skin infections**\r\n\r\nMild to moderate skin or skin structure infections caused by Streptococcus pyogenes or Staphylococcus aureus may be treated with erythromycin, however, resistant staphylococcal organisms may emerge. Erythromycin can also be used to treat erythrasma, an infectious condition caused by Corynebacterium minutissimum.\r\n\r\n\r\n**Gastrointestinal infections**\r\n\r\nIntestinal amebiasis caused by Entamoeba histolytica can be treated with oral erythromycin. Extraenteric amebiasis warrants treatment with other antimicrobial drugs.\r\n\r\n\r\n**Genital infections/STIs**\r\n\r\nErythromycin can be used as an alternative drug in treating acute pelvic inflammatory disease caused by N. gonorrheae in female patients who have demonstrated hypersensitivity or intolerance to penicillin. Syphilis, caused by Treponema pallidum, can be treated with erythromycin.  It serves as an alternative treatment for primary syphilis in patients who have demonstrated penicillin hypersensitivity. Erythromycin can also be used in the primary stage of primary syphilis. Another approved indication of erythromycin is to treat chlamydial infections that cause conjunctivitis of the newborn, pneumonia of infancy, and urogenital infections occurring in pregnancy. It is indicated as an alternative option to tetracyclines for the treatment of uncomplicated rectal, urethral and endocervical infections in adults caused by Chlamydia trachomatis. Erythromycin can be used in nongonococcal urethritis can be used when tetracyclines cannot be administered. Finally, erythromycin is indicated to treat nongonococcal urethritis due to Ureaplasma urealyticum.\r","Macrolides, such as erythromycin, stop bacterial growth by inhibiting protein synthesis and translation, treating bacterial infections. Erythromycin does not exert effects on nucleic acid synthesis. This drug has been shown to be active against most strains of the following microorganisms, effectively treating both in vitro and clinical infections. Despite this, it is important to perform bacterial susceptibility testing before administering this antibiotic, as resistance is a common issue that may affect treatment. \r\n\r\n**A note on antimicrobial resistance, pseudomembranous colitis, and hepatotoxicity**\r\n\r\nMany strains of Haemophilus influenzae are resistant to erythromycin alone but are found to be susceptible to erythromycin and sulfonamides used in combination. It is important to note that Staphylococci that are resistant to erythromycin may emerge during erythromycin and/or sulfonamide therapy. Pseudomembranous colitis has been reported with most antibacterial agents, including erythromycin, and may range in severity from mild to life-threatening. Therefore, the physician should consider this diagnosis in patients with diarrhea after the administration of antibacterial agents. Erythromycin can cause hepatic dysfunction, cholestatic jaundice, and abnormal liver transaminases, particularly when erythromycin estolate is administered.\r\n\r\n\r","In order to replicate, bacteria require a specific process of protein synthesis, enabled by ribosomal proteins. Erythromycin acts by inhibition of protein synthesis by binding to the 23S ribosomal RNA molecule in the 50S subunit of ribosomes in susceptible bacterial organisms.  It stops bacterial protein synthesis by inhibiting the transpeptidation/translocation step of protein synthesis and by inhibiting the assembly of the 50S ribosomal subunit. This results in the control of various bacterial infections. The strong affinity of macrolides, including erythromycin, for bacterial ribosomes, supports their broad‐spectrum antibacterial activities.\r\n\r","23S ribosomal RNA inhibitor; Motilin receptor agonist; Potassium voltage-gated channel subfamily H member 2 inhibitor","Indication associated"]
[74,"DB00201","approved","small molecule","Caffeine","1-methyltheobromine; 1,3,7-trimethyl-2,6-dioxopurine; 1,3,7-trimethylpurine-2,6-dione; 1,3,7-trimethylxanthine; 7-methyltheophylline; Anhydrous caffeine; Caffeine; Guaranine; Methyltheobromine; Theine","C8H10N4O2","CN1C=NC2=C1C(=O)N(C)C(=O)N2C","Caffeine is a drug of the methylxanthine class used for a variety of purposes, including certain respiratory conditions of the premature newborn, pain relief, and to combat drowsiness. Caffeine is similar in chemical structure to  and . It can be sourced from coffee beans, but also occurs naturally in various teas and cacao beans, which are different than coffee beans. Caffeine is also used in a variety of cosmetic products and can be administered topically, orally, by inhalation, or by injection.\r\n\r\nThe caffeine citrate injection, used for apnea of the premature newborn, was initially approved by the FDA in 1999. According to an article from 2017, more than 15 million babies are born prematurely worldwide. This correlates to about 1 in 10 births. Premature birth can lead to apnea and bronchopulmonary dysplasia, a condition that interferes with lung development and may eventually cause asthma or early onset emphysema in those born prematurely. Caffeine is beneficial in preventing and treating apnea and bronchopulmonary dysplasia in newborns, improving the quality of life of premature infants.","58-08-2","194.1906","Caffeine is indicated for the short term treatment of apnea of prematurity in infants and off label for the prevention and treatment of bronchopulmonary dysplasia caused by premature birth. In addition, it is indicated in combination with sodium benzoate to treat respiratory depression resulting from an overdose with CNS depressant drugs. Caffeine has a broad range of over the counter uses, and is found in energy supplements, athletic enhancement products, pain relief products, as well as cosmetic products.","Caffeine stimulates the central nervous system (CNS), heightening alertness, and sometimes causing restlessness and agitation. It relaxes smooth muscle, stimulates the contraction of cardiac muscle, and enhances athletic performance. Caffeine promotes gastric acid secretion and increases gastrointestinal motility. It is often combined in products with analgesics and ergot alkaloids, relieving the symptoms of migraine and other types of headaches. Finally, caffeine acts as a mild diuretic.","The mechanism of action of caffeine is complex, as it impacts several body systems, which are listed below. The effects as they relate to various body systems are described as follows:\r\n\r\n**General and cellular actions**\r\n\r\nCaffeine exerts several actions on cells, but the clinical relevance is poorly understood. One probable mechanism is the inhibition of nucleotide phosphodiesterase enzymes, adenosine receptors, regulation of calcium handling in cells, and participates in adenosine receptor antagonism. Phosphodiesterase enzymes regulate cell function via actions on second messengers cAMP and cGMP. This causes lipolysis through activation of hormone-sensitive lipases, releasing fatty acids and glycerol.\r\n\r\n**Respiratory**\r\n\r\nThe exact mechanism of action of caffeine in treating apnea related to prematurity is unknown, however, there are several proposed mechanisms, including respiratory center stimulation in the central nervous system, a reduced threshold to hypercapnia with increased response, and increased consumption of oxygen, among others. The blocking of the adenosine receptors enhances respiratory drive via an increase in brain medullary response to carbon dioxide, stimulating ventilation and respiratory drive, while increasing contractility of the diaphragm.\r\n\r\n**Central nervous system**\r\n\r\nCaffeine demonstrates antagonism of all 4 adenosine receptor subtypes (A1, A2a, A2b, A3) in the central nervous system. Caffeine's effects on alertness and combatting drowsiness are specifically related to the antagonism of the A2a receptor.\r\n\r\n**Renal system**\r\n\r\nCaffeine has diuretic effects due to is stimulatory effects on renal blood flow, increase in glomerular filtration, and increase in sodium excretion.\r\n\r\n**Cardiovascular system**\r\n\r\nAdenosine receptor antagonism at the A1 receptor by caffeine stimulates inotropic effects in the heart. Blocking of adenosine receptors promotes catecholamine release, leading to stimulatory effects occurring in the heart and the rest of the body.  In the blood vessels, caffeine exerts direct antagonism of adenosine receptors, causing vasodilation. It stimulates the endothelial cells in the blood vessel wall to release nitric oxide, potentiating blood vessel relaxation. Catecholamine release, however, antagonizes this and exerts inotropic and chronotropic effects on the heart, ultimately leading to vasoconstriction. Finally, caffeine is shown to raise systolic blood pressure measurements by 5 to 10 mmHg when it is not taken regularly, versus no effect in those who consume it regularly. The vasoconstricting effects of caffeine are beneficial in migraines and other types of headache, which are normally caused by vasodilation in the brain.","Adenosine receptor A1 antagonist; cAMP-specific 3',5'-cyclic phosphodiesterase 4B inhibitor; Adenosine receptor A2a antagonist; Ryanodine receptor 1; Cyclic nucleotide phosphodiesterase inhibitor; DNA-dependent protein kinase catalytic subunit inhibitor; Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform inhibitor; Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform inhibitor; Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform inhibitor; Inositol 1,4,5-trisphosphate receptor inhibitor; Serine-protein kinase ATM inhibitor; Adenosine receptor A2b antagonist; Adenosine receptor A3 antagonist; Phosphodiesterase enzymes inhibitor","Indication associated"]
[75,"DB00203","approved; investigational","small molecule","Sildenafil","1-((3-(4,7-Dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo(4,3-d)pyrimidin-5-yl)-4-ethoxyphenyl)sulfonyl)-4-methylpiperazine; Sildenafil","C22H30N6O4S","CCCC1=NN(C)C2=C1N=C(NC2=O)C1=CC(=CC=C1OCC)S(=O)(=O)N1CCN(C)CC1","In eliciting its mechanism of action, sildenafil ultimately prevents or minimizes the breakdown of cyclic guanosine monophosphate (cGMP) by inhibiting cGMP specific phosphodiesterase type 5 (PDE5) . The result of doing so allows cGMP present in both the penis and pulmonary vasculature to elicit smooth muscle relaxation and vasodilation that subsequently facilitates relief in pulmonary arterial hypertension and the increased flow of blood into the spongy erectile tissue of the penis that consequently allows it to grow in size and become erect and rigid .\r\n\r\nInterestingly enough, it is precisely via this mechanism why sildenafil was at first researched as a potential treatment for angina - or chest pain associated with inadequate blood flow to the heart - before being serendipitously indicated for treating erectile dysfunction in the late 1980s . Nevertheless, it is because of this mechanism that sildenafil is also indicated for treating pulmonary arterial hypertension but is also additionally notorious for interacting with various anti-anginal or anti-hypertensive agents to develop potentially rapid, excessive, and/or fatal hypotensive crises .\r\n\r\nRegardless, sildenafil, among a variety of other similar or related PDE5 inhibitors, has become a common and effective treatment for erectile dysfunction and since its formal approval for medical use in the public in 1998 , continues to see millions of prescriptions written for it internationally. Although the medication has historically been most popularly recognized as Pfizer's brand name Viagra, sildenafil is currently available generically and even as a non-prescription over the counter medication in some countries .","139755-83-2","474.576","Sildenafil is a phosphodiesterase-5 (PDE5) inhibitor that is predominantly employed for two primary indications:\r\n\r\n(1) the treatment of erectile dysfunction ; and\r\n\r\n(2) treatment of pulmonary hypertension, where:\r\na) the US FDA specifically indicates sildenafil for the treatment of pulmonary arterial hypertension (PAH) (WHO Group I) in adults to improve exercise ability and delay clinical worsening . The delay in clinical worsening was demonstrated when sildenafil was added to background epoprostenol therapy . Studies establishing effectiveness were short-term (12 to 16 weeks), and included predominately patients with New York Heart Association (NYHA) Functional Class II-III symptoms and idiopathic etiology (71%) or associated with connective tissue disease (CTD) (25%) ;\r\n\r\nb) the Canadian product monograph specifically indicates sildenafil for the treatment of primary pulmonary arterial hypertension (PPH) or pulmonary hypertension secondary to connective tissue disease (CTD) in adult patients with WHO functional class II or III who have not responded to conventional therapy . In addition, improvement in exercise ability and delay in clinical worsening was demonstrated in adult patients who were already stabilized on background epoprostenol therapy ; and\r\n\r\nc) the EMA product information specifically indicates sildenafil for the treatment of adult patients with pulmonary arterial hypertension classified as WHO functional class II and III, to improve exercise capacity . Efficacy has been shown in primary pulmonary hypertension and pulmonary hypertension associated with connective tissue disease . The EMA label also indicates sildenafil for the treatment of pediatric patients aged 1 year to 17 years old with pulmonary arterial hypertension . Efficacy in terms of improvement of exercise capacity or pulmonary hemodynamics has been shown in primary pulmonary hypertension and pulmonary hypertension associated with congenital heart disease .","In vitro studies have shown that sildenafil is selective for phosphodiesterase-5 (PDE5) . Its effect is more potent on PDE5 than on other known phosphodiesterases . In particular, there is a 10-times selectivity over PDE6 which is involved in the phototransduction pathway in the retina . There is an 80-times selectivity over PDE1, and over 700-times over PDE 2, 3, 4, 7, 8, 9, 10 and 11 . And finally, sildenafil has greater than 4,000-times selectivity for PDE5 over PDE3, the cAMP-specific phosphodiesterase isoform involved in the control of cardiac contractility .\r\n\r\nIn eight double-blind, placebo-controlled crossover studies of patients with either organic or psychogenic erectile dysfunction, sexual stimulation resulted in improved erections, as assessed by an objective measurement of hardness and duration of erections (via the use of RigiScan®), after sildenafil administration compared with placebo . Most studies assessed the efficacy of sildenafil approximately 60 minutes post-dose . The erectile response, as assessed by RigiScan®, generally increased with increasing sildenafil dose and plasma concentration . The time course of effect was examined in one study, showing an effect for up to 4 hours but the response was diminished compared to 2 hours .\r\n\r\nSildenafil causes mild and transient decreases in systemic blood pressure which, in the majority of cases, do not translate into clinical effects . After chronic dosing of 80 mg, three times a day to patients with systemic hypertension the mean change from baseline in systolic and diastolic blood pressure was a decrease of 9.4 mmHg and 9.1 mmHg respectively . After chronic dosing of 80 mg, three times a day to patients with pulmonary arterial hypertension lesser effects in blood pressure reduction were observed (a reduction in both systolic and diastolic pressure of 2 mmHg) . At the recommended dose of 20 mg three times a day no reductions in systolic or diastolic pressure were seen .\r\n\r\nSingle oral doses of sildenafil up to 100 mg in healthy volunteers produced no clinically relevant effects on ECG . After chronic dosing of 80 mg three times a day to patients with pulmonary arterial hypertension no clinically relevant effects on the ECG were reported either .\r\n\r\nIn a study of the hemodynamic effects of a single oral 100 mg dose of sildenafil in 14 patients with severe coronary artery disease (CAD) (> 70 % stenosis of at least one coronary artery), the mean resting systolic and diastolic blood pressures decreased by 7 % and 6 % respectively compared to baseline . Mean pulmonary systolic blood pressure decreased by 9% . Sildenafil showed no effect on cardiac output and did not impair blood flow through the stenosed coronary arteries .\r\n\r\nMild and transient differences in color discrimination (blue/green) were detected in some subjects using the Farnsworth-Munsell 100 hue test at 1 hour following a 100 mg dose, with no effects evident after 2 hours post-dose . The postulated mechanism for this change in color discrimination is related to inhibition of PDE6, which is involved in the phototransduction cascade of the retina . Sildenafil has no effect on visual acuity or contrast sensitivity. In a small size placebo-controlled study of patients with documented early age-related macular degeneration (n = 9), sildenafil (single dose, 100 mg) demonstrated no significant changes in visual tests conducted (which included visual acuity, Amsler grid, color discrimination simulated traffic light, and the Humphrey perimeter and photostress test) .","Sildenafil is an oral therapy for erectile dysfunction . In the natural setting, i.e. with sexual stimulation, it restores impaired erectile function by increasing blood flow to the penis .\r\n\r\nThe physiological mechanism responsible for the erection of the penis involves the release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation . Nitric oxide then activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood .\r\n\r\nSildenafil is a potent and selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum, where PDE5 is responsible for degradation of cGMP . Sildenafil has a peripheral site of action on erections . Sildenafil has no direct relaxant effect on isolated human corpus cavernosum but potently enhances the relaxant effect of NO on this tissue . When the NO/cGMP pathway is activated, as occurs with sexual stimulation, inhibition of PDE5 by sildenafil results in increased corpus cavernosum levels of cGMP . Therefore sexual stimulation is required in order for sildenafil to produce its intended beneficial pharmacological effects .\r\n\r\nMoreover, apart from the presence of PDE5 in the corpus cavernosum of the penis, PDE5 is also present in the pulmonary vasculature . Sildenafil, therefore, increases cGMP within pulmonary vascular smooth muscle cells resulting in relaxation . In patients with pulmonary arterial hypertension, this can lead to vasodilation of the pulmonary vascular bed and, to a lesser degree, vasodilatation in the systemic circulation .","cGMP-specific 3',5'-cyclic phosphodiesterase inhibitor; Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma inhibitor; Retinal cone rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma inhibitor","Indication associated"]
[76,"DB00204","approved; investigational","small molecule","Dofetilide","beta-((p-Methanesulfonamidophenethyl)methylamino)methanesulfono-p-phenetidide; Dofetilide","C19H27N3O5S2","CN(CCOC1=CC=C(NS(C)(=O)=O)C=C1)CCC1=CC=C(NS(C)(=O)=O)C=C1","Dofetilide is a class III antiarrhythmic agent that is approved by the Food and Drug Administration (FDA) for the maintenance of sinus rhythm in individuals prone to the formation of atrial fibrillation and flutter, and for the chemical cardioversion to sinus rhythm from atrial fibrillation and flutter.","115256-11-6","441.565","For the maintenance of normal sinus rhythm (delay in time to recurrence of atrial fibrillation/atrial flutter ) in patients with atrial fibrillation/atrial flutter of greater than one week duration who have been converted to normal sinus rhythm","Dofetilide is an antiarrhythmic drug with Class III (cardiac action potential duration prolonging) properties and is indicated for the maintenance of normal sinus rhythm. Dofetilide increases the monophasic action potential duration in a predictable, concentration-dependent manner, primarily due to delayed repolarization. At concentrations covering several orders of magnitude, Dofetilide blocks only IKr with no relevant block of the other repolarizing potassium currents (e.g., IKs, IK1). At clinically relevant concentrations, Dofetilide has no effect on sodium channels (associated with Class I effect), adrenergic alpha-receptors, or adrenergic beta-receptors.","The mechanism of action of Dofetilide is a blockade of the cardiac ion channel carrying the rapid component of the delayed rectifier potassium current, IKr. This inhibition of potassium channels results in a prolongation of action potential duration and the effective refractory period of accessory pathways (both anterograde and retrograde conduction in the accessory pathway).","Potassium voltage-gated channel subfamily H member 2 inhibitor; Potassium channel subfamily K member 2 inhibitor; ATP-sensitive inward rectifier potassium channel 12 inhibitor","Indication associated"]
[77,"DB00206","approved; investigational","small molecule","Reserpine","(−)-reserpine; (3beta,16beta,17alpha,18beta,20alpha)-11,17-Dimethoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]yohimban-16-carboxylic acid methyl ester; 3,4,5-trimethoxybenzoyl methyl reserpate; Reserpin; Reserpine","C33H40N2O9","[H][C@]12C[C@@H](OC(=O)C3=CC(OC)=C(OC)C(OC)=C3)[C@H](OC)[C@@H](C(=O)OC)[C@@]1([H])C[C@@]1([H])N(CCC3=C1NC1=C3C=CC(OC)=C1)C2","An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use.","50-55-5","608.6787","For the treatment of hypertension","Reserpine is an adrenergic blocking agent used to treat mild to moderate hypertension via the disruption of norepinephrine vesicular storage. The antihypertensive actions of Reserpine are a result of its ability to deplete catecholamines from peripheral sympathetic nerve endings. These substances are normally involved in controlling heart rate, force of cardiac contraction and peripheral resistance.","Reserpine's mechanism of action is through inhibition of the ATP/Mg<sup>2+</sup> pump responsible for the sequestering of neurotransmitters into storage vesicles located in the presynaptic neuron. The neurotransmitters that are not sequestered in the storage vesicle are readily metabolized by monoamine oxidase (MAO) causing a reduction in catecholamines.","Synaptic vesicular amine transporter inhibitor; Chromaffin granule amine transporter inhibitor; Baculoviral IAP repeat-containing protein 5","Therapeutic strategy associated"]
[78,"DB00208","approved","small molecule","Ticlopidine",null,"C14H14ClNS","ClC1=CC=CC=C1CN1CCC2=C(C1)C=CS2","Ticlopidine is an effective inhibitor of platelet aggregation. It is a prodrug that is metabolised to an active form, which blocks the ADP receptor that is involved in GPIIb/IIIa receptor activation leading to platelet aggregation. Ticlopidine is marketed under the brand name Ticlid and is indicated for patients who cannot take aspirin or in whom aspirin has not worked to prevent a thrombotic stroke. The FDA label includes a black-box warning of neutropenia, aplastic anemia, thrombotic thrombocytopenia purpura, and agranulocytosis, so it is necessary to monitor patients' WBC and platelets when they are taking ticlopidine.","55142-85-3","263.786","Used in patients, who have had a stroke or stroke precursors and who cannot take aspirin or aspirin has not worked, to try to prevent another thrombotic stroke.\r","Ticlopidine is a prodrug that is metabolised to an as yet undetermined metabolite that acts as a platelet aggregation inhibitor. Inhibition of platelet aggregation causes a prolongation of bleeding time. In its prodrug form, ticlopidine has no significant in vitro activity at the concentrations attained in vivo.","The active metabolite of ticlopidine prevents binding of adenosine diphosphate (ADP) to its platelet receptor, impairing the ADP-mediated activation of the glycoprotein GPIIb/IIIa complex. It is proposed that the inhibition involves a defect in the mobilization from the storage sites of the platelet granules to the outer membrane. No direct interference occurs with the GPIIb/IIIa receptor. As the glycoprotein GPIIb/IIIa complex is the major receptor for fibrinogen, its impaired activation prevents fibrinogen binding to platelets and inhibits platelet aggregation. By blocking the amplification of platelet activation by released ADP, platelet aggregation induced by agonists other than ADP is also inhibited by the active metabolite of ticlopidine.","P2Y purinoceptor 12 antagonist","Therapeutic strategy associated"]
[79,"DB00210","approved","small molecule","Adapalene","6-(3-(1-Adamantyl)-4-methoxyphenyl)-2-naphthoic acid; Adapalene","C28H28O3","COC1=C(C=C(C=C1)C1=CC2=C(C=C1)C=C(C=C2)C(O)=O)C12CC3CC(CC(C3)C1)C2","Acne vulgaris is a multifactorial disorder of the pilosebaceous unit involving increased sebum production, inflammation, and hyperproliferation/hyperkeratinization of the follicular infundibulum. It is also associated with _Cutibacterium acnes_ (also known as _Propionibacterium acnes_). Adapalene is a third-generation topical retinoid used for the treatment of acne vulgaris. Adapalene has similar efficacy but a superior safety profile compared to tretinoin.  is more efficacious than adapalene but is designated as pregnancy category X and hence is contraindicated in pregnant women. Adapalene can also be combined with benzoyl peroxide (BPO), which possesses bactericidal properties, and either adapalene alone, or adapalene BPO combination products, are commonly used to treat mild-to-severe acne.\r\n\r\nDifferin®, produced by Galderma Labs, was first granted FDA approval on May 31st, 1996, as a 0.1% adapalene topical solution. Differin was later made available as 0.1% gel, cream, or lotion, or 0.3% gel products. On December 8th, 2008, Galderma Labs gained FDA approval for Epiduo®, a 0.1% adapalene, 2.5% BPO combination gel.","106685-40-9","412.5201","Adapalene is indicated for the topical treatment of acne vulgaris in patients aged 12 and over.","Adapalene is anticomedogenic, preventing the formation of new comedones and inflammatory lesions, and also acts to reduce inflammation by modulating the innate immune response. Like other retinoid compounds, adapalene is chemically stable but photosensitive; use with sunscreen is recommended. Minor skin irritations, including erythema, scaling, dryness, and stinging/burning, have been reported.","Adapalene is used for the treatment/maintenance of mild-to-severe acne (acne vulgaris). Acne is a multifactorial condition, and evidence exists to support multiple mechanisms of action for adapalene. Adapalene binds to retinoic acid receptor (RAR)-beta and RAR-gamma; this complex subsequently binds to one of three retinoid X receptors (RXRs), which as a complex is capable of binding DNA to modulate transcriptional activity. Although the full extent of transcriptional modulation is not described, retinoid activation is generally known to affect cellular proliferation and differentiation, and adapalene has been shown to inhibit HeLa cell proliferation and human keratinocyte differentiation. These effects primarily account for adapalene's comedolytic and anticomedogenic properties.\r\n\r\nIn addition, adapalene modulates the immune response by down-regulating toll-like receptor 2 (TLR-2) expression and inhibiting the transcription factor activator protein 1 (AP-1). TLR-2 recognizes _Cutibacterium acnes_ (formerly _Propionibacterium acnes_), the bacterium primarily associated with acne. TLR-2 activation causes nuclear translocation of AP-1 and downstream pro-inflammatory gene regulation. Therefore, adapalene has a general anti-inflammatory effect, which reduces inflammation-mediated acne symptoms.\r\n\r\nWhen used with benzoyl peroxide, which possesses free radical-mediated bactericidal effects, the combination acts synergistically to reduced comedones and inflammatory lesions.","Retinoic acid receptor beta agonist; Retinoic acid receptor gamma agonist; Retinoic acid receptor RXR-beta agonist; Retinoic acid receptor RXR-gamma agonist; Retinoic acid receptor RXR-alpha agonist; Transcription factor AP-1 antagonist; Toll-like receptor 2 antagonist; Retinoic acid receptor alpha; Aspartate aminotransferase, cytoplasmic inhibitor","Therapeutic strategy associated"]
[80,"DB00212","experimental","small molecule","Remikiren","Remikiren","C33H50N4O6S","CC(C)(C)S(=O)(=O)C[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CC1CCCCC1)[C@@H](O)[C@@H](O)C1CC1","Remikiren is an orally active, high specificity renin inhibitor.","126222-34-2","630.838","For the treatment of hypertension and heart failure","Remikiren is an orally available renin inhibitor with an established blood pressure-lowering effect in patients with essential hypertension. No data are available on the renal effects of remikiren in humans. In patients with essential hypertension, a single oral dose of remikiren can induce a renal vasodilation, without affecting the GFR and despite a significant decrease in blood pressure. This systemic and renal hemodynamic response is more pronounced in case of a more activated renin-angiotensin system.","Several in vivo experiments have shown that remikiren is specific for renin and does not decrease arterial pressure by an unrelated mechanism.","Renin inhibitor","Indication associated"]
[81,"DB00214","approved","small molecule","Torasemide","1-Isopropyl-3-((4-m-toluidino-3-pyridyl)sulfonyl)urea; N-(((1-Methylethyl)amino)carbonyl)-4-((3-methylphenyl)amino)-3-pyridinesulfonamide; Torasemide; Torsemide","C16H20N4O3S","CC(C)NC(=O)NS(=O)(=O)C1=C(NC2=CC=CC(C)=C2)C=CN=C1","Torasemide is a high-ceiling loop diuretic. Structurally, it is a pyridine-sulfonylurea used as an antihypertensive agent. Torasemide was first approved for clinical use by the FDA in 1993.","56211-40-6","348.42","Torasemide is indicated for the treatment of edema associated with congestive heart failure, renal or hepatic diseases. From this condition, it has been observed that torasemide is very effective in cases of kidney failure.\r\n\r\nAs well, torasemide is approved to be used as an antihypertensive agent either alone or in combination with other antihypertensives.","It is widely known that administration of torasemide can attenuate renal injury and reduce the severity of acute renal failure. This effect is obtained by increasing urine output and hence, facilitating fluid, acid-base and potassium control. This effect is obtained by the increase in the excretion of urinary sodium and chloride.\r\n\r\nSeveral reports have indicated that torasemide presents a long-lasting diuresis and less potassium excretion which can be explained by the effect that torasemide has on the renin-angiotensin-aldosterone system. This effect is very similar to the effect observed with the administration of combination therapy with  and  and it is characterized by a decrease in plasma brain natriuretic peptide and improved measurements of left ventricular function. \r\n\r\nAbove the aforementioned effect, torasemide presents a dual effect .in which the inhibition of aldosterone which donates torasemide with a potassium-sparing action.\r\n\r\nTorasemide has been shown to reduce extracellular fluid volume and blood pressure in hypertensive patients suffering from chronic kidney disease. As well, some reports have indicated that torasemide can reduce myocardial fibrosis by reducing the collagen accumulation. This effect is suggested to be related to the decrease in aldosterone which in order has been shown to reduce the production of the enzyme procollagen type I carboxy-terminal proteinase which is known to be overexpressed in heart failure patients.","As mentioned above, torasemide is part of the loop diuretics and thus, it acts by reducing the oxygen demand in the medullary thick ascending loop of Henle by inhibiting the Na+/K+/Cl- pump on the luminal cell membrane surface. This action is obtained by the binding of torasemide to a chloride ion-binding site of the transport molecule.\r\n\r\nTorasemide is known to have an effect in the renin-angiotensin-aldosterone system by inhibiting the downstream cascade after the activation of angiotensin II. This inhibition will produce a secondary effect marked by the reduction of the expression of aldosterone synthase, TGF-B1 and thromboxane A2 and a reduction on the aldosterone receptor binding.","Solute carrier family 12 member 1 inhibitor; Solute carrier family 12 member 2 inhibitor","Therapeutic strategy associated"]
[82,"DB00215","approved","small molecule","Citalopram","Citalopram; Nitalapram","C20H21FN2O","CN(C)CCCC1(OCC2=C1C=CC(=C2)C#N)C1=CC=C(F)C=C1","Citalopram belongs to a class of antidepressant agents known as selective _serotonin-reuptake inhibitors_ (SSRIs) and is widely used to treat the symptoms of depression. Its chemical structure is unrelated to that of other SSRIs or of tricyclic, tetracyclic, or other prescribed antidepressants .  Citalopram is also known as _Celexa_, and available in tablet and solution forms .  This drug was initially approved by the FDA in 1998 .","59729-33-8","324.3919","For the treatment of depression, as indicated by the FDA label . Off-label indications include but are not limited to: treatment of sexual dysfunction, post-stroke behavioural changes, ethanol abuse, obsessive-compulsive disorder (OCD) in children, and diabetic neuropathy , , , , , , , .","Citalopram belongs to a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs). It has been found to relieve or manage symptoms of depression, anxiety, eating disorders and obsessive-compulsive disorder among other mood disorders. The antidepressant, anti-anxiety, and other actions of citalopram are linked to its inhibition of CNS central uptake of serotonin . Serotonergic abnormalities have been reported in patients with mood disorders. Behavioral and neuropsychological of effects of serotonin include the regulation of mood, perception, reward, anger, aggression, appetite, memory, sexuality, and attention, as examples. The onset of action for depression is approximately 1 to 4 weeks. The complete response may take 8-12 weeks after initiation of citalopram .\r\n\r\n <i>In vitro</i> studies demonstrate that citalopram is a strong and selective inhibitor of neuronal serotonin reuptake and has weak effects on norepinephrine and dopamine central reuptake. The chronic administration of citalopram has been shown to downregulate central norepinephrine receptors, similar to other drugs effective in the treatment of major depressive disorder. Citalopram does not inhibit monoamine oxidase .","\r\nThe mechanism of action of citalopram results from its inhibition of CNS neuronal reuptake of serotonin (5-HT) .  The molecular target for citalopram is the serotonin transporter (solute carrier family 6 member 4, _SLC6A4_), inhibiting its serotonin reuptake in the synaptic cleft .\r\n\r\nCitalopram binds with significantly less affinity to histamine, acetylcholine, and norepinephrine receptors than tricyclic antidepressant drugs . This drug has no or neglible affinity for _5-HT1A_, _5-HT2A_, _dopamine D_1 and _D2_, _α1-_, _α2_-, and_ β­ adrenergic_, _histamine H1_, _gamma-aminobutyric acid_ (GABA), _muscarinic_,  _cholinergic_, and _benzodiazepine_ receptors. Antagonism of _muscarinic_, _histaminergic_, and _adrenergic receptors_ is thought to be associated with several anticholinergic, sedative, and cardiovascular effects of other psychotropic drugs .","Sodium-dependent serotonin transporter inhibitor; Histamine H1 receptor binder","Indication associated"]
[83,"DB00216","approved; investigational","small molecule","Eletriptan","Eletriptan","C22H26N2O2S","CN1CCC[C@@H]1CC1=CNC2=C1C=C(CCS(=O)(=O)C1=CC=CC=C1)C=C2","Eletriptan is a second generation triptan drug developed by Pfizer Inc for the treatment of migraine headaches.","143322-58-1","382.519","For the acute treatment of migraine with or without aura in adults.","Eletriptan is a selective 5-hydroxytryptamine 1B/1D receptor agonist. In the anesthetized dog, eletriptan has been shown to reduce carotid arterial blood flow, with only a small increase in arterial blood pressure at high doses. While the effect on blood flow was selective for the carotid arterial bed, decreases in coronary artery diameter were observed. Eletriptan has also been shown to inhibit trigeminal nerve activity in the rat.","Eletriptan binds with high affinity to 5-HT1B, 5-HT1D and 5-HT1F receptors, has modest affinity for 5-HT1A, 5-HT1E, 5-HT2B and 5-HT7 receptors, and little or no affinity for 5-HT2A, 5-HT2C, 5-HT3, 5-HT4, 5-HT5A and 5-HT6 receptors. In contrast, eletriptan displays insignificant pharmacological activity at adrenergic alpha1, alpha2, or beta; dopaminergic D1 or D2; muscarinic; or opioid receptors. While the full mechanism of action of 5-HT receptor agonists in relieving migrains is not fully elucidated, it is proposed that the activation of 5-HT1 receptors located on intracranial blood vessels leads to vasoconstriction that correlates with the relief of migraine headaches. It is also proposed that the activation of 5-HT1 receptors on sensory nerve endings in the trigeminal system leads to the inhibition of release of pro-inflammatory neuropeptides.","5-hydroxytryptamine receptor 1D agonist; 5-hydroxytryptamine receptor 1B agonist; 5-hydroxytryptamine receptor 1F agonist; 5-hydroxytryptamine receptor 1A agonist","Therapeutic strategy associated"]
[84,"DB00217","approved","small molecule","Bethanidine","Betanidine; Bethanidine; N,N'-dimethyl-N''-(phenylmethyl)-guanidine","C10H15N3","CN\\C(NCC1=CC=CC=C1)=N/C","A guanidinium antihypertensive agent that acts by blocking adrenergic transmission.","55-73-2","177.2462","For the treatment of hypertension.","Bethanidine is a guanidinium antihypertensive agent that acts by blocking adrenergic transmission. The precise mode of action is not clear. Although bethanidine may produce adverse effects, they are beneficial in severe hypertension and produce fewer side effects than guanethidine.","Bethanidine, a guanidine derivative, is a peripherally acting antiadrenergic agent which primarily acts as an alpha2a adrenergic agonist. Bethanidine effectively decreases blood pressure by suppressing renin secretion or interfering with function of the sympathetic nervous system.","Alpha-2 adrenergic receptors agonist; ATP-sensitive inward rectifier potassium channel 1 inhibitor; Beta adrenergic receptor antagonist","Therapeutic strategy associated"]
[85,"DB00218","approved; investigational","small molecule","Moxifloxacin","1-Cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-((4as,7as)-octahydro-6H-pyrrolo(3,4-b)pyridin-6-yl)-4-oxo-3-quinolinecarboxylic acid; Moxifloxacin","C21H24FN3O4","[H][C@]12CN(C[C@@]1([H])NCCC2)C1=C(F)C=C2C(=O)C(=CN(C3CC3)C2=C1OC)C(O)=O","Moxifloxacin is a synthetic fluoroquinolone antibiotic agent. Bayer AG developed the drug (initially called BAY 12-8039) and it is marketed worldwide (as the hydrochloride) under the brand name Avelox (in some countries also Avalox) for oral treatment.","151096-09-2","401.4314","For the treatment of sinus and lung infections such as sinusitis, pneumonia, and secondary infections in chronic bronchitis. Also for the treatment of bacterial conjunctivitis (pinkeye).","Moxifloxacin is a quinolone/fluoroquinolone antibiotic. Moxifloxacin can be used to treat infections caused by the following bacteria: Aerobic Gram-positive microorganisms: <i>Corynebacterium</i> species, <i>Micrococcus luteus</i>, <i>Staphylococcus aureus</i>, <i>Staphylococcus epidermidis</i>, <i>Staphylococcus haemolyticus</i>, <i>Staphylococcus hominis</i>, <i>Staphylococcus warneri</i>, <i>Streptococcus pneumoniae</i>, and <i>Streptococcus viridans</i> group. Aerobic Gram-negative microorganisms: <i>Acinetobacter lwoffii</i>, <i>Haemophilus influenzae</i>, and <i>Haemophilus parainfluenzae</i>. Other microorganisms: <i>Chlamydia trachomatis</i>.<br/>Moxifloxacin is bactericidal and its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase, which allows the untwisting required to replicate one DNA double helix into two. Notably the drug has 100 times higher affinity for bacterial DNA gyrase than for mammalian. Moxifloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria.","The bactericidal action of moxifloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV. DNA gyrase is an essential enzyme that is involved in the replication, transcription and repair of bacterial DNA. Topoisomerase IV is an enzyme known to play a key role in the partitioning of the chromosomal DNA during bacterial cell division.","DNA topoisomerase 4 subunit A inhibitor; DNA gyrase subunit A inhibitor; DNA topoisomerase 2-alpha inhibitor","Indication associated"]
[86,"DB00223","approved","small molecule","Diflorasone","(6α,11β,16β)-6,9-difluoro-11,17,21-trihydroxy-16-methylpregna-1,4-diene-3,20-dione; Diflorasone","C22H28F2O5","[H][C@@]12C[C@H](C)[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])C[C@H](F)C2=CC(=O)C=C[C@]12C","Diflorasone is a topical corticosteroid used to treat itching and inflammation of the skin.","2557-49-5","410.4515","For relief of the inflammatory and pruritic manifestations of corticosteroid responsive dermatoses.","Like other topical corticosteroids, diflorasone has anti-inflammatory, antipruritic, and vasoconstrictive properties. Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Diflorasone is a potent topical corticosteroid that should not be used with occlusive dressings. It is recommended that treatment should be limited to 2 consecutive weeks and therapy should be discontinued when adequate results have been achieved.","The precise mechanism of the antiinflammatory activity of topical steroids in the treatment of steroid-responsive dermatoses, in general, is uncertain. However, corticosteroids are thought to act by the induction of phospholipase A<sub>2</sub> inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A<sub>2</sub>.","Glucocorticoid receptor agonist","Therapeutic strategy associated"]
[87,"DB00226","approved","small molecule","Guanadrel",null,"C10H19N3O2","NC(N)=NCC1COC2(CCCCC2)O1","Guanadrel is an antihypertensive agent and postganglionic adrenergic blocking agent.","40580-59-4","213.2768","Used to treat and control hypertension.","High blood pressure adds to the work load of the heart and arteries. If it continues for a long time, the heart and arteries may not function properly. This can damage the blood vessels of the brain, heart, and kidneys resulting in a stroke, heart failure, or kidney failure. High blood pressure may also increase the risk of heart attacks. These problems may be less likely to occur if blood pressure is controlled. Guanadrel works by controlling nerve impulses along certain nerve pathways. As a result, it relaxes the blood vessels so that blood passes through them more easily. This helps to lower blood pressure.","Guanadrel is an adrenergic neuron inhibitor that slowly displaces norepinephrine from its storage in nerve endings. It blocks the release of norepinephrine in response to the sympathetic nerve stimulation, leading to reduced arteriolar vasoconstriction, especially the reflex increase in sympathetic tone that occurs with a change in position.","Sodium-dependent noradrenaline transporter partial agonist","Indication associated"]
[88,"DB00227","approved; investigational","small molecule","Lovastatin","(1S,3R,7S,8S,8aR)-1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-(2-(2R,4R)-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl)-1-naphthalenyl (S)-2-methyl-butyrate; 2β,6α-dimethyl-8alpha-(2-methyl-1-oxobutoxy)-mevinic acid lactone; 6-alpha-methylcompactin; 6alpha-methylcompactin; 6α-methylcompactin; Lovastatin; Mevinolin","C24H36O5","[H][C@]12[C@H](C[C@@H](C)C=C1C=C[C@H](C)[C@@H]2CC[C@@H]1C[C@@H](O)CC(=O)O1)OC(=O)[C@@H](C)CC","Lovastatin, also known as the brand name product Mevacor, is a lipid-lowering drug and fungal metabolite derived synthetically from a fermentation product of _Aspergillus terreus_. Originally named Mevinolin, lovastatin belongs to the statin class of medications, which are used to lower the risk of cardiovascular disease and manage abnormal lipid levels by inhibiting the endogenous production of cholesterol in the liver. More specifically, statin medications competitively inhibit the enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) Reductase, which catalyzes the conversion of HMG-CoA to mevalonic acid and is the third step in a sequence of metabolic reactions involved in the production of several compounds involved in lipid metabolism and transport including cholesterol, low-density lipoprotein (LDL) (sometimes referred to as \"bad cholesterol\"), and very low-density lipoprotein (VLDL). Prescribing of statin medications is considered standard practice following any cardiovascular events and for people with a moderate to high risk of development of CVD, such as those with Type 2 Diabetes. The clear evidence of the benefit of statin use coupled with very minimal side effects or long term effects has resulted in this class becoming one of the most widely prescribed medications in North America.\r\n\r\nLovastatin and other drugs from the statin class of medications including , , , , and  are considered first-line options for the treatment of dyslipidemia. Increasing use of the statin class of drugs is largely due to the fact that cardiovascular disease (CVD), which includes heart attack, atherosclerosis, angina, peripheral artery disease, and stroke, has become a leading cause of death in high-income countries and a major cause of morbidity around the world. Elevated cholesterol levels, and in particular, elevated low-density lipoprotein (LDL) levels, are an important risk factor for the development of CVD. Use of statins to target and reduce LDL levels has been shown in a number of landmark studies to significantly reduce the risk of development of CVD and all-cause mortality. Statins are considered a cost-effective treatment option for CVD due to their evidence of reducing all-cause mortality including fatal and non-fatal CVD as well as the need for surgical revascularization or angioplasty following a heart attack. Evidence has shown that even for low-risk individuals (with <10% risk of a major vascular event occurring within 5 years) statins cause a 20%-22% relative reduction in major cardiovascular events (heart attack, stroke, coronary revascularization, and coronary death) for every 1 mmol/L reduction in LDL without any significant side effects or risks.\r\n\r\nWhile all statin medications are considered equally effective from a clinical standpoint,  is considered the most potent; doses of 10 to 40mg  per day were found in clinical studies to result in a 45.8% to 54.6% decrease in LDL cholesterol levels, while lovastatin has been found to have an average decrease in LDL-C of 25-40%. Potency is thought to correlate to tissue permeability as the more lipophilic statins such as lovastatin are thought to enter endothelial cells by passive diffusion, as opposed to hydrophilic statins such as  and  which are taken up into hepatocytes through OATP1B1 (organic anion transporter protein 1B1)-mediated transport. Despite these differences in potency, several trials have demonstrated only minimal differences in terms of clinical outcomes between statins.","75330-75-5","404.5396","Lovastatin is indicated to reduce the risk of myocardial infarction, unstable angina, and the need for coronary revascularization procedures in individuals without symptomatic cardiovascular disease, average to moderately elevated total-C and LDL-C, and below average HDL-C. It is indicated as an intervention alternative in individuals presenting dyslipidemia at risk of developing atherosclerotic vascular disease. The administration of this agent should be accompanied by the implementation of a fat and cholesterol-restricted diet.\r\n\r\nTherapy with lipid-altering agents should be a component of multiple risk factor intervention in those individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Lovastatin is indicated as an adjunct to diet for the reduction of elevated total-C and LDL-C levels in patients with primary hypercholesterolemia (Types IIa and IIb2), when the response to diet restricted in saturated fat and cholesterol and to other nonpharmacological measures alone has been inadequate.\r\n\r\nLovastatin is also indicated to slow the progression of coronary atherosclerosis in patients with coronary heart disease as part of a treatment strategy to lower total-C and LDL-C to target levels.\r\n\r\nLovastatin is indicated as an adjunct to diet to reduce total-C, LDL-C and apolipoprotein B levels in adolescent boys and girls with Heterozygous Familial Hypercholesterolemia (HeFH) who are at least one year post-menarche, 10 to 17 years of age, with HeFH if after an adequate trial of diet therapy the following findings are present: LDL-C remains greater than 189 mg/dL or LDL-C remains greater than 160 mg/dL and there is a positive family history of premature cardiovascular disease or two or more other CVD risk factors are present in the adolescent patient.\r\n\r\nBefore administering lovastatin, it is important to rule out the presence of secondary causes of hypercholesterolemia and a lipid profile should be performed.\r\n\r\nPrescribing of statin medications is considered standard practice following any cardiovascular events and for people with a moderate to high risk of development of CVD. Statin-indicated conditions include diabetes mellitus, clinical atherosclerosis (including myocardial infarction, acute coronary syndromes, stable angina, documented coronary artery disease, stroke, trans ischemic attack (TIA), documented carotid disease, peripheral artery disease, and claudication), abdominal aortic aneurysm, chronic kidney disease, and severely elevated LDL-C levels.","Lovastatin is an oral antilipemic agent which reversibly inhibits HMG-CoA reductase. It is used to lower total cholesterol, low density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apoB), non-high density lipoprotein-cholesterol (non-HDL-C), and trigleride (TG) plasma concentrations while increasing HDL-C concentrations. High LDL-C, low HDL-C and high TG concentrations in the plasma are associated with increased risk of atherosclerosis and cardiovascular disease. The total cholesterol to HDL-C ratio is a strong predictor of coronary artery disease and high ratios are associated with higher risk of disease. Increased levels of HDL-C are associated with lower cardiovascular risk. By decreasing LDL-C and TG and increasing HDL-C, lovastatin reduces the risk of cardiovascular morbidity and mortality.\r\n\r\nElevated cholesterol levels, and in particular, elevated low-density lipoprotein (LDL) levels, are an important risk factor for the development of CVD. Use of statins to target and reduce LDL levels has been shown in a number of landmark studies to significantly reduce the risk of development of CVD and all-cause mortality. Statins are considered a cost-effective treatment option for CVD due to their evidence of reducing all-cause mortality including fatal and non-fatal CVD as well as the need for surgical revascularization or angioplasty following a heart attack. Evidence has shown that even for low-risk individuals (with <10% risk of a major vascular event occurring within 5 years) statins cause a 20%-22% relative reduction in major cardiovascular events (heart attack, stroke, coronary revascularization, and coronary death) for every 1 mmol/L reduction in LDL without any significant side effects or risks. Clinical studies have shown that lovastatin reduces LDL-C and total cholesterol by 25-40%. The 50% inhibitory dose is known to be of 46 mcg/kg which is translated into a reduction of approximately 30% of plasma cholesterol.\r\n\r\n**Myopathy/Rhabdomyolysis**\r\n\r\nLovastatin, like other inhibitors of HMG-CoA reductase, occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase (CK) above ten times the upper limit of normal (ULN). Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred. The risk of myopathy is dose-related and is increased by high levels of HMG-CoA reductase inhibitory activity in plasma. In a clinical study (EXCEL) in which patients were carefully monitored and some interacting drugs were excluded, there was one case of myopathy among 4933 patients randomized to lovastatin 20 to 40 mg daily for 48 weeks, and 4 among 1649 patients randomized to 80 mg daily.\r\n\r\nPredisposing factors for myopathy include advanced age (≥65 years), female gender, uncontrolled hypothyroidism, and renal impairment. Chinese patients may also be at increased risk for myopathy. In most cases, muscle symptoms and CK increases resolved when treatment was promptly discontinued.\r\n\r\nThe risk of myopathy during treatment with lovastatin may be increased with concurrent administration of interacting drugs such as , , , , and strong inhibitors of the CYP3A4 enzyme.  Cases of myopathy, including rhabdomyolysis, have been reported with HMG-CoA reductase inhibitors coadministered with , and caution should therefore be exercised when prescribing these two medications together.\r\n\r\nReal-world data from observational studies has suggested that 10-15% of people taking statins may experience muscle aches at some point during treatment.\r\n\r\n**Liver Dysfunction**\r\n\r\nPersistent increases (to more than 3 times the upper limit of normal) in serum transaminases occurred in 1.9% of adult patients who received lovastatin for at least one year in early clinical trials. When the drug was interrupted or discontinued in these patients, the transaminase levels usually fell slowly to pretreatment levels. The increases usually appeared 3 to 12 months after the start of therapy with lovastatin, and were not associated with jaundice or other clinical signs or symptoms. In the EXCEL study, the incidence of persistent increases in serum transaminases over 48 weeks was 0.1% for placebo, 0.1% at 20 mg/day, 0.9% at 40 mg/day, and 1.5% at 80 mg/day in patients on lovastatin. However, in post-marketing experience with lovastatin, symptomatic liver disease has been reported rarely at all dosages.","Lovastatin is a lactone which is readily hydrolyzed _in vivo_ to the corresponding β-hydroxyacid and strong inhibitor of HMG-CoA reductase, a hepatic microsomal enzyme which catalyzes the conversion of HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A ) to mevalonate, an early rate-limiting step in cholesterol biosynthesis. At therapeutic lovastatin doses, HMG-CoA reductase is not completely blocked, thereby allowing biologically necessary amounts of mevalonate to be available. Because the conversion of HMG-CoA to mevalonate is an early step in the biosynthetic pathway for cholesterol, therapy with lovastatin would not be expected to cause an accumulation of potentially toxic sterols.\r\n\r\nLovastatin acts primarily in the liver, where decreased hepatic cholesterol concentrations stimulate the upregulation of hepatic low density lipoprotein (LDL) receptors which increase hepatic uptake of LDL. Lovastatin also inhibits hepatic synthesis of very low density lipoprotein (VLDL). The overall effect is a decrease in plasma LDL and VLDL and a significant reduction in the risk of development of CVD and all-cause mortality.\r\n\r\nA significant effect on LDL-C reduction was seen within 2 weeks of initiation of lovastatin, and the maximum therapeutic response occurred within 4-6 weeks. The response was maintained during continuation of therapy. Single daily doses given in the evening were more effective than the same dose given in the morning, perhaps because cholesterol is synthesized mainly at night. When therapy with lovastatin is stopped, total cholesterol has been shown to return to pre-treatment levels.\r\n\r\nIn vitro and in vivo animal studies also demonstrate that lovastatin exerts vasculoprotective effects independent of its lipid-lowering properties, also known as the pleiotropic effects of statins. This includes improvement in endothelial function, enhanced stability of atherosclerotic plaques, reduced oxidative stress and inflammation, and inhibition of the thrombogenic response.\r\n\r\nStatins have also been found to bind allosterically to β2 integrin function-associated antigen-1 (LFA-1), which plays an important role in leukocyte trafficking and in T cell activation.\r\n\r\nLovastatin has been reported to have beneficial effects on certain cancers. This includes a multi-factorial stress-triggered cell death (apoptosis) and DNA degradation response in breast cancer cells. It has also been shown to inhibit histone deacetylase 2 (HDAC2) activity and increase the accumulation of acetylated histone-H3 and the expression of p21(WAF/CIP) in human cancer cells, suggesting that statins might serve as novel HDAC inhibitors for cancer therapy and chemoprevention.","3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor; Integrin alpha-L inhibitor; Histone deacetylase 2 inhibitor","Therapeutic strategy associated"]
[89,"DB00230","approved; investigational","small molecule","Pregabalin","(S)-3-Isobutyl GABA; 3-Isobutyl GABA; Pregabalin","C8H17NO2","CC(C)C[C@H](CN)CC(O)=O","Pregabalin is structurally similar to gamma-aminobutyric acid (GABA) - an inhibitory neurotransmitter. It may be used to manage neuropathic pain, postherpetic neuralgia, and fibromyalgia among other conditions. Although as per the FDA Label the mechanism of action has not been definitively defined, there is evidence that pregabalin exerts its effects by binding to the α2δ subunit of voltage-dependent calcium channels. Pregabalin is marketed by Pfizer under the trade name Lyrica and Lyrica Cr (extended release). It may have dependence liability if misused but the risk appears to be highest in patients with current or past substance use disorders.","148553-50-8","159.2261","Pregabalin is indicated for the management of neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, fibromyalgia, neuropathic pain associated with spinal cord injury, and as adjunctive therapy for the treatment of partial-onset seizures in patients 1 month of age and older.","Although the structure of pregabalin is similar to gamma-aminobutyric acid (GABA), it does not bind to GABA receptors. Instead, it binds the alpha2-delta subunit of presynaptic voltage-gated calcium channels in the central nervous system. Pregabalin does not modulate dopamine receptors, serotonin receptors, opiate receptors, sodium channels or cyclooxygenase activity.","Although the mechanism of action has not been fully elucidated, studies involving structurally related drugs suggest that presynaptic binding of pregabalin to voltage-gated calcium channels is key to the antiseizure and antinociceptive effects observed in animal models.  \r\n\r\nBy binding presynaptically to the alpha2-delta subunit of voltage-gated calcium channels in the central nervous system, pregabalin modulates the release of several excitatory neurotransmitters including glutamate, substance-P, norepinephrine, and calcitonin gene related peptide. In addition, pregabalin prevents the alpha2-delta subunit from being trafficked from the dorsal root ganglia to the spinal dorsal horn, which may also contribute to the mechanism of action. \r\n\r\nAlthough pregabalin is a structural derivative of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), it does not bind directly to GABA or benzodiazepine receptors.","Voltage-dependent calcium channel subunit alpha-2/delta-1","Indication associated"]
[90,"DB00232","withdrawn","small molecule","Methyclothiazide","Methyclothiazide","C9H11Cl2N3O4S2","CN1C(CCl)NC2=CC(Cl)=C(C=C2S1(=O)=O)S(N)(=O)=O","A thiazide diuretic with properties similar to those of hydrochlorothiazide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p825)","135-07-9","360.237","For use in the management of hypertension either as the sole therapeutic agent or to enhance the effect of other antihypertensive drugs in the more severe forms of hypertension. Also used as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy.","Methyclothiazide, a diuretic-antihypertensive agent, is a member of the benzothiadiazine (thiazide) class of drugs. Methyclothiazide has a per mg natriuretic activity approximately 100 times that of the prototype thiazide, chlorothiazide. At maximal therapeutic dosages, all thiazides are approximately equal in their diuretic/natriuretic effects. Like other benzothiadiazines, methyclothiazide also has antihypertensive properties, and may be used for this purpose either alone or to enhance the antihypertensive action of other drugs.","Methyclothiazide appears to block the active reabsorption of chloride and possibly sodium in the ascending loop of Henle, altering electrolyte transfer in the proximal tubule. This results in excretion of sodium, chloride, and water and, hence, diuresis. As a diuretic, methyclothiazide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like methyclothiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of methyclothiazide is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle.","Solute carrier family 12 member 1 inhibitor; Carbonic anhydrase 1 inhibitor; Carbonic anhydrase 2 inhibitor; Carbonic anhydrase 4 inhibitor","Therapeutic strategy associated"]
[91,"DB00234","approved; experimental","small molecule","Reboxetine","Reboxetine","C19H23NO3","[H][C@@]1(CNCCO1)[C@H](OC1=CC=CC=C1OCC)C1=CC=CC=C1","Reboxetine is an antidepressant drug used in the treatment of clinical depression, panic disorder and ADD/ADHD. Its mesylate (i.e. methanesulfonate) salt is sold under tradenames including Edronax, Norebox, Prolift, Solvex, Davedax or Vestra. Reboxetine has two chiral centers, but it only exists as two enantiomers, (R,R)-(-)- and (S,S)-(+)-reboxetine.","71620-89-8","313.397","For the treatment of clinical depression.","Reboxetine is a selective noradrenaline reuptake inhibitor (NaRI), the first drug of new antidepressant class. Reboxetine is an a-ariloxybenzyl derivative of morpholine. Reboxetine is primarily used to treat depression but has also been found useful in the treatment of narcolepsy and panic disorders.","Reboxetine is a selective inhibitor of noradrenaline reuptake. It inhibits noradrenaline reuptake <i>in vitro</i> to a similar extent to the tricyclic antidepressant desmethylimipramine. Reboxetine does not affect dopamine or serotonin reuptake and it has low <i>in vivo</i> and <i>in vitro</i> affinity for adrenergic, cholinergic, histaminergic, dopaminergic and serotonergic receptors.","Sodium-dependent noradrenaline transporter inhibitor","Indication associated"]
[92,"DB00240","approved","small molecule","Alclometasone","(7alpha,11beta,16alpha)-7-chloro-11,17,21-trihydroxy-16-methylpregna-1,4-diene-3,20-dione; 7α-Chloro-16α-methylprednisolone; Alclometasone","C22H29ClO5","[H][C@@]12C[C@@H](C)[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])[C@H](Cl)CC2=CC(=O)C=C[C@]12C","Alclometasone is synthetic glucocorticoid steroid for topical use in dermatology as anti-inflammatory, antipruritic, antiallergic, antiproliferative and vasoconstrictive agent.","67452-97-5","408.916","For the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses.","Alclometasone is a synthetic corticosteroid for topical dermatologic use. The corticosteroids constitute a class of primarily synthetic steroids used topically as anti-inflammatory and antipruritic agents. Alclometasone is a selective glucocorticoid receptor agonist.","The mechanism of the anti-inflammatory activity of the topical steroids, in general, is unclear. However, corticosteroids are thought to act by the induction of phospholipase A<sub>2</sub> inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A<sub>2</sub>. Alclometasone initially binds the corticosteroid receptor. This complex migrates to the nucleus where it binds to different glucocorticoid response elements on the DNA. This in turn enhances and represses various genes, especially those involved in inflammatory pathways.","Glucocorticoid receptor agonist","Therapeutic strategy associated"]
[93,"DB00244","approved","small molecule","Mesalazine","3-carboxy-4-hydroxyaniline; 5-aminosalicylic acid; 5-ASA; m-Aminosalicylic acid; Mesalamine; Mesalazine","C7H7NO3","NC1=CC(C(O)=O)=C(O)C=C1","An anti-inflammatory agent, structurally related to the salicylates and non-steroidal anti-inflammatory drugs like acetylsalicylic acid, which is active in inflammatory bowel disease . It is considered to be the active moiety of sulphasalazine. (From Martindale, The Extra Pharmacopoeia, 30th ed) Although demonstrably effective in treating and maintaining remission for ulcerative colitis, mesalazine has historically faced a number of issues regarding its lack of stability as a pharmaceutical agent . Throughout the late seventies and the eighties, important research initiatives developed stable mesalazine formulations like the eudragit-S coating of Asacol brand mesalazine and the Pentasa brand's encapsulation of mesalazine within microgranules . In the present day, contemporary research regarding novel methods to stabilize mesalazine continues and interest in the agent's capacity to decrease inflammatory activity and subsequently potentially reduce the risk of colorectal cancer in conditions like ulcerative colitis is maintained.","89-57-6","153.1354","Mesalazine is indicated for the induction of remission in patients with active or mild to moderate acute exacerbations of ulcerative colitis and for the maintenance of remission of ulcerative colitis , . Prescribing information for mesalazine in the UK also indicates the medication for the maintenance of remission of Crohn's ileo-colitis .","Mesalazine is one of the two components of sulphasalazine, the other being sulphapyridine. It is the latter which is responsible for the majority of the side effects associated with sulphasalazine therapy whilst mesalazine is known to be the active moiety in the treatment of ulcerative colitis .\r\n\r\nThe pharmacodynamic actions of mesalazine occur in the colonic/rectal mucosae local to the delivery of drug from mesalazine tablets into the lumen . There is information suggesting that the severity of colonic inflammation in ulcerative colitis patients treated with mesalazine is inversely correlated with mucosal concentrations of mesalazine . Plasma concentrations representing systemically absorbed mesalazine are not believed to contribute extensively to efficacy .","Although the mechanism of action of mesalazine is not fully understood, it is believed to possess a topical anti-inflammatory effect on colonic epithelial cells . Mucosal production of arachidonic acid metabolites, both through the cyclooxygenase pathways, i.e., prostanoids, and through the lipoxygenase pathways, i.e., leukotrienes and hydroxyeicosatetraenoic acids, is increased in patients with chronic inflammatory bowel disease, and it is possible that mesalazine diminishes inflammation by blocking cyclooxygenase and inhibiting prostaglandin production in the colon .\r\n\r\nFurthermore, mesalazine also has the potential to inhibit the activation of Nuclear Factor kappa B (NKkB) and consequently the production of key of pro-inflammatory cytokines . It has been proposed that reduced expression of PPAR gamma nuclear receptors (gamma form of peroxisome proliferator-activated receptors) may be implicated in ulcerative colitis . There is evidence that mesalazine produces pharmacodynamic effects through direct activation of PPAR gamma receptors in the colonic/rectal epithelium as well .\r\n\r\nMoreover, since increased leukocyte migration, abnormal cytokine production, increased production of arachidonic acid metabolites, particularly leukotriene B4, and increased free radical formation in the inflamed intestinal tissue are all present in patients with inflammatory bowel disease it is also believed that mesalazine has in-vitro and in-vivo pharmacological effects that inhibit leukocyte chemotaxis, decrease cytokine and leukotriene production and scavenge for free radicals .","Prostaglandin G/H synthase 2 inhibitor; Prostaglandin G/H synthase 1 inhibitor; Arachidonate 5-lipoxygenase inhibitor; Peroxisome proliferator-activated receptor gamma agonist; Inhibitor of nuclear factor kappa-B kinase subunit alpha inhibitor; Inhibitor of nuclear factor kappa-B kinase subunit beta inhibitor; Myeloperoxidase","Therapeutic strategy associated"]
[94,"DB00250","approved; investigational","small molecule","Dapsone","1,1'-sulfonylbis(4-aminobenzene); 1,1'-Sulfonylbis[4-aminobenzene]; 4-(4-amino-benzenesulfonyl)-phenylamine; 4-(4-aminophenylsulfonyl)aniline; 4-(4-aminophenylsulfonyl)benzenamine; 4-aminophenyl sulfone; 4,4'-dapsone; 4,4'-diaminodiphenyl sulfone; 4,4'-Diaminodiphenyl sulphone; 4,4'-Diaminodiphenylsulfone; 4,4'-sulfonylbisaniline; 4,4'-Sulfonylbisbenzenamine; 4,4'-Sulfonylbisbenzeneamine; 4,4'-Sulfonyldianilin; 4,4'-sulfonyldianiline; bis(4-aminophenyl)sulfone; Bis(p-aminophenyl) sulfone; DADPS; Dapsone; DDS; Diaphenylsulfone; p-aminophenyl sulfone; p,p-sulphonylbisbenzamine; p,p-sulphonylbisbenzenamine; p,p'-diaminodiphenyl sulfone","C12H12N2O2S","NC1=CC=C(C=C1)S(=O)(=O)C1=CC=C(N)C=C1","A sulfone active against a wide range of bacteria but mainly employed for its actions against mycobacterium leprae. Its mechanism of action is probably similar to that of the sulfonamides which involves inhibition of folic acid synthesis in susceptible organisms. It is also used with pyrimethamine in the treatment of malaria. (From Martindale, The Extra Pharmacopoeia, 30th ed, p157-8)","80-08-0","248.301","For the treatment and management of leprosy and dermatitis herpetiformis.","Dapsone is a sulfone with anti-inflammatory immunosuppressive properties as well as antibacterial and antibiotic properties. Dapsone is the principal drug in a multidrug regimen recommended by the World Health Organization for the treatment of leprosy. As an anti-infective agent, it is also used for treating malaria and, recently, for Pneumocystic carinii pneumonia in AIDS patients. Dapsone is absorbed rapidly and nearly completely from the gastrointestinal tract. Dapsone is distributed throughout total body water and is present in all tissues. However, it tends to be retained in skin and muscle and especially in the liver and kidney: traces of the drug are present in these organs up to 3 weeks after therapy cessation.","Dapsone acts against bacteria and protozoa in the same way as sulphonamides, that is by inhibiting the synthesis of dihydrofolic acid through competition with para-amino-benzoate for the active site of dihydropteroate synthetase. The anti-inflammatory action of the drug is unrelated to its antibacterial action and is still not fully understood.","Inactive dihydropteroate synthase 2 inhibitor; Dihydropteroate synthase 1 inhibitor","Therapeutic strategy associated"]
[95,"DB00253","approved","small molecule","Medrysone","11beta-Hydroxy-6alpha-methylpregn-4-ene-3,20-dione; Medrysone","C22H32O3","[H][C@@]12CC[C@H](C(C)=O)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])C[C@H](C)C2=CC(=O)CC[C@]12C","Medrysone is a corticosteroid used in ophthalmology.","2668-66-8","344.4877","For the treatment of allergic conjunctivitis, vernal conjunctivitis, episcleritis, and epinephrine sensitivity.","Medrysone is a topical anti-inflammatory corticoidsteroids for ophthalmic use. In patients with increased intraocular pressure and in those susceptible to a rise in intraocular pressure, there is less effect on pressure with medrysone than with dexamethasone or betamethasone. Corticoidsteroids inhibit the edema, fibrin deposition, capillary dilation, and phagocytic migration of the acute inflammatory response, as well as capillary proliferation, deposition of collagen, and scar formation.","There is no generally accepted explanation for the mechanism of action of ocular corticosteroids. However, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2. Initially, the drug binds to the glucocorticoid receptor in the cytosol. This migrates to the nucleus and binds to genetic elements which cause activation and repression of the involved genes in the inflammatory pathway.","Glucocorticoid receptor agonist","Therapeutic strategy associated"]
[96,"DB00261","approved","small molecule","Anagrelide","Anagrelide","C10H7Cl2N3O","ClC1=CC=C2N=C3NC(=O)CN3CC2=C1Cl","Anagrelide is a platelet-reducing agent used to lower dangerously elevated platelet levels (i.e. to treat thrombocythemia) in patients with myeloproliferative neoplasms. It is an oral imidazoquinazoline that was first approved for use in the US in 1997. It appears to carry a better response rate than other thrombocythemia treatments (e.g. , ) and may be better tolerated.","68475-42-3","256.088","Anagrelide is indicated for the treatment of thrombocythemia, secondary to malignant neoplasms, to reduce platelet count and the associated risk of thrombosis. It is also beneficial in the amelioration of thrombocythemia symptoms including thrombo-hemorrhagic events.","Anagrelide decreases platelet counts by suppressing transcription factors necessary for the synthesis and maturation of platelet-producing cells. The drug itself appears to have a relatively short residence time in the body necessitating twice or four times daily dosing. However, given that the pharmacological effect of anagrelide therapy is reliant on a gradual suppression of platelet-producing cells, it may take 7 to 14 days for its administration to be reflected in reduced platelet counts - for this reason any changes to anagrelide doses should not exceed 0.5 mg/day in any one week.\r\n\r\nEvidence from animal studies suggests anagrelide may impair female fertility. Female patients of reproductive age should be advised of the potential for adverse effects on fertility prior to initiating therapy.","The exact mechanism by which anagrelide lowers platelet count is unclear. Evidence from human trials suggests a dose-related suppression of megakaryocyte maturation, the cells responsible for platelet production - blood drawn from patients receiving anagrelide showed a disruption to the post-mitotic phase of megakaryocyte development and a subsequent reduction in their size and ploidy. This may be achieved via indirect suppression of certain transcription factors required for megakaryocytopoeisis, including GATA-1 and FOG-1.\r\n\r\nAnagrelide is a known inhibitor of phosphodiesterase 3A (PDE3A), although its platelet-lowering effects appear unrelated to this inhibition. While PDE3 inhibitors, as a class, can inhibit platelet aggregation, this effect is only seen at higher anagrelide doses (i.e. greater than those required to reduce platelet count). Modulation of PDE3A has been implicated in causing cell cycle arrest and apoptosis in cancer cells expressing both PDE3A and SLFN12, and may be of value in the treatment of gastrointestinal stromal tumours.","cGMP-inhibited 3',5'-cyclic phosphodiesterase A inhibitor","Therapeutic strategy associated"]
[97,"DB00263","approved; vet_approved","small molecule","Sulfisoxazole","3,4-Dimethyl-5-sulfanilamidoisoxazole; 3,4-Dimethyl-5-sulfonamidoisoxazole; 3,4-Dimethyl-5-sulphanilamidoisoxazole; 3,4-Dimethyl-5-sulphonamidoisoxazole; 3,4-Dimethylisoxazole-5-sulfanilamide; 3,4-Dimethylisoxazole-5-sulphanilamide; 4-Amino-N-(3,4-dimethyl-5-isoxazolyl)benzenesulfonamide; 4-Amino-N-(3,4-dimethyl-5-isoxazolyl)benzenesulphonamide; 5-(4-Aminophenylsulfonamido)-3,4-dimethylisoxazole; 5-(p-Aminobenzenesulfonamido)-3,4-dimethylisoxazole; 5-(p-Aminobenzenesulphonamido)-3,4-dimethylisoxazole; 5-Sulfanilamido-3,4-dimethylisoxazole; 5-Sulphanilamido-3,4-dimethyl-isoxazole; N'-(3,4)Dimethylisoxazol-5-yl-sulphanilamide; N1-(3,4-dimethyl-5-isoxazolyl)sulfanilamide; N1-(3,4-dimethyl-5-isoxazolyl)sulphanilamide; Sulfadimethylisoxazole; Sulfafurazol; Sulfafurazole; Sulfaisoxazole; Sulfasoxazole; Sulfisonazole; Sulfisoxasole; Sulfisoxazol; Sulfisoxazole; Sulfofurazole; Sulphadimethylisoxazole; Sulphafurazol; Sulphafurazole; Sulphaisoxazole; Sulphisoxazol; Sulphofurazole","C11H13N3O3S","CC1=NOC(NS(=O)(=O)C2=CC=C(N)C=C2)=C1C","A short-acting sulfonamide antibacterial with activity against a wide range of gram- negative and gram-positive organisms.","127-69-5","267.304","For the treatment of severe, repeated, or long-lasting urinary tract infections, meningococcal meningitis, acute otitis media, trachoma, inclusion conjunctivitis, nocardiosis, chancroid, toxoplasmosis, malaria and other bacterial infections.","Sulfisoxazole is a sulfonamide antibiotic. The sulfonamides are synthetic bacteriostatic antibiotics with a wide spectrum against most gram-positive and many gram-negative organisms. However, many strains of an individual species may be resistant. Sulfonamides inhibit multiplication of bacteria by acting as competitive inhibitors of <i>p</i>-aminobenzoic acid in the folic acid metabolism cycle. Bacterial sensitivity is the same for the various sulfonamides, and resistance to one sulfonamide indicates resistance to all. Most sulfonamides are readily absorbed orally. However, parenteral administration is difficult, since the soluble sulfonamide salts are highly alkaline and irritating to the tissues. The sulfonamides are widely distributed throughout all tissues. High levels are achieved in pleural, peritoneal, synovial, and ocular fluids. Although these drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections. Their antibacterial action is inhibited by pus.","Sulfisoxazole is a competitive inhibitor of the enzyme dihydropteroate synthetase. It inhibits bacterial synthesis of dihydrofolic acid by preventing the condensation of the pteridine with para-aminobenzoic acid (PABA), a substrate of the enzyme dihydropteroate synthetase. The inhibited reaction is necessary in these organisms for the synthesis of folic acid.","Dihydropteroate synthase inhibitor","Indication associated"]
[98,"DB00264","approved; investigational","small molecule","Metoprolol","(RS)-Metoprolol; 1-(isopropylamino)-3-[4-(2-methoxyethyl)phenoxy]propan-2-ol; DL-metoprolol; Metoprolol","C15H25NO3","COCCC1=CC=C(OCC(O)CNC(C)C)C=C1","Metoprolol is a selective beta-1 blocker commonly employed as the succinate and tartrate derivatives depending if the formulation is designed to be of immediate release or extended release. The possibility of the generation of these formulations comes from the lower systemic bioavailability of the succinate derivative. To this date, it is one of the preferred beta-blockers in general clinical guidelines and it is widely prescribed in the Netherlands, New Zealand, and the US. Metoprolol was developed since 1969 by US Pharmaceutical Holdings I and FDA approved in 1978.","51384-51-1","267.3639","Metoprolol is indicated for the treatment of angina, heart failure, myocardial infarction, atrial fibrillation, atrial flutter and hypertension.\r\n\r\nSome off-label uses of metoprolol include supraventricular tachycardia and thyroid storm.\r\n\r\nAll the indications of metoprolol are part of cardiovascular diseases. These conditions correspond to a number of diseases that involve the function of the heart and blood vessels. The underlying causes of these conditions are variable and can be due to genetic disposition, lifestyle decisions such as smoking, obesity, diet, and lack of exercise, and comorbidity with other conditions such as diabetes. The cardiovascular diseases are the leading cause of death on a global scale.","Administration of metoprolol in normal subjects is widely reported to produce a dose-dependent reduction on heart rate and cardiac output. This effect is generated due to a decreased cardiac excitability, cardiac output, and myocardial oxygen demand. In the case of arrhythmias, metoprolol produces its effect by reducing the slope of the pacemaker potential as well as suppressing the rate of atrioventricular conduction.\r\n\r\nThe Metoprolol Atherosclerosis Prevention in Hypertensives (MAPHY) trial showed a significant improvement in sudden cardiac death and myocardial infarction when patients were given with metoprolol as compared with diuretics. As well, in clinical trials performed in 1990, metoprolol reduces mortality and re-infarction in 17% of the individuals when administered chronically after an episode of myocardial infarction.","Metoprolol is a beta-1-adrenergic receptor inhibitor specific to cardiac cells with negligible effect on beta-2 receptors. This inhibition decreases cardiac output by producing negative chronotropic and inotropic effects without presenting activity towards membrane stabilization nor intrinsic sympathomimetics.","Beta-1 adrenergic receptor antagonist; Beta-2 adrenergic receptor antagonist","Therapeutic strategy associated"]
[99,"DB00270","approved; investigational","small molecule","Isradipine","Isradipine","C19H21N3O5","COC(=O)C1=C(C)NC(C)=C(C1C1=CC=CC2=NON=C12)C(=O)OC(C)C","Isradipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. It is structurally related to felodipine, nifedipine, and nimodipine and is the most potent calcium-channel blocking agent of the DHP class. Isradipine binds to calcium channels with high affinity and specificity and inhibits calcium flux into cardiac and arterial smooth muscle cells. It exhibits greater selectivity towards arterial smooth muscle cells owing to alternative splicing of the alpha-1 subunit of the channel and increased prevalence of inactive channels in smooth muscle cells. Isradipine may be used to treat mild to moderate essential hypertension.","75695-93-1","371.3871","For the management of mild to moderate essential hypertension. It may be used alone or concurrently with thiazide-type diuretics.","Isradipine decreases arterial smooth muscle contractility and subsequent vasoconstriction by inhibiting the influx of calcium ions through L-type calcium channels. Calcium ions entering the cell through these channels bind to calmodulin. Calcium-bound calmodulin then binds to and activates myosin light chain kinase (MLCK). Activated MLCK catalyzes the phosphorylation of the regulatory light chain subunit of myosin, a key step in muscle contraction. Signal amplification is achieved by calcium-induced calcium release from the sarcoplasmic reticulum through ryanodine receptors. Inhibition of the initial influx of calcium decreases the contractile activity of arterial smooth muscle cells and results in vasodilation. The vasodilatory effects of isradipine result in an overall decrease in blood pressure.","Isradipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. There are at least five different types of calcium channels in <i>Homo sapiens</i>: L-, N-, P/Q-, R- and T-type. CCBs target L-type calcium channels, the major channel in muscle cells that mediates contraction. Similar to other DHP CCBs, isradipine binds directly to inactive calcium channels stabilizing their inactive conformation. Since arterial smooth muscle depolarizations are longer in duration than cardiac muscle depolarizations, inactive channels are more prevalent in smooth muscle cells. Alternative splicing of the alpha-1 subunit of the channel gives isradipine additional arterial selectivity. At therapeutic sub-toxic concentrations, isradipine has little effect on cardiac myocytes and conduction cells.","Voltage-dependent L-type calcium channel subunit alpha-1C inhibitor; Voltage-dependent calcium channel subunit alpha-2/delta-1 inhibitor; Voltage-dependent L-type calcium channel subunit beta-2 inhibitor; Voltage-dependent T-type calcium channel subunit alpha-1H inhibitor; Voltage-dependent calcium channel subunit alpha-2/delta-2 inhibitor; Voltage-dependent L-type calcium channel subunit alpha-1D inhibitor; Voltage-dependent L-type calcium channel subunit alpha-1S inhibitor","Indication associated"]
[100,"DB00277","approved","small molecule","Theophylline","1,3-dimethyl-7H-purine-2,6-dione; 1,3-dimethylxanthine; Theophyllin; Theophylline anhydrous; Theophylline, anhydrous","C7H8N4O2","CN1C2=C(NC=N2)C(=O)N(C)C1=O","A methylxanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Mechanistically, theophylline acts as a phosphodiesterase inhibitor, adenosine receptor blocker, and histone deacetylase activator. Theophylline is marketed under several brand names such as Uniphyl and Theochron, and it is indicated mainly for asthma, bronchospasm, and COPD.","58-55-9","180.164","For the treatment of the symptoms and reversible airflow obstruction associated with chronic asthma and other chronic lung diseases, such as emphysema and chronic bronchitis.","Theophylline, an xanthine derivative chemically similar to caffeine and theobromine, is used to treat asthma and bronchospasm. Theophylline has two distinct actions in the airways of patients with reversible (asthmatic) obstruction; smooth muscle relaxation (i.e., bronchodilation) and suppression of the response of the airways to stimuli (i.e., non-bronchodilator prophylactic effects).","Theophylline relaxes the smooth muscle of the bronchial airways and pulmonary blood vessels and reduces airway responsiveness to histamine, methacholine, adenosine, and allergen. Theophylline competitively inhibits type III and type IV phosphodiesterase (PDE), the enzyme responsible for breaking down cyclic AMP in smooth muscle cells, possibly resulting in bronchodilation. Theophylline also binds to the adenosine A2B receptor and blocks adenosine mediated bronchoconstriction. In inflammatory states, theophylline activates histone deacetylase to prevent transcription of inflammatory genes that require the acetylation of histones for transcription to begin.","Adenosine receptor A1 antagonist; Adenosine receptor A2a antagonist; Adenosine receptor A2b antagonist; cAMP-specific 3',5'-cyclic phosphodiesterase 4B inhibitor; cGMP-specific 3',5'-cyclic phosphodiesterase inhibitor; cAMP-specific 3',5'-cyclic phosphodiesterase 4A inhibitor; cGMP-inhibited 3',5'-cyclic phosphodiesterase A inhibitor; Histone deacetylase 2 activator; Copine-1; Minor histocompatibility antigen H13; Nodal modulator 1; Poly [ADP-ribose] polymerase 1; Protein RIC-3; Tubulin monoglycylase TTLL3","Therapeutic strategy associated"]
[101,"DB00278","approved; investigational","small molecule","Argatroban","Argatroban; Argatroban anhydrous","C23H36N6O5S","C[C@@H]1CCN([C@H](C1)C(O)=O)C(=O)[C@H](CCCNC(N)=N)NS(=O)(=O)C1=CC=CC2=C1NCC(C)C2","Argatroban is a direct, selective thrombin inhibitor. The American College of Cardiologists (ACC) recommend using bivalirudin or argatroban in patients who have had, or at risk for, heparin induced thrombocytopenia (HIT) and are undergoing percutaneous coronary intervention. Argatroban is a non-heparin anticoagulant shown to both normalize platelet count in patients with HIT and prevent the formation of thrombi. Parental anticoagulants must be stopped and a baseline activated partial thromboplastin time must be obtained prior to administering argatroban.","74863-84-6","508.64","Argatroban is indicated for prevention and treatment of thrombosis caused by heparin-induced thrombocytopenia (HIT). It is also indicated for use in patients with, or at risk for, HIT who are undergoing percutaneous coronary intervention.","Argatroban is a synthetic direct thrombin inhibitor derived from L-arginine indicated as an anticoagulant for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia. Argatroban is a direct thrombin inhibitor that reversibly binds to the thrombin active site. Argatroban does not require the co-factor antithrombin III for antithrombotic activity. Argatroban exerts its anticoagulant effects by inhibiting thrombin-catalyzed or -induced reactions, including fibrin formation; activation of coagulation factors V, VIII, and XIII; protein C; and platelet aggregation. Argatroban is highly selective for thrombin with an inhibitory constant (K<sub>i</sub>) of 0.04 &micro;M. At therapeutic concentrations, Argatroban has little or no effect on related serine proteases (trypsin, factor Xa, plasmin, and kallikrein).\r\nArgatroban is capable of inhibiting the action of both free and clot-associated thrombin.","Argatroban exerts its anticoagulant effects by inhibiting thrombin-catalyzed or -induced reactions, including fibrin formation; activation of coagulation factors V, VIII, and XIII; protein C; and platelet aggregation.","Prothrombin inhibitor","Therapeutic strategy associated"]
[102,"DB00279","approved; vet_approved","small molecule","Liothyronine","3,3',5-triiodo-L-thyronine; 3,5,3'-Triiodo-L-thyronine; 3,5,3'-Triiodothyronine; 4-(4-hydroxy-3-iodophenoxy)-3,5-diiodo-L-phenylalanine; L-3,5,3'-Triiodothyronine; L-T3; O-(4-hydroxy-3-iodophenyl)-3,5-diiodo-L-tyrosine; T3; Triiodothyronine","C15H12I3NO4","N[C@@H](CC1=CC(I)=C(OC2=CC(I)=C(O)C=C2)C(I)=C1)C(O)=O","Liothyronine is a thyroidal hormone T3 which is normally produced by the thyroid gland in a ratio 4:1 when compared with T4: T3. Liothyronine is the active form of thyroxine which is composed in a basic chemical structure by a tyrosine with bound iodine. The exogenous liothyronine product was developed by King Pharmaceuticals and FDA approved in 1956.","6893-02-3","650.9735","Liothyronine is officially approved for the following indications:\r\n\r\n- Replacement therapy in primary (thyroidal), secondary (pituitary) and tertiary (hypothalamic) congenital or acquired hypothyroidism.\r\n\r\n- As an adjunct therapy to surgery and radioiodine in the management of thyroid cancer.\r\n\r\n- As a diagnostic agent in suppression tests for mild hyperthyroidism or thyroid gland autonomy.\r\n\r\nIn general terms, exogenous liothyronine is used to replace insufficient hormonal production and restore T3 plasma levels.\r\n\r\nThe lack of liothyronine can be presented as a pale and puffy face, coarse,  brittle hair, dry skin, croaky voice and constipation as well as irregular periods, drowsiness, and lethargy.\r\n\r\nLiothyronine should never be used in the suppression of benign nodules and nontoxic diffuse goiter in iodine-sufficient patients nor in the treatment of hyperthyroidism during the recovery phase of subacute thyroiditis.","In hormonal replacement, liothyronine is more potent and present a faster action when compared to levothyroxine but the time of action is significantly shorter. The type of treatment needs to be well evaluated as the fast correction of thyroid hormones in certain diseases presents additional risks such as heart failure. The onset of activity is observed a few hours after administration and the maximum effect is observed after 2-3 days.\r\n\r\nTreatment with liothyronine has been shown to produce normal plasma levels of T3 hormone but to have no effect on the T4 plasma concentration.","Liothyronine replaces endogenous thyroid hormone and then exerts its physiologic effects by controlling DNA transcription and protein synthesis. This effect on DNA is obtained by the binding of liothyronine to the thyroid receptors attached to DNA. Exogenous liothyronine exerts all the normal effects of the endogenous thyroid T3 hormone. Hence, it increases energy expenditure, accelerates the rate of cellular oxidation stimulating growth, maturation, and metabolism of the body tissues, aids in myelination of nerves and development of synaptic processes in the nervous system and enhances carbohydrate and protein metabolism.","Thyroid hormone receptor alpha agonist; Thyroid hormone receptor beta agonist; Proliferating cell nuclear antigen antagonist","Target associated"]
[103,"DB00281","approved; vet_approved","small molecule","Lidocaine","2-(Diethylamino)-2',6'-acetoxylidide; 2-(Diethylamino)-N-(2,6-dimethylphenyl)acetamide; alpha-diethylamino-2,6-dimethylacetanilide; Lidocaine; Lignocaine; α-diethylamino-2,6-dimethylacetanilide","C14H22N2O","CCN(CC)CC(=O)NC1=C(C)C=CC=C1C","Ever since its discovery and availability for sale and use in the late 1940s, lidocaine has become an exceptionally commonly used medication . In particular, lidocaine's principal mode of action in acting as a local anesthetic that numbs the sensations of tissues means the agent is indicated for facilitating local anesthesia for a large variety of surgical procedures . It ultimately elicits its numbing activity by blocking sodium channels so that the neurons of local tissues that have the medication applied on are transiently incapable of signaling the brain regarding sensations . In doing so, however, it can block or decrease muscle contractile, resulting in effects like vasodilation, hypotension, and irregular heart rate, among others . As a result, lidocaine is also considered a class Ib anti-arrhythmic agent . Nevertheless, lidocaine's local anesthetic action sees its use in many medical situations or circumstances that may benefit from its action, including the treatment of premature ejaculation .\r\n\r\nRegardless, lidocaine is currently available as a relatively non-expensive generic medication that is written for in millions of prescriptions internationally on a yearly basis. It is even included in the World Health Organization's List of Essential Medicines .","137-58-6","234.3373","Lidocaine is an anesthetic of the amide group indicated for production of local or regional anesthesia by infiltration techniques such as percutaneous injection and intravenous regional anesthesia by peripheral nerve block techniques such as brachial plexus and intercostal and by central neural techniques such as lumbar and caudal epidural blocks .","Excessive blood levels of lidocaine can cause changes in cardiac output, total peripheral resistance, and mean arterial pressure . With central neural blockade these changes may be attributable to the block of autonomic fibers, a direct depressant effect of the local anesthetic agent on various components of the cardiovascular system, and/or the beta-adrenergic receptor stimulating action of epinephrine when present . The net effect is normally a modest hypotension when the recommended dosages are not exceeded .\r\n\r\nIn particular, such cardiac effects are likely associated with the principal effect that lidocaine elicits when it binds and blocks sodium channels, inhibiting the ionic fluxes required for the initiation and conduction of electrical action potential impulses necessary to facilitate muscle contraction . Subsequently, in cardiac myocytes, lidocaine can potentially block or otherwise slow the rise of cardiac action potentials and their associated cardiac myocyte contractions, resulting in possible effects like hypotension, bradycardia, myocardial depression, cardiac arrhythmias, and perhaps cardiac arrest or circulatory collapse .\r\n\r\nMoreover, lidocaine possesses a dissociation constant (pKa) of 7.7 and is considered a weak base . As a result, about 25% of lidocaine molecules will be un-ionized and available at the physiological pH of 7.4 to translocate inside nerve cells, which means lidocaine elicits an onset of action more rapidly than other local anesthetics that have higher pKa values . This rapid onset of action is demonstrated in about one minute following intravenous injection and fifteen minutes following intramuscular injection . The administered lidocaine subsequently spreads rapidly through the surrounding tissues and the anesthetic effect lasts approximately ten to twenty minutes when given intravenously and about sixty to ninety minutes after intramuscular injection .\r\n\r\nNevertheless, it appears that the efficacy of lidocaine may be minimized in the presence of inflammation . This effect could be due to acidosis decreasing the amount of un-ionized lidocaine molecules, a more rapid reduction in lidocaine concentration as a result of increased blood flow, or potentially also because of increased production of inflammatory mediators like peroxynitrite that elicit direct actions on sodium channels .","Lidocaine is a local anesthetic of the amide type . It is used to provide local anesthesia by nerve blockade at various sites in the body . It does so by stabilizing the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby effecting local anesthetic action . In particular, the lidocaine agent acts on sodium ion channels located on the internal surface of nerve cell membranes . At these channels, neutral uncharged lidocaine molecules diffuse through neural sheaths into the axoplasm where they are subsequently ionized by joining with hydrogen ions . The resultant lidocaine cations are then capable of reversibly binding the sodium channels from the inside, keeping them locked in an open state that prevents nerve depolarization . As a result, with sufficient blockage, the membrane of the postsynaptic neuron will ultimately not depolarize and will thus fail to transmit an action potential . This facilitates an anesthetic effect by not merely preventing pain signals from propagating to the brain but by aborting their generation in the first place .\r\n\r\nIn addition to blocking conduction in nerve axons in the peripheral nervous system, lidocaine has important effects on the central nervous system and cardiovascular system . After absorption, lidocaine may cause stimulation of the CNS followed by depression and in the cardiovascular system, it acts primarily on the myocardium where it may produce decreases in electrical excitability, conduction rate, and force of contraction .","Sodium channel protein type 10 subunit alpha inhibitor; Sodium channel protein type 9 subunit alpha inhibitor; Sodium channel protein type 5 subunit alpha inhibitor; Epidermal growth factor receptor antagonist; Sodium channel protein type 4 subunit alpha; Alpha-1-acid glycoprotein 1; Alpha-1-acid glycoprotein 2","Therapeutic strategy associated"]
[104,"DB00282","approved","small molecule","Pamidronic acid","Pamidronate; Pamidronic acid","C3H11NO7P2","NCCC(O)(P(O)(O)=O)P(O)(O)=O","Pamidronic acid is a second generation, nitrogen containing bisphosphonate similar to  and . Pamidronic acid was first described in the literature in 1977. The second generation bisphosphonates are less common as third generation bisphosphonates, such as , , , and  are becoming more popular.\r\n\r\nPamidronic acid was granted FDA approval on 31 October 1991.","40391-99-9","235.0695","Pamidronate is indicated to treat moderate to severe hypercalcemia of malignancy, moderate to severe Paget's disease of bone, osteolytic bone metastases of breast cancer, and osteolytic lesions of multiple myeloma.","Pamidronic acid is a second generation, nitrogen containing bisphosphonate that inhibits osteoclast mediated bone loss It has a wide therapeutic index and a long duration of action as it can be given every 3-4 weeks for certain indications. Patients should be counselled regarding the risk of elevated blood urea nitrogen, renal tubular necrosis, and nephrotoxicity.","Bisphosphonates are taken into the bone where they bind to hydroxyapatite. Bone resorption by osteoclasts causes local acidification, releasing the bisphosphonate, which is taken into the osteoclast by fluid-phase endocytosis. Endocytic vesicles become acidified, releasing bisphosphonates into the cytosol of osteoclasts where they act.\r\n\r\nOsteoclasts mediate resorption of bone. When osteoclasts bind to bone they form podosomes, ring structures of F-actin. Disruption of the podosomes causes osteoclasts to detach from bones, preventing bone resorption.\r\n\r\nNitrogen containing bisphosphonates such as pamidronate are known to induce apoptosis of hematopoietic tumor cells by inhibiting the components of the mevalonate pathway farnesyl diphosphate synthase, farnesyl diphosphate, and geranylgeranyl diphosphate. These components are essential for post-translational prenylation of GTP-binding proteins like Rap1. The lack of prenylation of these proteins interferes with their function, and in the case of Rap1, leads to apoptosis. pamidronate also activated caspases 3 and 9 which further contribute to apoptosis.","Farnesyl pyrophosphate synthase inhibitor; Hydroxylapatite antagonist; Geranylgeranyl pyrophosphate synthase inhibitor; Caspase-3 activator; Caspase-9 activator","Therapeutic strategy associated"]
[105,"DB00286","approved","small molecule","Conjugated estrogens","Conjugated equine estrogens; Conjugated estrogens; Estrogens, Conjugated; Estrogens,conjugated",null,null,"The conjugated estrogens are noncrystalline mixtures of purified female sex hormones obtained either by its isolation from the urine of pregnant mares or by synthetic generation from vegetal material. Both of these products are later conjugated to natrium sulfate by ester bonds in order to make them more water soluble. \r\n\r\nThe conjugated estrogen product contains a mix of estrogen from which about 50% is represented by estrone sulfate followed by 25% of equilin sulfate, 15% of 17-alpha-dehydroequilenin sulfate, 3% of equilenin sulfate, 5% of 17-alpha and 17-beta-dihydroequilenin sulfate, 2% of 17-alpha-estradiolsulfate and 3% of 17-beta-estradiolsulfate. It also presents a large number of unidentified molecules with weak estrogenic activity as well as non-human molecules when it is obtained from pregnant mares urine. \r\n\r\nThe conjugated estrogen mixture was approved for marketing in US in 1942 based on the efficacy against certain conditions. However, until 1986 official clinical trials were performed and this product was determined to be effective for the treatment of osteoporosis. The currently approved product of conjugated estrogens was developed by Wyeth Ayerst and FDA approved in 2003.","12126-59-9",null,"The conjugated estrogens are indicated for several different conditions including:\r\n\r\n- Treatment of moderate to severe vasomotor symptoms due to menopause.\r\n- Treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause.\r\n- Treatment of hypoestrogenism due to hypogonadism, castration or primary ovarian failure.\r\n- Palliative treatment of breast cancer in appropriately selected patients with metastatic disease.\r\n- Palliative treatment of androgen-dependent carcinoma of the prostate.\r\n- Preventive therapy of postmenopausal osteoporosis.","The binding of estrogens to the estrogen receptor produces the activation of nuclear receptors in order to bind to estrogen response elements in certain target genes. This mechanistic cascade results in histone acetylation, alteration of chromatin conformation and the initiation of transcription of certain specific drugs.\r\n\r\nIn preclinical studies, the conjugated estrogens are known to have a similar estrogenic potency than estrone and the equilin components of the conjugated estrogens have similar potency in the liver when compared to bioidentical estradiol. It has also been tested and confirmed that conjugated estrogens present a selective estrogen receptor modulator profile which allows it to have a large beneficial effect on the bone and cardiovascular system.\r\n\r\nClinically, the administration of conjugated estrogens is known to promote vasomotor stability, maintain genitourinary function, and normal growth and development of female sex hormones. It has also been shown to prevent accelerated bone loss by inhibiting bone resorption and restoring the balance of bone resorption. In the hormonal area, it is shown to inhibit luteinizing hormone and decrease the serum concentration of testosterone.","The conjugated estrogens, equally to the normal physiological estrogen, work by agonistically binding to the estrogen receptors alpha and beta. The estrogen receptors vary in quantity and proportion according to the tissues and hence, the activity of this conjugated estrogens is very variable.\r\n\r\nThe activity made by the conjugated estrogens is driven by the increase in the synthesis of DNA, RNA and various proteins in responsive tissues which in order will reduce the release of gonadotropin-releasing hormone, follicle-stimulating hormone and leuteinizing hormone.\r\n\r\nThe specific mechanism of action cannot be described only in terms of total estrogenic action as the pharmacokinetic profile, the tissue specificity and the tissue metabolism is different for each component of the product.","Estrogen receptor alpha agonist; Estrogen receptor beta agonist","Indication associated"]
[106,"DB00287","approved","small molecule","Travoprost","isopropyl (Z)-7-((1R,2R,3R,5S)-3,5-dihydroxy-2-{(1E,3R)-3-hydroxy-4-[(α,α,α-trifluoro-m-tolyl)oxy]-1-butenyl}cyclopentyl)-5-heptenoate","C26H35F3O6","CC(C)OC(=O)CCC\\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\\C=C\\[C@@H](O)COC1=CC=CC(=C1)C(F)(F)F","Travoprost ophthalmic solution is a topical medication used for controlling the progression of glaucoma or ocular hypertension, by reducing intraocular pressure . It is a synthetic prostaglandin F2alpha analog . Having been a well-received therapeutic agent with demonstrated efficacy and safety, travoprost is currently approved by the US FDA as a first-line treatment for lowering intraocular pressure in patients with open-angle glaucoma or ocular hypotension . Furthermore, this approval also solidifies the medication as the first and only prostaglandin analog approved by the FDA for first-line treatment of glaucoma patients that does not contain the preservative benzalkonium chloride . Moreover, travoprost is also currently approved in the EU for the decrease of elevated intraocular pressure in paediatric patients aged 2 months to < 18 years with ocular hypertension or paediatric glaucoma .","157283-68-6","500.5477","Travoprost ophthalmic solution is indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension .\r\n\r\nTravoprost is also currently indicated for the decrease of elevated intraocular pressure in paediatric patients aged 2 months to < 18 years with ocular hypertension or paediatric glaucoma .","Travoprost, an isopropyl ester prodrug, is a synthetic prostaglandin F2 alpha analog that is rapidly hydrolyzed by esterases in the cornea to its biologically active free acid . The travoprost free acid is potent and highly selective for the FP prostanoid receptor .","Travoprost, a prostaglandin F2α analogue, is a highly selective full agonist which has a high affinity for the prostaglandin FP receptor, and facilitates reductions in intraocular pressure by increasing the outflow of aqueous humour via trabecular meshwork and uveoscleral pathways . Reduction of the intraocular pressure in man starts about 2 hours after administration and maximum effect is reached after 12 hours. Significant lowering of intraocular pressure can be maintained for periods exceeding 24 hours with a single dose .","Prostaglandin F2-alpha receptor agonist","Indication associated"]
[107,"DB00288","approved","small molecule","Amcinonide","Triamcinolonacetatcyclopentanonid","C28H35FO7","[H][C@@]12C[C@H]3OC4(CCCC4)O[C@@]3(C(=O)COC(C)=O)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])CCC2=CC(=O)C=C[C@]12C","Amcinonide is a corticosteroid.","51022-69-6","502.5717","For the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses.","Amcinonide is a topical corticosteroid. The topical corticosteroids constitute a class of primarily synthetic steroids used as anti-inflammatory and antipruritic agents. Amcinonide reduces or inhibits the actions of chemicals in the body that cause inflammation, redness, and swelling. The mechanism of anti-inflammatory activity of the topical corticosteroids is unclear. Various laboratory methods, including vasoconstrictor assays, are used to compare and predict potencies and/or clinical efficacies of the topical corticosteroids. There is some evidence to suggest that a recognizable correlation exists between vasoconstrictor potency and therapeutic efficacy in man. When in an ointment form, amcinonide also helps the skin maintain moisture.","The mechanism of the anti-inflammatory activity of the topical steroids, in general, is unclear. However, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2. Amcinonide has affinity for the glucocorticoid receptor. It has weak affinity for the progesterone receptor, and virtually no affinity for the mineralocorticoid, estrogen, or androgen receptors.","Glucocorticoid receptor agonist; Annexin A1 agonist","Therapeutic strategy associated"]
[108,"DB00301","approved; investigational","small molecule","Flucloxacillin","(2S,5R,6R)-6-({[3-(2-chloro-6-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]carbonyl}amino)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; 3-(2-Chloro-6-fluorophenyl)-5-methyl-4-isoxazolylpenicillin; Floxacillin; Flucloxacillin","C19H17ClFN3O5S","[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)C1=C(C)ON=C1C1=C(Cl)C=CC=C1F)C(O)=O","Antibiotic analog of .","5250-39-5","453.872","Used to treat bacterial infection by susceptible microorganisms.","Flucloxacillin is a penicillin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. The name \"penicillin\" can either refer to several variants of penicillin available, or to the group of antibiotics derived from the penicillins. Flucloxacillin has <i>in vitro</i> activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of Flucloxacillin results from the inhibition of cell wall synthesis and is mediated through flucloxacillin binding to penicillin binding proteins (PBPs). Flucloxacillin is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases.","By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, flucloxacillin inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that flucloxacillin interferes with an autolysin inhibitor.","Penicillin-binding protein 1A inhibitor","Indication associated"]
[109,"DB00303","approved; investigational","small molecule","Ertapenem","(1R,5S,6S,8R,2'S,4'S)-2-(2-(3-carboxyphenylcarbamoyl)pyrrolidin-4-ylthio)-6-(1-hydroxyethyl)-1-methylcarbapenem-3-carboxylic acid; (4R,5S,6S)-3-((3S,5S)-5-((3-carboxyphenyl)carbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-hydroxyethyl)-4-methyl-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid; Ertapenem","C22H25N3O7S","[H][C@]12[C@@H](C)C(S[C@]3([H])CN[C@@]([H])(C3)C(=O)NC3=CC=CC(=C3)C(O)=O)=C(N1C(=O)[C@]2([H])[C@@H](C)O)C(O)=O","Ertapenem is a carbapenem antibiotic drug that is marketed under the trade name Invanz by Merck & Co. pharmaceutical company.  It is structurally similar to  and possesses a 1-beta-methyl group.","153832-46-3","475.515","For the treatment the following moderate to severe infections caused by susceptible isolates of the designated microorganisms: (1) complicated intra-abdominal infections due to <i>Escherichia coli</i>, <i>Clostridium clostridioforme</i>, <i>Eubacterium lentum</i>, <i>Peptostreptococcus</i> species, <i>Bacteroides fragilis</i>, <i>Bacteroides distasonis</i>, <i>Bacteroides ovatus</i>, <i>Bacteroides thetaiotaomicron</i>, or <i>Bacteroides uniformis</i>, (2) complicated skin and skin structure infections, including diabetic foot infections without osteomyelitis due to <i>Staphylococcus aureus</i> (methicillin susceptible isolates only), <i>Streptococcus agalactiae</i>, <i>Streptococcus pyogenes</i>, <i>Escherichia coli</i>, <i>Klebsiella pneumoniae</i>, <i>Proteus mirabilis</i>, <i>Bacteroides fragilis</i>, <i>Peptostreptococcus</i> species, <i>Porphyromonas asaccharolytica</i>, or <i>Prevotella bivia</i>, (3) community acquired pneumonia due to <i>Streptococcus pneumoniae</i> (penicillin susceptible isolates only) including cases with concurrent bacteremia, <i>Haemophilus influenzae</i> (beta-lactamase negative isolates only), or <i>Moraxella catarrhalis</i>, (4) complicated urinary tract infections including pyelonephritis due to <i>Escherichia coli</i>, including cases with concurrent bacteremia, or <i>Klebsiella pneumoniae</i>, (5) acute pelvic infections including postpartum endomyometritis, septic abortion and post surgical gynecologic infections due to <i>Streptococcus agalactiae</i>, <i>Escherichia coli</i>, <i>Bacteroides fragilis</i>, <i>Porphyromonas asaccharolytica</i>, <i>Peptostreptococcus</i> species, or <i>Prevotella bivia</i>.","Ertapenem has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria.","The bactericidal activity of ertapenem results from the inhibition of cell wall synthesis and is mediated through ertapenem binding to penicillin binding proteins (PBPs). In <i>Escherichia coli</i>, it has strong affinity toward PBPs 1a, 1b, 2, 3, 4 and 5 with preference for PBPs 2 and 3. Ertapenem is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases. Ertapenem is hydrolyzed by metallo-beta-lactamases.","Penicillin-binding protein 2 inhibitor; Penicillin-binding protein 2 inhibitor; Peptidoglycan synthase FtsI inhibitor; Peptidoglycan synthase FtsI inhibitor; D-alanyl-D-alanine carboxypeptidase DacB inhibitor; Penicillin-binding protein 1A inhibitor; Penicillin-binding protein 1B inhibitor; D-alanyl-D-alanine carboxypeptidase DacC inhibitor","Indication associated"]
[110,"DB00308","approved","small molecule","Ibutilide","Ibutilide; N-(4-{4-[ethyl(heptyl)amino]-1-hydroxybutyl}phenyl)methanesulfonamide","C20H36N2O3S","CCCCCCCN(CC)CCCC(O)C1=CC=C(NS(C)(=O)=O)C=C1","Ibutilide is a Class III antiarrhythmic agent available in intravenous formulations. It is indicated for the conversion of acute atrial flutter and recent onset atrial fibrillation to normal sinus rhythm (NSR).","122647-31-8","384.576","Indicated for the rapid conversion of atrial fibrillation or atrial flutter of recent onset to sinus rhythm.","Ibutilide prolongs the action potential duration and increases both atrial and ventricular refractoriness in vivo, i.e., class III electrophysiologic effects. Voltage clamp studies indicate that ibutilide, at nanomolar concentrations, delays repolarization by activation of a slow, inward current (predominantly sodium), rather than by blocking outward potassium currents, which is the mechanism by which most other class III antiarrhythmics act.","Ibutilide is a 'pure' class III antiarrhythmic drug, used intravenously against atrial flutter and fibrillation. At a cellular level it exerts two main actions: induction of a persistent Na+ current sensitive to dihydropyridine Ca<sup>2+</sup> channel blockers and potent inhibition of the cardiac rapid delayed rectifier K<sup>+</sup> current, by binding within potassium channel pores. In other words, Ibutilide binds to and alters the activity of hERG potassium channels, delayed inward rectifier potassium (IKr) channels and L-type (dihydropyridine sensitive) calcium channels","Voltage-dependent L-type calcium channel subunit alpha-1C activator; Voltage-dependent L-type calcium channel subunit beta-1 activator; Potassium voltage-gated channel subfamily H member 2 inhibitor; Voltage-dependent calcium channel subunit alpha-2/delta-1 activator; Voltage-dependent calcium channel gamma-1 subunit activator; Potassium channel subfamily K member 1 inhibitor; Potassium channel subfamily K member 6 inhibitor; Potassium voltage-gated channel subfamily H member 6 inhibitor; Potassium voltage-gated channel subfamily H member 7 inhibitor; ATP-sensitive inward rectifier potassium channel 11 inhibitor","Indication associated"]
[111,"DB00310","approved","small molecule","Chlorthalidone","1-keto-3-(3'-sulfamyl-4'-chlorophenyl)-3-hydroxyisoindoline; 1-oxo-3-(3-sulfamyl-4-chlorophenyl)-3-hydroxyisoindoline; 2-chloro-5-(1-hydroxy-3-oxo-1-isoindolinyl)benzenesulfonamide; 2-chloro-5-(2,3-dihydro-1-hydroxy-3-oxo-1H-isoindol-1-yl)benzenesulfonamide; 3-(4'-chloro-3'-sulfamoylphenyl)-3-hydroxyphthalimidine; 3-hydroxy-3-(4-chloro-3-sulfamylphenyl)phthalimidine; Chlorphthalidolone; Chlortalidone; Chlorthalidone; Phthalamodine; Phthalamudine","C14H11ClN2O4S","NS(=O)(=O)C1=C(Cl)C=CC(=C1)C1(O)NC(=O)C2=CC=CC=C12","Chlorthalidone is a thiazide-like diuretic used for the treatment of hypertension and for management of edema caused by conditions such as heart failure or renal impairment. Chlorthalidone improves blood pressure and swelling by preventing water absorption from the kidneys through inhibition of the Na+/Cl− symporter in the distal convoluted tubule cells in the kidney. The exact mechanism of chlorthalidone's anti-hypertensive effect is under debate, however, it is thought that increased diuresis results in decreased plasma and extracellular fluid volume, decreased cardiac output and therefore overall reduction in blood pressure.\r\n\r\nChlorthalidone is considered first-line therapy for management of uncomplicated hypertension as there is strong evidence from meta-analyses that thiazide diuretics such as chlorthalidone reduce the risk of stroke, myocardial infarction, heart failure, and cardiovascular all-cause mortality in patients with hypertension. In particular, the ALLHAT trial confirmed the role of thiazide diuretics as first-line therapy and demonstrated that chlorthalidone had a statistically significant lower incidence of stroke and heart failure when compared to , , or . Further studies have indicated that low-dose thiazides are as good as, and in some secondary endpoints, better than β-blockers, ACE inhibitors, Calcium Channel Blockers or ARBs.\r\n\r\nChlorthalidone has been shown to have a number of pleiotropic effects that differentiate it from other diuretics such as . In addition to its antihypertensive effects, chlorthalidone has also been shown to decrease platelet aggregation and vascular permeability, as well as promote angiogenesis in vitro, which is thought to be partly the result of reductions in carbonic anhydrase–dependent pathways. These pathways may play a role in chlorthalidone's cardiovascular risk reduction effects.","77-36-1","338.766","Chlorthalidone is indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effect of other antihypertensive drugs in the more severe forms of hypertension.\r\n\r\nChlorthalidone is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy.\r\n\r\nChlorthalidone has also been found useful in edema due to various forms of renal dysfunction, such as nephrotic syndrome, acute glomerulonephritis, and chronic renal failure.",null,"Chlorthalidone prevents reabsorption of sodium and chloride through inhibition of the Na+/Cl- symporter in the cortical diluting segment of the ascending limb of the loop of Henle. Reduction of sodium reabsorption subsequently reduces extracellular fluid and plasma volume via an osmotic, sodium-driven diuresis. By increasing the delivery of sodium to the distal renal tubule, Chlorthalidone indirectly increases potassium excretion via the sodium-potassium exchange mechanism. The exact mechanism of chlorthalidone's anti-hypertensive effect is under debate, however, it is thought that increased diuresis results in decreased plasma and extracellular fluid volume which therefore requires decreased cardiac output and overall lowers blood pressure. Chlorthalidone has also been shown to decrease platelet aggregation and vascular permeability, as well as promote angiogenesis in vitro, which is thought to be partly the result of reductions in carbonic anhydrase–dependent pathways. These pathways may play a role in chlorthalidone's cardiovascular risk reduction effects.","Solute carrier family 12 member 1 inhibitor; Carbonic anhydrase 1 inhibitor","Therapeutic strategy associated"]
[112,"DB00313","approved; investigational","small molecule","Valproic acid","2-n-propyl-n-valeric acid; 2-propyl-pentanoic acid; 2-Propylpentanoic Acid; 2-Propylvaleric Acid; 4-heptanecarboxylic acid; di-n-propylacetic acid; Dipropylacetic acid; DPA; n-DPA; Valproate; Valproic acid; VPA","C8H16O2","CCCC(CCC)C(O)=O","Valproic acid, or valproate, is an fatty acid derivative and anticonvulsant originally synthesized in 1881 by Beverly S. Burton. It enjoyed use as a popular organic solvent in industry and pharmaceutical manufacturing for nearly a century. In 1963, a serendipitous discovery was made by George Carraz during his investigations into the anticonvulsant effects of khelline when he found that all of his samples, dissolved in valproic acid, exerted a similar degree of anticonvulsive activity. It first received approval on February 28, 1978 from the FDA under the trade name Depakene.\r\n\r\nSince then, it has been investigated for neuroprotective, anti-manic, and anti-migraine effects. It is currently a compound of interest in the field of oncology for its anti-proliferative effects and is the subject of many clinical trials in a variety of cancer types.","99-66-1","144.2114","**Indicated** for: \r\n\r\n1) Use as monotherapy or adjunctive therapy in the management of complex partial seizures and simple or complex absence seizures. \r\n\r\n2) Adjunctive therapy in the management of multiple seizure types that include absence seizures. \r\n\r\n3) Prophylaxis of migraine headaches.\r\n\r\n4) Acute management of mania associated with bipolar disorder.\r\n\r\n\r\n**Off-label** uses include:\r\n \r\n1) Maintenance therapy for bipolar disorder.\r\n\r\n2) Treatment for acute bipolar depression.\r\n\r\n3) Emergency treatment of status epilepticus.","Valproate has been shown to reduce the incidence of complex partial seizures and migraine headaches. It also improves symptom control in bipolar mania. Although the exact mechanisms responsible are unknown, it is thought that valproate produces increased cortical inhibition to contribute to control of neural synchrony. It is also thought that valproate exerts a neuroprotective effect preventing damage and neural degeneration in epilepsy, migraines, and bipolar disorder.\r\n\r\nValproate is hepatotoxic and teratogenic. The reasons for this are unclear but have been attributed to the genomic effects of the drug.\r\n\r\nA small proof-of concept study found that valproate increases clearance of human immunodeficiency virus (HIV) when combined with highly active antiretroviral therapy (HAART) by reactivating the virus to allow clearance, however, a larger multicentre trial failed to show a significant effect on HIV reservoirs when added to HAART. The FDA labeling contains a warning regarding HIV reactivation during valproate use..","The exact mechanisms by which valproate exerts it's effects on epilepsy, migraine headaches, and bipolar disorder are unknown however several pathways exist which may contribute to the drug's action.\r\n\r\nValproate is known to inhibit succinic semialdehyde dehydrogenase. This inhibition results in an increase in succinic semialdehyde which acts as an inhibitor of GABA transaminase ultimately reducing GABA metabolism and increasing GABAergic neurotransmission. As GABA is an inhibitory neurotransmitter, this increase results in increased inhibitory activity. A possible secondary contributor to cortical inhibition is a direct suppression of voltage gated sodium channel activity and indirect suppression through effects on GABA.\r\n\r\nIt has also been suggested that valproate impacts the extracellular signal-related kinase pathway (ERK). These effects appear to be dependent on mitogen-activated protein kinase (MEK) and result in the phosphorylation of ERK1/2. This activation increases expression of several downstream targets including ELK-1 with subsequent increases in c-fos, growth cone-associated protein-43 which contributes to neural plasticity, B-cell lymphoma/leukaemia-2 which is an anti-apoptotic protein, and brain-derived neurotrophic factor (BDNF) which is also involved in neural plasticity and growth. Increased neurogenesis and neurite growth due to valproate are attributed to the effects of this pathway. An additional downstream effect of increased BDNF expression appears to be an increase in GABA<sub>A</sub> receptors which contribute further to increased GABAergic activity.\r\n\r\nValproate exerts a non-competitive indirect inhibitory effect on myo-inosital-1-phophate synthetase. This results in reduced de novo synthesis of inositol monophosphatase and subsequent inositol depletion. It is unknown how this contributed to valproate's effects on bipolar disorder but  is known to exert a similar inositol-depleting effect. Valproate exposure also appears to produce down-regulation of protein kinase C proteins (PKC)-α and -ε which are potentially related to bipolar disorder as PKC is unregulated in the frontal cortex of bipolar patients. This is further supported by a similar reduction in PKC with lithium. The inhibition of the PKC pathway may also be a contributor to migraine prophylaxis. Myristoylated alanine-rich C kinase substrate, a PKC substrate, is also downregulated by valproate and may contribute to changes in synaptic remodeling through effects on the cytoskeleton.\r\n\r\nValproate also appears to impact fatty acid metabolism. Less incorporation of fatty acid substrates in sterols and glycerolipids is thought to impact membrane fluidity and result in increased action potential threshold potentially contributing to valproate's antiepileptic action. Valproate has been found to be a non-competitive direct inhibitor of brain microsomal long-chain fatty acyl-CoA synthetase. Inhibition of this enzyme decreases available arichidonyl-CoA, a substrate in the production of inflammatory prostaglandins. It is thought that this may be a mechanism behind valproate's efficacy in migraine prophylaxis as migraines are routinely treated with non-steroidal anti-inflammatory drugs which also inhibit prostaglandin production.\r\n\r\nFinally, valproate acts as a direct histone deactylase (HDAC) inhibitor. Hyperacetylation of lysine residues on histones promoted DNA relaxation and allows for increased gene transcription. The scope of valproate's genomic effects is wide with 461 genes being up or down-regulated. The relation of these genomic effects to therapeutic value is not fully characterized however H3 and H4 hyperacetylation correlates with improvement of symptoms in bipolar patients. Histone hyperacetylation at the BDNF gene, increasing BDNF expression, post-seizure is known to occur and is thought to be a neuroprotective mechanism which valproate may strengthen or prolong. H3 hyperacetylation is associated with a reduction in glyceraldehyde-3-phosphate dehydrogenase, a pro-apoptotic enzyme, contributing further to valproate's neuroprotective effects.","Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial inhibitor; Histone deacetylase 9 inhibitor; 2-oxoglutarate dehydrogenase, mitochondrial inhibitor; Succinate-semialdehyde dehydrogenase, mitochondrial inhibitor; Sodium channel protein inhibitor; Histone deacetylase 2 inhibitor; Peroxisome proliferator-activated receptor alpha; Peroxisome proliferator-activated receptor delta; Peroxisome proliferator-activated receptor gamma","Therapeutic strategy associated"]
[113,"DB00321","approved","small molecule","Amitriptyline","10,11-dihydro-5-(γ-dimethylaminopropylidene)-5H-dibenzo(a,d)cycloheptene; 10,11-dihydro-N,N-dimethyl-5H-dibenzo(a,d)heptalene-Δ5,γ-propylamine; 3-(10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5-ylidene)-N,N-dimethyl-1-propanamine; 3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-N,N-dimethylpropan-1-amine; 5-(3-dimethylaminopropylidene)-10,11-dihydro-5H-dibenzo(a,d)cycloheptatriene; 5-(3-dimethylaminopropylidene)-10,11-dihydro-5H-dibenzo(a,d)cycloheptene; 5-(γ-dimethylaminopropylidene)-5H-dibenzo[a,d][1,4]cycloheptadiene; Amitriptyline","C20H23N","CN(C)CCC=C1C2=CC=CC=C2CCC2=CC=CC=C12","Amitriptyline hydrochloride, also known as _Elavil_,  is a tricyclic antidepressant (TCA) with analgesic properties, widely used to treat depression and neuropathic pain .  It was originally approved by the FDA in 1977 and manufactured by Sandoz .","50-48-6","277.4033","This drug in indicated for the following conditions :\r\n\r\nMajor depressive disorder in adults\r\n\r\nManagement of neuropathic pain in adults\r\n\r\nProphylactic treatment of chronic tension-type headache (CTTH) in adults\r\n\r\nProphylactic treatment of migraine in adults\r\n\r\nTreatment of nocturnal enuresis in children aged 6 years and above when organic pathology, including spina bifida and related disorders, have been excluded and no response has been achieved to all other non-drug and drug treatments, including antispasmodics and vasopressin-related products. This product should only be prescribed by a healthcare professional with expertise in the management of persistent enuresis \r\n\r\nOff-label uses: irritable bowel syndrome, sleep disorders, diabetic neuropathy, agitation, fibromyalgia, and insomnia","**Effects in pain and depression**\r\n\r\nAmitriptyline is a tricyclic antidepressant and an analgesic. It has anticholinergic and sedative properties . \r\nClinical studies have shown that oral amitriptyline achieves, at a minimum, good to moderate response in up to 2/3 of patients diagnosed with post-herpetic neuralgia and 3/4 of patients diagnosed with diabetic neuropathic pain, and neurogenic pain syndromes that are frequently unresponsive to narcotic analgesics. Amitriptyline has also shown efficacy in diverse groups of patients with chronic non-malignant pain. There have also been some studies showing efficacy in managing fibromyalgia (an off-label use of this drug) , .\r\n\r\n**Cardiovascular and Anticholinergic Effects**\r\n\r\nAmitriptyline has strong anticholinergic properties and may cause ECG changes and quinidine-like effects on the heart . Amitriptyline may inhibit ion channels, which are necessary for cardiac repolarization (hERG channels), in the upper micromolar range of therapeutic plasma concentrations. Therefore, amitriptyline may increase the risk for cardiac arrhythmia . Orthostatic hypotension and tachycardia can be a problem in elderly patients receiving this drug at normal doses for depression. There is evidence in the literature that these effects may occur, rarely, at the lower dosages utilized in the treatment of pain. As with any other tricyclic antidepressant agent, increased glucose levels can occur with amitriptyline . \r\n\r\n**Effects on seizure threshold**\r\n\r\nThis drug also decreases the convulsive threshold and causes alterations in EEG and sleep patterns .","The mechanism of action of this drug is not fully elucidated. It is suggested that amitriptyline inhibits the membrane pump mechanism responsible for the re-uptake of transmitter amines, such as norepinephrine and serotonin, thereby increasing their concentration at the synaptic clefts of the brain , .   These amines are important in regulating mood.  The monoamine hypothesis in depression, one of the oldest hypotheses, postulates that deficiencies of serotonin (5-HT) and/or norepinephrine (NE) neurotransmission in the brain lead to depressive effects .   This drug counteracts these mechanisms, and this may be the mechanism of amitriptyline in improving depressive symptoms.\r\n\r\nWhether its analgesic effects are related to its mood-altering activities or attributable to a different, less obvious pharmacological action (or a combination of both) is unknown .","Sodium-dependent noradrenaline transporter inhibitor; Sodium-dependent serotonin transporter inhibitor; 5-hydroxytryptamine receptor 2A antagonist; 5-hydroxytryptamine receptor 1A inhibitor&inducer; Delta-type opioid receptor agonist; Kappa-type opioid receptor agonist; High affinity nerve growth factor receptor agonist&activator; BDNF/NT-3 growth factors receptor agonist; Alpha-1A adrenergic receptor antagonist&inhibitor; Alpha-1D adrenergic receptor antagonist; Alpha-2A adrenergic receptor antagonist&agonist; Histamine H1 receptor antagonist; Potassium voltage-gated channel subfamily KQT member 2 inhibitor; Potassium voltage-gated channel subfamily A member 1 inhibitor; Histamine H2 receptor blocker; Histamine H4 receptor binder; Sigma non-opioid intracellular receptor 1 agonist; 5-hydroxytryptamine receptor 2C antagonist; Alpha-1B adrenergic receptor antagonist; 5-hydroxytryptamine receptor 7 antagonist; 5-hydroxytryptamine receptor 1D binder; Mu-type opioid receptor binder; 5-hydroxytryptamine receptor 1B binder; 5-hydroxytryptamine receptor 6 antagonist; Potassium voltage-gated channel subfamily KQT member 3 inhibitor; 5-hydroxytryptamine receptor 1C antagonist; Muscarinic acetylcholine receptor ligand; HERG human cardiac K+ channel blocker","Indication associated"]
[114,"DB00324","approved; investigational","small molecule","Fluorometholone","(1R,2S,8S,10S,11S,14R,15S,17S)-14-acetyl-1-fluoro-14,17-dihydroxy-2,8,15-trimethyltetracyclo[8.7.0.02,7.011,15]heptadeca-3,6-dien-5-one; 9-Fluoro-11beta,17-dihydroxy-6alpha-methylpregna-1,4-diene-3,20-dione; Fluorometholone","C22H29FO4","[H][C@@]12CC[C@](O)(C(C)=O)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])C[C@H](C)C2=CC(=O)C=C[C@]12C","A glucocorticoid employed, usually as eye drops, in the treatment of allergic and inflammatory conditions of the eye. It has also been used topically in the treatment of various skin disorders. (From Martindale, The Extra Pharmacopoeia, 30th ed, p732)","426-13-1","376.4617","For the ophthalmic treatment of corticosteroid-responsive inflammation of the palpebral and bulbar conjunctiva, cornea and anterior segment of the globe.","Corticosteroids such as fluorometholone inhibit the inflammatory response to a variety of inciting agents and probably delay or slow healing. They inhibit the edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation associated with inflammation.","There is no generally accepted explanation for the mechanism of action of ocular corticosteroids. However, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2. Their primary target is the cytosolic glucocorticoid receptor. After binding the receptor the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes.","Glucocorticoid receptor agonist","Therapeutic strategy associated"]
[115,"DB00325","approved; investigational","small molecule","Nitroprusside","Nitroferricyanide","C5FeN6O","O=N[Fe--](C#N)(C#N)(C#N)(C#N)C#N","Nitroprusside serves as a source of nitric oxide, a potent peripheral vasodilator that affects both arterioles and venules (venules more than arterioles). Nitroprusside is often administered intravenously to patients who are experiencing a hypertensive emergency.","15078-28-1","215.938","For immediate reduction of blood pressure of patients in hypertensive crises, reduce bleeding during surgery, and for the treatment of acute congestive heart failure","Nitroprusside a powerful vasodilator relaxes the vascular smooth muscle and produce consequent dilatation of peripheral arteries and veins. Other smooth muscle (e.g., uterus, duodenum) is not affected. Sodium nitroprusside is more active on veins than on arteries.","One molecule of sodium nitroprusside is metabolized by combination with hemoglobin to produce one molecule of cyanmethemoglobin and four CN- ions; methemoglobin, obtained from hemoglobin, can sequester cyanide as cyanmethemoglobin; thiosulfate reacts with cyanide to produce thiocyanate; thiocyanate is eliminated in the urine; cyanide not otherwise removed binds to cytochromes. Cyanide ion is normally found in serum; it is derived from dietary substrates and from tobacco smoke. Cyanide binds avidly (but reversibly) to ferric ion (Fe+++), most body stores of which are found in erythrocyte methemoglobin (metHgb) and in mitochondrial cytochromes. When CN is infused or generated within the bloodstream, essentially all of it is bound to methemoglobin until intraerythrocytic methemoglobin has been saturated. \r\n\r\nSodium nitroprusside is further broken down in the circulation to release nitric oxide (NO), which activates guanylate cyclase in the vascular smooth muscle. This leads to increased production of intracellular cGMP, which stimulates calcium ion movement from the cytoplasm to the endoplasmic reticulum, reducing the level of available calcium ions that can bind to calmodulin. This ultimately results in vascular smooth muscle relaxation and vessel dilation.","Atrial natriuretic peptide receptor 1 agonist","Indication associated"]
[116,"DB00326","approved","small molecule","Calcium glucoheptonate","calcium (2ξ)-D-gluco-heptonate; calcium bis[(2ξ)-D-glycero-D-gulo-heptonate]; calcium bis[(2ξ)-D-glycero-D-ido-heptonate]; calcium bis[(3R,4S,5R,6R)-2,3,4,5,6,7-hexahydroxyheptanoate]; Calcium gluceptate; Calcium glucoheptonate; Calcium glucoheptonate (1:2)","C14H26CaO16","[Ca++].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O","Calcium supplements such as calcium gluceptate are taken by individuals who are unable to get enough calcium in their regular diet or who have a need for more calcium. They are used to prevent or treat several conditions that may cause hypocalcemia (not enough calcium in the blood). The body needs calcium to make strong bones. Calcium is also needed for the heart, muscles, and nervous system to work properly.","29039-00-7","490.425","For treatment of mild hypocalcemia due to neonatal tetany, tetany due to parathyroid deficiency or vitamin D deficiency, and alkalosis, as prophylaxis of hypocalcemia during exchange transfusions, in the treatment of intestinal malabsorption, and to replenish electrolytes.","Calcium supplements such as calcium gluceptate are taken by individuals who are unable to get enough calcium in their regular diet or who have a need for more calcium. They are used to prevent or treat several conditions that may cause hypocalcemia (not enough calcium in the blood). The body needs calcium to make strong bones. Calcium is also needed for the heart, muscles, and nervous system to work properly. The bones serve as a storage site for the body's calcium. They are continuously giving up calcium to the bloodstream and then replacing it as the body's need for calcium changes from day to day. When there is not enough calcium in the blood to be used by the heart and other organs, your body will take the needed calcium from the bones. When you eat foods rich in calcium, the calcium will be restored to the bones and the balance between your blood and bones will be maintained.","Calcium gluceptate replenishes the deminished levels of calcium in the body, returning them to normal levels.",null,"Indication associated"]
[117,"DB00328","approved; investigational","small molecule","Indomethacin","{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetic acid; 1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetic acid; Indometacin; Indomethacin","C19H16ClNO4","COC1=CC2=C(C=C1)N(C(=O)C1=CC=C(Cl)C=C1)C(C)=C2CC(O)=O","Indometacin, or indomethacin, is a non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic, and antipyretic properties. NSAIDs consist of agents that are structurally unrelated; the NSAID chemical classification of indometacin is an indole-acetic acid derivative with the chemical name 1- (p-chlorobenzoyl)25-methoxy-2-methylindole-3-acetic acid. The pharmacological effect of indometacin is not fully understood, however, it is thought to be mediated through potent and nonselective inhibition of the enzyme cyclooxygenase (COX), which is the main enzyme responsible for catalyzes the rate-limiting step in prostaglandin and thromboxane biosynthesis via the arachidonic acid (AA) pathway. Indometacin was first discovered in 1963 and it was first approved for use in the U.S. by the Food and Drug Administration in 1965,  along with other acetic acid derivatives such as  and  that were also developed during the 1960s. Since then, indometacin has been extensively studied in clinical trials as one of the most potent NSAIDs in blocking prostaglandin synthesis and was among the first NSAIDs to be used in the symptomatic treatment of migraine and for headaches that eventually became known as “indomethacin-responsive” headache disorders. \r\n\r\nMost commonly used in rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, acute shoulder pains, and acute gouty arthritis, indometacin is currently available as oral capsules as well as other methods of administration, including rectal and intravenous formulations. Intravenous indometacin is administered to close a hemodynamically significant patent ductus arteriosus, as indicated by clinical evidence, in premature infants. Ophthalmic indometacin has been studied and used in the symptomatic treatment of postoperative ocular inflammation and pain and/or complications after cataract surgery. Although deemed effective in reducing ocular inflammation in clinical studies, topical NSAIDs were also associated with a potential reduction in corneal sensitivity accompanied by an increased risk of superficial punctate keratitis and subjective symptoms of discomfort, including pain, burning or pricking, or a tingling sensation after instillation into the cul‐de‐sac.","53-86-1","357.788","Oral indometacin is indicated for symptomatic management of moderate to severe rheumatoid arthritis including acute flares of chronic disease, moderate to severe ankylosing spondylitis, moderate to severe osteoarthritis, acute painful shoulder (bursitis and/or tendinitis) and acute gouty arthritis.\r\n \r\nIntravenous indometacin is indicated to induce closure of a hemodynamically significant patent ductus arteriosus in premature infants weighing between 500 and 1750 g when after 48 hours usual medical management (e.g., fluid restriction, diuretics, digitalis, respiratory support, etc.) is ineffective.","Indometacin is an NSAID with analgesic and antipyretic properties that exerts its pharmacological effects by inhibiting the synthesis of factors involved in pain, fever, and inflammation. Its therapeutic action does not involve pituitary-adrenal stimulation. Indometacin primarily works by suppressing inflammation in rheumatoid arthritis by providing relief of pain as well as reducing fever, swelling, and tenderness. This effectiveness has been demonstrated by a reduction in the extent of joint swelling, the average number of joints displaying symptoms of inflammation, and the severity of morning stiffness. Increased mobility was demonstrated by a decrease in total walking time and by improved functional capability seen as an increase in grip strength. In clinical trials, indometacin was shown to be effective in relieving the pain, reducing the fever, swelling, redness, and tenderness of acute gouty arthritis. Due to its pharmacological actions, the use of indometacin is associated with the risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, as well as gastrointestinal effects such as bleeding, ulceration, and perforation of the stomach or intestines.\r\n\r\nIn a study of healthy individuals, acute oral and intravenous indometacin therapy resulted in a transiently diminished basal and CO2 stimulated cerebral blood flow; this effect disappeared in one study after one week of oral treatment. The clinical significance of this effect has not been established. Compared to other NSAIDs, it is suggested that indometacin is a more potent vasoconstrictor that is more consistent in decreasing cerebral blood flow and inhibiting CO2 reactivity. There have been studies that show indometacin directly inhibiting neuronal activity to some extent in the trigeminocervical complex after either superior salivatory nucleus or dural stimulation.","Indometacin is a nonspecific and reversible inhibitor of the cyclo-oxygenase (COX) enzyme or prostaglandin G/H synthase. There are two identified isoforms of COX: COX-1 is universally present in most body tissues and is involved in the synthesis of the prostaglandins and thromboxane A2, while COX-2 is expressed in response to injury or inflammation. Constitutively expressed, the COX-1 enzyme is involved in gastric mucosal protection, platelet, and kidney function by catalyzing the conversion of arachidonic acid to prostaglandin (PG) G2 and PGG2 to PGH2. COX-2 is constitutively expressed and highly inducible by inflammatory stimuli. It is found in the central nervous system, kidneys, uterus, and other organs. COX-2 also catalyzes the conversion of arachidonic acid to PGG2 and PGG2 to PGH2. In the COX-2-mediated pathway, PGH2 is further converted to PGE2 and PGI2 (also known as prostacyclin). PGE2 is involved in mediating inflammation, pain, and fever. Decreasing levels of PGE2 leads to reduced inflammatory reactions. Indometacin is known to inhibit both isoforms of COX, however, with greater selectivity for COX-1, which accounts for its increased adverse gastric effects relative to other NSAIDs. It binds to the enzyme's active site and prevents the interaction between the enzyme and its substrate, arachidonic acid. Indometacin, unlike other NSAIDs, also inhibits phospholipase A2, the enzyme responsible for releasing arachidonic acid from phospholipids. The analgesic, antipyretic and anti-inflammatory effects of indomethacin as well as adverse reactions associated with the drug occur as a result of decreased prostaglandin synthesis. Its antipyretic effects may be due to action on the hypothalamus, resulting in increased peripheral blood flow, vasodilation, and subsequent heat dissipation.\r\n\r\nThe exact mechanism of action of indometacin in inducing closure of a patent ductus arteriosus is not fully understood; however, it is thought to be through inhibition of prostaglandin synthesis. At birth, the ductus arteriosus is normally closed as the tension of the oxygen increases significantly after birth. Patent ductus arteriosus in premature infants is associated with congenital heart malformations where PGE1 mediates an opposite effect to that of oxygen. PGE1 dilates the ductus arteriosus through smooth muscle relaxation and prevents the closure of the ductus arteriosus. By inhibiting the synthesis of prostaglandins, indometacin promotes the closure of ductus arteriosus.\r\n\r\nIndometacin has been described as possessing anticancer and antiviral properties through activation of protein kinase R (PKR) and downstream phosphorylation of eIF2α, inhibiting protein synthesis.","Prostaglandin G/H synthase 1 inhibitor; Prostaglandin G/H synthase 2 inhibitor; Phospholipase A2, membrane associated inhibitor; Prostaglandin reductase 2 inhibitor; Peroxisome proliferator-activated receptor gamma activator; Lactoylglutathione lyase inhibitor; Prostaglandin D2 receptor 2 other/unknown; Peroxisome proliferator-activated receptor alpha agonist; Aldo-keto reductase family 1 member C3 inhibitor; Interferon-induced, double-stranded RNA-activated protein kinase inducer","Therapeutic strategy associated"]
[118,"DB00333","approved","small molecule","Methadone","(+-)-Methadone; (+/-)-Methadone; (±)-methadone; 6-Dimethylamino-4,4-diphenyl-3-heptanone; dl-Methadone; Methadone","C21H27NO","CCC(=O)C(CC(C)N(C)C)(C1=CC=CC=C1)C1=CC=CC=C1","Methadone is a potent synthetic analgesic that works as a full µ-opioid receptor (MOR) agonist and N-methyl-d-aspartate (NMDA) receptor antagonist. As a full MOR agonist, methadone mimics the natural effects of the body's opioids, endorphins, and enkephalins through the release of neurotransmitters involved in pain transmission. It also has a number of unique characteristics that have led to its increased use in the last two decades; in particular, methadone has a lower risk of neuropsychiatric toxicity compared to other opioids (due to a lack of active metabolites), minimal accumulation in renal failure, good bioavailability, low cost, and a long duration of action. \r\n\r\nDue to its unique mechanism of action, methadone is particularly useful for the management of hard to treat pain syndromes such as neuropathic pain and cancer pain requiring higher and more frequent doses of shorter-acting opioids. Compared with , the gold standard reference opioid, methadone also acts as an agonist of κ- and σ-opioid receptors, as an antagonist of the N-methyl-D-aspartate (NMDA) receptor, and as an inhibitor of serotonin and norepinephrine uptake. Specifically by inhibiting the NMDA receptor, methadone dampens a major excitatory pain pathway within the central nervous system. Compared to other opioids, methadone's effects on NMDA inhibition may explain it's improved analgesic efficacy and reduced opioid tolerance.\r\n\r\nMethadone shares similar effects and risks of other opioids such as , , , and . However, it also has a unique pharmacokinetic profile. Compared with short-acting and even extended-release formulations of , methadone displays a comparatively longer duration of action and half-life. These effects make methadone a good option for the treatment of severe pain and addiction as fewer doses are needed to maintain analgesia and prevent opioid withdrawal symptoms. However, methadone also has an unpredictable half-life with interindividual variability, which leads to an unpredictable risk of respiratory depression and overdose when initiating or titrating therapy.\r\n\r\nOverall, methadone's pharmacological actions result in analgesia, suppression of opioid withdrawal symptoms, sedation, miosis, sweating, hypotension, bradycardia, nausea and vomiting (via binding within the chemoreceptor trigger zone), and constipation. At higher doses, methadone use can result in respiratory depression, overdose, and death.\r\n\r\nTreatment of opioid addiction with methadone, , or slow-release oral  (SROM) is termed Opioid Agonist Treatment (OAT) or Opioid Substitution Therapy (OST). The intention of substitution of illicit opioids with the long-acting opioids used in OAT is to prevent withdrawal symptoms for 24-36 hours following dosing to ultimately reduce cravings and drug-seeking behaviours. Use of OAT is also intended to lead to social stabilization by reducing crime rates, incarceration, use of illicit opioids such as  or , and ultimately marginalization. Illegally purchased opioids present many other harms in addition to overdose as they can be injected and may be laced with other substances that increase the risk of harm or overdose. Provision of OAT is often combined with education about harm reduction including use of clean needles and injection supplies in an effort to reduce the risks associated with injection drug use such as contraction of HIV and Hepatitis C and other complications including skin infections, abscesses, or endocarditis.","76-99-3","309.4452","Methadone is indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatment options are inadequate. It's recommended that use is reserved for use in patients for whom alternative treatment options (eg, nonopioid analgesics, opioid combination products) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.\r\n\r\nMethadone is also indicated for detoxification treatment of opioid addiction (heroin or other morphine-like drugs), and for maintenance substitution treatment for opioid dependence in adults in conjunction with appropriate social and medical services.","Overall, methadone's pharmacological actions result in analgesia, suppression of opioid withdrawal symptoms, sedation, miosis (through binding to receptors in the pupillary muscles), sweating, hypotension, bradycardia, nausea and vomiting (via binding within the chemoreceptor trigger zone), and constipation. Like many basic drugs, methadone also enters mast cells and releases histamine by a non-immunological mechanism leading to flushing, pruritus, and urticaria, which can commonly be misattributed to an allergic reaction. \r\n\r\nCompared to other opioids, methadone has fewer active metabolites and therefore a lower risk of neuropsychiatric toxicity. This means that higher doses needed to manage severe pain or addiction are less likely to result in delirium, hyperalgesia, or seizures.\r\n\r\nSimilar to morphine, both methadone isomers are 5-HT(3) receptor antagonists, although l-methadone produces greater inhibition than d-methadone. \r\n\r\nMethadone's effects are reversible by naloxone with a pA2 value similar to its antagonism of morphine.\r\n\r\n\r\n**Dependence and Tolerance**\r\n\r\nAs with other opioids, tolerance and physical dependence may develop upon repeated administration of methadone and there is a potential for development of psychological dependence. Physical dependence and tolerance reflect the neuroadaptation of the opioid receptors to chronic exposure to an opioid and are separate and distinct from abuse and addiction. Tolerance, as well as physical dependence, may develop upon repeated administration of opioids, and are not by themselves evidence of an addictive disorder or abuse.\r\n\r\nPatients on prolonged therapy should be tapered gradually from the drug if it is no longer required for pain control. Withdrawal symptoms may occur following abrupt discontinuation of therapy or upon administration of an opioid antagonist. Some of the symptoms that may be associated with abrupt withdrawal of an opioid analgesic include body aches, diarrhea, gooseflesh, loss of appetite, nausea, nervousness or restlessness, anxiety, runny nose, sneezing, tremors or shivering, stomach cramps, tachycardia, trouble with sleeping, unusual increase in sweating, palpitations, unexplained fever, weakness and yawning.\r\n\r\n\r\n**Cardiac Conduction Effects**\r\n\r\nLaboratory studies, both in vivo and in vitro, have demonstrated that methadone inhibits cardiac potassium channels and prolongs the QT interval. Cases of QT interval prolongation and serious arrhythmia (torsades de pointes) have been observed during treatment with methadone. These cases appear to be more commonly associated with, but not limited to, higher dose treatment (> 200 mg/day). Methadone should be administered with particular caution to patients already at risk for development of prolonged QT interval (e.g., cardiac hypertrophy, concomitant diuretic use, hypokalemia, hypomagnesemia). Careful monitoring is recommended when using methadone in patients with a history of cardiac conduction disease, those taking medications affecting cardiac conduction, and in other cases where history or physical exam suggest an increased risk of dysrhythmia.\r\n\r\n\r\n**Respiratory Depression and Overdose**\r\n\r\nSerious, life-threatening, or fatal respiratory depression may occur with use of methadone. Patients should be\r\nmonitored for respiratory depression, especially during initiation of methadone or following a dose increase.\r\n\r\nRespiratory depression is of particular concern in elderly or debilitated patients as well as in those suffering from conditions accompanied by hypoxia or hypercapnia when even moderate therapeutic doses may dangerously decrease pulmonary ventilation. Methadone should be administered with extreme caution to patients with conditions accompanied by hypoxia, hypercapnia, or decreased respiratory reserve such as: asthma, chronic obstructive pulmonary disease or cor pulmonale, severe obesity, sleep apnea syndrome, myxedema, kyphoscoliosis, and CNS depression or coma. In these patients, even usual therapeutic doses of methadone may decrease respiratory drive while simultaneously increasing airway resistance to the point of apnea. Alternative, non-opioid analgesics should be considered, and methadone should be employed only under careful medical supervision at the lowest effective dose.\r\n\r\nInfants exposed in-utero or through breast milk are at risk of life-threatening respiratory depression upon delivery or when nursed. \r\n\r\nMethadone's peak respiratory depressant effects typically occur later, and persist longer than its peak analgesic effects, in the short-term use setting. These characteristics can contribute to cases of iatrogenic overdose, particularly during treatment initiation and dose titration.\r\n\r\n\r\n**Head Injury and Increased Intracranial Pressure**\r\n\r\nThe respiratory depressant effects of opioids and their capacity to elevate cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury, other intracranial lesions or a pre-existing increase in intracranial pressure. Furthermore, opioids produce effects which may obscure the clinical course of patients with head injuries. In such patients, methadone must be used with caution, and only if it is deemed essential.\r\n\r\n\r\n**Incomplete Cross-tolerance between Methadone and other Opioids**\r\n\r\nPatients tolerant to other opioids may be incompletely tolerant to methadone. Incomplete cross-tolerance is of particular concern for patients tolerant to other µ-opioid agonists who are being converted to methadone, thus making the determination of dosing during opioid conversion complex. Deaths have been reported during conversion from chronic, high-dose treatment with other opioid agonists. A high degree of “opioid tolerance” does not eliminate the possibility of methadone overdose, iatrogenic or otherwise.\r\n\r\nCrosstolerance between morphine and methadone has been demonstrated, as steady-state plasma methadone concentrations required for effectiveness (C50%) were higher in abstinent rats previously dosed with morphine, as compared to controls.\r\n\r\n\r\n**Misuse, Abuse, and Diversion of Opioids**\r\n\r\nMethadone is a mu-agonist opioid with an abuse liability similar to morphine. Methadone, like morphine and other opioids used for analgesia, has the potential for being abused and is subject to criminal diversion.\r\n\r\nMethadone can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when dispensing Methadone in situations where the clinician is concerned about an increased risk of misuse, abuse, or diversion.\r\n\r\n\r\n**Hypotensive Effect**\r\n\r\nThe administration of methadone may result in severe hypotension in patients whose ability to maintain normal blood pressure is compromised (e.g., severe volume depletion).\r\n\r\n\r\n**Gastrointestinal Effects**\r\n\r\nMethadone and other morphine-like opioids have been shown to decrease bowel motility and cause constipation. This primarily occurs through agonism of opioid receptors in the gut wall. Methadone may obscure the diagnosis or clinical course of patients with acute abdominal conditions.\r\n\r\n\r\n**Sexual Function/Reproduction**\r\n\r\nReproductive function in human males may be decreased by methadone treatment. Reductions in ejaculate volume and seminal vesicle and prostate secretions have been reported in methadone-treated individuals. In addition, reductions in serum testosterone levels and sperm motility, and abnormalities in sperm morphology have been reported. Long-term use of opioids may be associated with decreased sex hormone levels and symptoms such as low libido, erectile dysfunction, or infertility.","Methadone is a synthetic opioid analgesic with full agonist activity at the µ-opioid receptor. While agonism of the µ-opioid receptor is the primary mechanism of action for the treatment of pain, methadone also acts as an agonist of κ- and σ-opioid receptors within the central and peripheral nervous systems. Interestingly, methadone differs from  (which is considered the gold standard reference opioid) in its antagonism of the N-methyl-D-aspartate (NMDA) receptor and its strong inhibition of serotonin and norepinephrine uptake, which likely also contributes to its antinociceptive activity. \r\n\r\nMethadone is administered as a 50:50 racemic mixture of (R)- and (S)-stereoisomers, with (R)-methadone demonstrating ~10-fold higher affinity and potency for the µ-opioid receptor than the (S) stereoisomer. The analgesic activity of the racemate is almost entirely due to the (R)-isomer, while the (S)-isomer lacks significant respiratory depressant activity but does have antitussive effects.\r\n\r\nWhile methadone shares similar effects and risks of other opioids such as , , , and  it has a number of unique pharmacokinetic and pharmacodynamic properties that distinguish it from them and make it a useful agent for the treatment of opioid addiction. For example, methadone abstinence syndrome, although qualitatively similar to that of morphine, differs in that the onset is slower, the course is more prolonged, and the symptoms are less severe.","Mu-type opioid receptor agonist; NMDA receptor antagonist; Delta-type opioid receptor agonist; 5-hydroxytryptamine receptor 3A antagonist; Neuronal acetylcholine receptor subunit alpha-7 agonist; Neuronal acetylcholine receptor subunit alpha-3 antagonist; Neuronal acetylcholine receptor subunit alpha-4 antagonist; Neuronal acetylcholine receptor subunit beta-2 antagonist","Therapeutic strategy associated"]
[119,"DB00334","approved; investigational","small molecule","Olanzapine","2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine; Olanzapin","C17H20N4S","CN1CCN(CC1)C1=NC2=CC=CC=C2NC2=C1C=C(C)S2","Olanzapine is a thienobenzodiazepine classified as an atypical or second-generation antipsychotic agent. The second-generation antipsychotics were introduced in the 90s and quickly gained traction due to their impressive efficacy, reduced risk for extrapyramidal side effects and reduced susceptibility to drug-drug interactions. Olanzapine very closely resembles  and only differs by two additional methyl groups and the absence of a chloride moiety. It was discovered by scientists at Eli Lilly and approved to be marketed in the US in 1996.","132539-06-1","312.432","Olanzapine was initially used orally and intramuscularly for the chronic treatment of schizophrenia in patients over 13 years old and other psychiatric disorders such as bipolar I disorder including mixed or manic episodes. \r\n\r\nOlanzapine is also indicated, in combination with lithium or valproate for the short-term treatment of acute manic or mixed episodes associated with bipolar I disorder in adults.\r\n\r\nAs well, olanzapine is indicated, in combination with fluoxetine for the treatment of episodes of depression associated with bipolar disorder type 1 and treatment-resistant depression in patients over 10 years old.\r\n\r\nOlanzapine is also approved for the management of psychomotor agitation associated with schizophrenia and bipolar I mania.\r\n\r\nSchizophrenia is a complex biochemical brain disorder that affects the person's ability to differentiate reality. It is usually observed as the presence of delusions, hallucinations, social withdrawal and disturbed thinking.\r\n\r\nBipolar disorder is a mental health condition defined by periods of extreme mood disturbances. It is categorized in different types from which type 1 is known to involve episodes of severe mania and often depression while type 2 presents less severe forms of mania.\r\n\r\nOlanzapine is also indicated in combination with  for the treatment of bipolar I disorder, either as an adjunct to lithium or valproate or as monotherapy for the acute treatment of manic or mixed episodes or as maintenance therapy, and for the treatment of schizophrenia in adults.","The effect of olanzapine in the D2 receptor is reported to produce the positive effects of this drug such as a decrease in hallucinations, delusions, disorganized speech, disorganized thought, and disorganized behavior. On the other hand, its effect on the serotonin 5HT2A receptor prevents the onset of anhedonia, flat affect, alogia, avolition and poor attention. Based on the specific mechanism of action, olanzapine presents a higher affinity for the dopamine D2 receptor when compared to the rest of the dopamine receptor isotypes. This characteristic significantly reduces the presence of side effects.\r\n\r\nClinical trials for the original use of olanzapine demonstrated significant effectiveness in the treatment of schizophrenia and bipolar disorder in adults and acute manic or mixed episodes associated with bipolar disorder in adolescents.\r\n\r\nThe effect of olanzapine on dopamine and serotonin receptors has been suggested to reduce chemotherapy-induced nausea and vomiting as those receptors are suggested to be involved in this process. For this effect, several clinical trials have been conducted and it has been shown that olanzapine can produce a significant increase in total control of nausea and vomiting. In a high-level study of the effect of olanzapine for this condition, a complete response on the delay phase was observed in 84% of the individual and control of emesis of over 80% despite the phase.","The activity of olanzapine is achieved by the antagonism of multiple neuronal receptors including the dopamine receptor D1, D2, D3 and D4 in the brain, the serotonin receptors 5HT2A, 5HT2C, 5HT3 and 5HT6, the alpha-1 adrenergic receptor, the histamine receptor H1 and multiple muscarinic receptors.\r\n\r\nAs abovementioned, olanzapine presents a wide profile of targets, however, its antagonistic effect towards the dopamine D2 receptor in the mesolimbic pathway is key as it blocks dopamine from having a potential action at the post-synaptic receptor. The binding of olanzapine to the dopamine D2 receptors is easily dissociable and hence, it allows for a certain degree of dopamine neurotransmission.\r\n\r\nOn the other hand, olanzapine acts in the serotonin 5HT2A receptors in the frontal cortex in a similar manner than the reported on dopamine D2 receptors. This determined effect allows for a decrease in adverse effects.","5-hydroxytryptamine receptor 2A antagonist; Dopamine D2 receptor antagonist; Dopamine D1 receptor antagonist; Dopamine D5 receptor antagonist; Dopamine D3 receptor antagonist; Dopamine D4 receptor antagonist; 5-hydroxytryptamine receptor 2C antagonist; 5-hydroxytryptamine receptor 3A antagonist; 5-hydroxytryptamine receptor 6 antagonist; Histamine H1 receptor antagonist; Alpha-1A adrenergic receptor antagonist; Alpha-1B adrenergic receptor antagonist; Muscarinic acetylcholine receptor M1 antagonist; Muscarinic acetylcholine receptor M2 antagonist; Muscarinic acetylcholine receptor M3 antagonist; Muscarinic acetylcholine receptor M4 antagonist; D(1) dopamine receptor antagonist; Beta adrenergic receptor inhibitor; 5-hydroxytryptamine receptor 1 inhibitor; GABA(A) Receptor Benzodiazepine Binding Site inhibitor","Indication associated"]
[120,"DB00335","approved","small molecule","Atenolol","1-p-Carbamoylmethylphenoxy-3-isopropylamino-2-propanol; 2-(p-(2-Hydroxy-3-(isopropylamino)propoxy)phenyl)acetamide; 4-(2-Hydroxy-3-((1-methylethyl)amino)propoxy)benzeneacetamide; Atenolol","C14H22N2O3","CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1","Atenolol is a cardioselective beta-blocker used in a variety of cardiovascular conditions. \r\n\r\nSir James Black, a Scottish pharmacologist, pioneered the use of beta-blockers for the management of angina pectoris in 1958 for which he received the Nobel Prize. Beta-blockers quickly became popular in clinical use and where subsequently investigated for use in myocardial infarction, arrhythmias, and hypertension during the 1960s. Later they continued to be investigated for use in heart failure throughout the 1970-1980s. Atenolol itself was developed early on in this history by Alvogen Malta under the trade name Tenormin and received FDA approval in September, 1981.\r\n\r\nDespite being one of the most widely prescribed beta blockers, evidence suggests atenolol may not significantly reduce mortality, and only modestly reduce the risk of cardiovascular disease in patients with hypertension. A Cochrane review of patients being treated for primary hypertension shows that atenolol shows a risk ratio of 0.88 for cardiovascular disease risk and a risk ratio of 0.99 for mortality. Similar results have been found in other meta-analyses. A meta-analysis of over 145,000 patients showed the risk of stroke in patients taking atenolol may depend on the age of the patient. The use of atenolol may need to be based on more patient factors than hypertension alone.","29122-68-7","266.3361","**Indicated** for:\r\n\r\n1) Management of hypertension alone and in combination with other antihypertensives.\r\n\r\n2) Management of angina pectoris associated with coronary atherosclerosis.\r\n\r\n3) Management of acute myocardial infarction in hemodynamically stable patients with a heart rate greater than 50 beats per minutes and a systolic blood pressure above 100 mmHg.\r\n\r\n**Off-label** uses include:\r\n\r\n1) Secondary prevention of myocardial infarction.\r\n\r\n2) Management of heart failure.\r\n\r\n3) Management of atrial fibrillation.\r\n\r\n4) Management of supraventricular tachycardia.\r\n\r\n5) Management of ventricular arrythmias such as congenital long-QT and arrhythmogenic right ventricular cardiomyopathy.\r\n\r\n6) Management of symptomatic thyrotoxicosis in combination with .\r\n\r\n7) Prophylaxis of migraine headaches.\r\n\r\n8) Management of alcohol withdrawal.","Atenolol is a cardio-selective beta-blocker and as such exerts most of its effects on the heart. It acts as an antagonist to sympathetic innervation and prevents increases in heart rate, electrical conductivity, and contractility in the heart due to increased release of norepinephrine from the peripheral nervous system. Together the decreases in contractility and rate produce a reduction in cardiac output resulting in a compensatory increase in peripheral vascular resistance in the short-term. This response later declines to baseline with long-term use of atenolol. More importantly, this reduction in the work demanded of the myocardium also reduces oxygen demand which provides therapeutic benefit by reducing the mismatch of oxygen supply and demand in settings where coronary blood flow is limited, such as in coronary atherosclerosis. Reducing oxygen demand, particularly due to exercise, can reduce the frequency of angina pectoris symptoms and potentially improve survival of the remaining myocardium after myocardial infarction. The decrease in rate of sinoatrial node potentials, electrical conduction, slowing of potentials traveling through the atrioventricular node, and reduced frequency of ectopic potentials due to blockade of adrenergic beta receptors has led to benefit in arrhythmic conditions such as atrial fibrillation by controlling the rate of action potential generation and allowing for more effective coordinated contractions. Since a degree of sympathetic activity is necessary to maintain cardiac function, the reduced contractility induced by atenolol may precipitate or worsen heart failure, especially during volume overload.\r\n\r\nThe effects of atenolol on blood pressure have been established, although it is less effective than alternative beta-blockers, but the mechanism has not yet been characterized. As a β1 selective drug, it does not act via the vasodilation produced by non-selective agents. Despite this there is a sustained reduction in peripheral vascular resistance, and consequently blood pressure, alongside a decrease in cardiac output. It is thought that atenolol's antihypertensive activity may be related to action on the central nervous system (CNS) or it's inhibition of the renin-aldosterone-angiotensin system rather than direct effects on the vasculature.\r\n\r\nAtenolol produces CNS effects similar to other beta-blockers, but does so to a lesser extent due to reduces ability to cross the blood-brain barrier. It has the potential to produce fatigue, depression, and sleep disturbances such as nightmares or insomnia. The exact mechanisms behind these have not been characterized but their occurrence must be considered as they represent clinically relevant adverse effects.\r\n\r\nAtenolol exerts some effects on the respiratory system although to a much lesser extent than non-selective beta-blockers. Interaction with β2 receptors in the airways can produce bronchoconstriction by blocking the relaxation of bronchial smooth muscle mediated by the sympathetic nervous system. The same action can interfere with β-agonist therapies used in asthma and chronic obstructive pulmonary disease.\r\n\r\nUnlike some other beta-blocker drugs, atenolol does not have intrinsic sympathomimetic or membrane stabilizing activity nor does it produce changes in glycemic control.","Atenolol is a cardioselective beta-blocker, called such because it selectively binds to the β1-adrenergic receptor as an antagonist up to a reported 26 fold more than β2 receptors. Selective activity at the β1 receptor produces cardioselectivity due to the higher population of this receptor in cardiac tissue. Some binding to β2 and possibly β3 receptors can still occur at therapeutic dosages but the effects mediated by antagonizing these are significantly reduced from those of non-selective agents. β1 and β2 receptors are G<sub>s</sub> coupled therefore antagonism of their activation reduces activity of adenylyl cyclase and its downstream signalling via cyclic adenosime monophosphate and protein kinase A (PKA). \r\n\r\nIn cardiomyocytes PKA is thought to mediate activation of L-type calcium channels and ryanodine receptors through their phosphorylation. L-type calcium channels can then provide an initial rise in intracellular calcium and trigger the ryanodine receptors to release calcium stored in the sarcoplasmic reticulum (SR) and increased contractility. PKA also plays a role in the cessation of contraction by phosphorylating phospholamban which in turn increases the affinity of SR Ca<sup>2+</sup> ATPase to increase reuptake of calcium into the SR. It also phophorylates troponin I to reduce affinity of the protein for calcium. Both of these events lead to a reduction in contraction which, when coupled with the initial increase in contraction, allows for faster cycling and consequently higher heart rate with increased contractility. L-type calcium channels are also a major contributor to cardiac depolarization and their activation can increase frequency of action potentials and possibly the incidence of ectopic potentials. \r\n\r\nSimilar inihibitory events occur in the bronchial smooth muscle to mediate relaxation including phosphorylation of myosin light-chain kinase, reducing its affinity for calcium. PKA also inhibits the excitatory G<sub>q</sub> coupled pathway by phosphorylating the inositol trisphosphate receptor and phospholipase C resulting in inhibition of intracellular calcium release. Antagonism of this activity by beta-blocker agents like atenolol can thus cause increased bronchoconstriction.\r","Beta-1 adrenergic receptor antagonist; Beta-2 adrenergic receptor antagonist","Therapeutic strategy associated"]
[121,"DB00337","approved; investigational","small molecule","Pimecrolimus","33-Epi-chloro-33-desoxyascomycin; Pimecrolimus","C43H68ClNO11","[H][C@]1(CC[C@H](Cl)[C@@H](C1)OC)\\C=C(/C)[C@@]1([H])OC(=O)[C@]2([H])CCCCN2C(=O)C(=O)[C@]2(O)O[C@@]([H])([C@H](C[C@H]2C)OC)[C@H](C[C@@H](C)C\\C(C)=C\\[C@@H](CC)C(=O)C[C@H](O)[C@H]1C)OC","Pimecrolimus is an immunomodulating agent that was first marketed by Novartis under the trade name Elidel. It is now promoted in Canada by Galderma since early 2007. It is currently available as a topic cream used in the treatment of atopic dermatitis (eczema).","137071-32-0","810.46","For treatment of mild to moderate atopic dermatitis.","Pimecrolimus is a chemical that is used to treat atopic dermatitis (eczema). Atopic dermatitis is a skin condition characterized by redness, itching, scaling and inflammation of the skin. The cause of atopic dermatitis is not known; however, scientists believe that it may be due to activation of the immune system by various environmental or emotional triggers. Scientists do not know exactly how pimecrolimus reduces the manifestations of atopic dermatitis, but pimecrolimus reduces the action of T-cells and mast cells which are part of the immune system and contribute to responses of the immune system. Pimecrolimus prevents the activation of T-cells by blocking the effects of chemicals (cytokines) released by the body that stimulate T-cells. Pimecrolimus also reduces the ability of mast cells to release chemicals that promote inflammation.","Pimecrolimus binds with high affinity to macrophilin-12 (FKBP-12) and inhibits the calcium-dependent phosphatase, calcineurin. As a consequence, it inhibits T cell activation by blocking the transcription of early cytokines. In particular, pimecrolimus inhibits at nanomolar concentrations Interleukin-2 and interferon gamma (Th1-type) and Interleukin-4 and Interleukin-10 (Th2-type) cytokine synthesis in human T cells. Also, pimecrolimus prevents the release of inflammatory cytokines and mediators from mast cells in vitro after stimulation by antigen/lgE.","Serine/threonine-protein kinase mTOR potentiator; Peptidyl-prolyl cis-trans isomerase FKBP1A potentiator","Therapeutic strategy associated"]
[122,"DB00341","approved","small molecule","Cetirizine","Cetirizine","C21H25ClN2O3","OC(=O)COCCN1CCN(CC1)C(C1=CC=CC=C1)C1=CC=C(Cl)C=C1","Cetirizine, also commonly known as _Zyrtec_, is an orally active second-generation histamine H1 antagonist proven effective in the treatment of various allergic symptoms, such as sneezing, coughing, nasal congestion, hives, and other symptoms , . \r\n\r\nOne of the most common uses for this drug is for a condition called _allergic rhinitis_. The prevalence of allergic rhinitis in the United States is about 15% according to physician diagnoses, and up to 30%, according to self-reported nasal symptoms. Allergic rhinitis is associated with multiple missed or unproductive days at work and school, problems with sleep, and other difficulties with day to day activities for many individuals . Furthermore, some antihistamine agents that are used to treat this condition cause undesirable, sedating effects . \r\n\r\nCetirizine is one of the first second-generation H1 antihistamines (SGAHs) formulated to selectively inhibit the H1 receptor without sedating effects .","83881-51-0","388.888","**Seasonal Allergic Rhinitis**: Indicated for the relief of symptoms associated with seasonal allergic rhinitis caused by allergens such as ragweed, grass and tree pollens in adults and children 2 years of age and above. Symptoms treated effectively include sneezing, rhinorrhea, nasal pruritus, ocular pruritus, tearing, and redness of the eyes . \r\n\r\n**Perennial allergic rhinitis**: This drug is indicated for the relief of symptoms associated with perennial allergic rhinitis due to allergens including dust mites, animal dander, and molds in adults and children 6 months of age and older. Symptoms treated effectively include sneezing, rhinorrhea, postnasal discharge, nasal pruritus, ocular pruritus, and tearing . \r\n\r\n**Chronic urticaria**: Cetirizine is indicated for the treatment of the uncomplicated skin manifestations of chronic idiopathic urticaria in adults and children 6 months of age and older. It markedly reduces the occurrence, severity, and duration of hives and significantly reduces pruritus .","**General effects and respiratory effects**\r\n\r\nCetirizine, the active metabolite of the piperazine H<sub>1</sub>-receptor antagonist hydroxyzine, minimizes or eliminates the symptoms of chronic idiopathic urticaria, perennial allergic rhinitis, seasonal allergic rhinitis, allergic asthma, physical urticaria, and atopic dermatitis.\r\nThe clinical efficacy of cetirizine for allergic respiratory diseases has been well established in numerous trials . \r\n\r\n**Effects on urticaria/anti-inflammatory effects**\r\n\r\nIt has anti-inflammatory properties that may play a role in asthma management . There is evidence that cetirizine improves symptoms of urticaria. Marked clinical inhibition of a wheal and flare response occurs in infants, children as well as adults within 20 minutes of one oral dose and lasts for 24 h .  Concomitant use of cetirizine reduces the duration and dose of topical anti-inflammatory formulas used for the treatment of atopic dermatitis .","Cetirizine, a metabolite of _hydroxyzine_, is an antihistamine drug.  Its main effects are achieved through selective inhibition of peripheral H1 receptors. The antihistamine activity of cetirizine has been shown in a variety of animal and human models. _In vivo_ and _ex vivo_ animal models have shown insignificant anticholinergic and antiserotonergic effects. In clinical studies, however, dry mouth was found to be more frequent with cetirizine than with a placebo. In vitro receptor binding studies have demonstrated no detectable affinity of cetirizine for histamine receptors  other than the H1 receptors. Studies with radiolabeled cetirizine administration in the rat have demonstrated insignificant penetration into the brain. _Ex vivo_ studies in the mouse have shown that systemically administered cetirizine does not occupy cerebral H1 receptors significantly .","Histamine H1 receptor antagonist","Therapeutic strategy associated"]
[123,"DB00343","approved; investigational","small molecule","Diltiazem","(+)-cis-5-[2-(dimethylamino)ethyl]-2,3-dihydro-3-hydroxy-2-(p-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one acetate ester; (2S-cis)-3-(acetyloxy)-5-[2-(dimethylamino)ethyl]-2,3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one; (2S,3S)-5-(2-(dimethylamino)ethyl)-2-(4-methoxyphenyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepin-3-yl acetate; Acetic acid (2S,3S)-5-(2-dimethylamino-ethyl)-2-(4-methoxy-phenyl)-4-oxo-2,3,4,5-tetrahydro-benzo[b][1,4]thiazepin-3-yl ester; d-cis-diltiazem","C22H26N2O4S","COC1=CC=C(C=C1)[C@@H]1SC2=C(C=CC=C2)N(CCN(C)C)C(=O)[C@@H]1OC(C)=O","Diltiazem is a benzothiazepine derivative with antihypertensive and vasodilating properties. Approved in 1982 by the FDA, it is a member of the non-dihydropyridine calcium channel blockers drug class. It works through various mechanisms of action, but it primarily works by inhibiting the calcium influx into cardiac and vascular smooth muscle during depolarization. Compared to dihydropyridine drugs, such as , that preferentially act on vascular smooth muscle and  that directly acts on the heart muscle, diltiazem displays an intermediate specificity to target both the cardiac and vascular smooth muscle. Being a potent vasodilator, diltiazem is used clinically as an antihypertensive, anti-arrhythmic, and as an anti-anginal agent  for the management of cardiovascular conditions such as hypertension, chronic stable angina, atrial fibrillation, atrial flutter. Apart from its main FDA-approved indications, diltiazem has also been used for numerous off-label indications, such as anal fissures (in topical formulations), migraine prophylaxis, pulmonary hypertension, and rest-related cramps in the lower extremities. Typically available in extended-release oral and intravenous formulations, diltiazem is marketed under various brand names with Cardizem and Tiazac being the most common ones.","42399-41-7","414.518","**Oral**\r\n\r\nIndicated for the management of hypertension, to lower blood pressure, alone or in combination with other antihypertensive agents.\r\n\r\nIndicated for use to improve exercise tolerance in patients with chronic stable angina.\r\n\r\nIndicated for the management of variant angina (Prinzmetal's angina).\r\n\r\n**Intravenous**\r\n\r\nIndicated for the short-term management of atrial fibrillation or atrial flutter for temporary control of rapid ventricular rate.\r\n\r\nIndicated for the rapid conversion of paroxysmal supraventricular tachycardias (PSVT) to sinus rhythm. This includes AV nodal reentrant tachycardias and reciprocating tachycardias associated with an extranodal accessory pathway such as the WPW syndrome or short PR syndrome.\r\n\r\n**Off-label**\r\n\r\nIndicated for off-label uses in anal fissures (as topical formulation), migraine prophylaxis, cramps in lower leg related to rest, pulmonary hypertension, idiopathic dilated cardiomyopathy, and proteinuria associated with diabetic nephropathy.","Diltiazem is an antihypertensive and vasodilating agent that works by relaxing the vascular muscle and reducing blood pressure. This is related to the long-term therapeutic effects, as lowering the blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions. Diltiazem inhibits the influx of extracellular calcium ions across the myocardial and vascular smooth muscle cell membranes during depolarization. Diltiazem is classified as a negative inotrope (decreased force) and negative chronotrope (decreased rate). It is also considered a rate-control drug as it reduces heart rate. Diltiazem is exerts hemodynamic actions by reducing blood pressure, systemic vascular resistance, the rate-pressure product, and coronary vascular resistance while increasing coronary blood flow. Diltiazem decreases sinoatrial and atrioventricular conduction in isolated tissues and has a negative inotropic effect in isolated preparations. In supraventricular tachycardia, diltiazem prolongs AV nodal refractories.\r\n\r\nAs the magnitude of blood pressure reduction is related to the degree of hypertension, the antihypertensive effect of diltiazem is most pronounced in individuals with hypertension. In a randomized, double-blind, parallel-group, dose-response study involving patients with essential hypertension, there was a reduction in the diastolic blood pressure by 1.9, 5.4, 6.1, and 8.6 mmHg in the patients receiving diltiazem at doses of 120, 240, 360, and 540 mg, respectively. In patients receiving placebo, there was a reduction in the diastolic blood pressure by 2.6 mmHg.In a randomized, double-blind study involving patients with chronic stable angina, variable doses of diltiazem administered at night all caused an increased exercise tolerance in the after 21 hours, compared to placebo. In the NORDIL study of patients with hypertension, the therapeutic effectiveness of diltiazem in reducing cardiovascular morbidity and mortality was assessed. When using the combined primary endpoint as fatal and non-fatal stroke, myocardial infarction, and other cardiovascular death, fatal and non-fatal stroke was shown to be reduced by 25% in the diltiazem group. Although the clinical significance to this effect remains unclear, it is suggested that diltiazem may exert a protective role against cerebral stroke in hypertensive patients.","Excitation of cardiac muscle involves the activation of a slow calcium inward current that is induced by L-type slow calcium channels, which are voltage-sensitive, ion-selective channels associated with a high activation threshold and slow inactivation profile. L-type calcium channels are the main current responsible for the late phase of the pacemaker potential. Acting as the main Ca2+ source for contraction in smooth and cardiac muscle, activation of L-type calcium channels allows the influx of calcium ions into the muscles upon depolarization and excitation of the channel. It is proposed that this cation influx may also trigger the release of additional calcium ions from intracellular storage sites. Diltiazem is a slow calcium channel blocker that binds to the extracellular site of the alpha-1C subunit of the channel, which is thought to be the S5-6 linker region of the transmembrane domain IV and/or S6 segment of domain III.  Diltiazem can get access to this binding site from either the intracellular or extracellular side, but it requires a voltage-induced conformational changes in the membrane. Diltiazem inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes. In isolated human atrial and ventricular myocardium, diltiazem suppressed tension over the range of membrane potentials associated with calcium channel activity but had little effect on the tension-voltage relations at more positive potentials. This effect is thought to be mediated by the voltage-dependent block of the L-type calcium channels and inhibition of calcium ion release from the ER stores, without altering the sodium-calcium coupled transport or calcium sensitivity of myofilaments. Through inhibition of inward calcium current, diltiazem exerts a direct ionotropic and energy sparing effect on the myocardium. Diltiazem fslows atrioventricular nodal conduction, which is due to its ability to impede slow channel function.\r\n\r\nReduced intracellular calcium concentrations equate to increased smooth muscle relaxation resulting in arterial vasodilation and therefore, decreased blood pressure. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload. Through its actions on reducing calcium levels in cardiac and vascular smooth muscles, diltiazem causes a reduction in the contractile processes of the myocardial smooth muscle cells and vasodilation of the coronary and systemic arteries, including epicardial and subendocardial. This subsequently leads to increased oxygen delivery to the myocardial tissue, improved cardiac output due to increased stroke volume, decreased total peripheral resistance, decreased systemic blood pressure and heart rate, and decreased afterload. Diltiazem lowers myocardial oxygen demand through a reduction in heart rate, blood pressure, and cardiac contractility; this leads to a therapeutic effect in improving exercise tolerance in chronic stable angina.","Voltage-dependent calcium channel gamma-1 subunit blocker; Voltage-dependent L-type calcium channel subunit alpha-1C blocker","Therapeutic strategy associated"]
[124,"DB00344","approved","small molecule","Protriptyline","3-(5H-dibenzo[a,d][7]annulen-5-yl)-N-methylpropan-1-amine; 3-(5H-dibenzo[a,d]cyclohepten-5-yl)-N-methyl-1-propanamine; 5-(3-methylaminopropyl)-5H-dibenzo[a,d]cycloheptene; 7-(3-methylaminopropyl)-1,2:5,6-dibenzocycloheptatriene; Amimetilina; N-methyl-5H-dibenzo[a,d]cycloheptene-5-propanamine; N-methyl-5H-dibenzo[a,d]cycloheptene-5-propylamine; Protriptyline","C19H21N","CNCCCC1C2=CC=CC=C2C=CC2=CC=CC=C12","Protriptyline hydrochloride is a dibenzocycloheptene-derivative tricyclic antidepressant (TCA). TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, protriptyline does not affect mood or arousal, but may cause sedation. In depressed individuals, protriptyline exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. In addition, TCAs down-regulate cerebral cortical &beta;-adrenergic receptors and sensitize post-synaptic serotonergic receptors with chronic use. The antidepressant effects of TCAs are thought to be due to an overall increase in serotonergic neurotransmission. TCAs also block histamine H<sub>1</sub> receptors, alpha<sub>1</sub>-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively. See toxicity section below for a complete listing of side effects. Protriptyline may be used for the treatment of depression.","438-60-8","263.3767","For the treatment of depression.","Protriptyline is a tricyclic antidepressant. It was thought that tricyclic antidepressants work by inhibiting the reuptake of the neurotransmitters norepinephrine and serotonin by nerve cells. The effectiveness of antidepressants appear after approximately two weeks following recommended adminsitration schedule. Gradual changes are thought to occur in the cerebral cortex and hippocampus, involved in emotion regulation as part of the limbic system, as receptor sensitivity is enhanced. While &alpha;<sub>1</sub> and &beta;<sub>1</sub> receptors are sensitized, &alpha;<sub>2</sub> receptors are desensitized (leading to increased noradrenaline production). Tricyclics are also reported to alter the perceptions of pain, including neuropathic or neuralgic pain, so they may exhibit analgesic properties. The mechanism of action behind this analgesic property is not fully understood; however, it is thought to involve modulation of endogenous opioid systems in the CNS via an indirect serotonergic route. Tricyclic antidepressants are also effective in relieving migraine prophylaxis, but not in abortion of acute migraine attack, potentially via their serotonergic effects.","Protriptyline acts by decreasing the reuptake of norepinephrine and serotonin (5-HT).","Sodium-dependent noradrenaline transporter inhibitor; Sodium-dependent serotonin transporter inhibitor","Indication associated"]
[125,"DB00346","approved; investigational","small molecule","Alfuzosin","(±)-N-[3-[(4-amino-6,7-dimethoxy-2-quinazolinyl)methylamino]propyl]tetrahydro-2-furamide; Alfuzosin; N-[3-[(4-amino-6,7-dimethoxy-quinazolin-2-yl)- methyl-amino]propyl] tetrahydrofuran- 2-carboxamide","C19H27N5O4","COC1=CC2=C(C=C1OC)C(N)=NC(=N2)N(C)CCCNC(=O)C1CCCO1","Benign prostatic hyperplasia (BPH) refers to a benign growth or hyperplasia of the prostate and leads to lower urinary tract symptoms in men, such as urgency, frequency and changes to urine flow. The prevalence of BPH is as high as 50%-60% for males in their 60's, and this prevalence increases to 80%-90% of those over 70. Alfuzosin is an alpha-1 adrenergic blocker used in the symptomatic treatment of BPH that works by relaxing the muscles in the prostate and bladder neck. It was initially approved by the FDA in 2003 and is marketed by several pharmaceutical companies.","81403-80-7","389.4488","Alfuzosin is used to treat the signs and symptoms of benign prostatic hyperplasia (BPH).","By selectively inhibiting alpha adrenergic receptors in the lower urinary tract, alfuzosin causes smooth muscle relaxation in the bladder neck and prostate, improving urine flow, thereby reducing BPH symptoms. Additionally, alfuzosin reduces the vasoconstrictor effect of catecholamines (epinephrine and norepinephrine), leading to peripheral vasodilation. This leads to a risk of postural hypotension/syncope, and prescribing information warns that caution should be exercised in patients who take nitrates, antihypertensives, or have experienced decreased blood pressure after using other medications.","Alpha(1)-adrenoreceptors  are found in the prostate, bladder base, bladder neck, prostatic capsule, and prostatic urethra; their activation may lead to contraction of smooth muscle and urinary symptoms in patients with BPH. Alfuzosin selectively binds to and inhibits alpha(1)-adrenergic receptors in the lower urinary tract. This leads to the relaxation of smooth muscle in both the prostate and bladder neck, resulting in the improvement in urine flow and a reduction of urinary symptoms.","Alpha-1A adrenergic receptor antagonist; Alpha-1B adrenergic receptor antagonist; Alpha-1D adrenergic receptor antagonist; Alpha-1 adrenergic receptors antagonist","Therapeutic strategy associated"]
[126,"DB00350","approved; investigational","small molecule","Minoxidil","2,4-Diamino-6-piperidinopyrimidine 3-oxide; 6-Piperidin-1-ylpyrimidine-2,4-diamine 3-oxide","C9H15N5O","NC1=CC(=NC(N)=[N+]1[O-])N1CCCCC1","A potent direct-acting peripheral vasodilator (vasodilator agents) that reduces peripheral resistance and produces a fall in blood pressure.","38304-91-5","209.2483","For the treatment of severe hypertension and in the topical treatment (regrowth) of androgenic alopecia in males and females and stabilisation of hair loss in patients with androgenic alopecia.","Minoxidil is an orally effective direct acting peripheral vasodilator that reduces elevated systolic and diastolic blood pressure by decreasing peripheral vascular resistance. Minoxidil is also used topically to treat androgenetic alopecia. Microcirculatory blood flow in animals is enhanced or maintained in all systemic vascular beds. In man, forearm and renal vascular resistance decline; forearm blood flow increases while renal blood flow and glomerular filtration rate are preserved. The predominant site of minoxidil action is arterial. Venodilation does not occur with minoxidil; thus, postural hypotension is unusual with its administration. The antihypertensive activity of minoxidil is due to its sulphate metabolite, minoxidil sulfate.","Minoxidil is thought to promote the survival of human dermal papillary cells (DPCs) or hair cells by activating both extracellular signal-regulated kinase (ERK) and Akt and by preventing cell death by increasing the ratio of BCl<sup>-</sup>2/Bax. Minoxidil may stimulate the growth of human hairs by prolonging anagen through these proliferative and anti-apoptotic effects on DPCs. Minoxidil, when used as a vasodilator, acts by opening adenosine triphosphate-sensitive potassium channels in vascular smooth muscle cells. This vasodilation may also improve the viability of hair cells or hair follicles.","ATP-sensitive inward rectifier potassium channel 1 inducer; Prostaglandin G/H synthase 1 inducer; Renin","Therapeutic strategy associated"]
[127,"DB00351","approved; investigational; vet_approved","small molecule","Megestrol acetate","17-Acetoxy-6-methylpregna-4,6-diene-3,20-dione; 17-Hydroxy-6-methylpregna-4,6-diene-3,20-dione 17-acetate; 17alpha-Acetoxy-6-dehydro-6-methylprogesterone; 17alpha-Hydroxy-6-methylpregna-4,6-diene-3,20-dione acetate; 17α-Acetoxy-6-dehydro-6-methylprogesterone; 17α-Hydroxy-6-methylpregna-4,6-diene-3,20-dione acetate; 6-Dehydro-6-methyl-17alpha-acetoxyprogesterone; 6-Dehydro-6-methyl-17α-acetoxyprogesterone; 6-Methyl-17alpha-acetoxypregna-4,6-diene-3,20-dione; 6-Methyl-17alpha-hydroxy-delta(sup 6)-progesterone acetate; 6-Methyl-17α-acetoxypregna-4,6-diene-3,20-dione; 6-Methyl-17α-hydroxy-delta(sup 6)-progesterone acetate; 6-Methyl-6-dehydro-17alpha-acetoxyprogesterone; 6-Methyl-6-dehydro-17α-acetoxyprogesterone; 6-Methyl-delta(sup 4,6)-pregnadien-17alpha-ol-3,20-dione acetate; 6-Methyl-delta(sup 4,6)-pregnadien-17α-ol-3,20-dione acetate; 6-Methyl-delta(sup 6)-dehydro-17alpha-acetoxyprogesterone; 6-Methyl-delta(sup 6)-dehydro-17α-acetoxyprogesterone; Megestrol acetate; MGA","C24H32O4","[H][C@@]12CC[C@](OC(C)=O)(C(C)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])C=C(C)C2=CC(=O)CC[C@]12C","17-Hydroxy-6-methylpregna-3,6-diene-3,20-dione. A progestational hormone used most commonly as the acetate ester. As the acetate, it is more potent than progesterone both as a progestagen and as an ovulation inhibitor. It has also been used in the palliative treatment of breast cancer.","595-33-5","384.516","For the treatment of anorexia, cachexia, or an unexplained, significant weight loss in patients with a diagnosis of acquired immunodeficiency syndrome (AIDS). Also used for the palliative management of recurrent, inoperable, or metastatic breast cancer, endometrial cancer, and prostate cancer in Canada and some other countries.","Megestrol is a synthetic progestin and has the same physiologic effects as natural progesterone. These effects include induction of secretory changes in the endometrium, increase in basal body temperature, pituitary inhibition, and production of withdrawal bleeding in the presence of estrogen. Mestrogel has slight glucocorticoid activity and very slight mineralocorticoid activity. This drug has no estrogenic, androgenic, or anabolic activity. The precise mechanism of megestrol&rsquo;s antianorexic and anticachetic effects is unknown. Initially developed as a contraceptive, it was first evaluated in breast cancer treatment in 1967.","The precise mechanism by which megestrol acetate produces effects in anorexia and cachexia is unknown at the present time, but its progestin antitumour activity may involve suppression of luteinizing hormone by inhibition of pituitary function. Studies also suggest that the megestrol's weight gain effect is related to its appetite-stimulant or metabolic effects rather than its glucocorticoid-like effects or the production of edema. It has also been suggested that megestrol may alter metabolic pathyways via interferences with the production or action of mediators such as cachectin, a hormone that inhibits adipocyte lipogenic enzymes.","Progesterone receptor agonist; Glucocorticoid receptor agonist","Therapeutic strategy associated"]
[128,"DB00356","approved","small molecule","Chlorzoxazone","2-hydroxy-5-chlorobenzoxazole; 5-chloro-2-benzoxazolinone; 5-chloro-2-benzoxazolol; 5-chloro-2-benzoxazolone; 5-chloro-2-hydroxybenzoxazole; 5-chloro-2(3H)-benzoxazolone; 5-chloro-3H-benzooxazol-2-one; 5-chlorobenzoxazolidone; 5-chlorobenzoxazolin-2-one; Chlorzoxane","C7H4ClNO2","ClC1=CC2=C(OC(=O)N2)C=C1","A centrally acting central muscle relaxant with sedative properties. It is claimed to inhibit muscle spasm by exerting an effect primarily at the level of the spinal cord and subcortical areas of the brain. (From Martindale, The Extra Pharmacopoea, 30th ed, p1202)","95-25-0","169.565","For the relief of discomfort associated with acute painful musculoskeletal conditions.","Chlorzoxazone is a centrally-acting agent for painful musculoskeletal conditions. Data available from animal experiments as well as human study indicate that chlorzoxazone acts primarily at the level of the spinal cord and subcortical areas of the brain where it inhibits multisynaptic reflex a.c. involved in producing and maintaining skeletal muscle spasm of varied etiology. The clinical result is a reduction of the skeletal muscle spasm with relief of pain and increased mobility of the involved muscles.","Chlorzoxazone inhibits degranulation of mast cells, subsequently preventing the release of histamine and slow-reacting substance of anaphylaxis (SRS-A), mediators of type I allergic reactions. Chlorzoxazone also may reduce the release of inflammatory leukotrienes. Chlorzoxazone may act by inhibiting calcium and potassium influx which would lead to neuronal inhibition and muscle relaxation. Data available from animal experiments as well as human study indicate that chlorzoxazone acts primarily at the level of the spinal cord and subcortical areas of the brain where it inhibits multisynaptic reflex arcs involved in producing and maintaining skeletal muscle spasm","Calcium-activated potassium channel subunit alpha-1","Therapeutic strategy associated"]
[129,"DB00360","approved; investigational","small molecule","Sapropterin","(−)-(6R)-2-amino-6-((1R,2S)-1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4(3H)-pteridinone; (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin; (6R)-L-erythro-tetrahydrobiopterin; 2-Amino-6-(1,2-dihydroxypropyl)-5,6,7,8-tetrahydoro-4(1H)-pteridinone; 5,6,7,8-Tetrahydrobiopterin; 6R-5,6,7,8-tetrahydrobiopterin; 6R-BH4; 6R-L-5,6,7,8-tetrahydrobiopterin; R-THBP; Sapropterin; Tetrahydrobiopterin","C9H15N5O3","[H][C@@]1(CNC2=C(N1)C(=O)NC(N)=N2)[C@@H](O)[C@H](C)O","Sapropterin (tetrahydrobiopterin or BH4) is a cofactor in the synthesis of nitric oxide. It is also essential in the conversion of phenylalanine to tyrosine by the enzyme phenylalanine-4-hydroxylase; the conversion of tyrosine to L-dopa by the enzyme tyrosine hydroxylase; and conversion of tryptophan to 5-hydroxytryptophan via tryptophan hydroxylase.","62989-33-7","241.2471","For the treatment of tetrahydrobiopterin (BH4) deficiency.","Tetrahydrobiopterin (BH4) is used to convert several amino acids, including phenylalanine, to other essential molecules in the body including neurotransmitters. Tetrahydrobiopterin deficiency can be caused by mutations in GTP cyclohydrolase 1 (GCH1), 6-pyruvoyl-tetrahydropterin synthase/dimerization cofactor of hepatocyte nuclear factor 1 alpha (PCBD1), 6-pyruvoyltetrahydropterin synthase (PTS), and quinoid dihydropteridine reductase (QDPR) genes. These genes make the enzymes that are critical for producing and recycling tetrahydrobiopterin. If one of the enzymes fails to function correctly because of a gene mutation, little or no tetrahydrobiopterin is produced. As a result, phenylalanine from the diet builds up in the bloodstream and other tissues and can damage nerve cells in the brain. High levels of phenylalanine can result in signs and symptoms ranging from temporary low muscle tone to mental retardation, movement disorders, difficulty swallowing, seizures, behavioral problems, progressive problems with development, and an inability to control body temperature.","Tetrahydrobiopterin (BH4) is a natural co-factor or co-enzyme for phenylalanine-4-hydroxylase (PAH),Tetrahydrobiopterine, and tryptophan-5-hydroxylase. Tetrahydrobiopterin is also a natural co-factor for nitrate oxide synthase. Therefore BH4 is required for the conversion of phenylalanine to tyrosine, for the production of epinephrine (adrenaline) and the synthesis of the monoamine neuro-transmitters, serotonin, dopamine, and norepinephrine (noradrenaline). It is also involved in apoptosis and other cellular events mediated by nitric oxide production. As a coenzyme, BH4 reacts with molecular oxygen to form an active oxygen intermediate that can hydroxylate substrates. In the hydroxylation process, the co-enzyme loses two electrons and is regenerated in vivo in an NADH-dependent reaction. As a co-factor for PAH, tetrahydrobiopterin allows the conversion of phenylalanine to tyrosine and reduces the level of phenylalanine in the bloodstream, thereby reducing the toxic effects of of this amino acid. Normal serum concentrations of phenylalanine are 100 micomolar, while elevated (toxic) levels are typically >1200 micromolar. Individuals with a deficiency in tetrahydrobiopterin are not able to efficiently convert phenylalanine to tyrosine. The excess levels provided by tetrahydrobiopterin supplementation help improve enzyme efficiency. As a co-factor for tyrosine hydroxylase, BH4 facilitates the conversion of tyrosine to L-dopa while as a co-factor for tryptophan hydroxylase, BH4 allows the conversion of tryptophan to 5-hydroxytryptophan, which is then converted to serotonin.","Phenylalanine-4-hydroxylase cofactor; Nitric oxide synthase, endothelial cofactor; Tyrosine 3-monooxygenase cofactor; Tryptophan 5-hydroxylase 1 cofactor","Therapeutic strategy associated"]
[130,"DB00361","approved; investigational","small molecule","Vinorelbine","5'-Noranhydrovinblastine; Vinorelbine","C45H54N4O8","[H][C@@]12N(C)C3=CC(OC)=C(C=C3[C@@]11CCN3CC=C[C@](CC)([C@@]13[H])[C@@]([H])(OC(C)=O)[C@]2(O)C(=O)OC)[C@]1(C[C@@]2([H])CN(CC(CC)=C2)CC2=C1NC1=CC=CC=C21)C(=O)OC","Vinorelbine is an anti-mitotic chemotherapy drug that is used in the treatment of several types of malignancies, including breast cancer and non-small cell lung cancer (NSCLC) .  It was initially approved in the USA in 1990's for the treatment of NSCLC .\r\n\r\nIt is a third-generation vinca alkaloid. The introduction of third-generation drugs (vinorelbine, gemcitabine, taxanes) in platinum combination improved survival of patients with advanced NSCLC, with very similar results from the various drugs. Treatment toxicities are considerable in the combination treatment setting .\r\n\r\nA study was done on the clearance rate of vinorelbine on individuals with various single polymorphonuclear mutations.  It was found that there was 4.3-fold variation in vinorelbine clearance across the cohort, suggesting a strong influence of genetics on the clearance of this drug .","71486-22-1","778.947","\r\n Vinorelbine tartrate is indicated for adults in the treatment of advanced non-small cell lung cancer (NSCLC), as a single therapy or in combination with other chemotherapeutic drugs .\r\n\r\nUsed in relapsed or refractory Hodgkin lymphoma, in combination with other chemotherapy agents .\r\n \r\nFor the treatment of desmoid tumor or aggressive fibromatosis, in combination with methotrexate .\r\n\r\nFor the treatment of recurrent or metastatic squamous cell head and neck cancer .\r\n\r\nFor the treatment of recurrent ovarian cancer .\r\n\r\nFor the treatment of metastatic breast cancer, in patients previously treated with anthracyline and/or taxane therapy .\r\n\r\nFor the treatment of HER2-positive, trastuzumab-resistant, advanced breast cancer in patients previously treated with a taxane, in combination with trastuzumab and everolimus .\r","\r\nVinorelbine is a semi-synthetic vinca-alkaloid with a wide spectrum of anti-tumor activity. The vinca-alkaloids are considered spindle poisons. They work by interfering with the polymerization of tubulin, a protein responsible for building the microtubule system which appears during cell division in proliferating cancer cells .","Vinca alkaloids are structurally similar compounds composed of two multi-ringed units, _vindoline_, and _catharanthine_. _Vinorelbine tartrate_ is a vinca alkaloid in which the catharanthine component is the target of structural modification , .\r\n\r\nThis structural modification contributes to unique pharmacologic properties.The antitumor activity of vinorelbine tartrate is believed to be owed to the inhibition of mitosis at metaphase via its interaction with tubulin .\r\n\r\nVinorelbine is a mitotic spindle poison that interferes with chromosomal segregation during mitosis, also known as cell division. It pauses cells at the _G2/M_ phases, when present at concentrations close to the half maximal inhibitory concentration (IC50). Microtubules, which are derived from polymers of tubulin, are the main target of vinorelbine. \r\n\r\nThe chemical modification used to produce vinorelbine allows for the opening of the eight-member catharanthine ring with the formation of both a covalent and reversible bond with tubulin .\r\n\r\nThe relative contribution of different microtubule-associated proteins in the production of tubulin vary between neural tissue and proliferating cells and this has important functional implications. The ability of vinorelbine to bind specifically to mitotic rather than other microtubules has been shown and may suggest that neurotoxicity is less likely to be a problem than with the molecular mechanism of action . \r\n\r\nAs with other anti-microtubule agents, vinorelbine is known to contribute apoptosis in malignant cells. The exact mechanisms by which this process occurs are complex and many details are yet to be elucidated. The disarray of the microtubule structure has a number of effects, including the induction of tumor suppressor gene _p53_ and activation/inactivation of a number of protein kinases involved in essential signaling pathways, including _p21 WAF1/CIP1_ and _Ras/Raf_, _PKC/PKA_. These molecular changes lead to phosphorylation and consequently inactivation of the apoptosis inhibitor _Bcl2_. This, in turn, results in a decrease in the formation of heterodimers between _Bcl2_ and the pro-apoptotic gene _BAX_, stimulating the sequence of cell apoptosis .\r\n\r\nVinorelbine tartrate also possibly interferes with amino acid, cyclic AMP and glutathione metabolism, calmodulin-dependent Ca++-transport ATPase activity, cellular respiration, and nucleic acid and lipid biosynthesis .\r","Tubulin beta chain antagonist&inhibitor","Therapeutic strategy associated"]
[131,"DB00365","approved; investigational; withdrawn","small molecule","Grepafloxacin","Grepafloxacin","C19H22FN3O3","CC1CN(CCN1)C1=C(F)C(C)=C2C(=O)C(=CN(C3CC3)C2=C1)C(O)=O","Grepafloxacin is an oral broad-spectrum quinoline antibacterial agent used to treat bacterial infections. Due to the QTc-prolonging potential, as indicated by the changes in the QT interval on the electrocardiogram, and the risk for cardiovascular adverse events, grepafloxacin was withdrawn in the United States.","119914-60-2","359.3947","For treatment of adults with mild to moderate infections caused by susceptible strains of <i>Haemophilus influenzae</i>, <i>Streptococcus pneumoniae</i>, or <i>Moraxella catarrhalis</i>.","Grepafloxacin has in vitro activity against a wide range of gram-positive and gram-negative aerobic microorganisms, as well as some atypical microorganisms.","Grepafloxacin exerts its antibacterial activity by inhibiting bacterial topoisomerase II (DNA gyrase) and topoisomerase IV, essential enzymes for duplication, transcription, and repair of bacterial DNA.","DNA gyrase subunit A inhibitor; DNA topoisomerase 4 subunit A inhibitor","Indication associated"]
[132,"DB00367","approved; investigational","small molecule","Levonorgestrel","(-)-13-Ethyl-17-hydroxy-18,19-dinor-17alpha-pregn-4-en-20-yn-3-one; (8R,9S,10R,13S,14S,17R)-13-ethyl-17-ethynyl-17-hydroxy- 1,2,6,7,8,9,10,11,12,13,14,15,16, 17- tetradecahydrocyclopenta[a] phenanthren-3-one; 13-beta-Ethyl-17alpha-ethynyl-17beta-hydroxygon-4-en-3-one; 13-Ethyl-17-alpha-ethynyl-17-beta-hydroxy-4-gonen-3-one; 13-Ethyl-17-alpha-ethynylgon-4-en-17-beta-ol-3-one; 17-alpha-Ethinyl-13-beta-ethyl-17-beta-hydroxy-4-estren-3-one; 17-alpha-Ethynyl-13-ethyl-19-nortestosterone; 17-Ethynyl-18-methyl-19-nortestosterone; 17alpha-Ethynyl-13beta-ethyl-3-oxo-4-estren-17beta-ol; 17alpha-Ethynyl-17-hydroxy-18-methylestr-4-en-3-one; 17alpha-Ethynyl-18-homo-19-nortestosterone; 18-Methyl-17-alpha-ethynyl-19-nortestosterone; 18-Methylnorethisterone; d(-)-Norgestrel","C21H28O2","[H][C@@]12CC[C@@](O)(C#C)[C@@]1(CC)CC[C@]1([H])[C@@]3([H])CCC(=O)C=C3CC[C@@]21[H]","Levonorgestrel (LNG) is a synthetic progestogen similar to  used in contraception and hormone therapy. Also known as Plan B, it is used as a single agent in emergency contraception, and as a hormonal contraceptive released from an intrauterine device, commonly referred to as an IUD. Some of these devices are known as Jaydess, Kyleena, and Mirena.  A subdermal implant of levonorgestrel that slowly releases the hormone over a long-term period is also available.  In addition to the above uses, levonorgestrel is used as a component of long-term combination contraceptives. \r\n\r\nGlobally, levonorgestrel is the most commonly used emergency contraceptive. It was initially granted FDA approval in 1982 and was the first emergency contraceptive containing only progesterone, showing high levels of efficacy and a lack of estrogenic adverse effects when compared to older emergency contraceptive regimens.","797-63-7","312.4458","**Emergency contraception**\r\n\r\nLevonorgestrel, in the single-agent emergency contraceptive form, is indicated for the prevention of pregnancy after the confirmed or suspected failure of contraception methods or following unprotected intercourse. It is distributed by prescription for patients under 17, and over the counter for those above this age. This levonorgestrel-only form of contraception is not indicated for regular contraception and must be taken as soon as possible within 72 hours after intercourse. It has shown a lower efficacy when it is used off label within 96 hours.\r\n\r\n**Long-term contraception or nonemergency contraception**\r\n\r\nIn addition to the above indication in emergency contraception, levonorgestrel is combined with other contraceptives in contraceptive formulations designed for regular use, for example with ethinyl estradiol. It is used in various hormone-releasing intrauterine devices for long-term contraception ranging for a duration of 3-5 years. Product labeling for Mirena specifically mentions that it is recommended in women who have had at least 1 child. A subdermal implant is also available for the prevention of pregnancy for up to 5 years.\r\n\r\n**Hormone therapy and off-label uses**\r\n\r\nLevonorgestrel is prescribed in combination with estradiol as hormone therapy during menopause to manage vasomotor symptoms and to prevent osteoporosis.Off-label, levonorgestrel may be used to treat menorrhagia, endometrial hyperplasia, and endometriosis.","Levonorgestrel prevents pregnancy by interfering with ovulation, fertilization, and implantation. The levonorgestrel-only containing emergency contraceptive tablet is 89% effective if it is used according to prescribing information within 72 hours after intercourse. The intrauterine and implantable devices releasing levonorgestrel are more than 99% in preventing pregnancy. Levonorgestrel utilized as a component of hormonal therapy helps to prevent endometrial carcinoma associated with unopposed estrogen administration.","**Mechanism of action on ovulation**\r\n\r\nOral contraceptives containing levonorgestrel suppress gonadotropins, inhibiting ovulation. Specifically, levonorgestrel binds to progesterone and androgen receptors and slows the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus. This process results in the suppression of the normal physiological luteinizing hormone (LH) surge that precedes ovulation. It inhibits the rupture of follicles and viable egg release from the ovaries. Levonorgestrel has been proven to be more effective when administered before ovulation.\r\n\r\n**Mechanism of action in cervical mucus changes**\r\n\r\nSimilar to other levonorgestrel-containing contraceptives, the intrauterine (IUD) forms of levonorgestrel likely prevent pregnancy by increasing the thickness of cervical mucus, interfering with the movement and survival of sperm, and inducing changes in the endometrium, where a fertilized ovum is usually implanted. Levonorgestrel is reported to alter the consistency of mucus in the cervix, which interferes with sperm migration into the uterus for fertilization. Levonorgestrel is not effective after implantation has occurred. \r\nInterestingly, recent evidence has refuted the commonly believed notion that levonorgestrel changes the consistency of cervical mucus when it is taken over a short-term period, as in emergency contraception. Over a long-term period, however, levonorgestrel has been proven to thicken cervical mucus. The exact mechanism of action of levonorgestrel is not completely understood and remains a topic of controversy and ongoing investigation.\r\n\r\n*Effects on implantation**\r\n\r\nThe effects of levonorgestrel on endometrial receptivity are unclear, and the relevance of this mechanism to the therapeutic efficacy of levonorgestrel is contentious. Prescribing information for levonorgestrel IUDs state that they exert local morphological changes to the endometrium (e.g. stromal pseudodecidualization, glandular atrophy) that may play a role in their contraceptive activity.\r\n\r\n**Mechanism of action in hormone therapy**\r\n\r\nWhen combined with estrogens for the treatment of menopausal symptoms and prevention of osteoporosis, levonorgestrel serves to lower the carcinogenic risk of unopposed estrogen therapy via the inhibition of endometrial proliferation. Unregulated endometrial proliferation sometimes leads to endometrial cancer after estrogen use.","Progesterone receptor modulator; 3-oxo-5-alpha-steroid 4-dehydrogenase 1 inhibitor; Estrogen receptor alpha other/unknown; Androgen receptor binder; Sex hormone-binding globulin inhibitor&binder; Glucocorticoid receptor binder","Indication associated"]
[133,"DB00373","approved","small molecule","Timolol","(S)-1-(tert-butylamino)-3-[(4-morpholin-4-yl-1,2,5-thiadiazol-3-yl)oxy]propan-2-ol; Timolol anhydrous","C13H24N4O3S","[H][C@](O)(CNC(C)(C)C)COC1=NSN=C1N1CCOCC1","Timolol is a nonselective beta-adrenergic antagonist given in an eye drop solution to reduce intraocular pressure, or pressure in the eyes. It is also used in tablet form as a drug to treat hypertension. Timolol was first approved by the FDA in 1978. This drug is marketed by several manufacturers  and is an effective agent for the management of conditions such as open-angle glaucoma and hypertension.","26839-75-8","316.42","Ophthalmic timolol is indicated for the treatment of increased intraocular pressure in patients with ocular hypertension or open-angle glaucoma. The oral form of this drug is used to treat high blood pressure. In certain cases, timolol is used in the prevention of migraine headaches.","Timolol, when administered by the ophthalmic route, rapidly reduces intraocular pressure. When administered in the tablet form, it reduces blood pressure, heart rate, and cardiac output, and decreases sympathetic activity.. This drug has a fast onset of action, usually occurring within 20 minutes of the administration of an ophthalmic dose. Timolol maleate can exert pharmacological actions for as long as 24 hours if given in the 0.5% or 0.25% doses.\r\n\r","Timolol competes with adrenergic neurotransmitters for binding to beta(1)-adrenergic receptors in the heart and the beta(2)-receptors in the vascular and bronchial smooth muscle. This leads to diminished actions of catecholamines, which normally bind to adrenergic receptors and exert sympathetic effects leading to an increase in blood pressure and heart rate. Beta(1)-receptor blockade by timolol leads to a decrease in both heart rate and cardiac output during rest and exercise, and a decrease in both systolic and diastolic blood pressure. In addition to this, a reduction in reflex orthostatic hypotension may also occur. The blockade of beta(2) receptors by timolol in the blood vessels leads to a decrease in peripheral vascular resistance, reducing blood pressure.\r\n\r\nThe exact mechanism by which timolol reduces ocular pressure is unknown at this time, however, it likely decreases the secretion of aqueous humor in the eye. According to one study, the reduction of aqueous humor secretion may occur through the decreased blood supply to the ciliary body resulting from interference with the active transport system or interference with prostaglandin biosynthesis.","Beta-1 adrenergic receptor antagonist; Beta-2 adrenergic receptor antagonist; Lysozyme","Indication associated"]
[134,"DB00374","approved; investigational","small molecule","Treprostinil","Treprostinil","C23H34O5","[H][C@]12C[C@@H](O)[C@H](CC[C@@H](O)CCCCC)[C@@]1([H])CC1=C(C2)C(OCC(O)=O)=CC=C1","Treprostinil is a synthetic analogue of prostacyclin, used to treat pulmonary hypertension.","81846-19-7","390.5131","For use as a continuous subcutaneous infusion or intravenous infusion (for those not able to tolerate a subcutaneous infusion) for the treatment of pulmonary arterial hypertension in patients with NYHA Class II-IV symptoms to diminish symptoms associated with exercise.","Pulmonary arterial hypertension (PAH) is a disease in which blood pressure is abnormally high in the arteries between the heart and lungs. PAH is characterized by symptoms of shortness of breath during physical exertion. The condition can ultimately lead to heart failure. Treprostinil is a potent oral antiplatelet agent. The major pharmacologic actions of treprostinil are direct vasodilation of pulmonary and systemic arterial vascular beds and inhibition of platelet aggregation. In animals, the vasodilatory effects reduce right and left ventricular afterload and increase cardiac output and stroke volume. Other studies have shown that treprostinil causes a dose-related negative inotropic and lusitropic effect. No major effects on cardiac conduction have been observed.","The major pharmacological actions of treprostinil are direct vasodilation of pulmonary and systemic arterial vascular beds and inhibition of platelet aggregation. In addition to treprostinil's direct vasodilatory effects, it also inhibits inflammatory cytokine. As a synthetic analogue of prostacyclin, it binds to the prostacyclin receptor, which subsequently induces the aforementioned downstream effects.","Prostacyclin receptor agonist; Peroxisome proliferator-activated receptor delta agonist; P2Y purinoceptor 12 agonist","Therapeutic strategy associated"]
[135,"DB00375","approved","small molecule","Colestipol","Colestipol; Copolymer of bis(2-aminoethyl)amine and 2-(chloromethyl)oxirane; Epichlorohydrin-tetraethylenepentamine polymer",null,null,"Bile acid sequestrants like colestipol have been in use since the 1970s. And even though such an agent may very well be useful in reducing elevated cholesterol levels and decreasing the risk for atherosclerotic vascular disease due to hypercholesterolemia, colestipol is still generally only employed as an adjunct therapy and the relatively physical nature of its pharmacological activity sometimes limits its usefulness.\r\n\r\nIn particular, as colestipol's general mechanism of action ultimately results in the decreased absorption and enhanced secretion of bile acids and lipids in the feces, patients who take complicated medication regimens, experience constipation or biliary obstruction, etc. may not be good candidates for using the agent owing to its physical effects on the gut.\r\n\r\nAlternatively, colestipol predominantly elicits its activities within the gut environment because it undergoes little absorption and metabolism. The resultant lack of systemic exposure consequently means the medication generally demonstrates very few adverse effects inside the body.","26658-42-4",null,"Colestipol is indicated as adjunctive therapy to diet for the reduction of elevated serum total and low-density lipoprotein cholesterol (LDL-C) in patients with primary hypercholesterolemia (a condition that features elevated LDL-C) who do not respond adequately to dietary changes .\r\n\r\nTherapy with lipid-altering agents like colestipol should be a component of multiple risk factor intervention in those individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia . Treatment should begin and continue with dietary therapy . In general, a minimum of six months of intensive dietary therapy and counseling should be carried out prior to initiation of drug therapy such as that with colestipol . Shorter periods may be considered in patients with severe elevations of LDL-C or with definite coronary heart disease .\r\n\r\nAlthough colestipol is effective in all types of hypercholesterolemia, some regional prescribing information note in particular that it is medically most appropriate in patients with Fredrickson's type II hyperlipoproteinemia . Nevertheless, in patients with combined hypercholesterolemia and hypertriglyceridemia, although colestipol may be helpful in reducing elevated cholesterol, it is not formally indicated where hypertriglyceridemia is the abnormality of greatest concern .","Cholesterol is the major, and probably the sole precursor of bile acids . During normal digestion, bile acids are secreted via the bile from the liver and gall bladder into the intestines . Bile acids emulsify the fat and lipid materials present in food, thus facilitating absorption . A major portion of the bile acids secreted is reabsorbed from the intestines and returned via the portal circulation to the liver, thus completing the enterohepatic cycle . Only very small amounts of bile acids are found in normal serum .\r\n\r\nColestipol hydrochloride binds bile acids in the intestine forming a complex that is excreted in the feces . This nonsystemic action results in a partial removal of the bile acids from the enterohepatic circulation, preventing their reabsorption . Since colestipol hydrochloride is an anion exchange resin, the chloride anions of the resin can be replaced by other anions, usually those with a greater affinity for the resin than the chloride ion .","Colestipol is a lipid-lowering polymer that binds with bile acids in the intestine forming a complex that is excreted in the feces . This non-systemic action results in a continuous, partial removal of bile acids from the enterohepatic circulation preventing their reabsorption . This increased fecal loss of bile acids due to colestipol hydrochloride administration leads to increased oxidation of cholesterol to bile acids . This results in an increase in the number of hepatic low-density lipoprotein (LDL) receptors, and consequently an increased uptake of LDL and a decrease in serum/plasma beta lipoprotein or total and LDL cholesterol levels . Although hydrochloride produces an increase in the hepatic synthesis of cholesterol in man, serum cholesterol levels fall .","Bile acids binder","Indication associated"]
[136,"DB00380","approved; withdrawn","small molecule","Dexrazoxane","(+)-(S)-4,4'-Propylenedi-2,6-piperazinedione; (+)-1,2-Bis(3,5-dioxo-1-piperazinyl)propane; 4-[(2S)-2-(3,5-dioxopiperazin-1-yl)propyl]piperazine-2,6-dione; Dexrazoxane; Dextrorazoxane","C11H16N4O4","C[C@@H](CN1CC(=O)NC(=O)C1)N1CC(=O)NC(=O)C1","An antimitotic agent with immunosuppressive properties. Dexrazoxane, the (+)-enantiomorph of razoxane, provides cardioprotection against anthracycline toxicity. It appears to inhibit formation of a toxic iron-anthracycline complex. \r\nThe Food and Drug Administration has designated dexrazoxane as an orphan drug for use in the prevention or reduction in the incidence and severity of anthracycline-induced cardiomyopathy.","24584-09-6","268.2691","For reducing the incidence and severity of cardiomyopathy associated with doxorubicin administration in women with metastatic breast cancer who have received a cumulative doxorubicin hydrochloride dose of 300 mg/m^2 and would benefit from continued doxorubicin therapy. Also approved for the treatment of extravasation from intravenous anthracyclines.","Dexrazoxane is a cardioprotective agent for use in conjunction with doxorubicin indicated for reducing the incidence and severity of cardiomyopathy associated with doxorubicin administration in women with metastatic breast cancer who have received a cumulative doxorubicin dose. Patients receiving anthracycline-derivative antineoplastic agents may experience three types of cardiotoxicity: acute transient type; chronic, subacute type (related to cumulative dose and has a more indolent onset later on); and a late-onset type that manifests years after therapy, mainly in patients that have been exposed to the drug as a child. Although the exact mechanism of anthracycline-induced cardiotoxicity is not known, it has shown to exert a variety of actions that may result in the development of cardiotoxicity. In animals, anthracyclines cause a selective inhibition of cardiac muscle gene expression for α-actin, troponin, myosin light-chain 2, and the M isoform of creatine kinase. This may lead to myofibrillar loss associated with anthracycline-induced cardiotoxicity. Anthracyclines may also cause myocyte damage via calcium overload, altered myocardial adrenergic function, release of vasoactive amines, and proinflammatory cytokines. Furthermore, it has been suggested that the main cause of anthracycline-induced cardiotoxicity is associated with free-radical damage to DNA. The drugs intercalate DNA, chelate metal ions to produce drug-metal complexes, and generate superoxide radicals via oxidation-reduction reactions. Anthracyclines also contain a quinone structure that can undergo reduction via NADPH-dependent reactions to produce a semiquinone free radical that initiates a cascade of superoxide and hydroxide radical generation. Chelation of metal ions, particularly iron, by anthracyclines results in an anthracycline-metal complex that catalyzes the generation of reactive oxygen free radicals. This complex is a powerful oxidant that can initiate lipid peroxidation in the absence of oxygen free radicals. The toxicity induced by antrhacyclines may be exacerbated in cardiac cells, as these cells do not possess sufficient amounts of certain enzymes (e.g., superoxide dismutase, catalase, glutathione peroxidase) involved in detoxifying free radicals and protecting the cells from subsequent damage.","The mechanism by which dexrazoxane exerts its cardioprotective activity is not fully understood. Dexrazoxane is a cyclic derivative of EDTA that readily penetrates cell membranes. Results of laboratory studies suggest that dexrazoxane (a prodrug) is converted intracellularly to a ring-opened bidentate chelating agent that chelates to free iron and interferes with iron-mediated free radical generation thought to be responsible, in part, for anthracycline-induced cardiomyopathy. It should be noted that dexrazoxane may also be protective through its inhibitory effect on topoisomerase II.","DNA topoisomerase 2-alpha inhibitor; DNA topoisomerase 2-beta","Therapeutic strategy associated"]
[137,"DB00381","approved","small molecule","Amlodipine","(RS)-3-ethyl 5-methyl 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate; 3-Ethyl 5-methylester, (±)-2-[(2-aminoethoxy)methyl]-4-(o-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylate; Amlodipine free base","C20H25ClN2O5","CCOC(=O)C1=C(COCCN)NC(C)=C(C1C1=CC=CC=C1Cl)C(=O)OC","Amlodipine, initially approved by the FDA in 1987, is a popular antihypertensive drug belonging to the group of drugs called _dihydropyridine calcium channel blockers_.  Due to their selectivity for the peripheral blood vessels, dihydropyridine calcium channel blockers are associated with a lower incidence of myocardial depression and cardiac conduction abnormalities than other calcium channel blockers .\r\n\r\nAmlodipine is commonly used in the treatment of high blood pressure and angina. Amlodipine has antioxidant properties and an ability to enhance the production of nitric oxide (NO), an important vasodilator that decreases blood pressure .  The option for single daily dosing of amlodipine is an attractive feature of this drug .","88150-42-9","408.876","Amlodipine may be used alone or in combination with other antihypertensive and antianginal agents for the treatment of the following conditions :\r\n\r\n• Hypertension \r\n\r\n• Coronary artery disease\r\n\r\n• Chronic stable angina\r\n\r\n• Vasospastic angina (Prinzmetal’s or Variant angina) \r\n\r\n• Angiographically documented coronary artery disease in patients without heart failure or an ejection fraction < 40%","**General pharmacodynamic effects**\r\n\r\nAmlodipine has a strong affinity for cell membranes, modulating calcium influx by inhibiting selected membrane calcium channels. This drug's unique binding properties allow for its long-acting action and less frequent dosing regimen , .  \r\n\r\n**Hemodynamic effects**\r\n\r\nAfter the administration of therapeutic doses of amlodipine to patients diagnosed with hypertension, amlodipine causes vasodilation, which results in a reduction of supine and standing blood pressure. During these blood pressure reductions, there are no clinically significant changes in heart rate or plasma catecholamine levels with long-term use. Acute intravenous administration of amlodipine reduces arterial blood pressure and increases heart rate in patients with chronic stable angina, however, chronic oral administration of amlodipine in clinical studies did not cause clinically significant alterations in heart rate or blood pressures in patients diagnosed with angina and normal blood pressure. With long-term, once daily oral administration, antihypertensive effectiveness is maintained for at least 24 hours . \r\n\r\n**Electrophysiologic effects**\r\n\r\nAmlodipine does not change sinoatrial (SA) nodal function or atrioventricular (AV) conduction in animals or humans. In patients who were diagnosed with chronic stable angina, the intravenous administration of 10 mg of amlodipine did not cause clinically significant alterations A-H and H-V conduction and sinus node recovery time after cardiac pacing. Patients administered amlodipine with concomitant beta-blockers produced similar results. In clinical trials in which amlodipine was given in combination with beta-blockers to patients diagnosed with hypertension or angina, no adverse effects on electrocardiographic parameters were noted. In clinical studies comprised of angina patients alone, amlodipine did not change electrocardiographic intervals or produce high degrees of AV block . \r\n\r\n**Effects on angina**\r\n\r\nAmlodipine relieves the symptoms of chest pain associated with angina. In patients diagnosed with angina, daily administration of a single amlodipine dose increases total exercise time, the time to angina onset, and the time to 1 mm ST-segment depression on ECG studies, decreases anginal attack frequency, and decreases the requirement for nitroglycerin tablets .","**Mechanism of action on blood pressure**\r\n\r\nAmlodipine is considered a peripheral arterial vasodilator that exerts its action directly on vascular smooth muscle to lead to a reduction in peripheral vascular resistance, causing a decrease in blood pressure. Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker) that inhibits the influx of calcium ions into both vascular smooth muscle and cardiac muscle. Experimental studies imply that amlodipine binds to both _dihydropyridine_ and _nondihydropyridine_ binding sites, located on cell membranes. The contraction of cardiac muscle and vascular smooth muscle are dependent on the movement of extracellular calcium ions into these cells by specific ion channels. Amlodipine blocks calcium ion influx across cell membranes with selectivity. A stronger effect of amlodipine is exerted on vascular smooth muscle cells than on cardiac muscle cells . Direct actions of amlodipine on vascular smooth muscle result in reduced blood pressure . \r\n\r\n**Mechanism of action in angina**\r\n\r\nThe exact mechanism by which amlodipine relieves the symptoms of angina have not been fully elucidated to this date, however, the mechanism of action is likely twofold:\r\n\r\nAmlodipine has a dilating effect on peripheral arterioles, reducing the total peripheral resistance (afterload) against which the cardiac muscle functions. Since the heart rate remains stable during amlodipine administration, the reduced work of the heart reduces both myocardial energy use and oxygen requirements .\r\n\r\nDilatation of the main coronary arteries and coronary arterioles, both in healthy and ischemic areas, is another possible mechanism of amlodipine reduction of blood pressure. The dilatation causes an increase in myocardial oxygen delivery in patients experiencing coronary artery spasm (Prinzmetal's or variant angina) and reduces coronary vasoconstriction caused by smoking .","Voltage-dependent L-type calcium channel subunit alpha-1C inhibitor; Voltage-dependent N-type calcium channel subunit alpha-1B inhibitor; Voltage-dependent L-type calcium channel subunit beta-1 inhibitor; Voltage-dependent calcium channel subunit alpha-2/delta-3 inhibitor; Carbonic anhydrase 1 inhibitor; Sphingomyelin phosphodiesterase inhibitor; Voltage-dependent T-type calcium channel subunit alpha-1I inhibitor; Voltage-dependent N-type calcium channel inhibitor","Therapeutic strategy associated"]
[138,"DB00384","approved","small molecule","Triamterene","6-phenylpteridine-2,4,7-triamine; Teridin; Triamterene","C12H11N7","NC1=NC(N)=C2N=C(C(N)=NC2=N1)C1=CC=CC=C1","Triamterene (2,4,7-triamino-6-phenylpteridine) is a potassium-sparing diuretic that is used in the management of hypertension. It works by promoting the excretion of sodium ions and water while decreasing the potassium excretion in the distal part of the nephron in the kidneys by working on the lumenal side. Since it acts on the distal nephron where only a small fraction of sodium ion reabsorption occurs, triamterene is reported to have limited diuretic efficacy. Due to its effects on increased serum potassium levels, triamterene is associated with a risk of producing hyperkalemia. Triamterene is a weak antagonist of folic acid, and a photosensitizing drug. \r\n\r\nTriamterene was approved by the Food and Drug Administration in the U.S. in 1964. Currently, triamterene is used in the treatment of edema associated with various conditions as monotherapy and is approved for use with other diuretics to enhance diuretic and potassium-sparing effects. It is also found in a combination product with hydrochlorothiazide that is used for the management of hypertension or treatment of edema in patients who develop hypokalemia on hydrochlorothiazide alone.","396-01-0","253.2626","Triamterene is indicated for the treatment of edema associated with congestive heart failure, cirrhosis of the liver, and the nephrotic syndrome; also in steroid-induced edema, idiopathic edema, and edema due to secondary hyperaldosteronism.\r\n\r\nTriamterene in combination with hydrochlorothiazide is indicated for the managment of hypertension or treatment of edema in patients who develop hypokalemia following hydrochlorothiazide monotherapy, and in patients who require thiazide diuretic and in whom the development of hypokalemia cannot be risked. Triamterene allows the maintenance of potassium balance when given in combination with loop diuretics and thiazides.","Triamterene, a relatively weak, potassium-sparing diuretic and antihypertensive, is used in the management of hypertension and edema. It primarily works on the distal nephron in the kidneys; it acts from the late distal tubule to the collecting duct to inhibit Na+ reabsorption and decreasing K+ excretion. As triamterene tends to conserve potassium more strongly than promoting Na+ excretion, it can cause an increase in serum potassium, which may result in hyperkalemia potentially associated with cardiac irregularities. In healthy volunteers administered with oral triamterene, there was an increase in the renal clearnace of sodium and magnesium, and a decrease in the clearance of uric acid and creatinine due to its effect of reducing glomerular filtration renal plasma flow. Triamterene does not affect calcium excretion. In clinical trials, the use of triamterene in combination with hydrochlorothiazide resulted an enhanced blood pressure-lowering effects of hydrochlorothiazide.","Triamterene inhibits the epithelial sodium channels (ENaC) located on the lumenal side in the late distal convoluted tubule and collecting tubule , which are transmembrane channels that normally promotes sodium uptake and potassium secretion. In the late distal tubule to the collecting duct, sodium ions are actively reabsorbed via ENaC on the lumnial membrane and are extruded out of the cell into the peritubular medium by a sodium-potassium exchange pump, the Na-K-ATPase, with water following passively. Triamterene exerts a diuretic effect on the distal renal tubule to inhibit the reabsorption of sodium ions in exchange for potassium and hydrogen ions and its natriuretic activity is limited by the amount of sodium reaching its site of action. Its action is antagonistic to that of adrenal mineralocorticoids, such as aldosterone, but it is not an inhibitor or antagonist of aldosterone. Triamterene maintains or increases the sodium excretionm, thereby increasing the excretion of water, and reduces the excess loss of potassium, hydrogen and chloride ions by inhibiting the distal tubular exchange mechanism. Due to its diuretic effect, triamterene rapidly and reversibly reduces the lumen-negative transepithelial potential difference by almost complete abolition of Na+ conductance without altering K+ conductance. This reduces the driving force for potassium movement into the tubular lumen and thus decreases potassium excretion.  Triamterene is similar in action to  but, unlike amiloride, increases the urinary excretion of magnesium.","Amiloride-sensitive sodium channel subunit gamma inhibitor; Amiloride-sensitive sodium channel subunit alpha inhibitor; Amiloride-sensitive sodium channel subunit beta inhibitor; Amiloride-sensitive sodium channel subunit delta inhibitor","Therapeutic strategy associated"]
[139,"DB00394","approved; investigational","small molecule","Beclomethasone dipropionate","(11β,16β)-9-chloro-11-hydroxy-16-methyl-17,21-bis(1-oxopropoxy)pregna-1,4-diene-3,20-dione; 9-chloro-11β-hydroxy-16β-methylpregna-1,4-diene-3,20-dione 17,21-dipropionate; 9-chloro-16β-methyl-11β,17,21-trihydroxypregna-1,4-diene-3,20-dione 17,21-dipropionate; beclometasone 17,21-dipropionate; Beclometasone dipropionate; Beclometasone dipropionate anhydrous; Beclomethasone dipropionate","C28H37ClO7","[H][C@@]12C[C@H](C)[C@](OC(=O)CC)(C(=O)COC(=O)CC)[C@@]1(C)C[C@H](O)[C@@]1(Cl)[C@@]2([H])CCC2=CC(=O)C=C[C@]12C","Beclomethasone dipropionate is a second-generation synthetic corticosteroid agent  and a diester of beclomethasone, which is structurally similar to . It is a prodrug of an active metabolite beclomethasone 17-monopropionate (17-BMP) which acts on the glucocorticoid receptor to mediates its therapeutic action. Beclomethasone dipropionate itself posesses weak glucocorticoid receptor binding affinity and is rapidly converted into 17-BMP upon administration. Formulations for oral inhalation, intranasal, and topical use are available for beclomethasone dipropionate. Beclomethasone dipropionate became first available in a pressurized metered-dose inhaler in 1972 and later in a dry powder inhaler and an aqueous nasal spray. Due to its anti-inflammatory, antipruritic, and anti-allergy properties, beclomethasone dipropionate is used in various inflammatory conditions, such as asthma, allergic rhinitis, and dermatoses to reduce symptoms. When inhaled, it is proposed that beclomethasone dipropionate remains active locally in the lung without causing significant side effects associated with systemic corticosteroids. Compared to earlier corticosteroids such as  and , beclomethasone dipropionate is reported to be less irritating to the nasal mucosa with a longer duration of action when administered intranasally.","5534-09-8","521.042","Indicated for oral inhalation use in the maintenance treatment of asthma as prophylactic therapy in patients 5 years of age and older. The aerosol form of beclomethasone diproprionate is not indicated for the relief of acute bronchospasm.\r\n\r\nIndicated for intranasal use to relieve the symptoms of seasonal or perennial allergic and nonallergic (vasomotor) rhinitis and prevent the recurrence of nasal polyps following surgical removal.\r\n\r\nIndicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients 13 years of age and older. Corticosteroid-responsive dermatoses include psoriasis, contact dermatitis (dermatitis venenata), atopic dermatitis (infantile eczema, allergic dermatitis), neurodermatitis (lichen simplex chronicus, lichen planus, eczema, eczematous dermatitis), intertrigo, dyshidroses (pompholyx), seborrheic dermatitis, exfoliative dermatitis, solar dermatitis, stasis dermatitis, and anogenital and senile pruritus.","Inflammatory conditions, including asthma, dermatoses, and allergic rhinitis, involve the activation of cascades by inflammatory mediators. Inflammation is a primary defense mechanism and the homeostatic response of the immune system; however, a prolonged inflammatory response in certain disorders may lead to tissue damage, pain, and swelling. Beclomethasone dipropionate works by attenuating the inflammatory responses associated with asthma, allergic rhinitis, nasal polyps, and corticosteroid-responsive dermatoses. It suppresses the actions of inflammatory cells, such as mast cells, eosinophils, basophils, lymphocytes, macrophages, and neutrophils. It also inhibits the release of inflammatory mediators, such as histamine, eicosanoids, leukotrienes, and cytokines. Beclomethasone dipropionate is reported to exhibit potent topical activity while possessing low systemic effects. \r\n\r\nBeclomethasone dipropionate is a corticosteroid drug with anti-inflammatory and vasoconstrictive effects used to treat chronic inflammatory processes such as asthma, allergic rhinitis, corticosteroid-responsive dermatoses. When inhaled, it improves lung function, decreases airway hyper-reactivity, and reduces the severity of asthmatic symptoms. Although inhaled corticosteroids, including beclomethasone dipropionate, are reported to mainly act locally in the lungs, systemic effects such as disruption of hypothalamic-pituitary-adrenal (HPA) axis function, bone turnover, osteoporosis, and growth suppression may still be observed with chronic use or high dose administration. There were varying findings from clinical studies examining the effect of beclomethasone dipropionate on growth suppression in pediatric patients. It was shown to suppress the hypothalamo-pituitary-adrenal (HPA) axis in a dose-dependent manner. HPA axis is a central hormonal response system to stress and activation of HPA axis leads to the production of endogenous steroid hormone production. Long-term use of high-dose systemic corticosteroids, including those inhaled, was often associated with signs and symptoms of adrenal insufficiency when exposed to stress conditions, such as trauma, surgery, or infections. As corticosteroids work by suppressing the immune system, there may be an increased risk for developing infections. Cases of _Candida albicans_ infection of the mouth and throat have been reported with inhaled beclomethasone dipropionate therapy.","Beclomethasone dipropionate is a corticosteroid and prodrug that is rapidly activated by hydrolysis to the active monoester, 17 monopropionate (17-BMP), which mediates anti-inflammatory actions. 17-BMP has been shown _in vitro_ to exhibit a binding affinity for the human glucocorticoid receptor which is approximately 13 times that of dexamethasone and 25 times that of beclomethasone dipropionate. Upon binding of the ligand, the glucocorticoid receptors dimerize and translocate into the nucleus, where they subsequently bind to glucocorticoid response elements (GRE) on glucocorticoid-responsive genes, leading to changes in transcription. There are several proposed mechanisms for the anti-inflammatory action of corticosteroids. Corticosteroids may work by increasing the transcription of genes coding for anti-inflammatory proteins, including lipocortin-1 and interleukin-10. Corticosteroids were also shown to inhibit the expression of multiple genes that encode pro-inflammatory factors, such as cytokines, chemokines, and adhesion molecules, that are activated during the chronic inflammatory process. This is thought to be due to the direct inhibitory interaction between activated glucocorticoid receptors and activated pro-inflammatory transcription factors, such as nuclear factor-kappa B and activator protein-1. Chronic inflammation is often characterized by enhanced expression of these transcription factors that bind to and activate coactivator molecules, which then acetylate core histones to switch on gene transcription to further amplify the inflammatory process. Corticosteroids suppress the multiple inflammatory gene expression by promoting histone deacetylation, resulting in tighter coiling of DNA and reduced access of transcription factors to their binding sites.","Glucocorticoid receptor agonist","Therapeutic strategy associated"]
[140,"DB00397","approved; vet_approved; withdrawn","small molecule","Phenylpropanolamine","(+-)-Norephedrine; (+-)-Phenylpropanolamine; Norephedrine; Phenylpropanolamine; PPA","C9H13NO","CC(N)C(O)C1=CC=CC=C1","Phenylpropanolamine is a sympathomimetic agent that acts as a nonselective adrenergic receptor agonist and norepinephrine reuptake inhibitor. It has been used as a decongestant and appetite suppressant. Currently, it is withdrawn from the market in Canada and the United States due to the risk for hemorrahgic strokes.","14838-15-4","151.209","For the treatment of nasal congestion, control of urinary incontinence, priapism and obesity.","Phenylpropanolamine (PPA), a sympathomimetic agent structurally similar to pseudoephedrine, is used to treat nasal congestion. Phenylpropanolamine is found in appetite suppressant formulations and with guaifenesinin in cough-cold formulations. In 2000, the FDA requested that all drug companies discontinue marketing products containing phenylpropanolamine, due to an increased risk of hemorrhagic stroke in women who used phenylpropanolamine.","Phenylpropanolamine acts directly on alpha- and, to a lesser degree, beta-adrenergic receptors in the mucosa of the respiratory tract. Stimulation of alpha-adrenergic receptors produces vasoconstriction, reduces tissue hyperemia, edema, and nasal congestion, and increases nasal airway patency. PPA indirectly stimulates beta-receptors, producing tachycardia and a positive inotropic effect.","Dopamine D1 receptor partial agonist; Beta-1 adrenergic receptor agonist; Beta-2 adrenergic receptor agonist; Alpha-2 adrenergic receptors","Indication associated"]
[141,"DB00399","approved","small molecule","Zoledronic acid","(1-hydroxy-2-(1H-imidazol-1-yl)ethylidene)bisphosphonic acid; (1-hydroxy-2-imidazol-1-ylethylidene)diphosphonic acid; Anhydrous Zoledronic Acid; Zol; Zoledronate; Zoledronic acid; Zoledronic Acid Anhydrous; Zoledronic Acid, Anhydrous","C5H10N2O7P2","OC(CN1C=CN=C1)(P(O)(O)=O)P(O)(O)=O","Zoledronic acid, or CGP 42'446, is a third generation, nitrogen containing bisphosphonate similar to , , and . Zoledronic acid is used to treat and prevent multiple forms of osteoporosis, hypercalcemia of malignancy, multiple myeloma, bone metastases from solid tumors, and Paget’s disease of bone. Zoledronic acid was first described in the literature in 1994.\r\n\r\nZoledronic acid was granted FDA approval on 20 August 2001.","118072-93-8","272.0896","Zoledronic acid is indicated to treat hypercalcemia of malignancy, multiple myeloma, bone metastases from solid tumors, osteoporosis in men and postmenopausal women, glucocorticoid induced osteoporosis, and Paget's disease of bone in men and women. Zoledronic acid is also indicated for the prevention of osteoporosis in post menopausal women and glucocorticoid induced osteoporosis.","Zoledronic acid is a third generation, nitrogen containing bisphosphonate that inhibits osteoclast function and prevents bone resorption. The therapeutic window is wide as patients are unlikely to suffer severe effects from overdoses and the duration of action is long. Patients should be counselled regarding the risk of electrolyte deficiencies, renal impairment, osteonecrosis of the jaw, atypical femoral fractures, bronchoconstriction, hepatic impairment, hypocalcemia, and embryo-fetal toxicity.","Bisphosphonates are taken into the bone where they bind to hydroxyapatite. Bone resorption by osteoclasts causes local acidification, releasing the bisphosphonate, which is taken into the osteoclast by fluid-phase endocytosis. Endocytic vesicles become acidified, releasing bisphosphonates into the cytosol of osteoclasts where they act.\r\n\r\nOsteoclasts mediate resorption of bone. When osteoclasts bind to bone they form podosomes, ring structures of F-actin. Etidronic acid also inhibits V-ATPases in the osteoclast, though the exact subunits are unknown, preventing F-actin from forming podosomes. Disruption of the podosomes causes osteoclasts to detach from bones, preventing bone resorption.\r\n\r\nNitrogen containing bisphosphonates such as zoledronate are known to induce apoptosis of hematopoietic tumor cells by inhibiting the components of the mevalonate pathway farnesyl diphosphate synthase, farnesyl diphosphate, and geranylgeranyl diphosphate. These components are essential for post-translational prenylation of GTP-binding proteins like Rap1. The lack of prenylation of these proteins interferes with their function, and in the case of Rap1, leads to apoptosis. zoledronate also activated caspases which further contribute to apoptosis.","Farnesyl pyrophosphate synthase inhibitor; Geranylgeranyl pyrophosphate synthase inhibitor; Hydroxylapatite antagonist&binder","Therapeutic strategy associated"]
[142,"DB00401","approved","small molecule","Nisoldipine","isobutyl methyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate; Nisoldipine","C20H24N2O6","COC(=O)C1=C(C)NC(C)=C(C1C1=CC=CC=C1[N+]([O-])=O)C(=O)OCC(C)C","Nisoldipine is a 1,4-dihydropyridine calcium channel blocker. It acts primarily on vascular smooth muscle cells by stabilizing voltage-gated L-type calcium channels in their inactive conformation. By inhibiting the influx of calcium in smooth muscle cells, nisoldipine prevents calcium-dependent smooth muscle contraction and subsequent vasoconstriction. Nisoldipine may be used in alone or in combination with other agents in the management of hypertension.","63675-72-9","388.4144","For the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents.","Nisoldipine, a dihydropyridine calcium-channel blocker, is used alone or with an angiotensin-converting enzyme inhibitor, to treat hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina. Nisoldipine is similar to other peripheral vasodilators. Nisoldipine inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.","By deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, Nisoldipine inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.","Voltage-dependent L-type calcium channel subunit alpha-1C inhibitor; Voltage-dependent calcium channel subunit alpha-2/delta-1 inhibitor; Voltage-dependent L-type calcium channel subunit beta-2 inhibitor; Voltage-dependent L-type calcium channel subunit alpha-1D inhibitor; Voltage-dependent L-type calcium channel subunit alpha-1S inhibitor","Indication associated"]
[143,"DB00404","approved; illicit; investigational","small molecule","Alprazolam","8-Chloro-1-methyl-6-phenyl-4H-s-triazolo(4,3-a)(1,4)benzodiazepine; Alprazolam","C17H13ClN4","CC1=NN=C2CN=C(C3=CC=CC=C3)C3=C(C=CC(Cl)=C3)N12","Alprazolam is a triazolobenzodiazepine indicated for the treatment of anxiety and panic disorders. It is mainly metabolized by CYP3As and so is contraindicated with CYP3A inhibitors like ketoconazole and itraconazole. Benzodiazepine treatment should be stopped gradually by tapering down a patient's dose to avoid withdrawal symptoms. Alprazolam's adverse effects are generally related to the sedation it can cause. Alprazolam has been mixed with alcohol as a drug of abuse to potentiate the sedative effects of the drug which may lead to coma and death. Alprazolam was given FDA approval on October 16, 1981.","28981-97-7","308.765","Alprazolam is indicated for the acute treatment of generalized anxiety disorder in adults. Alprazolam is also indicated, either as a standard or extended-release formulation, for the treatment of panic disorder with or without agoraphobia in adults.\r\n\r\nAlprazolam may also be prescribed off-label for insomnia, premenstrual syndrome, and depression.","Alprazolam is a benzodiazepine that binds γ-aminobutyric acid (GABA) type-A receptors (GABA<sub>A</sub>Rs) to enhance their inhibitory effect on neurotransmission, specifically in the brain. Concomitant use with opioids may result in profound sedation, respiratory depression, coma, and death; patients taking benzodiazepines and opioids concurrently may require lower doses of one or both medications, depending on their clinical situation. Patients with pre-existing impaired respiratory function are at increased risk of adverse effects including death during treatment with benzodiazepines. In addition, due to its CNS depressant effects, patients taking alprazolam should avoid operating heavy machinery or driving and should avoid other CNS depressants such as alcohol. As with other benzodiazepines, alprazolam carries a risk of abuse, misuse, and addiction, which is higher in predisposed individuals and may require strict monitoring. Cessation of therapy may result in acute or protracted withdrawal symptoms, which may be life-threatening; the patient dose should be gradually tapered whenever discontinuation or reduced dosage are necessary. Newborns born to mothers using alprazolam later in pregnancy may suffer from sedation and withdrawal symptoms. As CYP3A is required for the initial step in alprazolam metabolism, alprazolam is contraindicated in patients taking strong CYP3A inhibitors, such as ketoconazole and itraconazole; milder CYP3A inhibitors still necessitate alprazolam dosage adjustments. Lastly, benzodiazepines may have negative effects, such as panic disorders, increased suicide incidence, and episodes of mania/hypomania, in patients suffering from depression.","Neurotransmission relies on excitatory and inhibitory signalling. γ-aminobutyric acid (GABA) type-A receptors (GABA<sub>A</sub>Rs) are members of the pentameric ligand-gated ion channel (PLGIC) superfamily located synaptically and perisynaptically to mediate phasic inhibition and extrasynaptically to mediate tonic inhibition. GABA<sub>A</sub>Rs comprise a variety of subunits from a homologous family whose members are named based on sequence identity as one of α1-6, β1-3, γ1-3, δ, ε, θ, π, and ρ1-3. Each subunit possesses an extracellular (ECD), transmembrane (TMD), and intracellular (ICD) domain; inter-subunit interfaces are the primary points of neurotransmitter and modulator binding, described by coordination of the principal (+) and complementary (-) sites in each subunit. Binding of GABA to GABA<sub>A</sub>Rs induces pore opening, rapid flow of chloride ions, and synaptic hyperpolarization, which in turn manifests as an inhibitory signal.\r\n\r\nThe most prevalent GABA<sub>A</sub>Rs _in vivo_ are the α1β2γ2 receptors, which contain both GABA (β+/α-) and benzodiazepine (BZD, α+/γ-) binding sites in the intersubunit interfaces of the relevant subunits. In general, any receptors containing an α<sub>x</sub>/γ<sub>z</sub> interface, where x = 1-3,5 and z = 1-3, have potential high-affinity BZD binding sites, although small sequence differences between subunits may alter binding affinity to individual molecules. The α4 and α6 subunits, in which an otherwise conserved histidine is replaced by arginine, do not bind traditional BZD ligands such as diazepam and hence are considered \"diazepam-insensitive\". GABA binding results in a series of conformational changes in the ECDs of GABA<sub>A</sub>R β subunits, \"locking\" each to its neighbouring α- interface. The binding of alprazolam in the high-affinity BZD site stabilizes the α+/γ- interface and facilitates the conformational changes that lead to pore opening, hence functioning as a positive allosteric modulator.\r\n\r\nThe exact manner in which GABA<sub>A</sub>R allosteric modulation mediates the therapeutic and unwanted effects of benzodiazepines remains unclear. Earlier studies suggested that the primary factor was the α subunit composition, with α1-containing receptors mediating the sedative effects, α2/3-containing receptors the anxiolytic effects, and α5-containing receptors the memory effects of benzodiazepines. More recent studies suggest a more complex set of factors including subunit composition, physiological location, neuronal circuit, and nerve cell type. To further complicate matters, there may be up to five distinct BZD binding sites on GABA<sub>A</sub>Rs, with site 1 corresponding to the classical high-affinity α+/γ- interface. The effects of binding at sites 2-4 are not fully understood and likely impart greater complexity to benzodiazepine pharmacological action.","GABA(A) Receptor positive allosteric modulator; GABA(A) Receptor Benzodiazepine Binding Site ligand","Indication associated"]
[144,"DB00414","approved; investigational; withdrawn","small molecule","Acetohexamide","1-((p-Acetylphenyl)sulfonyl)-3-cyclohexylurea; 1-[(4-acetylbenzene)sulfonyl]-3-cyclohexylurea 4-acetyl-N-(cyclohexylcarbamoyl)benzenesulfonamide; Acetohexamide; N-(p-Acetylphenylsulfonyl)-N'-cyclohexylurea","C15H20N2O4S","CC(=O)C1=CC=C(C=C1)S(=O)(=O)NC(=O)NC1CCCCC1","A sulfonylurea hypoglycemic agent that is metabolized in the liver to 1-hydrohexamide. Acetohexamide has been discontinued in the US market.","968-81-0","324.395","Used in the management of diabetes mellitus type 2 (adult-onset).","Acetohexamide is an intermediate-acting, first-generation oral sulfonylurea. It lowers blood sugar by stimulating the pancreatic beta cells to secrete insulin and by helping the body use insulin efficiently. Due to its primary action on the pancreatic beta cells, the drug is only effective when there are functional pancreatic beta cells that can produce insulin granules. Acetohexamide has one-third the potency of chlorpropamide, and twice the potency of tolbutamide; however, similar hypoglycemic efficacy occurs with equipotent dosage of sulfonylureas.","Sulfonylureas such as acetohexamide bind to an ATP-dependent K<sup>+</sup> channel on the cell membrane of pancreatic beta cells. This inhibits a tonic, hyperpolarizing outflux of potassium, which causes the electric potential over the membrane to become more positive. This depolarization opens voltage-gated Ca<sup>2+</sup> channels. The rise in intracellular calcium leads to increased fusion of insulin granulae with the cell membrane, and therefore increased secretion of (pro)insulin.","ATP-sensitive inward rectifier potassium channel 1 inhibitor","Indication associated"]
[145,"DB00436","approved","small molecule","Bendroflumethiazide","±-3-benzyl-3,4-dihydro-6-(trifluoromethyl)-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide; 6-trifluoromethyl-3-benzyl-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine 1,1-dioxide; Bendrofluazide; Bendroflumethiazide; Benzhydroflumethiazide","C15H14F3N3O4S2","NS(=O)(=O)C1=CC2=C(NC(CC3=CC=CC=C3)NS2(=O)=O)C=C1C(F)(F)F","A thiazide diuretic with actions and uses similar to those of hydrochlorothiazide. It has been used in the treatment of familial hyperkalemia, hypertension, edema, and urinary tract disorders. (From Martindale, The Extra Pharmacopoeia, 30th ed, p810)","73-48-3","421.415","For the treatment of high blood pressure and management of edema related to heart failure.","Bendroflumethiazide, a thiazide diuretic, removes excess water from the body by increasing how often you urinate (pass water) and also widens the blood vessels which helps to reduce blood pressure. It inhibits Na<sup>+</sup>/Cl<sup>-</sup> reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue.","As a diuretic, bendroflumethiazide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like bendroflumethiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of bendroflumethiazide is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle.","Solute carrier family 12 member 3 inhibitor; Calcium-activated potassium channel subunit alpha-1 inducer; Carbonic anhydrase 1 inhibitor; Carbonic anhydrase 2 inhibitor; Carbonic anhydrase 4 inhibitor","Therapeutic strategy associated"]
[146,"DB00438","approved","small molecule","Ceftazidime","CAZ; Ceftazidime anhydrous","C22H22N6O7S2","[O-]C(=O)C1=C(CS[C@]2([H])[C@H](NC(=O)C(=N/OC(C)(C)C(O)=O)\\C3=CSC(N)=N3)C(=O)N12)C[N+]1=CC=CC=C1","Bacteria possess a cell wall comprising a glycopeptide polymer commonly known as peptidoglycan, which is synthesized and remodelled through the action of a family of enzymes known as \"penicillin-binding proteins\" (PBPs). β-lactam antibiotics, including cephalosporins, are PBP inhibitors that, through inhibition of essential PBPs, result in impaired cell wall homeostasis, loss of cell integrity, and ultimately bacterial cell death. Ceftazidime is a third-generation cephalosporin with broad-spectrum antibacterial activity, including against some treatment-resistant bacteria such as _Pseudomonas aeruginosa_.\r\n\r\nCeftazidime was approved by the FDA on July 19, 1985, and is currently available either alone or in combination with the non-β-lactam β-lactamase inhibitor  to treat a variety of bacterial infections.","72558-82-8","546.576","Ceftazidime is indicated for the treatment of lower respiratory tract infections, skin and skin structure infections, urinary tract infections, bacterial septicemia, bone and joint infections, gynecologic infections, intra-abdominal infections (including peritonitis), and central nervous system infections (including meningitis) caused by susceptible bacteria.\r\n\r\nCeftazidime is indicated in combination with  to treat infections caused by susceptible Gram-negative organisms, including complicated intra-abdominal infections (cIAI), in conjunction with , and complicated urinary tract infections (cUTI), including pyelonephritis, in patients aged three months and older. This combination is also indicated to treat hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) in patients aged 18 years and older.\r\n\r\nIn all cases, to mitigate the risk of bacterial resistance and preserve clinical efficacy, ceftazidime should only be used for infections that are confirmed or strongly suspected to be caused by susceptible bacterial strains.","Ceftazidime is a semisynthetic, broad-spectrum, third-generation cephalosporin antibiotic that is bactericidal through inhibition of enzymes responsible for cell-wall synthesis, primarily penicillin-binding protein 3 (PBP3). Among cephalosporins, ceftazidime is notable for its resistance to numerous β-lactamases and its broad spectrum of activity against Gram-negative bacteria, including _Pseudomonas aeruginosa_. However, it is less active than first- and second-generation cephalosporins against _Staphylococcus aureus_ and other Gram-positive bacteria and also has low activity against anaerobes. Ceftazidime has confirmed activity against clinically relevant Gram-negative bacteria including _Citrobacter_ spp., _Enterobacter_ spp., _Klebsiella_ spp., _Proteus_ spp., _Serratia spp., _Escherichia coli_, _Haemophilus influenzae_, _Neisseria meningitidis_, _Pseudomonas aeruginosa_, and some Gram-positive bacteria including _Staphylococcus_ spp. and _Streptococcus_ spp. There are also _in vitro_ data for ceftazidime efficacy against a wide variety of other bacteria, such as _Acinetobacter baumannii_ and _Neisseria gonorrhoeae_, but no clear clinical studies to support the use of ceftazidime for infections caused by these bacteria.\r\n\r\nAlthough β-lactam antibiotics like ceftazidime are generally well tolerated, there remains a risk of serious acute hypersensitivity reactions, which is higher in patients with a known allergy to ceftazidime or any other β-lactam antibiotic. As with all antibiotics, ceftazidime may result in the overgrowth of non-susceptible organisms and potentially serious effects including _Clostridium difficile_-associated diarrhea (CDAD); CDAD should be considered in patients who develop diarrhea and, in confirmed cases, supportive care initiated immediately. Ceftazidime is primarily renally excreted such that high and prolonged serum concentrations can occur in patients with renal insufficiency, leading to seizures, nonconvulsive status epilepticus (NCSE), encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia. Treatment may lead to the development or induction of resistance with a risk of treatment failure. Periodic susceptibility testing should be considered, and monotherapy failure may necessitate the addition of another antibiotic such as an aminoglycoside. Cephalosporin use may decrease prothrombin activity, which may be improved by exogenous vitamin K. Inadvertent intra-arterial administration of ceftazidime may result in distal necrosis.","The bacterial cell wall, which is located at the periphery of Gram-positive bacteria and within the periplasm of Gram-negative bacteria, comprises a glycopeptide polymer synthesized through cross-linking of glycans to peptide stems on alternating saccharides, which is known commonly as peptidoglycan. Cell wall formation, recycling, and remodelling require numerous enzymes, including a family of enzymes with similar active site character despite distinct and sometimes overlapping roles as carboxypeptidases, endopeptidases, transpeptidases, and transglycosylases, known as \"penicillin-binding proteins\" (PBPs). The number of PBPs differs between bacteria, in which some are considered essential and others redundant. In general, inhibition of one or more essential PBPs results in impaired cell wall homeostasis, loss of cell integrity, and is ultimately bactericidal.\r\n\r\nCeftazidime is a semisynthetic third-generation cephalosporin with broad activity against numerous Gram-negative and some Gram-positive bacteria. Like other β-lactam antibiotics, ceftazidime exhibits its bactericidal effect primarily through direct inhibition of specific PBPs in susceptible bacteria. _In vitro_ experiments in Gram-negative bacteria such as _Escherichia coli_, _Pseudomonas aeruginosa_, _Acinetobacter baumannii_, and _Klebsiella pneumoniae_ suggest that ceftazidime primarily binds to PBP3, with weaker binding to PBP1a/1b and PBP2 as well; although binding to other PBPs, such as PBP4, is detectable, the concentrations required are much greater than those achieved clinically. Similarly, ceftazidime showed binding to _Staphylococcus aureus_ PBP 1, 2, and 3 with a much lower affinity for PBP4. Recent data for _Mycobacterium abcessus_ suggest that ceftazidime can inhibit PonA1, PonA2, and PbpA at intermediate concentrations.","Peptidoglycan synthase FtsI inhibitor; Penicillin-binding protein 1A inhibitor; Penicillin-binding protein 1B inhibitor; Penicillin-binding protein 2 inhibitor","Indication associated"]
[147,"DB00439","approved; withdrawn","small molecule","Cerivastatin","Cerivastatin","C26H34FNO5","COCC1=C(C2=CC=C(F)C=C2)C(\\C=C\\[C@@H](O)C[C@@H](O)CC(O)=O)=C(C(C)C)N=C1C(C)C","On August 8, 2001 the U.S. Food and Drug Administration (FDA) announced that Bayer Pharmaceutical Division voluntarily withdrew Baycol from the U.S. market, due to reports of fatal Rhabdomyolysis, a severe adverse reaction from this cholesterol-lowering (lipid-lowering) product. It has also been withdrawn from the Canadian market.","145599-86-6","459.5503","Used as an adjunct to diet for the reduction of elevated total and LDL cholesterol levels in patients with primary hypercholesterolemia and mixed dyslipidemia (Fredrickson Types IIa and IIb) when the response to dietary restriction of saturated fat and cholesterol and other non-pharmacological measures alone has been inadequate.","Cerivastatin, a competitive HMG-CoA reductase inhibitor effective in lowering LDL cholesterol and triglycerides, is used to treat primary hypercholesterolemia and mixed dyslipidemia (Fredrickson types IIa and IIb).","Cerivastatin competitively inhibits hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, the hepatic enzyme responsible for converting HMG-CoA to mevalonate. As mevalonate is a precursor of sterols such as cholesterol, this results in a decrease in cholesterol in hepatic cells, upregulation of LDL-receptors, and an increase in hepatic uptake of LDL-cholesterol from the circulation.","3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor","Target associated"]
[148,"DB00440","approved; vet_approved","small molecule","Trimethoprim","2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine; 5-[(3,4,5-trimethoxyphenyl)methyl]-2,4-pyrimidinediamine","C14H18N4O3","COC1=CC(CC2=CN=C(N)N=C2N)=CC(OC)=C1OC","Trimethoprim is an antifolate antibacterial agent that inhibits bacterial dihydrofolate reductase (DHFR), a critical enzyme that catalyzes the formation of tetrahydrofolic acid (THF) - in doing so, it prevents the synthesis of bacterial DNA and ultimately continued bacterial survival. Trimethoprim is often used in combination with  due to their complementary and synergistic mechanisms but may be used as a monotherapy in the treatment and/or prophylaxis of urinary tract infections. It is structurally and chemically related to , another antifolate antimicrobial used in the treatment of plasmodial infections.","738-70-5","290.3177","As a monotherapy, trimethoprim is indicated for the treatment of acute episodes of uncomplicated urinary tract infections caused by susceptible bacteria, including _E. coli._, _K. pneumoniae_, _Enterobacter spp._, _P. mirabilis_, and coagulase-negative _Staphylococcus_ species. In various formulations in combination with , trimethoprim is indicated for the following infections caused by bacteria with documented susceptibility: urinary tract infections, acute otitis media in pediatric patients (when clinically indicated), acute exacerbations of chronic bronchitis in adults, enteritis caused by susceptible _Shigella_, prophylaxis and treatment of _Pneumocystis jiroveci_ pneumonia, and travelers' diarrhea caused by enterotoxigenic _E. coli_.\r\n\r\nTrimethoprim is available as an ophthalmic solution in combination with  for the treatment of acute bacterial conjunctivitis, blepharitis, and blepharoconjunctivitis caused by susceptible bacteria.","Trimethoprim exerts its antimicrobial effects by inhibiting an essential step in the synthesis of bacterial nucleic acids and proteins. It has shown activity against several species of gram-negative bacteria, as well as coagulase-negative _Staphylococcus_ species.  Resistance to trimethoprim may arise via a variety of mechanisms, including alterations to the bacterial cell wall, overproduction of dihydrofolate reductase, or production of resistant dihydrofolate reductase. Rarely, trimethoprim can precipitate the development of blood disorders (e.g. thrombocytopenia, leukopenia, etc.) which may be preceded by symptoms such as sore throat, fever, pallor, and or purpura - patients should be monitored closely for the development of these symptoms throught the course of therapy.\r\n\r\nAs antimicrobial susceptibility patterns are geographically distinct, local antibiograms should be consulted to ensure adequate coverage of relevant pathogens prior to use.","Trimethoprim is a reversible inhibitor of dihydrofolate reductase, one of the principal enzymes catalyzing the formation of tetrahydrofolic acid (THF) from dihydrofolic acid (DHF). Tetrahydrofolic acid is necessary for the biosynthesis of bacterial nucleic acids and proteins and ultimately for continued bacterial survival - inhibiting its synthesis, then, results in bactericidal activity. Trimethoprim binds with a much stronger affinity to bacterial dihydrofolate reductase as compared to its mammalian counterpart, allowing trimethoprim to selectively interfere with bacterial biosynthetic processes. \r\n\r\nTrimethoprim is often given in combination with sulfamethoxazole, which inhibits the preceding step in bacterial protein synthesis - given together, sulfamethoxazole and trimethoprim inhibit two consecutive steps in the biosynthesis of bacterial nucleic acids and proteins.  As a monotherapy trimethoprim is considered bacteriostatic, but in combination with sulfamethoxazole is thought to exert bactericidal activity.","Dihydrofolate reductase inhibitor","Indication associated"]
[149,"DB00441","approved","small molecule","Gemcitabine","2'-Deoxy-2',2'-difluorocytidine; 2',2'-Difluorodeoxycytidine; 4-amino-1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)pyrimidin-2(1H)-one","C9H11F2N3O4","NC1=NC(=O)N(C=C1)[C@@H]1O[C@H](CO)[C@@H](O)C1(F)F","Gemcitabine is a nucleoside analog and a chemotherapeutic agent. It was originally investigated for its antiviral effects, but it is now used as an anticancer therapy for various cancers. Gemcitabine is a cytidine analog with two fluorine atoms replacing the hydroxyl on the ribose. As a prodrug, gemcitabine is transformed into its active metabolites that work by replacing the building blocks of nucleic acids during DNA elongation, arresting tumour growth and promoting apoptosis of malignant cells. The structure, metabolism, and mechanism of action of gemcitabine are similar to , but gemcitabine has a wider spectrum of antitumour activity.\r\n\r\nGemcitabine is marketed as Gemzar and it is available as intravenous injection. It is approved by the FDA to treat advanced ovarian cancer in combination with , metastatic breast cancer in combination with , non-small cell lung cancer in combination with , and pancreatic cancer as monotherapy. It is also being investigated in other cancer and tumour types.","95058-81-4","263.1981","Gemcitabine is a chemotherapeutic agent used as monotherapy or in combination with other anticancer agents. \r\n\r\nIn combination with , it is indicated for the treatment of advanced ovarian cancer that has relapsed at least 6 months after completion of platinum-based therapy.\r\n\r\nGemcitabine in combination with  is indicated for the first-line treatment of patients with metastatic breast cancer after failure of prior anthracycline-containing adjuvant chemotherapy, unless anthracyclines were clinically contraindicated.\r\n\r\nIn combination with , gemcitabine is indicated for the first-line treatment of patients with inoperable, locally advanced (Stage IIIA or IIIB) or metastatic (Stage IV) non-small cell lung cancer (NSCLC). Dual therapy with cisplatin is also used to treat patients with Stage IV (locally advanced or metastatic) transitional cell carcinoma (TCC) of the bladder.\r\n\r\nGemcitabine is indicated as first-line treatment for patients with locally advanced (nonresectable Stage II or Stage III) or metastatic (Stage IV) adenocarcinoma of the pancreas. Gemcitabine is indicated for patients previously treated with .","Gemcitabine is a nucleoside analog that mediates its antitumour effects by promoting apoptosis of malignant cells undergoing DNA synthesis. More specifically, it blocks the progression of cells through the G1/S-phase boundary. Gemcitabine demonstrated cytotoxic effects against a broad range of cancer cell lines _in vitro_. It displayed schedule-dependent antitumour activity in various animal models and xenografts from human non-small cell lung cancer (NSCLC) and pancreatic cancer. Therefore, the antineoplastic effects of gemcitabine are enhanced through prolonged infusion time rather than higher dosage. Gemcitabine inhibited the growth of human xenografts from carcinoma of the lung, pancreas, ovaries, head and neck, and breast. In mice, gemcitabine inhibited the growth of human tumour xenografts from the breast, colon, lung or pancreas by 69 to 99%. In clinical trials of advanced NSCLC, gemcitabine monotherapy produced objective response rates ranging from 18 to 26%, with a median duration of response ranging from 3.3 to 12.7 months. Overall median survival time was 6.2 to 12.3 months. The combined use of cisplatin and gemcitabine produced better objective response rates compared to monotherapy. In patients with advanced pancreatic cancer, objective response rates in patients ranged from 5.to 12%, with a median survival duration of 3.9 to 6.3 months. In Phase II trials involving patients with metastatic breast cancer, treatment with gemcitabine alone or with adjuvant chemotherapies resulted in response rate ranging from 13 to 42% and median survival duration ranging from 11.5 to 17.8 months. In metastatic bladder cancer, gemcitabine has a response rate 20 to 28%. In Phase II trials of advanced ovarian cancer, patients treated with gemcitabine had response rate of 57.1%, with progression free survival of 13.4 months and median survival of 24 months.\r\n\r\nGemcitabine causes dose-limiting myelosuppression, such as anemia, leukopenia, neutropenia, and thrombocytopenia; however, events leading to discontinuation tend to occur less than 1% of the patients. Gemcitabine can elevate ALT, AST and alkaline phosphatase levels.","Gemcitabine is a potent and specific deoxycytidine analog. After uptake into malignant cells, gemcitabine is phosphorylated by deoxycytidine kinase to form gemcitabine monophosphate, which is then converted to the active compounds, gemcitabine diphosphate (dFdCDP) and gemcitabine triphosphate (dFdCTP). These active metabolites are nucleosides that mediate antitumour effects. dFdCTP competes with deoxycytidine triphosphate (dCTP) for incorporation into DNA, thereby competitively inhibiting DNA chain elongation. The non-terminal position of dFdCTP in the DNA chain prevents detection of dFdCTP in the chain and repair by proof-reading 3′5′-exonuclease: this process is referred to as \"masked DNA chain termination.\" Incorporation of dFdCTP into the DNA chain ultimately leads to chain termination, DNA fragmentation, and apoptotic cell death of malignant cells.\r\n\r\nGemcitabine has self-potentiating pharmacological actions that can increase the probability of successful incorporation of gemcitabine triphosphate into the DNA chain: dFdCDP inhibits ribonucleotide reductase, an enzyme responsible for catalyzing the reactions that generate dCTP for DNA synthesis. Since dFdCDP reduces the levels of dCTP, there is less competition for gemcitabine triphosphate for incorporation into DNA. Gemcitabine can also reduce metabolism and elimination of active metabolites from the target ce1l, prolonging high intracellular concentrations of the active metabolites. Such self-potentiating effects are not present with .","DNA cross-linking/alkylation; Ribonucleoside-diphosphate reductase large subunit inhibitor; Thymidylate synthase inhibitor; UMP-CMP kinase inhibitor","Therapeutic strategy associated"]
[150,"DB00443","approved; vet_approved","small molecule","Betamethasone","16β-Methyl-1,4-pregnadiene-9α-fluoro-11β,17α,21-triol-3,20-dione; 9-Fluoro-16β-methylprednisolone; 9α-Fluoro-16β-methylprednisolone; beta-Methasone alcohol; Betadexamethasone; Betamethasone","C22H29FO5","[H][C@@]12C[C@H](C)[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])CCC2=CC(=O)C=C[C@]12C","Betamethasone is a long-acting corticosteroid with immunosuppressive and antiinflammatory properties. It can be used topically to manage inflammatory skin conditions such as eczema, and parenterally to manage several disease states including autoimmune disorders. Betamethasone has potent glucocorticoid activity and negligible mineralocorticoid activity.","378-44-9","392.4611","As a member of the corticosteroid family, betamethasone is indicated for the treatment of several inflammatory conditions. As topical monotherapy, betamethasone is indicated to relieve pruritic and inflammatory symptoms of corticosteroid-responsive-dermatoses. Betamethasone can be used topically in combination with a vitamin D analog such as calcipotriene to treat plaque psoriasis. The corticosteroid is also available as an injectable suspension and can be used to manage a range of inflammatory conditions including endocrine disorders, gastrointestinal disorders, and rheumatic disorders among other conditions.\r","Corticosteroids bind to the glucocorticoid receptor inhibiting pro-inflammatory signals, while promoting anti-inflammatory signals. Corticosteroids have a wide therapeutic window as patients may require doses that are multiples of what the body naturally produces. Patients who require long-term treatment with a corticosteroid should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.","Glucocorticoids inhibit neutrophil apoptosis and demargination, and inhibit NF-Kappa B and other inflammatory transcription factors. They also inhibit phospholipase A2, leading to decreased formation of arachidonic acid derivatives. In addition, glucocorticoids promote anti-inflammatory genes like interleukin-10.\r\n\r\nCorticosteroids like betamethasone can act through nongenomic and genomic pathways. The genomic pathway is slower and occurs when glucocorticoids activate glucocorticoid receptors and initiate downstream effects that promote transcription of anti-inflammatory genes including phosphoenolpyruvate carboxykinase (PEPCK), IL-1-receptor antagonist, and tyrosine amino transferase (TAT). On the other hand, the nongenomic pathway is able to elicit a quicker response by modulating T-cell, platelet and monocyte activity through the use of existing membrane-bound receptors and second messengers.","Glucocorticoid receptor agonist","Therapeutic strategy associated"]
[151,"DB00447","approved; investigational; withdrawn","small molecule","Loracarbef","Anhydrous loracarbef; Loracarbef anhydrous; Loracarbef, anhydrous","C16H16ClN3O4","N[C@@H](C(=O)N[C@H]1[C@H]2CCC(Cl)=C(N2C1=O)C(O)=O)C1=CC=CC=C1","Loracarbef is a carbacephem antibiotic sometimes grouped together with the second-generation cephalosporin antibiotics. It is marketed under the trade name Lorabid.","76470-66-1","349.769","Used to treat upper respiratory tract bacterial infections, chronic bronchitis, pneumonia, sinusitis, pharyntitis and tonsillitis, skin absceses, urinary tract infections and pyelonephritis caused by <i>E. coli</i>, <i>S. pyogenes</i>, <i>S. aureus</i>, <i>S. saprphyticus</i>, <i>S. penumoniae</i>, <i>H. influenzae</i> and <i>M. catarrhalis</i>.","Loracarbef is considered a second generation cephalosporin antibiotic. The advantages of cephalosporin antibiotics include a broad range of activity, a safe record in children with almost no dose-related toxicity, and the lack of need to monitor levels. Adverse reactions are rare and consist primarily of hypersensitivity reactions with urticaria, nonspecific rash, and pruritus. Loracarbef can be used to treat a large number of bacterial infections caused by gram-negative and gram-positive bacteria, including upper respiratory tract bacterial infections, chronic bronchitis, pneumonia, sinusitis, pharyntitis and tonsillitis, skin absceses, urinary tract infections and pyelonephritis caused by <i>E. coli</i>, <i>S. pyogenes</i>, <i>S. aureus</i>, <i>S. saprphyticus</i>, <i>S. penumoniae</i>, <i>H. influenzae</i> and <i>M. catarrhalis</i>.","Loracarbef is an oral, synthetic beta-lactam antibiotic of the carbacephem class. Chemically, carbacephems differ from cephalosporin-class antibiotics in the dihydrothiazine ring where a methylene group has been substituted for a sulfur atom. Loracarbef has a spectrum of activity similar to that of the second generation cephalosporins. It is structurally identical to cefaclor except for a sulfur atom that has been replaced by a methylene group. This change gives greater chemical stability in solution and allows storage at room temperature. Loracarbef, like all b-lactams and cephalosporins, inhibits penicillin binding proteins, enzymes that create the cross-linkage of the peptidoglycan polymer. This binding leads to interference with the formation and remodeling of the cell wall structure.","Penicillin-binding protein 3 inhibitor; Penicillin-binding protein 1A inhibitor","Indication associated"]
[152,"DB00457","approved","small molecule","Prazosin","1-(4-Amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-furanylcarbonyl)piperazine; 2-(4-(2-Furoyl)piperazin-1-yl)-4-amino-6,7-dimethoxyquinazoline; Prazosin","C19H21N5O4","COC1=C(OC)C=C2C(N)=NC(=NC2=C1)N1CCN(CC1)C(=O)C1=CC=CO1","Prazosin, also known as _Minipress_, is a drug used to treat hypertension.  Prazosin is marketed by _Pfizer_ and was initially approved by the FDA in 1988 .  It belongs to the class of drugs known as alpha-1 antagonists , .  \r\n\r\nRecently, many studies have evaluated the benefits of this drug in controlling the symptoms of post-traumatic stress disorder (PTSD) and associated nightmares .","19216-56-9","383.4011","This drug is indicated for the treatment of hypertension (high blood pressure). Prazosin can be given alone or given with other blood pressure-lowering drugs, including diuretics or beta-adrenergic blocking agents .\r\n\r\nPrazosin does not negatively impact lung function, and therefore may be used to manage hypertension in patients who are asthmatic or patients with chronic obstructive lung disease (COPD).","**Effects on blood pressure**\r\n\r\nThe pharmacodynamic and therapeutic effect of this drug includes is a decrease in blood pressure as well as clinically significant decreases in cardiac output, heart rate, blood flow to the kidney, and glomerular filtration rate. The decrease in blood pressure may occur in both standing and supine positions . \r\n\r\nMany of the above effects are due to vasodilation of blood vessels caused by prazosin, resulting in decreased peripheral resistance , .  Peripheral resistance refers to the level resistance of the blood vessels to blood that flows through them. As the blood vessels constrict (narrow), the resistance increases and as they dilate (widen), and peripheral resistance decreases, lowering blood pressure .  \r\n\r\n**Effects on sleep disturbance related to post-traumatic stress disorder (PTSD)**\r\n\r\nSome studies have suggested that this drug improves sleep in patients suffering from insomnia related to nightmares and post-traumatic stress disorder, caused by hyperarousal . This effect likely occurs through the inhibition of adrenergic stimulation found in states of hyperarousal .","Alpha-adrenergic receptors are essential for the regulation of blood pressure in humans. Two types of alpha receptors, alpha 1 and alpha 2, both play a role in regulating blood pressure.  Alpha-1 receptors are postsynaptic (located after the nerve junction, or space between a nerve fiber and target tissue). In this case, the target tissue is the vascular smooth muscle .  These receptors, when activated, increase blood pressure . \r\n\r\nPrazosin inhibits the postsynaptic alpha-1 adrenoceptors. This inhibition blocks the vasoconstricting (narrowing) effect of catecholamines (epinephrine and norepinephrine) on the vessels, leading to peripheral blood vessel dilation.  Through blood vessel constriction by adrenergic receptor activation, epinephrine and norepinephrine normally act to increase blood pressure .\r","Alpha-1A adrenergic receptor antagonist; Alpha-1B adrenergic receptor antagonist; Alpha-1D adrenergic receptor antagonist; Potassium voltage-gated channel subfamily H member 2 inhibitor; Alpha-2A adrenergic receptor binder; Alpha-2B adrenergic receptor binder; Alpha-1 adrenergic receptors","Indication associated"]
[153,"DB00458","approved","small molecule","Imipramine","10,11-dihydro-N,N-dimethyl-5H-dibenz[b,f]azepine-5-propanamine; 5-[3-(dimethylamino)propyl]-10,11-dihydro-5H-dibenz[b,f]azepine; Imipramine; Imizine; N-(gamma-Dimethylaminopropyl)iminodibenzyl; N-(γ-dimethylaminopropyl)iminodibenzyl","C19H24N2","CN(C)CCCN1C2=CC=CC=C2CCC2=CC=CC=C12","Imipramine, the prototypical tricyclic antidepressant (TCA), is a dibenzazepine-derivative TCA. TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, imipramine does not affect mood or arousal, but may cause sedation. In depressed individuals, imipramine exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Tertiary amine TCAs, such as imipramine and amitriptyline, are more potent inhibitors of serotonin reuptake than secondary amine TCAs, such as nortriptyline and desipramine. TCAs also block histamine H<sub>1</sub> receptors, &alpha;<sub>1</sub>-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively . Imipramine has less sedative and anticholinergic effects than the tertiary amine TCAs, amitriptyline and clomipramine. Imipramine may be used to treat depression and nocturnal enuresis in children . Unlabeled indications include chronic and neuropathic pain (including diabetic neuropathy), panic disorder, attention-deficit/hyperactivity disorder (ADHD), and post-traumatic stress disorder (PTSD) .","50-49-7","280.4073","For the relief of symptoms of depression and as temporary adjunctive therapy in reducing enuresis in children aged 6 years and older . \r\n\r\nMay also be used off-label to manage panic disorders with or without agoraphobia, as a second line agent for ADHD in children and adolescents, to manage bulimia nervosa, for short-term management of acute depressive episodes in bipolar disorder and schizophrenia, for the treatment of acute stress disorder and posttraumatic stress disorder, and for symptomatic treatment of postherpetic neuralgia and painful diabetic neuropathy .","Imipramine is a tricyclic antidepressant with general pharmacological properties similar to those of structurally related tricyclic antidepressant drugs such as amitriptyline and doxepin. While it acts to block both, imipramine displays a much higher affinity for the serotonin reuptake transporter than for the norepinephrine reuptake transporter . Imipramine produces effects similar to other monoamine targeting antidepressants, increasing serotonin- and norepinephrine-based neurotransmission.\r\n\r\nThis modulation of neurotransmission produces a complex range of changes in brain structure and function along with an improvement in depressive symptoms. The changes include increases in hippocampal neurogenesis and reduced downregulation of this neurogenesis in response to stress . These implicate brain derived neurotrophic factor signalling as a necessary contributor to antidepressant effect although the link to the direct increase in monoamine neurotransmission is unclear.\r\n\r\nSerotonin reuptake targeting agents may also produce a down-regulation in β-adrenergic receptors in the brain .","Imipramine works by inhibiting the neuronal reuptake of the neurotransmitters norepinephrine and serotonin . It binds the sodium-dependent serotonin transporter and sodium-dependent norepinephrine transporter reducing the reuptake of norepinephrine and serotonin by neurons. Depression has been linked to a lack of stimulation of the post-synaptic neuron by norepinephrine and serotonin . Slowing the reuptake of these neurotransmitters increases their concentration in the synaptic cleft, producing knock-on effects in protein kinase signalling which is thought to contribute to changes in neurotransmission and brain physiology which relieves symptoms of depression .","Sodium-dependent noradrenaline transporter inhibitor; 5-hydroxytryptamine receptor 2A antagonist; Sodium-dependent serotonin transporter inhibitor; Histamine H1 receptor antagonist; Alpha-1A adrenergic receptor antagonist; Alpha-1D adrenergic receptor antagonist; Muscarinic acetylcholine receptor M1 antagonist; Muscarinic acetylcholine receptor M2 antagonist; Muscarinic acetylcholine receptor M3 antagonist; Muscarinic acetylcholine receptor M4 antagonist; Muscarinic acetylcholine receptor M5 antagonist; Potassium voltage-gated channel subfamily D member 2 inhibitor; Potassium voltage-gated channel subfamily D member 3 inhibitor; 5-hydroxytryptamine receptor 2C antagonist&binder; Alpha-1B adrenergic receptor antagonist; 5-hydroxytryptamine receptor 7 antagonist; D(1) dopamine receptor binder; Dopamine D2 receptor binder; Potassium voltage-gated channel subfamily H member 2 inhibitor; Sodium-dependent dopamine transporter inhibitor; 5-hydroxytryptamine receptor 1A activator; 5-hydroxytryptamine receptor 6 binder; Potassium voltage-gated channel subfamily H member 1; Alpha-1-acid glycoprotein 2","Indication associated"]
[154,"DB00460","approved; investigational","small molecule","Verteporfin",null,"C41H42N4O8","COC(=O)CCC1=C2NC(\\C=C3/N=C(/C=C4\\N\\C(=C/C5=N/C(=C\\2)/C(CCC(O)=O)=C5C)C(C=C)=C4C)C2=CC=C([C@@H](C(=O)OC)[C@@]32C)C(=O)OC)=C1C","Verteporfin, marketed as Visudyne, is a benzoporphyrin derivative. It is used as a photosensitizer in photodynamic therapy to eliminate abnormal blood vessels in wet form macular degeneration. Verteporfin accumulates in these abnormal blood vessels and, when stimulated by nonthermal red light with a wavelength of 693 nm in the presence of oxygen, produces highly reactive short-lived singlet oxygen and other reactive oxygen radicals, resulting in local damage to the endothelium and blockage of the vessels.","129497-78-5","718.7942","For the treatment of patients with predominantly classic subfoveal choroidal neovascularization due to age-related macular degeneration, pathologic myopia or presumed ocular histoplasmosis syndrome. Verteporfin can also be used to destroy tumors.","Verteporfin, otherwise known as benzoporphyrin derivative, is a medication used in conjunction with laser treatment to eliminate the abnormal blood vessels in the eye associated with conditions such as the wet form of macular degeneration. Verteporfin accumulates in these abnormal blood vessels and, when stimulated by nonthermal red light with a wavelength of 693 nm in the presence of oxygen, produces highly reactive short-lived singlet oxygen and other reactive oxygen radicals, resulting in local damage to the endothelium and blockage of the vessels.","Verteporfin is transported in the plasma primarily by lipoproteins. Once verteporfin is activated by light in the presence of oxygen, highly reactive, short-lived singlet oxygen and reactive oxygen radicals are generated. Light activation of verteporfin results in local damage to neovascular endothelium, resulting in vessel occlusion. Damaged endothelium is known to release procoagulant and vasoactive factors through the lipo-oxygenase (leukotriene) and cyclo-oxygenase (eicosanoids such as thromboxane) pathways, resulting in platelet aggregation, fibrin clot formation and vasoconstriction. Verteporfin appears to somewhat preferentially accumulate in neovasculature, including choroidal neovasculature. However, animal models indicate that the drug is also present in the retina. As singlet oxygen and reactive oxygen radicals are cytotoxic, Verteporfin can also be used to destroy tumor cells.",null,"Therapeutic strategy associated"]
[155,"DB00461","approved","small molecule","Nabumetone","4-(6-Methoxy-2-naphthalenyl)-2-butanone; 4-(6-Methoxy-2-naphthyl)-2-butanone; Nabumetone","C15H16O2","COC1=CC2=C(C=C1)C=C(CCC(C)=O)C=C2","Nabumetone was originally developed as a non-acidic non-steroidal anti-inflammatory drug (NSAID). It was thought to avoid trapping of the drug in the stomach by making it unable to dissociate into ions which was believed to reduce GI toxicity by limiting local action. While slightly reduced, possibly due to a degree of cyclooxygenase-2 selectivity (COX-2), nabumetone still produces significant adverse effects in the GI tract. The molecule itself is a pro-drug with its 6-methoxy-2-naphthylacetic acid (6-MNA) metabolite acting as a potent COX inhibitor similar in structure to . Nabumetone was developed by Smithkline Beecham under the trade name Relafen and first received FDA approval in December, 1991.","42924-53-8","228.2863","**Indicated** for:\r\n\r\n1) Symptomatic relief in rheumatoid arthritis.\r\n\r\n2) Symptomatic relief in osteoarthritis.","NSAIDs, like nabumetone, are well established as analgesics. NSAIDs reduce both peripheral and central sensitization of nociceptive neurons due to inflammation which contribute to hyperalgesia and allodynia. This sensitization occurs through reducing the action potential threshold in peripheral neurons, reducing the intensity of painful stimuli needed to produce a painful sensation. Centrally, activation of dorsal horn neurons occurs along with increased release of glutamate, calcitonin gene-related peptide (CGRP), and substance P which increase the transmission of painful stimuli. Coupled with this is an inhibition glycinergic neurons which normally inhibit pain transmission, a phenomenon known as disinhibition. Increased activity ofn-methyl d-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors leads to the establishment of central sensitization, allowing both mild painful and innocuous stimuli to produce action potentials in nociceptive projection neurons. NSAIDs are effective in reducing mild-moderate acute and chronic nociceptive pain, however, the usefulness of NSAIDs in neuropathic pain is limited.\r\n\r\nThe anti-inflammatory effect of NSAIDs is mediated by preventing vasodilation, increases in vascular permeability, and the release of cytokines from endothelial cells. These three effects together prevent immunocompetent cells from migrating to the site of injury thereby preventing additional damage and inflammation due to activation of the immune system at the site of damage. PGs also modulate T-helper cell activation and differentiation, an activity which is thought to be of importance in arthritic conditions.\r\n\r\nThe anti-pyretic effect of NSAIDs is mediated through preventing increases in temperature by prostaglandins (PGs) via the hypothalamus. Activation of this process by other inflammatory mediators relies upon subsequent action by PGs, therefore NSAIDs are able to reduce fever due to these mediators as well.\r\n\r\nThe adverse effects of NSAIDs are related to their therapeutic effects. The same vasodilatory action which occurs in inflammation also serves to regulate blood flow to the kidneys through the afferent renal arteries. NSAIDs are widely known as nephrotoxic agents as the reduction in PGs produces vasoconstriction of these arteries resulting in reduced blood flow to the kidneys and a subsequent decline in renal function. Reductions in mucus and HCO<sub>3</sub><sup>-</sup> secretion in the stomach increases the risk of ulceration by limiting the protection mediated by PGs. Lastly, COX-2 selective agents like nabumetone can unbalance prothrombotic and antithrombotic prostanoid generation leading to increased platelet aggregation and increased risk of thrombosis.","Nabumetone's active metabolite, 6-MNA, is an inhibitor of both COX-1 and COX-2 although it exhibits some COX-2 selectivity. Inhibition of COX-1 and COX-2 reduces conversion of arachidonic acid to PGs and thromboxane (TXA<sub>2</sub>). This reduction in prostanoid production is the common mechanism that mediates the effects of nambutone.\r\n\r\nPGE<sub>2</sub> is the primary PG involved in modulation of nociception. It mediates peripheral sensitization through a variety of effects. PGE<sub>2</sub> activates the G<sub>q</sub>-coupled EP<sub>1</sub> receptor leading to increased activity of the inositol trisphosphate/phospholipase C pathway. Activation of this pathway releases intracellular stores of calcium which directly reduces action potential threshold and activates protein kinase C (PKC) which contributes to several indirect mechanisms. PGE<sub>2</sub> also activates the EP<sub>4</sub> receptor, coupled to G<sub>s</sub>, which activates the adenylyl cyclase/protein kinase A (AC/PKA) signaling pathway. PKA and PKC both contribute to the potentiation of transient receptor potential cation channel subfamily V member 1 (TRPV1) potentiation, which increases sensitivity to heat stimuli. They also activate tetrodotoxin-resistant sodium channels and inhibit inward potassium currents. PKA further contributes to the activation of the P2X3 purine receptor and sensitization of T-type calcium channels. The activation and sensitization of depolarizing ion channels and inhibition of inward potassium currents serve to reduce the intensity of stimulus necessary to generate action potentials in nociceptive sensory afferents. PGE<sub>2</sub> act via EP<sub>3</sub> to increase sensitivity to bradykinin and via EP<sub>2</sub> to further increase heat sensitivity. Central sensitization occurs in the dorsal horn of the spinal cord and is mediated by the EP<sub>2</sub> receptor which couples to G<sub>s</sub>. Pre-synaptically, this receptor increases the release of pro-nociceptive neurotransmitters glutamate, CGRP, and substance P. Post-synaptically it increases the activity of AMPA and NMDA receptors and produces inhibition of inhibitory glycinergic neurons. Together these lead to a reduced threshold of activating, allowing low intensity stimuli to generate pain signals. PGI<sub>2</sub> is known to play a role via its G<sub>s</sub>-coupled IP receptor although the magnitude of its contribution varies. It has been proposed to be of greater importance in painful inflammatory conditions such as arthritis. By limiting sensitization, both peripheral and central, via these pathways NSAIDs can effectively reduce inflammatory pain.\r\n\r\nPGI<sub>2</sub> and PGE<sub>2</sub> contribute to acute inflammation via their IP and EP<sub>2</sub> receptors. Similarly to β adrenergic receptors these are G<sub>s</sub>-coupled and mediate vasodilation through the AC/PKA pathway. PGE<sub>2</sub> also contributes by increasing leukocyte adhesion to the endothelium and attracts the cells to the site of injury. PGD<sub>2</sub> plays a role in the activation of endothelial cell release of cytokines through its DP<sub>1</sub> receptor. PGI<sub>2</sub> and PGE<sub>2</sub> modulate T-helper cell activation and differentiation through IP, EP<sub>2</sub>, and EP<sub>4</sub> receptors which is believed to be an important activity in the pathology of arthritic conditions. By limiting the production of these PGs at the site of injury, NSAIDs can reduce inflammation.\r\n\r\nPGE<sub>2</sub> can cross the blood-brain barrier and act on excitatory G<sub>q</sub> EP<sub>3</sub> receptors on thermoregulatory neurons in the hypothalamus. This activation triggers an increase in heat-generation and a reduction in heat-loss to produce a fever. NSAIDs prevent the generation of PGE<sub>2</sub> thereby reducing the activity of these neurons.\r\n\r\nThe adverse effects of NSAIDs stem from the protective and regulatory roles of prostanoids which have been well-characterized. PGI<sub>2</sub> and PGE<sub>2</sub> regulate blood flow to the kidney by similar mechanisms to the vasodilation they produce in inflammation. Prevention of this regulation by NSAIDs produces vasoconstriction which limits renal function by reducing blood flow and the hydrostatic pressure which drives filtration. PGE<sub>2</sub> also regulates gastric protection via EP<sub>3</sub> receptors which are, in this location, coupled to G<sub>i</sub> which inhibits the AC/PKA pathway. This reduces the secretion of protons by H<sup>+</sup>/K<sup>+</sup> ATPase in parietal cells and increases the secretion of mucus and HCO<sub>3</sub><sup>-</sup> by superficial endothelial cells. Disruption of this protective action by NSAIDs lead to ulceration of the gastric mucosa. Lastly, disruption of PGI<sub>2</sub>, which opposes platelet aggregation, generation by COX-2 selective agents leads to an imbalance with TXA<sub>2</sub> generated by COX-1, which promotes aggregation of platelets, leading to increased risk of thrombosis. Since nabumetone is somewhat COX-2 selective it is thought to promote this imbalance and increase thrombotic risk.","Prostaglandin G/H synthase 2 inhibitor; Prostaglandin G/H synthase 1 inhibitor","Therapeutic strategy associated"]
[156,"DB00464","approved; investigational","small molecule","Sodium tetradecyl sulfate","7-Ethyl-2-methyl-4-undecanol sulfate sodium salt; 7-ethyl-2-methyl-4-undecanolsulfate, sodium salt; Sodium 2-methyl-7-ethylundecanol-4-sulfate; Sodium 7-ethyl-2-methyl-4-undecanol sulfate; Sodium tetradecyl sulfate; Sodium tetradecyl sulphate; Sodium tetradecylsulfate; STS; Tetradecyl sodium sulfate","C14H29NaO4S","[Na+].CCCCC(CC)CCC(CC(C)C)OS([O-])(=O)=O","An anionic surface-active agent used for its wetting properties in industry and used in medicine as an irritant and sclerosing agent for hemorrhoids and varicose veins.","139-88-8","316.43","For the treatment of small uncomplicated varicose veins of the lower extremities that show simple dilation with competent valves.","Sodium tetradecyl sulfate is an anionic surfactant which occurs as a white, waxy solid. It is used as a sclerosing agent in sclerotherapy. Sclerotherapy is an injection of a sclerosing agent directly through the skin into a lesion and is used primarily for slow-flow vascular anomalies, particularly for venous malformation and lymphatic malformation. Intravenous injection causes intima inflammation and thrombus formation. This usually occludes the injected vein. Subsequent formation of fibrous tissue results in partial or complete vein obliteration that may or may not be permanent.","Sodium tetradecyl sulfate is a potent toxin for endothelial cells in that brief exposure to even low concentrations are effective in stripping endothelium over a considerable distance and exposing highly thrombogenic endothelium in the process. Diluted sodium tetradecyl sulfate is also able to induce a hypercoagulable state, possibly by selective inhibition of protein C, and can also promote platelet aggregation.","Vitamin K-dependent protein C inhibitor; Vitamin K-dependent protein S inhibitor","Therapeutic strategy associated"]
[157,"DB00465","approved","small molecule","Ketorolac","rac-Ketorolac","C15H13NO3","OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1","Ketorolac is a Non-steroidal anti-inflammatory drug (NSAID) and is commercially available as an oral tablet, injectable, nasal spray and as an ophthalmic solution. \r\n\r\nIt's analgesic properties make it a useful pain management tool across many settings including postoperative pain, rheumatoid arthritis, osteoarthritis, menstrual disorders, headaches, spinal and soft tissue pain, and ankylosing spondylitis. Impressively, ketorolac has a similar efficacy to standard doses of morphine and meperidine making it a useful opioid sparing agent.","74103-06-3","255.2686","Ketorolac is a Non-steroidal anti-inflammatory drug (NSAID) and has antipyretic, analgesic and anti-inflammatory properties.  It is indicated for short term management of acute pain that requires the calibre of pain management offered by opioids.  Clinicians may choose to initiate ketorolac to manage post-operative pain, spinal and soft tissue pain, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, menstrual disorders and headaches among other ailments. Regardless of the etiology of pain, patients should use the lowest possible dose, and avoid using ketorolac for an extended period of time (ideally ≤ 5 days). A benefit of choosing ketorolac over other analgesics with similar potency is that that there does not appear to be a risk of dependence or tolerance with ketorolac use.","Ketorolac is a non-selective NSAID and acts by inhibiting both COX-1 and COX-2 enzymes which are normally responsible for converting arachidonic acid to prostaglandins. The COX-1 enzyme is constitutively active and can be found in platelets, gastric mucosa, and vascular endothelium. On the other hand, the COX-2 enzyme is inducible and mediates inflammation, pain and fever.  \r\n\r\nAs a result, inhibition of the COX-1 enzyme is linked to an increased risk of bleeding and risk of gastric ulceration, while the desired anti-inflammatory and analgesic properties are linked to inhibition of the COX-2 enzyme. Therefore, despite it's effectiveness in pain management, ketorolac should not be used long-term since this increases the risk of serious adverse effects such as gastrointestinal bleeding, peptic ulcers, and perforations.","Ketorolac inhibits key pathways in prostaglandin synthesis which is crucial to it's mechanism of action.  Although ketorolac is non-selective and inhibits both COX-1 and COX-2 enzymes, it's clinical efficacy is derived from it's COX-2 inhibition. The COX-2 enzyme is inducible and is responsible for converting arachidonic acid to prostaglandins that mediate inflammation and pain.  By blocking this pathway, ketorolac achieves analgesia and reduces inflammation. Ketorolac is administered as a racemic mixture; however, the \"S\" enantiomer is largely responsible for it's pharmacological activity.","Prostaglandin G/H synthase 2 inhibitor; Prostaglandin G/H synthase 1 inhibitor","Therapeutic strategy associated"]
[158,"DB00467","approved; investigational","small molecule","Enoxacin","1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-1,8-naphthyridine-3-carboxylic acid; 1-Ethyl-6-fluoro-4-oxo-7-piperazin-1-yl-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid","C15H17FN4O3","CCN1C=C(C(O)=O)C(=O)C2=CC(F)=C(N=C12)N1CCNCC1","A broad-spectrum 6-fluoronaphthyridinone antibacterial agent (fluoroquinolones) structurally related to nalidixic acid.","74011-58-8","320.3189","For the treatment of adults (&ge;18 years of age) with the following infections caused by susceptible strains of the designated microorganisms: (1) uncomplicated urethral or cervical gonorrhea due to <i>Neisseria gonorrhoeae</i>, (2) uncomplicated urinary tract infections (cystitis) due to <i>Escherichia coli</i>, <i>Staphylococcus epidermidis</i>, or <i>Staphylococcus saprophyticus</i>, and (3) complicated urinary tract infections due to <i>Escherichia coli</i>, <i>Klebsiella pneumoniae</i>, <i>Proteus mirabilis</i>, <i>Pseudomonas aeruginosa</i>, <i>Staphylococcus epidermidis</i>, or <i>Enterobacter cloacae</i>.","Enoxacin is a quinolone/fluoroquinolone antibiotic. Enoxacin is bactericidal and its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase, which allows the untwisting required to replicate one DNA double helix into two. Enoxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria. Enoxacin may be active against pathogens resistant to drugs that act by different mechanisms.","Enoxacin exerts its bactericidal action via the inhibition of the essential bacterial enzyme DNA gyrase (DNA Topoisomerase II).","DNA gyrase subunit A inhibitor; DNA topoisomerase 4 subunit A inhibitor; DNA topoisomerase 2-alpha inhibitor","Indication associated"]
[159,"DB00469","approved","small molecule","Tenoxicam",null,"C13H11N3O4S2","CN1C(C(=O)NC2=CC=CC=N2)=C(O)C2=C(C=CS2)S1(=O)=O","Tenoxicam, an antiinflammatory agent with analgesic and antipyretic properties, is used to treat osteoarthritis and control acute pain.","59804-37-4","337.37","For the treatment of rheumatoid arthritis, osteoarthritis, backache, and pain.","Tenoxicam, an antiinflammatory agent with analgesic and antipyretic properties, is used to treat osteoarthritis and control acute pain.","The antiinflammatory effects of tenoxicam may result from the inhibition of the enzyme cycooxygenase and the subsequent peripheral inhibition of prostaglandin synthesis. As prostaglandins sensitize pain receptors, their inhibition accounts for the peripheral analgesic effects of tenoxicam. Antipyresis may occur by central action on the hypothalamus, resulting in peripheral dilation, increased cutaneous blood flow, and subsequent heat loss.","Prostaglandin G/H synthase 2 inhibitor; Prostaglandin G/H synthase 1 inhibitor","Therapeutic strategy associated"]
[160,"DB00472","approved; vet_approved","small molecule","Fluoxetine","(+-)-N-Methyl-3-phenyl-3-((alpha,alpha,alpha-trifluoro-P-tolyl)oxy)propylamine; (+-)-N-Methyl-gamma-(4-(trifluoromethyl)phenoxy)benzenepropanamine; Fluoxetine","C17H18F3NO","CNCCC(OC1=CC=C(C=C1)C(F)(F)F)C1=CC=CC=C1","Fluoxetine is a 2nd generation antidepressant categorized as a selective serotonin reuptake inhibitor (SSRI). It gained FDA approval in 1987 and although it was initially intended for the treatment of depression, today it is commonly prescribed to manage depression in addition to various other pathologies.","54910-89-3","309.3261","Fluoxetine is indicated for both acute and maintenance treatment of major depressive disorder, obsessive compulsive disorder, and bulimia nervosa; however, it is only indicated for acute treatment of panic disorder independent of whether agoraphobia is present. Fluoxetine may also be used in combination with olanzapine to treat depression related to Bipolar I Disorder, and treatment resistant depression.","Fluoxetine blocks the serotonin reuptake transporter in the presynaptic terminal, which ultimately results in sustained levels of 5-hydroxytryptamine (5-HT) in certain brain areas. However, fluoxetine binds with relatively poor affinity to 5-HT, dopaminergic, adrenergic, cholinergic, muscarinic, and histamine receptors which explains why it has a far more desirable adverse effect profile compared to earlier developed classes of antidepressants such as tricyclic antidepressants.","The monoaminergic hypothesis of depression emerged in 1965 and linked depression with dysfunction of neurotransmitters such as noradrenaline and serotonin. Indeed, low levels of serotonin have been observed in the cerebrospinal fluid of patients diagnosed with depression. As a result of this hypothesis, drugs that modulate levels of serotonin such as fluoxetine were developed.\r\n\r\nFluoxetine is a selective serotonin reuptake inhibitor (SSRI) and as the name suggests, it exerts it's therapeutic effect by inhibiting the presynaptic reuptake of the neurotransmitter serotonin. As a result, levels of 5-hydroxytryptamine (5-HT) are increased in various parts of the brain. Further, fluoxetine has high affinity for 5-HT transporters, weak affinity for noradrenaline transporters and no affinity for dopamine transporters indicating that it is 5-HT selective.\r\n\r\nFluoxetine interacts to a degree with the 5-HT<sub>2C</sub> receptor and it has been suggested that through this mechanism, it is able to increase noradrenaline and dopamine levels in the prefrontal cortex.","Sodium-dependent serotonin transporter inhibitor; 5-hydroxytryptamine receptor 2C antagonist; Neuronal acetylcholine receptor subunit alpha-2 antagonist; Neuronal acetylcholine receptor subunit alpha-3 antagonist; Neuronal acetylcholine receptor subunit beta-4 antagonist; Cyclin-dependent kinases regulatory subunit 1; Potassium voltage-gated channel subfamily H member 2 inhibitor","Indication associated"]
[161,"DB00476","approved","small molecule","Duloxetine","(3S)-N-methyl-3-(1-naphthyloxy)-3-(2-thienyl)propan-1-amine; (S)-duloxetine; Duloxetine","C18H19NOS","CNCC[C@H](OC1=CC=CC2=CC=CC=C12)C1=CC=CS1","Duloxetine is a dual serotonin and norepinephrine reuptake inhibitor. It was originally discovered in 1993 and developed by Eli Lilly and Company as LY248686. Duloxetine first received approval from the FDA in August, 2004 as Cymbalta for the treatment of Major Depressive Disorder. It has since received approval for a variety of indications including the treatment of neuropathic pain, Generalized Anxiety disorder, osteoarthritis, and stress incontinence. Duloxetine continues to be investigated for the treatment of pain in cancer, surgery, and more.","116539-59-4","297.415","**Indicated** for:\r\n\r\n1) Management of Major Depressive Disorder.\r\n\r\n2) Management of Generalized Anxiety Disorder.\r\n\r\n3) Management of diabetic peripheral neuropathy.\r\n\r\n4) Management of fibromyalgia.\r\n\r\n5) Management of chronic musculoskeletal pain.\r\n\r\n6) Management of osteoarthritis of the knee in adults.\r\n\r\n7) Management of chronic lower back pain in adults.\r\n\r\n8) Management of stress urinary incontinence in adult women.\r\n\r\n**Off-label** uses include:\r\n\r\n1) Management of chemotherapy-induced peripheral neuropathy.\r\n\r\n2) Management of stress urinary incontinence in adult men after prostatectomy until recovery is complete.","Duloxetine, through increasing serotonin and norepinephrine concentrations in Onuf's nucleus, enhances glutamatergic activation of the pudendal motor nerve which innervates the external urethral sphinter. This enhanced signaling allows for stronger contraction. Increased contraction of this sphincter increases the pressure needed to produce an incontinence episode in stress urinary incontinence. Duloxetine has been shown to improve Patient Global Impression of Improvement and Incontinence Quality of Life scores. It has also been shown to reduce the median incontinence episode frequency at doses of 40 and 80 mg.\r\n\r\nAction at the dorsal horn of the spinal cord allows duloxetine to strengthen the the serotonergic and adrenergic pathways involved in descending inhibition of pain. This results in an increased threshold of activation necessary to transmit painful stimuli to the brain and effective relief of pain, particularly in neuropathic pain. Pain relief has been noted in a variety of painful conditions including diabetic peripheral neuropathy, fibromyalgia, and osteoarthritis using a range of pain assessment surveys.\r\n\r\nWhile duloxetine has been shown to be effective in both animal models of mood disorders and in clinical trials for the treatment of these disorders in humans, the broad scope of its pharmacodynamic effects on mood regulation in the brain has yet to be explained.\r\n\r\nIncreased blood pressure is a common side effect with duloxetine due to vasoconstriction mediated by the intended increase in norepinephrine signaling.","Duloxetine is a potent inhibitor of neuronal serotonin and norepinephrine reuptake and a less potent inhibitor of dopamine reuptake. Duloxetine has no significant affinity for dopaminergic, adrenergic, cholinergic, histaminergic, opioid, glutamate, and GABA receptors.\r\n\r\nAction on the external urinary sphincter is mediated via duloxetine's CNS effects. Increased serotonin and norepinephrine concentrations in Onuf's nucleus leads to increased activation of 5-HT<sub>2</sub>, 5-HT<sub>3</sub>, and α<sub>1</sub> adrenergic receptors. 5-HT<sub>2</sub> and α<sub>1</sub> are both G<sub>q</sub> coupled and their activation increases the activity of the inositol trisphosphate/phospholipase C (IP<sub>3</sub>/PLC) pathway. This pathway leads to release of intracellular calcium stores, increasing intracellular calcium concentrations, and facilitating neuronal excitability. 5-HT<sub>3</sub> functions as a ligand-gated sodium channel which allows sodium to flow into the neuron when activated. Increased flow of sodium into the neuron contributes to depolarization and activation of voltage gated channels involved in action potential generation. The combined action of these three receptors contributes to increased excitability of the pudendal motor nerve in response to glutamate.\r\n\r\nAlso related to duloxetine's action at the spinal cord is its modulation of pain. Increasing the concentration of serotonin and norepinephrine in the dorsal horn of the spinal cord increases descending inhibition of pain through activation of 5-HT<sub>1A</sub>, 5-HT<sub>1B</sub>, 5-HT<sub>1D</sub>, 5-HT<sub>2</sub>, 5-HT<sub>3</sub>, α<sub>1</sub>-adrenergic, and α<sub>2</sub>-adrenergic receptors. 5-HT<sub>2</sub>, 5-HT<sub>3</sub>, and α<sub>1</sub>-adrenergic mediate neuronal activation as described above. The activated neuron in this case is the GABAergic inhibitory interneuron which synapses onto the nociceptive projection neuron to inhibit the transmission of painful stimuli to the brain. The 5-HT<sub>1</sub> and α<sub>2</sub> receptors are G<sub>i</sub>/G<sub>o</sub> coupled and their activation leads to increased potassium current through inward rectifier channels and decreased adenylyl cyclase/protein kinase A signaling which contributes to neuronal inhibition. These inhibitory receptors are present on the projection neuron itself as well as the dorsal root ganglion which precedes it and serves to directly suppress the transmission of painful stimuli.\r\n\r\nThe mechanisms involved in duloxetine's benefits in depression and anxiety have not been fully elucidated. Dysfunctional serotonin and norepinephrine signaling are thought to be involved and increases in the availability of these neurotransmitters at the synaptic cleft thought to mediate a therapeutic effect. It is postulated that the involvement of serotonin and norepinephrine in area responsible for emotional modulation such as the limbic system contributes to the effects in mood disorders specifically but this has yet to be confirmed.\r\n\r\nDuloxetine's hypertensive effect is related to its intended pharmacological effect. Increased availability of norepinephrine leads to activation of adrenergic receptors on the vascular endothelium. Since the action of α<sub>1</sub> receptors predominates, vasoconstriction results as the G<sub>q</sub> coupled receptor mediates calcium release from the sarcoplasmic reticulum to facilitate smooth muscle contraction.","Sodium-dependent serotonin transporter inhibitor; Sodium-dependent noradrenaline transporter inhibitor; Sodium-dependent dopamine transporter inhibitor","Therapeutic strategy associated"]
[162,"DB00479","approved; investigational; vet_approved","small molecule","Amikacin","1-N-(L(−)-γ-amino-α-hydroxybutyryl)kanamycin A","C22H43N5O13","NCC[C@H](O)C(=O)N[C@@H]1C[C@H](N)[C@@H](O[C@H]2O[C@H](CN)[C@@H](O)[C@H](O)[C@H]2O)[C@H](O)[C@H]1O[C@H]1O[C@H](CO)[C@@H](O)[C@H](N)[C@H]1O","Amikacin is a semi-synthetic aminoglycoside antibiotic that is derived from kanamycin A. Amikacin is synthesized by acylation with the l-(-)-γ-amino-α-hydroxybutyryl side chain at the C-1 amino group of the deoxystreptamine moiety of kanamycin A.\r\n\r\nAmikacin's unique property is that it exerts activity against more resistant gram-negative bacilli such as Acinetobacter baumanii and Pseudomonas aeruginosa. Amikacin also exerts excellent activity against most aerobic gram-negative bacilli from the Enterobacteriaceae family, including Nocardia and some Mycobacterium (M. avium-intracellulare, M. chelonae, and M. fortuitum). M. avium-intracellulare (MAC) is a type of nontuberculous mycobacteria (NTM) found in water and soil. Symptoms of this disease include a persistent cough, fatigue, weight loss, night sweats, and shortness of breath and the coughing up of blood.\r\n\r\nSeveral forms of amikacin are used currently, including an intravenous (IV) or intramuscular (IM) injection. In September 2018, a liposomal inhalation suspension of this drug was approved by the FDA for the treatment of lung disease caused by Mycobacterium avium complex (MAC) bacteria in a small population of patients with the disease who do not respond to traditional treatment.","37517-28-5","585.6025","The amikacin sulfate injection is indicated in the short-term treatment of serious bacterial infections due to susceptible strains of gram-negative bacteria, including Pseudomonas species, Escherichia coli, species of indole-positive and indole-negative Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, as well as Acinetobacter (Mima-Herellea) species.\r\n\r\nClinical studies have shown amikacin sulfate injection to be effective in bacterial septicemia (including neonatal sepsis); in serious infections of the respiratory tract, bones and joints, central nervous system (including meningitis) and skin and soft tissue; intra-abdominal infections (including peritonitis); and in burns and postoperative infections (including post-vascular surgery).\r\n\r\nClinical studies have shown amikacin also to be effective in serious, complicated, and recurrent urinary tract infections due to the above organisms. Aminoglycosides, including amikacin, are not indicated in uncomplicated first-time episodes of urinary tract infections unless the causative organisms are not susceptible to antibiotics which are less toxic.\r\n\r\nIn September 2018, a new indication with a new dosage route was approved for this drug. Amikacin liposome inhalation suspension was approved for the treatment of lung disease caused by a group of bacteria, Mycobacterium avium complex (MAC) in a limited population of patients with the disease who do not respond to conventional treatment (refractory disease). This indication is approved under accelerated approval based on achieving sputum culture conversion (defined as 3 consecutive negative monthly sputum cultures) by Month 6 of treatment. Clinical benefit has not yet been established.\r\n\r\n**Important notes regarding Staphylococcus and Sensitivity testing:**\r\n\r\nStaphylococcus aureus, including methicillin-resistant strains, is the principal Gram-positive organism sensitive to amikacin.\r\nThe use of amikacin in the treatment of staphylococcal infections should be restricted only to second-line therapy, and should be limited to only those patients suffering from severe infections caused by susceptible strains of staphylococcus species who have failed to show sensitivity to other available antibiotics.\r\n\r\nBacteriologic studies should be performed to identify causative organisms and their susceptibilities to amikacin. Amikacin may be used as initial therapy in suspected gram-negative infections and therapy may be initiated before obtaining the results of susceptibility testing.","Amikacin is an aminoglycoside antibiotic. Aminoglycosides bind to the bacteria, causing misreading of t-RNA, leaving bacteria unable to synthesize proteins vital to their growth. Aminoglycosides are useful mainly in the treatment infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some mycobacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. Infections caused by Gram-positive bacteria can also be treated with aminoglycosides, however, other antibiotics may be more potent and less toxic to humans.","The primary mechanism of action of amikacin is the same as that for all aminoglycosides. It binds to bacterial 30S ribosomal subunits and interferes with mRNA binding and tRNA acceptor sites, interfering with bacterial growth. This leads to disruption of normal protein synthesis and production of non-functional or toxic peptides. Other actions have been postulated for drugs of this class. Amikacin, as well as the rest of the aminoglycosides, are generally bacteriocidal against gram-positive and gram-negative bacteria.","30S ribosomal protein S12 inhibitor","Indication associated"]
[163,"DB00480","approved","small molecule","Lenalidomide","1-oxo-2-(2,6-dioxopiperidin-3-yl)-4-aminoisoindoline; 3-(4-Amino-1-oxoisoindolin-2-yl)piperidine-2,6-dione; Lenalidomide","C13H13N3O3","NC1=CC=CC2=C1CN(C1CCC(=O)NC1=O)C2=O","Lenalidomide (previously referred to as CC-5013) is an immunomodulatory drug with potent antineoplastic, anti-angiogenic, and anti-inflammatory properties. It is a 4-amino-glutamyl analogue of   and like thalidomide, lenalidomide exists as a racemic mixture of the active S(-) and R(+) forms. However, lenalidomide is much safer and potent than thalidomide, with fewer adverse effects and toxicities. Thalidomide and its analogues, including lenalidomide, are referred to as immunomodulatory imide drugs (also known as cereblon modulators), which are a class of immunomodulatory drugs that contain an imide group. Lenalidomide works through various mechanisms of actions that promote malignant cell death and enhance host immunity. Available as oral capsules, lenalidomide is approved by the FDA and EU for the treatment of multiple myeloma, myelodysplastic syndromes, mantle cell lymphoma, follicular lymphoma, and marginal zone lymphoma in selected patients. Lenalidomide is available only under a special restricted distribution program.","191732-72-6","259.2606","Lenalidomide is indicated for the treatment of adult patients with multiple myeloma (MM) in combination with dexamethasone. It is also indicated as maintenance therapy in multiple myeloma following autologous hematopoietic stem cell transplantation (auto-HSCT).\r\n\r\nIt is indicated for the treatment of adult patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities.\r\n\r\nLenalidomide is indicated for the treatment of adult patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib.\r\n\r\nIn combination with a rituximab product, lenalidomide is indicated for the treatment of adult patients with previously treated follicular lymphoma (FL) or previously treated marginal zone lymphoma (MZL).","In hematological malignancies, the immune system is deregulated in the form of altered cytokine networks in the tumour microenvironment, defective T cell regulation of host-tumour immune interactions, and diminished NK cell activity. Lenalidomide is an immunomodulatory agent with antineoplastic, antiangiogenic, and anti-inflammatory properties. Lenalidomide exerts direct cytotoxicity by increasing apoptosis and inhibiting the proliferation of hematopoietic malignant cells. It delays tumour growth in nonclinical hematopoietic tumour models _in vivo_, including multiple myeloma. Lenalidomide also works to limit the invasion or metastasis of tumour cells and inhibits angiogenesis.\r\n\r\nLenalidomide also mediates indirect antitumour effects via its immunomodulatory actions: it inhibits the production of pro-inflammatory cytokines, which are implicated in various hematologic malignancies. Lenalidomide enhances the host immunity by stimulating T cell proliferation and enhancing the activity of natural killer (NK) cells. Lenalidomide is about 100–1000 times more potent in stimulating T cell proliferation than . _In vitro_, it enhances antibody-dependent cell-mediated cytotoxicity (ADCC), which is even more pronounced when used in combination with rituximab. Due to its anti-inflammatory properties, lenalidomide has been investigated in the context of inflammatory and autoimmune diseases, such as amyotrophic lateral sclerosis.","Lenalidomide is a drug with multiple mechanisms of action. Lenalidomide exerts immunomodulating effects by altering cytokine production, regulating T cell co-stimulation, and enhancing the NK cell-mediated cytotoxicity. Lenalidomide directly inhibits the cullin ring E3 ubiquitin ligase complex: upon binding to cereblon, a substrate adaptor of the complex, lenalidomide modulates substrate specificity of the complex to recruit substrate proteins of the ligase, including Ikaros (IKZF1), Aiolos (IKZF3), and CK1α. These substrates are then tagged for ubiquitination and subsequent proteasomal degradation. IKZF1 and IKZF3 are B-cell transcription factors that are essential for B-cell differentiation and survival of malignant cells. IKZF3 also regulates the expression of interferon regulatory factor 4 (IRF4), which is a transcription factor that regulates the aberrant myeloma-specific gene. The immunomodulatory actions of lenalidomide can be partly explained by the degradation of IKZF3, since it is a repressor of the interleukin 2 gene (IL2): as lenalidomide decreases the level of IKZF3, the production of IL-2 increases, thereby increasing the proliferation of natural killer (NK), NKT cells, and CD4+ T cells. Lenalidomide inhibits the production of pro-inflammatory cytokines TNF-α, IL-1, IL-6, and IL-12, while elevating the production of anti-inflammatory cytokine IL-10. Lenalidomide acts as a T-cell co-stimulatory molecule that promotes CD3 T-cell proliferation and increases the production of IL-2 and IFN-γ in T lymphocytes, which enhances NK cell cytotoxicity and ADCC. It inhibits the expression and function of T-regulatory cells, which are often overabundant in some hematological malignancies. \r\n\r\nLenalidomide directly exerts antitumour effects by inhibiting the proliferation and inducing apoptosis of tumour cells. Lenalidomide triggers the activation of pro-apoptotic caspase-8, enhances tumour cell sensitivity to FAS-induced apoptosis, and downregulates NF-κB, an anti-apoptotic protein. Independent of its immunomodulatory effects, lenalidomide mediates anti-angiogenic effects by inhibiting angiogenic growth factors released by tumour cells, such as vascular endothelial growth factor (VEGF), basic fibroblastic-growth factor (BFGF), and hepatocyte-growth factor. _In vitro_, lenalidomide inhibits cell adhesion molecules such as ICAM-1, LFA-1, β2 and β3 integrins, as well as gap-junction function, thereby preventing metastasis of malignant cells.","Protein cereblon inhibitor; Tumor necrosis factor ligand superfamily member 11 inhibitor; Cadherin-5 antagonist; Prostaglandin G/H synthase 2 negative modulator","Therapeutic strategy associated"]
[164,"DB00481","approved; investigational","small molecule","Raloxifene","(2-(4-Hydroxyphenyl)-6-hydroxybenzo(b)thien-3-yl)(4-(2-(1-piperidinyl)ethoxy)phenyl)methanone; Raloxifene","C28H27NO4S","OC1=CC=C(C=C1)C1=C(C(=O)C2=CC=C(OCCN3CCCCC3)C=C2)C2=C(S1)C=C(O)C=C2","Raloxifene is a second generation selective estrogen receptor modulator (SERM) that mediates anti-estrogenic effects on breast and uterine tissues, and estrogenic effects on bone, lipid metabolism, and blood coagulation. Exhibiting tissue-specific effects distinct from , raloxifene is the first of the benzothiophene group of antiestrogens to be labelled a SERM. Available in many countries worldwide, raloxifene was initially approved by the FDA in December, 1997 under the market name Evista® for the management and prevention of osteoporosis in postmenopausal women and reduction in risk for invasive breast cancer in postmenopausal women with osteoporosis or those who are at high risk for invasive breast cancer. However, it has a negligible effect on altering the development and progression of breast cancer itself. The most common causes of osteoporosis include postmenopausal deficiency of estrogen and age-related deterioration in bone homeostasis. Due to the risk of bone fractures that may lead to morbidities and reduced quality of life, the management of osteoporosis in postmenopausal women with the use of therapeutic agents in addition to concurrent therapies is critical. Due to the decline in estrogen levels in postmenopausal osteoporosis, hormone replacement therapy (HRT), such as estradiol, has been used to ameliorate the condition. However, due to the off-target actions by HRT, newer non-hormonal agents such as raloxifene and  have been developed to reduce adverse events through selective pharmacological actions on tissue-specific therapeutic targets.\r\n\r\nThe main effects of raloxifene are to preserve the bone mineral density and decrease the risk of breast cancer in postmenopausal women. Compared to estrogen and tamoxifen, raloxifene was not associated with an increased risk of uterine cancer and it does not cause endometrial proliferation. Although rare, there was an increased risk of venous thromboembolism during clinical trials of postmenopausal women receiving raloxifene. In addition, a clinical study consisting of postmenopausal women with documented coronary heart disease or at increased risk for coronary events showed an increased risk for fatal stroke with raloxifene therapy compared to placebo. It is strongly advised that the risk-benefit ratio is considered before starting raloxifene therapy in women at risk of thromboembolic disease or strokes, such as the prior history of stroke, transient ischemic attack, atrial fibrillation, hypertension, or cigarette smoking.","84449-90-1","473.583","Indicated for the prevention and treatment of osteoporosis in postmenopausal women, as well as prevention and treatment of corticosteroid-induced bone loss.\r\n\r\nIndicated for the reduction in the risk of invasive breast cancer in postmenopausal women with osteoporosis or postmenopausal women with a high risk for invasive breast cancer.","Raloxifene belongs to the selective estrogen receptor modulator (SERM) drug class that exhibits estrogenic effects on bone and lipid metabolism while mediating anti-estrogenic effects on uterine endometrium and breast tissues. On skeletal tissues, raloxifene stimulates bone-depositing osteoblasts and inhibits bone-resorbing osteoclasts to augument bone mineral density. Raloxifene produces estrogen-like effects on bone, reducing the resorption of bone and increasing bone mineral density in postmenopausal women, thus slowing the rate of bone loss. In three randomized, placebo-controlled trials in Europe, postmenopausal women receiving raloxifene at variable doses of 30 to 150 mg daily demonstrated significant increases in bone mineral density in the lumbar spine, total hip, femoral neck and total body compared to placebo. In the MORE and RUTH trials, there were fewer incidences of vertebral fractures in postmeopausal women receiving raloxifene compared to placebo. In a eight-week study evaluating short-term effects of raloxifene in healthy postmenopausal women, there was a decrease in the bone turnover markers, such as serum alkaline phosphatase level, serum osteocalcin level and urinary calcium excretion. \r\n\r\nRaloxifene was shown to inhibit estrogen-dependent proliferation of human breast cancer cells _in vitro_ and development of induced mammary tumors in rats _in vivo_. In adult female rats, raloxifene produced a greater regression of the mammary gland than . The MORE trial was a multicenter, randomized, double-blind clinical trial that investigated the long-term effects of the drug therapy in European and American postmenopausal women receiving raloxifene for 40 months. Additionally, a reduction in the incidence of invasive breast cancer was also demonstrates in the CORE and RUTH trials. Study findings demonstrated that compared to placebo, the risk of invasive breast cancer was decreased by 76% among postmenopausal women with osteoporosis. There was a decrease in the risk of estrogen receptor-positive breast cancer by 90% but there was no increase in the risk of endometrial cancer. Unlike hormone replacement therapy, raloxifene does not mediate proliferative or stimulatory effects on endometrial tissue. Findings from both animal and human studies demonstrated no significant changes in the histologic appearance of the endometrium.\r\n\r\nRaloxifene promotes estrogen-like effects on lipid metabolism. In a European trial that evaluated lipid profiles following raloxifene therapy over the 24-month period, there were significant decreases in the serum concentrations of total and low-density lipoprotein (LDL) cholesterol over a 24-month period of raloxifene therapy. Raloxifene is not associated with causing alterations in the serum levels of HDL cholesterol or triglycerides. As the HDL choesterol level is considered a strong inverse predictor of cardiovascular disease in women, the cardioprotective effects of raloxifene were questioned. Due to limited data on the long-term trials, it is not possible to determine whether the small lipid effects produced by raloxifene correlate with a smaller degree of cardioprotective activity compared with hormone replacement therapy.","Raloxifene is a selective estrogen receptor modulator that acts as both an estrogen agonist and antagonist via differential effects on the tissue-specific estrogen receptors. Based on the findings of competitive binding assays, raloxifene displays binding affinity that is similar to that of , the predominant circulating estrogen. Estrogens play variable roles at different tissues in females, including the bone, breasts, uterus and liver, by binding to the steroid nuclear hormone receptors, Estrogen Receptor alpha (ERα) or Estrogen Receptor beta (ERβ). These receptors are normally bound to the Heat Shock Protein 90 (Hsp90) when unbound to the ligand. Ligand binding induces a conformational change in the receptor that promotes dissociation of the receptor from Hsp90, dimerization and translocation into the nucleus. This movement into the nucleus allows the receptor to bind to genomic locations based on sequence recognition of the DNA binding domain, also known as the Estrogen Response Elements (EREs). \r\n\r\nIn bones, endogenous estrogens normally modulate multiple DNA response elements, including the gene-encoding transforming growth factor-β3 (TGF-β3), which is a cytokine embedded in the bone matrix. TGF-β3 plays an important role in bone remodelling by working with other cytokines to induce production of osteoblasts, such as IL-6, and attenuate the activity of osetoclasts. Estrogens typically maintain the bone integrity by inhibiting the cytokines that recruit osteoclasts and oppose the bone-resorbing, Ca2+-mobilizing action of parathyroid hormone. In contrast, estrogens promote osteoblast proliferation, augment the production of TGF-β3 and bone morphogenic proteins, and inhibit apoptosis. Mimicking the action of endogenous estrogen in bone tissues, raloxifene binds to the estrogen receptor to influence gene transcription through interactions with the estrogen response element (ERE) and a distinct DNA target, the raloxifene response element (RRE). It occupies the same ER ligand binding site as estrogen. Upon binding, raloxifene induces a conformational change of the receptor, allowing mediation of direct binding to transcriptional elements by accessory proteins. Increased expression of bone matrix proteins, such as alkaline phosphatase, osteonectin, osteocalcin and collagen may be seen. The agonistic or antagonistic action of raloxifene depends on the extent of recruitment of coactivators and corepressors to estrogen receptor (ER) target gene promotors. In breast tissues, raloxifene acts as an estrogen receptor antagonist to attenuate the estrogen-dependent proliferative effects of epithelial cell expansion. In addition to the antiproliferative effects, raloxifene prevents the production of cytokines and recruitment of macrophages and lymphocytes into tumor mass.","Estrogen receptor alpha agonist; Estrogen receptor beta agonist; Serpin B9; Trefoil factor 1","Therapeutic strategy associated"]
[165,"DB00482","approved; investigational","small molecule","Celecoxib","p-(5-p-Tolyl-3-(trifluoromethyl)pyrazol-1-yl)benzenesulfonamide","C17H14F3N3O2S","CC1=CC=C(C=C1)C1=CC(=NN1C1=CC=C(C=C1)S(N)(=O)=O)C(F)(F)F","Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is a nonsteroidal anti-inflammatory drug (NSAID) which is known for its decreased risk of causing gastrointestinal bleeding compared to other NSAIDS. It is used to manage symptoms of various types of arthritis pain and in familial adenomatous polyposis (FAP) to reduce precancerous polyps in the colon. It is marketed by Pfizer under the brand name Celebrex, and was initially granted FDA approval in 1998. \r\n\r\nInterestingly, selective COX-2 inhibitors (especially celecoxib), have been evaluated as potential cancer chemopreventive and therapeutic drugs in clinical trials for a variety of malignancies.","169590-42-5","381.372","Celecoxib is indicated for symptomatic treatment of adult osteoarthritis (OA) and adult rheumatoid arthritis (RA). Celecoxib is not a substitute for aspirin for cardiovascular event prophylaxis. \r\n\r\nIt may be also be used to treat acute pain from various sources, juvenile rheumatoid arthritis in children over 2, ankylosing spondylitis, and primary dysmenorrhea.\r\n\r\nCelecoxib, in combination with , is indicated for the management of acute pain in adults severe enough to require an opioid analgesic and in whom alternative treatments are inadequate.","\r\nCelecoxib inhibits cyclooxygenase 2 (COX-2) enzyme, reducing pain and inflammation. It is important to note that though the risk of bleeding with celecoxib is lower than with certain other NSAIDS, it exists nonetheless and caution must be observed when it is administered to those with a high risk of gastrointestinal bleeding.\r\n\r\n**A note on the risk of cardiovascular events**\r\n\r\nSignificant concerns regarding the safety of COX-2 selective NSAIDs emerged in the early 2000s. , another member of the COX-2 inhibitor drug class, also known as Vioxx, was withdrawn from the market due to prothrombotic cardiovascular risks. Following an FDA Advisory Committee meeting in 2005, in which data from large clinical outcome trials were evaluated, the FDA concluded that the risk for cardiovascular thrombotic events for both COX-2 selective NSAIDs and nonselective NSAIDs was evident. It was determined that the benefits of celecoxib treatment, however, outweighed the risks. Postmarketing cardiovascular outcomes trial (PRECISION) revealed that the lowest possible dose of celecoxib was similar in cardiovascular safety to moderate strength doses of both naproxen and ibuprofen. Patients who had previous cardiovascular events including acute MI, coronary revascularization, or coronary stent insertion were not evaluated in the trial. It is not advisable to administer NSAIDS to these groups of patients.\r","Unlike most NSAIDs, which inhibit both types of cyclooxygenases (COX-1 and COX-2), celecoxib is a selective noncompetitive inhibitor of cyclooxygenase-2 (COX-2) enzyme. COX-2 is expressed heavily in inflamed tissues where it is induced by inflammatory mediators. The inhibition of this enzyme reduces the synthesis of metabolites that include prostaglandin E2 (PGE2), prostacyclin (PGI2), thromboxane (TXA2), prostaglandin D2 (PGD2), and prostaglandin F2 (PGF2). Resultant inhibition of these mediators leads to the alleviation of pain and inflammation. \r\n\r\nBy inhibiting prostaglandin synthesis, non-steroidal anti-inflammatory drugs (NSAIDs) cause mucosal damage, ulceration and ulcer complication throughout the gastrointestinal tract. Celecoxib poses less of an ulceration risk than other NSAIDS, owing to its decreased effect on gastric mucosal prostaglandin synthesis when compared to placebo. \r\n\r\nCelecoxib exerts anticancer effects by binding to the cadherin-11 (CDH11)protein,  which is thought to be involved in the progression of tumors, and inhibiting the 3-phosphoinositide-dependent kinase-1 (PDK-1) signaling mechanism. In addition, celecoxib has been found to inhibit carbonic anhydrase enzymes 2 and 3, further enhancing its anticancer effects.\r\n\r\nAs mentioned in the pharmacodynamics section of this drug entry, celecoxib may cause an increased risk of thrombotic events. The risk of thrombosis resulting from COX-2 inhibition is caused by the vasoconstricting actions of thromboxane A2, leading to enhanced platelet aggregation, which is uncontrolled when the actions of prostacyclin, a platelet aggregation inhibitor, are suppressed through the inhibition of COX-2.","Prostaglandin G/H synthase 2 inhibitor; 3-phosphoinositide-dependent protein kinase 1 inhibitor; Carbonic anhydrase 2 inhibitor; Carbonic anhydrase 3 inhibitor; Cadherin-11 inhibitor","Therapeutic strategy associated"]
[166,"DB00484","approved","small molecule","Brimonidine","5-Bromo-6-(2-imidazolin-2-ylamino)quinoxaline; Bromoxidine","C11H10BrN5","BrC1=C(NC2=NCCN2)C=CC2=NC=CN=C12","Brimonidine is an alpha-adrenergic agonist and 2-imidazoline derivative that was first introduced in 1996. It is considered to be a third generation alpha-2 aadrenergic receptor agonist, since it displays preferential binding at alpha-2 adrenoceptors over alpha-1 receptors. Brimonidine displays a higher selectivity toward the alpha-2 adrenergic receptors than  or , which are also alpha-2 adrenergic agonists. Alpha-2 adrenergic agonists are members of the ocular hypotensive agent drug class that are used in the chronic treatment of glaucoma. Early treatment and management of glaucoma, which predominantly involves the lowering of intraocular pressure, is critical since glaucoma is considered to be a common cause of blindness worldwide. \r\n\r\nOphthalmically, brimonidine is used to lower intraocular pressure by reducing aqueous humor production and increasing uveoscleral outflow. Because it is oxidately stable, brimonidine is associated with fewer reports of ocular allergic reactions compared to other alpha-2 adrenergic agonists. The ophthalmic solution of brimonidine was first approved by the FDA in 1996 as Alphagan  and brimonidine is the only selective alpha-adrenergic receptor agonist approved for chronic treatment in glaucoma. Brimonidine is also found in ophthalmic solutions in combination with  under the market name Simbrinza for the reduction in intraocular pressure. Unlike nonselective beta-blockers used in ocular hypertension, brimonidine is not associated with significantly adverse cardiopulmonary side effects. Thus brimonidine is an effective and safe alternative to beta-blockers, in patients with, or at high risk for, cardiopulmonary disease. The topical form of brimonidine was approved by the FDA in August 2013 for the symptomatic treatment of persistent facial erythema of rosacea in adults. It is marketed under the brand name Mirvaso. Brimonidine is the first topical treatment approved for facial erythema of rosacea.","59803-98-4","292.135","**Opthalmic**\r\n\r\nIndicated for lowering intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension  as monotherapy or combination product with .\r\n\r\n**Topical**\r\n\r\nIndicated for the treatment of persistent (non-transient) facial erythema of rosacea in adults 18 years of age or older.","Brimonidine is a highly selective alpha-2 adrenergic receptor agonist that is 1000-fold more selective for the alpha2-adrenergic receptor than the alpha1-adrenergic receptor. This characteristic gives the drug some therapeutic advantages, since it reduces the risk of systemic side effects, such as systemic hypotension, bradycardia, and sedation. In addition, there is a reduction in the risk for developing alpha-1 mediated ocular unwanted effects, such as conjunctival blanching, mydriasis, and eyelid retraction. However, despite high alpha-2 receptor specificity, brimonidine may still produce alpha-1 adrenoceptor-mediated ocular effects, such as conjunctival vasoconstriction. Brimonidine has a peak ocular hypotensive effect occurring at two hours post-dosing. In a randomized, double-blind clinical study, ocular administration of 0.2% brimonidine in healthy volunteers resulted in a 23% reduction of mean intraocular pressure from baseline at 3 hours following administration. In comparative studies consisting of patients with open-angle glaucoma or ocular hypertension, the ocular hypotensive effect of brimonidine was maintained during treatment periods of up to 1 year. \r\n\r\nBrimonidine mediates vasoconstrictive effects and it was shown to exhibit anti-inflammatory properties in _ex vivo_ human skin model and _in vivo_ inflammation models. In a clinial trials consisting of adults with moderate to severe facial erythema of rosacea, brimonidine was shown to improve the extent of redness at 3 hours after application, compared to placebo. It was shown to be a potent vasoconstrictor of human subcutaneous vessels with a diameter of less than 200 µm. In _in vivo_ mouse inflammation models, brimonidine displayed anti-inflammatory properties by inhibiting edema. In a randomized, double-blind study, brimonidine reduced erythema for the 12 hours of the study in a dose-dependent manner.\r\n\r\nWhen adminsitered systemically, brimonidine was shown to cause cardiovascular effects by decreasing blood pressure, decreasing heart and respiratory rate, and prolonging the PR interval in the electrocardiogram. This is due to the targeting of adrenoceptors by the drug. Although the clinical significance has not been established, there is evidence that brimonidine exhibits neuroprotective activity in experimental models of cerebral ischemia and optic nerve injury. _In vitro_ studies show that brimonidine mediated protective effects on neuronal cells from kainate acid insult and on cultured retinal ganglion cells from glutamate-induced cytotoxicity, which is a possible mediator of secondary neuronal degeneration in human glaucoma. Neuroprotective actions of brimonidine were also demonstrated in rat models of acute retinal ischemia and chronic IOP elevation. It has been proposed that brimonidine may exert neuroprotective effects on the retina and optic nerve by enhancing intrinsic retinal ganglion cell survival mechanisms and/or induction of neuronal survival factors, such as bFGF. However, further investigations are needed to conclude on these possible therapeutic benefits of the drug.","In the eye, alpha-1 adrenoceptors play a role in vasoconstriction, mydriasis, eyelid retraction, and elevation of intraocular pressure (IOP) whereas alpha-2 adrenoceptors are responsible for IOP reduction via a complex Gi-coupled signaling cascade pathway. Activation of alpha-2 receptors leads to inhibition of adenylyl cyclase and reduction of cyclic AMP levels. As a result, there is a decrease in norpinephrine (NE) release at the synaptic junction, NE-induced stimulation of beta-2 adrenoceptors, and production of aqueous humor by the ciliary epithelium. An elevated IOP is the most significant risk factor for developing glaucomatous optic neuropathy, which is associated with progressive visual field loss and functional disability if left untreated. Regardless of the etiology of the disease, the aim of current therapies for glaucoma is to reduce IOP, as reduction of IOP significantly reduces the risk of progression of vision loss even when IOP is already within the normal range. When administered ophthalmically, brimonidine is rapidly absorbed into the eye, acts as an agonist at ocular alpha-2 adrenoceptors and lowers IOP via a dual mechanism of action. It is proposed that initial dosing of the drug causes a reduction in aqueous humour production and chronic dosing leads to an increase in uveoscleral outflow. Brimonidine does not affect episcleral venous pressure. By reducing IOP, brimonidine aims to reduce the likelihood of glaucomatous visual field loss in ocular hypertension, and slow the progression of visual field defect in established open-angle glaucoma. When applied topically on skin, brimonidine reduces erythema through direct vasocontriction of small arteries and veins. As brimonidine mediates a potent peripheral vasoconstrictive activity by selectively working on the alpha-2 adrenoceptors, the use of brimonidine is thought to be efficacious for the treatment of facial erythema of rosacea, which is thought to arise from vasomotor instability and abnormal vasodilation of the superficial cutaneous vasculature of the face.","Alpha-2A adrenergic receptor agonist; Alpha-2B adrenergic receptor agonist; Alpha-2C adrenergic receptor agonist","Therapeutic strategy associated"]
[167,"DB00487","approved","small molecule","Pefloxacin","Pefloxacine; PFLX","C17H20FN3O3","CCN1C=C(C(O)=O)C(=O)C2=CC(F)=C(C=C12)N1CCN(C)CC1","A synthetic broad-spectrum fluoroquinolone antibacterial agent active against most gram-negative and gram-positive bacteria.","70458-92-3","333.3574","For the treatment of uncomplicated gonococcal urethritis in males and for gram-negative-bacterial infections in the gastrointestinal system and the genitourinary tract.","Pefloxacin is a fluoroquinolone antibiotic. Flouroquinolones such as pefloxacin possess excellent activity against gram-negative aerobic bacteria such as <i>E.coli</i> and <i>Neisseria gonorrhoea</i> as well as gram-positive bacteria including <i>S. pneumoniae</i> and <i>Staphylococcus aureus</i>. They also posses effective activity against shigella, salmonella, campylobacter, gonococcal organisms, and multi drug resistant pseudomonas and enterobacter.","The bactericidal action of pefloxacin results from interference with the activity of the bacterial enzymes DNA gyrase and topoisomerase IV, which are needed for the transcription and replication of bacterial DNA. DNA gyrase appears to be the primary quinolone target for gram-negative bacteria. Topoisomerase IV appears to be the preferential target in gram-positive organisms. Interference with these two topoisomerases results in strand breakage of the bacterial chromosome, supercoiling, and resealing. As a result DNA replication and transcription is inhibited.","DNA topoisomerase 4 subunit A inhibitor; DNA gyrase subunit A inhibitor; DNA topoisomerase 2-alpha inhibitor; DNA topoisomerase 1 inhibitor","Indication associated"]
[168,"DB00489","approved","small molecule","Sotalol","4'-(1-hydroxy-2-(isopropylamino)ethyl)methane sulfonanilide; β-cardone","C12H20N2O3S","CC(C)NCC(O)C1=CC=C(NS(C)(=O)=O)C=C1","Sotalol is a methanesulfonanilide developed in 1960. It was the first of the class III anti arrhythmic drugs. Sotalol was first approved as an oral tablet on 30 October 1992. A racemic mixture of sotalol is currently formulated as a tablet, oral solution, and intravenous injection indicated for life threatening ventricular arrhythmias and maintaining normal sinus rhythm in atrial fibrillation or flutter.","3930-20-9","272.364","Sotalol is indicated to treat life threatening ventricular arrhytmias and maintain normal sinus rhythm in patients with atrial fibrillation or flutter. There are also oral solutions and intravenous injections indicated for patients requiring sotalol, but for whom a tablet would not be appropriate.","Sotalol is a competitive inhibitor of the rapid potassium channel. This inhibition lengthens the duration of action potentials and the refractory period in the atria and ventricles. The inhibition of rapid potassium channels is increases as heart rate decreases, which is why adverse effects like torsades de points is more likely to be seen at lower heart rates. L-sotalol also has beta adrenergic receptor blocking activity seen above plasma concentrations of 800ng/L. The beta blocking ability of sotalol further prolongs action potentials. D-sotalol does not have beta blocking activity but also reduces a patient's heart rate while standing or exercising. These actions combine to produce a negative inotropic effect that reduces the strength of contractility of muscle cells in the heart. Extension of the QT interval is also adversely associated with the induction of arrhythmia in patients.\r\n\r\nHyperglycemia is a greater risk for non insulin dependant diabetics than insulin dependant diabetics. Beta blockers inhibit insulin secretion which may cause hyperglycemia in type II diabetes mellitus. The risk of hypoglycemia is higher in insulin dependant diabetes than non insulin dependant diabetics. Beta blockers decrease secretion of insulin, which may mask hypoglycemia in an insulin dependant patient. Beta blockers also increase glucose uptake into cells which may prolong or potentiate hypoglycemia.\r\n\r\nFurther information regarding adverse reactions can be found here.","Sotalol inhibits beta-1 adrenoceptors in the myocardium as well as rapid potassium channels to slow repolarization, lengthen the QT interval, and slow and shorten conduction of action potentials through the atria. The action of sotalol on beta adrenergic receptors lengthens the sinus node cycle, conduction time through the atrioventricular node, refractory period, and duration of action potentials.","Potassium voltage-gated channel subfamily H member 2 inhibitor; Beta-1 adrenergic receptor antagonist; Beta-2 adrenergic receptor antagonist","Indication associated"]
[169,"DB00491","approved","small molecule","Miglitol",null,"C8H17NO5","OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO","Miglitol inhibits the breakdown complex carbohydrates into glucose. It is primarily used in diabetes mellitus type 2 for establishing greater glycemic control by preventing the digestion of carbohydrates (such as disaccharides, oligosaccharides, and polysaccharides) into monosaccharides which can be absorbed by the body.\r\n\r\nMiglitol should be taken at the start of a meal for maximal effect and the effect will depend on the amount of poly and oligosaccharides in the diet. Miglitol inhibits alpha-glucosidase, making less sugars available for digestion and reducing postprandial hyperglycemia.\r\n\r\nUnlike other drugs of the same class, miglitol is not metabolized and the unmetabolized drug is excreted by the kidneys.","72432-03-2","207.2243","For use as an adjunct to diet to improve glycemic control in patients with non-insulin-dependent diabetes mellitus (NIDDM) whose hyperglycemia cannot be managed with diet alone.","Miglitol, an oral alpha-glucosidase inhibitor, is a desoxynojirimycin derivative that delays the digestion of ingested carbohydrates, thereby resulting in a smaller rise in blood glucose concentration following meals. As a consequence of plasma glucose reduction, miglitol reduce levels of glycosylated hemoglobin in patients with Type II (non-insulin-dependent) diabetes mellitus. Systemic nonenzymatic protein glycosylation, as reflected by levels of glycosylated hemoglobin, is a function of average blood glucose concentration over time. Because its mechanism of action is different, the effect of miglitol to enhance glycemic control is additive to that of sulfonylureas when used in combination. In addition, miglitol diminishes the insulinotropic and weight-increasing effects of sulfonylureas. Miglitol has minor inhibitory activity against lactase and consequently, at the recommended doses, would not be expected to induce lactose intolerance.","In contrast to sulfonylureas, miglitol does not enhance insulin secretion. The antihyperglycemic action of miglitol results from a reversible inhibition of membrane-bound intestinal a-glucoside hydrolase enzymes. Membrane-bound intestinal a-glucosidases hydrolyze oligosaccharides and disaccharides to glucose and other monosaccharides in the brush border of the small intestine. In diabetic patients, this enzyme inhibition results in delayed glucose absorption and lowering of postprandial hyperglycemia.","Maltase-glucoamylase, intestinal antagonist&inhibitor; Lysosomal alpha-glucosidase antagonist; Neutral alpha-glucosidase AB antagonist; Neutral alpha-glucosidase C antagonist","Indication associated"]
[170,"DB00492","approved","small molecule","Fosinopril","Fosenopril; Fosinopril","C30H46NO7P","CCC(=O)O[C@@H](OP(=O)(CCCCC1=CC=CC=C1)CC(=O)N1C[C@@H](C[C@H]1C(O)=O)C1CCCCC1)C(C)C","Fosinopril is a phosphinic acid-containing ester prodrug that belongs to the angiotensin-converting enzyme (ACE) inhibitor class of medications. It is rapidly hydrolyzed to fosinoprilat, its principle active metabolite. Fosinoprilat inhibits ACE, the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). Fosinopril may be used to treat mild to moderate hypertension, as an adjunct in the treatment of congestive heart failure, and to slow the rate of progression of renal disease in hypertensive individuals with diabetes mellitus and microalbuminuria or overt nephropathy.","98048-97-6","563.672","For treating mild to moderate hypertension, use as an adjunct in treating congestive heart failure, and may be used to slow the rate of progression of renal disease in hypertensive individuals with diabetes mellitus and microalbuminuria or overt nephropathy.","Following oral administration, fosinopril is rapidly and completely hydrolyzed to its principle active metabolite, fosinoprilat. Hydrolysis is thought to occur in the gastrointestinal mucosa and liver. Fosinoprilat is a competitive inhibitor of ACE, a peptidyl dipeptidase that is part of the RAAS. The RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from the granular cells of the juxtaglomerular apparatus in the kidneys. In the blood stream, renin cleaves circulating angiotensinogen to ATI, which is subsequently cleaved to ATII by ACE. ATII increases blood pressure using a number of mechanisms. First, it stimulates the secretion of aldosterone from the adrenal cortex. Aldosterone travels to the distal convoluted tubule (DCT) and collecting tubule of nephrons where it increases sodium and water reabsorption by increasing the number of sodium channels and sodium-potassium ATPases on cell membranes. Second, ATII stimulates the secretion of vasopressin (also known as antidiuretic hormone or ADH) from the posterior pituitary gland. ADH stimulates further water reabsorption from the kidneys via insertion of aquaporin-2 channels on the apical surface of cells of the DCT and collecting tubules. Third, ATII increases blood pressure through direct arterial vasoconstriction. Stimulation of the Type 1 ATII receptor on vascular smooth muscle cells leads to a cascade of events resulting in myocyte contraction and vasoconstriction. In addition to these major effects, ATII induces the thirst response via stimulation of hypothalamic neurons. ACE inhibitors inhibit the rapid conversion of ATI to ATII and antagonize RAAS-induced increases in blood pressure. ACE (also known as kininase II) is also involved in the enzymatic deactivation of bradykinin, a vasodilator. Inhibiting the deactivation of bradykinin increases bradykinin levels and may further sustain the effects of fosinoprilat by causing increased vasodilation and decreased blood pressure.","There are two isoforms of ACE: the somatic isoform, which exists as a glycoprotein comprised of a single polypeptide chain of 1277; and the testicular isoform, which has a lower molecular mass and is thought to play a role in sperm maturation and binding of sperm to the oviduct epithelium. Somatic ACE has two functionally active domains, N and C, which arise from tandem gene duplication. Although the two domains have high sequence similarity, they play distinct physiological roles. The C-domain is predominantly involved in blood pressure regulation while the N-domain plays a role in hematopoietic stem cell differentiation and proliferation. ACE inhibitors bind to and inhibit the activity of both domains, but have much greater affinity for and inhibitory activity against the C-domain. Fosinoprilat, the active metabolite of fosinopril, competes with ATI for binding to ACE and inhibits and enzymatic proteolysis of ATI to ATII. Decreasing ATII levels in the body decreases blood pressure by inhibiting the pressor effects of ATII as described in the Pharmacology section above. Fosinoprilat also causes an increase in plasma renin activity likely due to a loss of feedback inhibition mediated by ATII on the release of renin and/or stimulation of reflex mechanisms via baroreceptors.","Angiotensin-converting enzyme inhibitor","Indication associated"]
[171,"DB00498","approved; investigational","small molecule","Phenindione","2-phenyl-1,3-diketohydrindene; 2-Phenyl-1,3-indandione; 2-phenyl-1,3(2H)-Indenedione; Phenindione; PID","C15H10O2","O=C1C(C(=O)C2=CC=CC=C12)C1=CC=CC=C1","An indandione that has been used as an anticoagulant. Phenindione has actions similar to warfarin, but it is now rarely employed because of its higher incidence of severe adverse effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p234)","83-12-5","222.2387","For the treatment of pulmonary embolism, cardiomyopathy, atrial fibrillation and flutter, cerebral embolism, mural thrombosis, and thrombophili. Also used for anticoagulant prophylaxis.","Phenindione thins the blood by antagonizing vitamin K which is required for the production of clotting factors in the liver. Anticoagulants such as Phenindione have no direct effect on an established thrombus, nor do they reverse ischemic tissue damage (damage caused by an inadequate blood supply to an organ or part of the body). However, once a thrombus has occurred, the goal of anticoagulant treatment is to prevent further extension of the formed clot and prevent secondary thromboembolic complications which may result in serious and possibly fatal sequelae. Phenindione has actions similar to warfarin, but it is now rarely employed because of its higer incidence of severe adverse effects.","Phenindione inhibits vitamin K reductase, resulting in depletion of the reduced form of vitamin K (vitamin KH2). As vitamin K is a cofactor for the carboxylation of glutamate residues on the N-terminal regions of vitamin K-dependent proteins, this limits the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulant proteins. The synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S is inhibited. Depression of three of the four vitamin K-dependent coagulation factors (factors II, VII, and X) results in decreased prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.","Vitamin K epoxide reductase complex subunit 1 inhibitor","Indication associated"]
[172,"DB00500","approved","small molecule","Tolmetin","1-Methyl-5-(4-methylbenzoyl)-pyrrole-2-acetic acid; 1-Methyl-5-p-toluoylpyrrole-2-acetic acid; 5-(p-Toluoyl)-1-methylpyrrole-2-acetic acid; Tolmetin","C15H15NO3","CN1C(CC(O)=O)=CC=C1C(=O)C1=CC=C(C)C=C1","A non-steroidal anti-inflammatory agent (anti-inflammatory agents, NON-steroidal) similar in mode of action to indomethacin.","26171-23-3","257.2845","For the relief of signs and symptoms of rheumatoid arthritis and osteoarthritis, including the treatment of acute flares long-term management. Also for treatment of juvenile rheumatoid arthritis.","Tolmetin is a nonsteroidal anti-inflammatory agent. Studies in animals have shown tolmetin to possess anti-inflammatory, analgesic and antipyretic activity. In the rat, tolmetin prevents the development of experimentally induced polyarthritis and also decreases established inflammation. In patients with either rheumatoid arthritis or osteaoarthritis, tolmetin is as effective as aspirin and indomethacin in controlling disease activity, but the frequency of the milder gastrointestinal adverse effects and tinnitus was less than in aspirin-treated patients, and the incidence of central nervous system adverse effects was less than in indomethacin-treated patients. In patients with juvenile rheumatoid arthritis, tolmetin is as effective as aspirin in controlling disease activity, with a similar incidence of adverse reactions. tolmetin has produced additional therapeutic benefit when added to a regimen of gold salts and, to a lesser extent, with corticosteroids. Tolmetin should not be used in conjunction with salicylates since greater benefit from the combination is not likely, but the potential for adverse reactions is increased.","The mode of action of tolmetin is not known. However, studies in laboratory animals and man have demonstrated that the anti-inflammatory action of tolmetin is not due to pituitary-adrenal stimulation. Tolmetin inhibits prostaglandin synthetase in vitro and lowers the plasma level of prostaglandin E in man. This reduction in prostaglandin synthesis may be responsible for the anti-inflammatory action. Tolmetin does not appear to alter the course of the underlying disease in man.","Prostaglandin G/H synthase 2 inhibitor; Prostaglandin G/H synthase 1 inhibitor","Therapeutic strategy associated"]
[173,"DB00504","approved","small molecule","Levallorphan",null,"C19H25NO","[H][C@@]12CCCC[C@@]11CCN(CC=C)[C@@H]2CC2=C1C=C(O)C=C2","An opioid antagonist with properties similar to those of naloxone; in addition it also possesses some agonist properties. It should be used cautiously; levallorphan reverses severe opioid-induced respiratory depression but may exacerbate respiratory depression such as that induced by alcohol or other non-opioid central depressants. (From Martindale, The Extra Pharmacopoeia, 30th ed, p683)","152-02-3","283.4079","For the complete or partial reversal of narcotic depression, including respiratory depression, induced by opioids.","Levallorphan, an opioid antagonist similar to naloxone, is used to treat drug overdoses. Levallorphan differs from naloxone in that it also possesses some agonist properties. It is an analogue of levelorphanol that counteracts the actions of narcotic analgesics such as morphine. It is used especially in the treatment of respiratory depression due to narcotic overdoses. Levallorphan prevents or reverses the effects of opioids including respiratory depression, sedation and hypotension. Also, it can reverse the psychotomimetic and dysphoric effects of agonist-antagonists such as pentazocine.","Levallorphan antagonizes opioid effects by competing for the same receptor sites. It binds to the opioid mu receptor and the nicotinic acetylcholine receptor alpha2/alpha3.","Mu-type opioid receptor partial agonist","Indication associated"]
[174,"DB00509","approved; investigational","small molecule","Dextrothyroxine","D-thyroxine; Dextrothyroxine; O-(4-hydroxy-3,5-diiodophenyl)-3,5-diiodo-D-tyrosine","C15H11I4NO4","N[C@H](CC1=CC(I)=C(OC2=CC(I)=C(O)C(I)=C2)C(I)=C1)C(O)=O","The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (monoiodotyrosine) and the coupling of iodotyrosines (diiodotyrosine) in the thyroglobulin. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form triiodothyronine which exerts a broad spectrum of stimulatory effects on cell metabolism.","51-49-0","776.87","Used to lower high cholesterol levels in the blood.","Dextrothyroxine, the dextrorotary isomer of the synthetic thyroxine, is a antihyperlipidemic.","Dextrothyroxine is a antihyperlipidemic. The mechanism of action is not completely understood, but dextrothyroxine apparently acts in the liver to stimulate formation of low-density lipoprotein (LDL) and, to a much greater extent, to increase catabolism of LDL. This leads to increased excretion of cholesterol and bile acids via the biliary route into the feces, with a resulting reduction in serum cholesterol and LDL. Dextrothyroxine has no significant effect on high-density lipoproteins (HDL).\r\nInherently, it will also bind to thyroid receptors and as it is a prohormone, it will bind as a substrate to iodide peroxidase.","Thyroid hormone receptor alpha agonist; Thyroid hormone receptor beta agonist; Thyroid peroxidase","Target associated"]
[175,"DB00519","approved","small molecule","Trandolapril","Trandolapril","C24H34N2O5","[H][C@@]12C[C@H](N(C(=O)[C@H](C)N[C@@H](CCC3=CC=CC=C3)C(=O)OCC)[C@@]1([H])CCCC2)C(O)=O","Trandolapril is a non-sulhydryl prodrug that belongs to the angiotensin-converting enzyme (ACE) inhibitor class of medications. It is metabolized to its biologically active diacid form, trandolaprilat, in the liver. Trandolaprilat inhibits ACE, the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). Trandolapril may be used to treat mild to moderate hypertension, to improve survival following myocardial infarction in clinically stable patients with left ventricular dysfunction, as an adjunct treatment for congestive heart failure, and to slow the rate of progression of renal disease in hypertensive individuals with diabetes mellitus and microalbuminuria or overt nephropathy.","87679-37-6","430.5372","For the treatment of mild to moderate hypertension, as an adjunct in the treatment of congestive heart failure (CHF), to improve survival following myocardial infarction (MI) in individuals who are hemodynamically stable and demonstrate symptoms of left ventricular systolic dysfunction or signs of CHF within a few days following acute MI, and to slow progression of renal disease in hypertensive patients with diabetes mellitus and microalbuminuria or overt nephropathy.","Trandolapril is the ethyl ester prodrug of a nonsulfhydryl ACE inhibitor, trandolaprilat. Trandolapril is deesterified in the liver to the diacid metabolite, trandolaprilat, which is approximately eight times more active as an inhibitor of ACE than its parent compound. ACE is a peptidyl dipeptidase that is part of the RAAS. The RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from the granular cells of the juxtaglomerular apparatus in the kidneys. In the blood stream, renin cleaves circulating angiotensinogen to ATI, which is subsequently cleaved to ATII by ACE. ATII increases blood pressure via a number of mechanisms. First, it stimulates the secretion of aldosterone from the adrenal cortex. Aldosterone travels to the distal convoluted tubule (DCT) and collecting tubule of nephrons where it increases sodium and water reabsorption by increasing the number of sodium channels and sodium-potassium ATPases on cell membranes. Second, ATII stimulates the secretion of vasopressin (also known as antidiuretic hormone or ADH) from the posterior pituitary gland. ADH stimulates further water reabsorption from the kidneys via insertion of aquaporin-2 channels on the apical surface of cells of the DCT and collecting tubules. Third, ATII increases blood pressure through direct arterial vasoconstriction. Stimulation of the Type 1 ATII receptor on vascular smooth muscle cells leads to a cascade of events resulting in myocyte contraction and vasoconstriction. In addition to these major effects, ATII induces the thirst response via stimulation of hypothalamic neurons. ACE inhibitors inhibit the rapid conversion of ATI to ATII and antagonize RAAS-induced increases in blood pressure. ACE (also known as kininase II) is also involved in the enzymatic deactivation of bradykinin, a vasodilator. Inhibiting the deactivation of bradykinin increases bradykinin levels and may further sustain the effects of trandolaprilat by causing increased vasodilation and decreased blood pressure. The blood pressure lowering effect of trandolaprilat is due to a decrease in peripheral vascular resistance, which is not accompanied by significant changes in urinary excretion of chloride or potassium or water or sodium retention.","There are two isoforms of ACE: the somatic isoform, which exists as a glycoprotein comprised of a single polypeptide chain of 1277; and the testicular isoform, which has a lower molecular mass and is thought to play a role in sperm maturation and binding of sperm to the oviduct epithelium. Somatic ACE has two functionally active domains, N and C, which arise from tandem gene duplication. Although the two domains have high sequence similarity, they play distinct physiological roles. The C-domain is predominantly involved in blood pressure regulation while the N-domain plays a role in hematopoietic stem cell differentiation and proliferation. ACE inhibitors bind to and inhibit the activity of both domains, but have much greater affinity for and inhibitory activity against the C-domain. Trandolaprilat, the active metabolite of trandolapril, competes with ATI for binding to ACE and inhibits and enzymatic proteolysis of ATI to ATII. Decreasing ATII levels in the body decreases blood pressure by inhibiting the pressor effects of ATII as described in the Pharmacology section above. Trandolaprilat also causes an increase in plasma renin activity likely due to a loss of feedback inhibition mediated by ATII on the release of renin and/or stimulation of reflex mechanisms via baroreceptors.","Angiotensin-converting enzyme inhibitor","Indication associated"]
[176,"DB00521","approved","small molecule","Carteolol",null,"C16H24N2O3","CC(C)(C)NCC(O)COC1=CC=CC2=C1CCC(=O)N2","A beta-adrenergic antagonist used as an anti-arrhythmia agent, an anti-angina agent, an antihypertensive agent, and an antiglaucoma agent.","51781-06-7","292.3734","For the treatment of intraocular hypertension and chronic open-angle glaucoma","Carteolol is a beta1 and beta2 (non-selective) adrenergic receptor-blocking agent that does not have significant intrinsic sympathomimetic, direct myocardial depressant, or local anesthetic (membrane-stabilizing) activity. Carteolol, when applied topically to the eye, has the action of reducing elevated, as well as normal, intraocular pressure, whether or not accompanied by glaucoma. Elevated intraocular pressure is a major risk factor in the pathogenesis of glaucomatous visual field loss and optic nerve damage. Carteolol reduces intraocular pressure with little or no effect on pupil size or accommodation in contrast to the miosis which cholinergic agents are known to produce.","The primary mechanism of the ocular hypotensive action of carteolol in reducing intraocular pressure is most likely a decrease in aqueous humor production. This process is initiated by the non-selective beta1 and beta2 adrenergic receptor blockade.","Beta-2 adrenergic receptor antagonist; Beta-1 adrenergic receptor partial agonist","Indication associated"]
[177,"DB00524","approved","small molecule","Metolazone","2-Methyl-3-o-tolyl-6-sulfamyl-7-chloro-1,2,3,4-tetrahydro-4-quinazolinone; 7-Chloro-1,2,3,4-tetrahydro-2-methyl-3-(2-methylphenyl)-4-oxo-6-quinazolinesulfonamide; 7-Chloro-1,2,3,4-tetrahydro-2-methyl-4-oxo-3-o-tolyl-6-quinazolinesulfonamide; Metolazone","C16H16ClN3O3S","CC1NC2=CC(Cl)=C(C=C2C(=O)N1C1=CC=CC=C1C)S(N)(=O)=O","A quinazoline-sulfonamide that is considered a thiazide-like diuretic which is long-acting so useful in chronic renal failure. It also tends to lower blood pressure and increase potassium loss.","17560-51-9","365.835","For the treatment of hypertension, alone or in combination with other antihypertensive drugs of a different class.","Metolazone is a quinazoline diuretic, with properties generally similar to the thiazide diuretics. A proximal action of metolazone has been shown in humans by increased excretion of phosphate and magnesium ions and by a markedly increased fractional excretion of sodium in patients with severely compromised glomerular filtration. This action has been demonstrated in animals by micropuncture studies.","The actions of metolazone result from interference with the renal tubular mechanism of electrolyte reabsorption. Metolazone acts primarily to inhibit sodium reabsorption at the cortical diluting site and to a lesser extent in the proximal convoluted tubule. Sodium and chloride ions are excreted in approximately equivalent amounts. The increased delivery of sodium to the distal tubular exchange site results in increased potassium excretion. Metolazone does not inhibit carbonic anhydrase. The antihypertensive mechanism of action of metolazone is not fully understood but is presumed to be related to its saluretic and diuretic properties.","Solute carrier family 12 member 3 inhibitor","Therapeutic strategy associated"]
[178,"DB00528","approved; investigational","small molecule","Lercanidipine","Lercanidipine","C36H41N3O6","COC(=O)C1=C(C)NC(C)=C(C1C1=CC(=CC=C1)[N+]([O-])=O)C(=O)OC(C)(C)CN(C)CCC(C1=CC=CC=C1)C1=CC=CC=C1","Lercanidipine is a calcium channel blocker of the dihydropyridine class. It is sold under various commercial names including Zanidip.","100427-26-7","611.7272","For the treatment of Hypertension, management of angina pectoris and Raynaud's syndrome","Lercanidipine, a dihydropyridine calcium-channel blocker, is used alone or with an angiotensin-converting enzyme inhibitor, to treat hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina. Lercanidipine is similar to other peripheral vasodilators. Lercanidipine inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.","By deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, Lercanidipine inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.","Voltage-dependent calcium channel gamma-1 subunit inhibitor","Indication associated"]
[179,"DB00533","approved; investigational; withdrawn","small molecule","Rofecoxib","3-phenyl-4-[4-(methylsulfonyl)phenyl]-2(5H)-furanone; 4-[4-(methylsulfonyl)phenyl]-3-phenyl-2(5H)-furanone","C17H14O4S","CS(=O)(=O)C1=CC=C(C=C1)C1=C(C(=O)OC1)C1=CC=CC=C1","Rofecoxib is used for the treatment of osteoarthritis, rheumatoid arthritis, acute pain in adults, and primary dysmenorrhea, as well as acute treatment of migraine attacks with or without auras. Rofecoxib is a solid. This compound belongs to the stilbenes. These are organic compounds containing a 1,2-diphenylethylene moiety. Stilbenes (C6-C2-C6 ) are derived from the common phenylpropene (C6-C3) skeleton building block. The introduction of one or more hydroxyl groups to a phenyl ring lead to stilbenoids. Rofecoxib has a half-life of 17 hours and its mean oral bioavailability at therapeutically recommended doses of 125, 25, and 50 mg is approximately 93%. The proteins that rofecoxib target include elastin and prostaglandin G/H synthase 2. Cytochrome P450 1A2, Cytochrome P450 3A4, Cytochrome P450 2C9, Cytochrome P450 2C8, and Prostaglandin G/H synthase 1 are known to metabolize rofecoxib. On September 30, 2004, Merck voluntarily withdrew rofecoxib from the market because of concerns about increased risk of heart attack and stroke associated with long-term, high-dosage use.","162011-90-7","314.356","For the treatment of osteoarthritis, rheumatoid arthritis, acute pain in adults, and primary dysmenorrhea, as well as acute treatment of migraine attacks with or without auras.","Rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is classified as a nonsteroidal anti-inflammatory drug (NSAID). Unlike celecoxib, rofecoxib lacks a sulfonamide chain and does not require CYP450 enzymes for metabolism. Like other NSAIDs, rofecoxib exhibits anti-inflammatory, analgesic, and antipyretic activity. NSAIDs appear to inhibit prostaglandin synthesis via the inhibition of cyclooxygenase (COX), which are responsible for catalyzing the formation of prostaglandins in the arachidonic acid pathyway. There are at least two isoenzymes, COX-1 and COX-2, that have been identified. Although the exact mechanisms have not been clearly established, NSAIDs exert their anti-inflammatory, analgesic, and antipyretic primarily through the inhibition of COX-2. The inhibition of COX-1 is principally responsible for the negative effects on the GI mucosa. As rofecoxib is selective for COX-2, it may be potentially associated with a decreased risk of certain adverse events, but more data is needed to fully evaulate the drug.","The anti-inflammatory, analgesic, and antipyretic effects of NSAIDs appear to result from the inhibition of prostaglandin synthesis. Although the exact mechanism of action has not been determined, these effects appear to be mediated through the inhibition of the COX-2 isoenzyme at the sites of inflammation with subsequent reduction in the synthesis of certain prostaglandins from their arachidonic acid precursors. Rofecoxib selectively inhibits the cyclooxygenase-2 (COX-2) enzyme, which is important for the mediation of inflammation and pain. Unlike non-selective NSAIDs, rofecoxib does not inhibit platelet aggregation. It also has little to no affinity for COX-1.","Prostaglandin G/H synthase 2 inhibitor; Elastin other/unknown","Therapeutic strategy associated"]
[180,"DB00535","approved","small molecule","Cefdinir","(6R,7R,Z)-7-(2-(2-aminothiazol-4-yl)-2-(hydroxyimino)acetamido)-8-oxo-3-vinyl-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid; (6R,7R)-7-{2-(2-Amino-thiazol-4-yl)-2-[(Z)-hydroxyimino]-acetylamino}-8-oxo-3-vinyl-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid; CFDN","C14H13N5O5S2","[H][C@]12SCC(C=C)=C(N1C(=O)[C@H]2NC(=O)C(=N/O)\\C1=CSC(N)=N1)C(O)=O","Cefdinir, also known as Omnicef, is a semi-synthetic, broad-spectrum antibiotic belonging to the third generation of the cephalosporin class. It has been proven to be effective for the treatment of common bacterial infections in the ear, sinus, throat, lungs, and skin. Cefdinir was approved by the FDA in 1997 to treat a variety of mild to moderate infections and was initially marketed by Abbvie. Because of its chemical structure, it is effective against organisms that are resistant to first-line cephalosporin therapy due to the production of beta-lactamase enzymes.","91832-40-5","395.414","Cefdinir is indicated to treat acute bacterial otitis media, acute maxillary sinusitis, community-acquired (CA) pneumonia, acute bacterial exacerbations of chronic bronchitis, pharyngitis/tonsillitis, and uncomplicated skin and skin structure infections in children and adults.\r\n\r\nThe organisms susceptible to cefdinir have been listed below in addition to their associated clinical condition that may be treated with cefdinir. Various beta-lactamase producing organisms may be treated, as indicated in certain sections below.\r\n\r\n**Respiratory**\r\nAcute bacterial exacerbations of chronic bronchitis caused by Haemophilus influenzae, Haemophilus parainfluenzae, Streptococcus pneumoniae (penicillin-susceptible only), and Moraxella catarrhalis\r\n\r\nCommunity-acquired pneumonia caused by Haemophilus influenzae, Haemophilus parainfluenzae, Streptococcus pneumoniae (penicillin-susceptible only), and Moraxella catarrhalis\r\n\r\n**Ear, nose, and throat** \r\nAcute bacterial otitis media caused by Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae (penicillin-susceptible only)\r\n\r\nTonsillitis caused by Streptococcus pyogenes\r\n\r\nPharyngitis caused by Streptococcus pyogenes\r\n\r\nAcute maxillary sinusitis caused by Haemophilus pneumoniae and Streptococcus pneumoniae (penicillin-susceptible only), and Moraxella catarrhalis\r\n\r\n**Skin and skin structure infections**\r\n\r\nUncomplicated skin and skin structure infections caused by Staphylococcus aureus and Streptococcus pyogenes","Cefdinir is a bactericidal agent that treats bacterial infections by interfering with cell wall synthesis.\r\nCefdinir exerts broad-spectrum activity against a variety of gram-positive and gram-negative bacterial infections. It is effective against several beta-lactamase enzyme producing bacteria. As a result, many organisms that are resistant to other cephalosporins may be susceptible to cefdinir.","Five-member thiazolidine rings that make up penicillins are replaced in cephalosporins by a six-member dihydrothiazine ring, conferring greater bactericidal activity. This This 6-member ring enables cefdinir and other cephalosporins to resist inactivation by certain bacterial enzymes.\r\n\r\nWith a mechanism similar to other beta-lactam antibiotics, the bactericidal activity of cefdinir is caused by the inhibition of cell wall synthesis via binding to penicillin-binding proteins (PBPs). Cefdinir, like other cephalosporins, penetrates the bacterial cell wall, combats inactivation by beta-lactamase enzymes, and inactivates penicillin-binding proteins. This interferes with the final step of transpeptidation in cell walls, eventually leading to cell lysis, which eventually leads to the death of bacteria that are susceptible to this drug. Cefdinir has shown affinity to penicillin protein binding proteins 2 and 3.  It has also been shown to inhibit transpeptidase enzymes of various bacteria, which may play a role in its bactericidal action. One in vitro study suggests that cefdinir inhibits myeloperoxidase release extracellularly. The impact of this potential drug target in relation to its mechanism of action is unknown.","Penicillin-binding protein 2 inhibitor; PBP3 inhibitor; Myeloperoxidase inhibitor; Peptidoglycan transpeptidase inhibitor","Indication associated"]
[181,"DB00537","approved; investigational","small molecule","Ciprofloxacin","1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid; 1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid; 1-Cyclopropyl-6-fluoro-4-oxo-7-piperazin-1-yl-1,4-dihydro-quinoline-3-carboxylic acid; 1-cyclopropyl-6-fluoro-4-oxo-7-piperazin-1-ylquinoline-3-carboxylic acid; 1-Cyclopropyl-6-fluoro-7-(4-methyl-piperazin-1-yl)-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid; 1-cyclopropyl-6-fluoro-7-hexahydro-1-pyrazinyl-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid; Ciprofloxacin","C17H18FN3O3","OC(=O)C1=CN(C2CC2)C2=CC(N3CCNCC3)=C(F)C=C2C1=O","Ciprofloxacin is a second generation fluoroquinolone that has spawned many derivative antibiotics. It is formulated for oral, intravenous, intratympanic, ophthalmic, and otic administration for a number of bacterial infections.\r\n\r\nThe first ciprofloxacin containing product was FDA approved on 22 October 1987.","85721-33-1","331.3415","Ciprofloxacin is only indicated in infections caused by susceptible bacteria.\r\n\r\nCiprofloxacin immediate release tablets, oral suspensions, and intravenous injections are indicated for the treatment of skin and skin structure infections, bone and joint infections, complicated intra-abdominal infections, nosocomial pneumonia, febrile neutropenia, adults who have inhaled anthrax, plague, chronic bacterial prostatitis, lower respiratory tract infections including acute exacerbations of chronic bronchitis, urinary tract infections, complicated urinary tract infections in pediatrics, complicated pyelonephritis in pediatrics, and acute sinusitis.\r\n\r\nA ciprofloxacin otic solution and otic suspension with hydrocortisone are indicated for acute otitis externa. Ciprofloxacin suspension with dexamethasone is indicated for acute otitis media in pediatric patients with tympanostomy tubes or acute otitis externa. A ciprofloxacin intratympanic injection is indicated for pediatric patients with bilateral otitis media with effusion who are having tympanostomy tubes placed or pediatric patients 6 months or older with acute otitis externa.\r\n\r\nA ciprofloxacin eye drop is indicated for bacterial corneal ulcers and conjunctivitis. A ciprofloxacin eye ointment is indicated for bacterial conjunctivitis.\r\n\r\nA ciprofloxacin extended release tablet is indicated for uncomplicated urinary tract infections, complicated urinary tract infections, and acute uncomplicated pyelonephritis.","Ciprofloxacin is a second generation fluoroquinolone that is active against many Gram negative and Gram positive bacteria. It produces its action through inhibition of bacterial DNA gyrase and topoisomerase IV. Ciprofloxacin binds to bacterial DNA gyrase with 100 times the affinity of mammalian DNA gyrase. There is no cross resistance between fluoroquinolones and other classes of antibiotics, so it may be of clinical value when other antibiotics are no longer effective. Ciprofloxain and its derivatives are also being investigated for its action against malaria, cancers, and AIDS.","Ciprofloxacin acts on bacterial topoisomerase II (DNA gyrase) and topoisomerase IV. Ciprofloxacin's targeting of the alpha subunits of DNA gyrase prevents it from supercoiling the bacterial DNA which prevents DNA replication.","DNA topoisomerase 4 subunit A inhibitor; DNA gyrase subunit A inhibitor; DNA topoisomerase 2-alpha inhibitor; Potassium voltage-gated channel subfamily H member 2; DNA gyrase subunit A; DNA topoisomerase 4 subunit A; DNA topoisomerase 4 subunit B; DNA gyrase subunit A; Multidrug resistance protein MdtK; Gyrase A; DNA gyrase subunit A","Indication associated"]
[182,"DB00539","approved; investigational","small molecule","Toremifene","Toremifene","C26H28ClNO","CN(C)CCOC1=CC=C(C=C1)C(=C(\\CCCl)C1=CC=CC=C1)\\C1=CC=CC=C1","A first generation nonsteroidal selective estrogen receptor modulator (SERM) that is structurally related to tamoxifen. Like tamoxifen, it is an estrogen agonist for bone tissue and cholesterol metabolism but is antagonistic on mammary and uterine tissue.","89778-26-7","405.96","For the treatment of metastatic breast cancer in postmenopausal women with estrogen receptor-positive or receptor-unknown tumors. Toremifene is currently under investigation as a preventative agent for prostate cancer in men with high-grade prostatic intraepithelial neoplasia and no evidence of prostate cancer.","Toremifene is an antineoplastic hormonal agent primarily used in the treatment of advanced breast cancer. Toremifene is a nonsteroidal agent that has demonstrated potent antiestrogenic properties in animal test systems. The antiestrogenic effects may be related to its ability to compete with estrogen for binding sites in target tissues such as breast. Toremifene inhibits the induction of rat mammary carcinoma induced by dimethylbenzanthracene (DMBA) and causes the regression of already established DMBA-induced tumors. In this rat model, Toremifene appears to exert its antitumor effects by binding the estrogen receptors. In cytosols derived from human breast adenocarcinomas, Toremifene competes with estradiol for estrogen receptor protein.","Toremifene is a nonsteroidal triphenylethylene derivative. Toremifene binds to estrogen receptors and may exert estrogenic, antiestrogenic, or both activities, depending upon the duration of treatment, animal species, gender, target organ, or endpoint selected. The antitumor effect of toremifene in breast cancer is believed to be mainly due to its antiestrogenic effects, in other words, its ability to compete with estrogen for binding sites in the cancer, blocking the growth-stimulating effects of estrogen in the tumor. Toremifene may also inhibit tumor growth through other mechanisms, such as induction of apoptosis, regulation of oncogene expression, and growth factors.","Estrogen receptor alpha modulator; Sex hormone-binding globulin","Therapeutic strategy associated"]
[183,"DB00540","approved","small molecule","Nortriptyline","10,11-dihydro-N-methyl-5H-dibenzo[a,d]cycloheptene-Δ5,γ-propylamine; 3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-N-methyl-1-propanamine; Demethylamitriptyline; Desmethylamitriptyline","C19H21N","CNCCC=C1C2=CC=CC=C2CCC2=CC=CC=C12","Nortriptyline hydrochloride, the active metabolite of , is a tricyclic antidepressant (TCA). It is used in the treatment of major depression and is also used off-label for chronic pain and other conditions.","72-69-5","263.3767","Nortriptyline is indicated for the relief of the symptoms of major depressive disorder (MDD). Some off-label uses for this drug include treatment of chronic pain, myofascial pain, neuralgia, and irritable bowel syndrome.","Nortriptyline exerts antidepressant effects likely by inhibiting the reuptake of serotonin and norepinephrine at neuronal cell membranes. It also exerts antimuscarinic effects through its actions on the acetylcholine receptor.","Though prescribing information does not identify a specific mechanism of action for nortriptyline, is believed that nortriptyline either inhibits the reuptake of the neurotransmitter serotonin at the neuronal membrane or acts at the level of the beta-adrenergic receptors. It displays a more selective reuptake inhibition for noradrenaline, which may explain increased symptom improvement after nortriptyline therapy. Tricyclic antidepressants do not inhibit monoamine oxidase nor do they affect dopamine reuptake. As with other tricyclics, nortriptyline displays affinity for other receptors including mACh receptors, histamine receptors, 5-HT receptors, in addition to other receptors.","Sodium-dependent noradrenaline transporter inhibitor; Sodium-dependent serotonin transporter inhibitor; 5-hydroxytryptamine receptor 2A antagonist; 5-hydroxytryptamine receptor 1A antagonist; Histamine H1 receptor antagonist; Alpha-1A adrenergic receptor antagonist; Alpha-1D adrenergic receptor antagonist; 5-hydroxytryptamine receptor 2C antagonist&downregulator; Alpha-1B adrenergic receptor antagonist; Alpha-2 adrenergic receptors antagonist; Beta adrenergic receptor antagonist; Dopamine D2 receptor antagonist; Sigma receptor binder; 5-hydroxytryptamine receptor 1C antagonist; Muscarinic acetylcholine receptor antagonist","Indication associated"]
[184,"DB00542","approved; investigational","small molecule","Benazepril",null,"C24H28N2O5","[H][C@@]1(CCC2=CC=CC=C2N(CC(O)=O)C1=O)N[C@@H](CCC1=CC=CC=C1)C(=O)OCC","Benazepril, brand name Lotensin, is a medication used to treat high blood pressure (hypertension), congestive heart failure, and chronic renal failure. Upon cleavage of its ester group by the liver, benazepril is converted into its active form benazeprilat, a non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor.","86541-75-5","424.4895","Benazepril is indicated for the treatment of hypertension. It may be used alone or in combination with thiazide diuretics.","Benazepril, an angiotensin-converting enzyme (ACE) inhibitor, is a prodrug which, when hydrolyzed by esterases to its active Benazeprilat, is used to treat hypertension and heart failure, to reduce proteinuria and renal disease in patients with nephropathies, and to prevent stroke, myocardial infarction, and cardiac death in high-risk patients. Benazepril and Benazeprilat inhibit angiotensin-converting enzyme (ACE) in human subjects and animals. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex.","Benazeprilat, the active metabolite of Benazepril, competes with angiotensin I for binding at the angiotensin-converting enzyme, blocking the conversion of angiotensin I to angiotensin II. Inhibition of ACE results in decreased plasma angiotensin II. As angiotensin II is a vasoconstrictor and a negative-feedback mediator for renin activity, lower concentrations result in a decrease in blood pressure and stimulation of baroreceptor reflex mechanisms, which leads to decreased vasopressor activity and to decreased aldosterone secretion.","Angiotensin-converting enzyme inhibitor","Indication associated"]
[185,"DB00543","approved","small molecule","Amoxapine","2-Chloro-11-(1-piperazinyl)dibenz(b,f)(1,4)oxazepine; Amoxapine; Desmethylloxapin","C17H16ClN3O","ClC1=CC2=C(OC3=CC=CC=C3N=C2N2CCNCC2)C=C1","Amoxapine, the <i>N</i>-demethylated derivative of the antipsychotic agent loxapine, is a dibenzoxazepine-derivative tricyclic antidepressant (TCA). TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, amoxapine does not affect mood or arousal, but may cause sedation. In depressed individuals, amoxapine exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. In addition, TCAs down-regulate cerebral cortical &beta;-adrenergic receptors and sensitize post-synaptic serotonergic receptors with chronic use. The antidepressant effects of TCAs are thought to be due to an overall increase in serotonergic neurotransmission. TCAs also block histamine H<sub>1</sub> receptors, &alpha;<sub>1</sub>-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively. See toxicity section below for a complete listing of side effects. Amoxapine may be used to treat neurotic and reactive depressive disorders, endogenous and psychotic depression, and mixed symptoms of depression and anxiety or agitation.","14028-44-5","313.781","For the relief of symptoms of depression in patients with neurotic or reactive depressive disorders as well as endogenous and psychotic depressions. May also be used to treat depression accompanied by anxiety or agitation.","Amoxapine is a tricyclic antidepressant of the dibenzoxazepine class, chemically distinct from the dibenzodiazepines, dibenzocycloheptenes, and dibenzoxepines. It has a mild sedative component to its action. The mechanism of its clinical action in man is not well understood. In animals, amoxapine reduced the uptake of nor-epinephirine and serotonin and blocked the response of dopamine receptors to dopamine. Amoxapine is not a monoamine oxidase inhibitor. Clinical studies have demonstrated that amoxapine has a more rapid onset of action than either amitriptyline or imipramine","Amoxapine acts by decreasing the reuptake of norepinephrine and serotonin (5-HT).","Sodium-dependent noradrenaline transporter inhibitor; Sodium-dependent serotonin transporter inhibitor; Dopamine D2 receptor antagonist; Dopamine D1 receptor antagonist; Alpha-2A adrenergic receptor antagonist; Alpha-1A adrenergic receptor antagonist; Muscarinic acetylcholine receptor M1 antagonist; Gamma-aminobutyric acid receptor subunit alpha-1 antagonist; 5-hydroxytryptamine receptor 2A antagonist; 5-hydroxytryptamine receptor 2C antagonist; 5-hydroxytryptamine receptor 6 antagonist; 5-hydroxytryptamine receptor 7 antagonist; Dopamine D3 receptor antagonist; Dopamine D4 receptor antagonist; Histamine H1 receptor antagonist; Alpha-1 adrenergic receptors antagonist; Muscarinic acetylcholine receptor antagonist; 5-hydroxytryptamine receptor 2B antagonist; 5-hydroxytryptamine receptor 3A antagonist; 5-hydroxytryptamine receptor 1A antagonist; 5-hydroxytryptamine receptor 1B antagonist; Alpha-2 adrenergic receptors antagonist; Histamine H4 receptor binder; GABA(A) Receptor binder; Sodium-dependent dopamine transporter binder","Indication associated"]
[186,"DB00547","approved","small molecule","Desoximetasone","(11β,16α)-9-fluoro-11,21-dihydroxy-16-methylpregna-1,4-diene-3,20-dione; 9alpha-fluoro-16alpha-methyl-delta(1)-corticosterone; Deoxymethasone; Desoximetasone; Desoxymethasone","C22H29FO4","[H][C@@]12C[C@@H](C)[C@H](C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])CCC2=CC(=O)C=C[C@]12C","A topical anti-inflammatory glucocorticoid used in dermatoses, skin allergies, psoriasis, etc.","382-67-2","376.4617","For the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses.","Like other topical corticosteroids, desoximetasone has anti-inflammatory, antipruritic, and vasoconstrictive properties. Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Desoximetasone is a potent topical corticosteroid that should not be used with occlusive dressings. It is recommended that treatment should be limited to 2 consecutive weeks and therapy should be discontinued when adequate results have been achieved.","The precise mechanism of the antiinflammatory activity of topical steroids in the treatment of steroid-responsive dermatoses, in general, is uncertain. However, corticosteroids are thought to act by the induction of phospholipase A<sub>2</sub> inhibitory proteins, collectively called lipocortins. This is achieved first by the drug binding to the glucocorticoid receptors which then translocates into the nucleus and binds to DNA causing various activations and repressions of genes. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A<sub>2</sub>.","Glucocorticoid receptor agonist","Therapeutic strategy associated"]
[187,"DB00549","approved; investigational","small molecule","Zafirlukast","4-(5-cyclopentyloxycarbonylamino-1-methyl-1H-indol-3-ylmethyl)-3-methoxy-N-o-tolylsulfonylbenzamide; cyclopentyl 3-(2-methoxy-4-((o-tolylsulfonyl)carbamoyl)benzyl)-1-methylindole-5-carbamate; Zafirlukast","C31H33N3O6S","COC1=CC(=CC=C1CC1=CN(C)C2=C1C=C(NC(=O)OC1CCCC1)C=C2)C(=O)NS(=O)(=O)C1=CC=CC=C1C","Zafirlukast is an oral leukotriene receptor antagonist (LTRA) for the maintenance treatment of asthma, often used in conjunction with an inhaled steroid and/or long-acting bronchodilator. It is available as a tablet and is usually dosed twice daily. Another leukotriene receptor antagonist is montelukast (Singulair), which is usually taken just once daily.\r\n\r\nZafirlukast blocks the action of the cysteinyl leukotrienes on the CysLT1 receptors, thus reducing constriction of the airways, build-up of mucus in the lungs and inflammation of the breathing passages.","107753-78-6","575.675","For the prophylaxis and chronic treatment of asthma.","Zafirlukast is a synthetic, selective peptide leukotriene receptor antagonist (LTRA) indicated for the prophylaxis and chronic treatment of asthma. Patients with asthma were found in one study to be 25-100 times more sensitive to the bronchoconstricting activity of inhaled LTD<sub>4</sub> than nonasthmatic subjects. <i>In vitro</i> studies demonstrated that zafirlukast antagonized the contractile activity of three leukotrienes (LTC<sub>4</sub>, LTD<sub>4</sub> and LTE<sub>4</sub>) in conducting airway smooth muscle from laboratory animals and humans. Zafirlukast prevented intradermal LTD<sub>4</sub>-induced increases in cutaneous vascular permeability and inhibited inhaled LTD<sub>4</sub>-induced influx of eosinophils into animal lungs.","Zafirlukast is a selective and competitive receptor antagonist of leukotriene D4 and E4 (LTD<sub>4</sub> and LTE4), components of slow-reacting substance of anaphylaxis (SRSA). Cysteinyl leukotriene production and receptor occupation have been correlated with the pathophysiology of asthma, including airway edema, smooth muscle constriction, and altered cellular activity associated with the inflammatory process, which contribute to the signs and symptoms of asthma.","Cysteinyl leukotriene receptor 1 antagonist","Therapeutic strategy associated"]
[188,"DB00554","approved; investigational","small molecule","Piroxicam","Piroxicam; Piroxicam betadex; Pyroxycam","C15H13N3O4S","CN1C(C(=O)NC2=NC=CC=C2)=C(O)C2=C(C=CC=C2)S1(=O)=O","A cyclooxygenase inhibiting, non-steroidal anti-inflammatory agent (NSAID) that is well established in treating rheumatoid arthritis and osteoarthritis and used for musculoskeletal disorders, dysmenorrhea, and postoperative pain. Its long half-life enables it to be administered once daily.","36322-90-4","331.346","For treatment of osteoarthritis and rheumatoid arthritis.","Piroxicam is in a class of drugs called nonsteroidal anti-inflammatory drugs (NSAIDs). Piroxicam works by reducing hormones that cause inflammation and pain in the body. Piroxicam is used to reduce the pain, inflammation, and stiffness caused by rheumatoid arthritis and osteoarthritis.","The antiinflammatory effect of Piroxicam may result from the reversible inhibition of cyclooxygenase, causing the peripheral inhibition of prostaglandin synthesis. The prostaglandins are produced by an enzyme called Cox-1. Piroxicam blocks the Cox-1 enzyme, resulting into the disruption of production of prostaglandins. Piroxicam also inhibits the migration of leukocytes into sites of inflammation and prevents the formation of thromboxane A2, an aggregating agent, by the platelets.","Prostaglandin G/H synthase 2 inhibitor; Prostaglandin G/H synthase 1 inhibitor","Therapeutic strategy associated"]
[189,"DB00555","approved; investigational","small molecule","Lamotrigine","3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine","C9H7Cl2N5","NC1=NC(N)=C(N=N1)C1=C(Cl)C(Cl)=CC=C1","Lamotrigine is an antiepileptic drug belonging in the phenyltriazine class. It is used in the treatment of both epilepsy and as a mood stabilizer in bipolar disorder. Lamotrigine is the first medication since lithium granted Food and Drug Administration (FDA) approval for the maintenance treatment of bipolar type I. It is approved for use in more than 30 countries.\r\n\r\nLamotrigine has relatively few side-effects and does not require laboratory monitoring. While it is indicated for epilepsy and bipolar disorders, there is evidence that lamotrigine could have some clinical efficacy in certain neuropathic pain states.","84057-84-1","256.091","Lamotrigine is indicated as adjunctive therapy for the following seizure types in patients ≥2 years of age: partial seizures, primary generalized tonic-clonic seizures, and generalized seizures due to Lennox-Gastaut syndrome.\r\n\r\nIt is also indicated for the process of conversion to drug monotherapy for those at least 16 years of age or older with partial seizures and currently are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single antiepileptic drug (AED).\r\n\r\nIn addition to the above, lamotrigine is also indicated for the maintenance treatment of bipolar I disorder, delaying the time to mood episodes (which may include mania, hypomania, depression, mixed episodes) in adults at least 18 years or older, who have been treated for acute mood symptoms with standard therapy.\r\n\r\nLimitations of use\r\n\r\nIt is important to note that lamotirigine should not be used in the treatment of acute mood episodes, as efficacy has not been established in this context.","Lamotrigine likely prevents seizures and prevents mood symptoms via stabilizing presynaptic neuronal membranes and preventing the release of excitatory neurotransmitters such as glutamate, which contribute to seizure activity. \r\n\r\nA note on cardiovascular effects\r\n\r\nThe metabolite of lamotrigine, 2-N-methyl metabolite (formed by glucuronidation), is reported to cause dose-dependent prolongations of the PR interval, widening of the QRS complex, and at higher doses, complete AV block. Although this harmful metabolite is only found in trace amounts in humans, plasma concentrations may increase in conditions that cause decreased drug glucuronidation, such as liver disease.","The exact mechanism of action of lamotrigine is not fully elucidated, as it may exert cellular activities that contribute to its efficacy in a range of conditions. Although chemically unrelated, lamotrigine actions resemble those of phenytoin and carbamazepine, inhibiting voltage-sensitive sodium channels, stabilizing neuronal membranes, thereby modulating the release of presynaptic excitatory neurotransmitters. \r\n\r\nLamotrigine likely acts by inhibiting sodium currents by selective binding to the inactive sodium channel, suppressing the release of the excitatory amino acid, glutamate. The mechanism of action of lamotrigine in reducing anticonvulsant activity is likely the same in managing bipolar disorder. Studies on lamotrigine have identified its binding to sodium channels in a fashion similar to local anesthetics, which could explain the demonstrated clinical benefit of lamotrigine in some neuropathic pain states. \r\n\r\nLamotrigine displays binding properties to several different receptors. In laboratory binding assays, it demonstrates weak inhibitory effect on the serotonin 5-HT3 receptor. Lamotrigine also weakly binds to Adenosine A1/A2 receptors, α1/α2/β adrenergic receptors, dopamine D1/D2 receptors, GABA A/B receptors, histamine H1 receptors, κ-opioid receptor (KOR), mACh receptors and serotonin 5-HT2 receptors with an IC50>100 µM. Weak inhibitory effects were observed at sigma opioid receptors. An in vivo study revealed evidence that lamotrigine inhibits Cav2.3 (R-type) calcium currents, which may also contribute to its anticonvulsant effects.","Voltage-dependent R-type calcium channel subunit alpha-1E (CACNA1E) inhibitor; Voltage-gated sodium channel alpha subunit inhibitor; Adenosine receptor A1 inhibitor; Adenosine receptor A2a inhibitor; Alpha-1A adrenergic receptor inhibitor; Alpha-2A adrenergic receptor inhibitor; Beta-1 adrenergic receptor inhibitor; D(1) dopamine receptor inhibitor; Dopamine D2 receptor agonist&inhibitor; GABA(A) Receptor antagonist&inducer; GABA(A) Receptor Benzodiazepine Binding Site inhibitor; Histamine H1 receptor antagonist; Kappa-type opioid receptor inhibitor; Acetylcholine receptor subunit alpha inhibitor; 5-hydroxytryptamine receptor 2A inhibitor; 5-hydroxytryptamine receptor 3A inhibitor; Glutamate receptor 1 inhibitor","Indication associated"]
[190,"DB00557","approved","small molecule","Hydroxyzine","Hychotine; Hydroxine; Hydroxizine; Hydroxizinum; Hydroxycine; Hydroxyzin; Hydroxyzine","C21H27ClN2O2","OCCOCCN1CCN(CC1)C(C1=CC=CC=C1)C1=CC=C(Cl)C=C1","Hydroxyzine is a first-generation histamine H<sub>1</sub>-receptor antagonist of the dephenylmethane and piperazine classes that exhibits sedative, anxiolytic, and antiemetic properties. It was first developed in 1955, and has since remained a relatively common treatment for allergic conditions such as pruritus, urticaria, dermatoses, and histamine-mediated pruritus. The active metabolite of hydroxyzine, , is also available as an active ingredient in allergic medications, and is responsible for much of its hydroxyzine's antihistaminic effect. Hydroxyzine is also used for generalized anxiety disorder, tension caused by psychoneurosis, and other conditions with manifestations of anxiety.","68-88-2","374.904","Hydroxyzine is indicated for the symptomatic relief of anxiety and tension associated with psychoneuroses, and as an adjunct in organic disease states in which anxiety is manifested. It is also indicated in the treatment of histamine-mediated pruritus and pruritus due to allergic conditions such as chronic urticaria.\r\n\r\nCanadian labeling states that hydroxyzine is also indicated in adults and children as a premedication prior to medical procedures, such as dental surgery. It is also used in the control of nausea and vomiting, excluding nausea and vomiting of pregnancy.","Hydroxyzine blocks the activity of histamine to relieve allergic symptoms such as pruritus. Activity at off-targets also allows for its use as a sedative anxiolytic and an antiemetic in certain disease states.\r\n\r\nHydroxyzine is relatively fast-acting, with an onset of effect that occurs between 15 and 60 minutes and a duration of action between 4-6 hours. Hydroxyzine may potentiate the effects of central nervous system (CNS) depressants following general anesthesia - patients maintained on hydroxyzine should receive reduced doses of any CNS depressants required. Hydroxyzine is reported to prolong the QT/QTc interval based on postmarketing reports of rare events of Torsade de Pointes, cardiac arrest, and sudden death, and should be used with caution in patients with an increased baseline risk for QTc prolongation.","The H<sub>1</sub> histamine receptor is responsible for mediating hypersensitivity and allergic reactions. Exposure to an allergen results in degranulation of mast cells and basophils, which then release histamine and other inflammatory mediators. Histamine binds to, and activates, H<sub>1</sub> receptors, which results in the further release of pro-inflammatory cytokines, such as interleukins, from basophils and mast cells. These downstream effects of histamine binding are responsible for a wide variety of allergic symptoms, such as pruritus, rhinorrhea, and watery eyes.\r\n\r\nHydroxyzine is a potent inverse agonist of histamine H<sub>1</sub>-receptors - inverse agonists are agents that are considered to have a \"negative efficacy\", so rather than simply blocking activity at a receptor they actively dampen its activity. Inverse agonism at these receptors is responsible for hydroxyzine's efficacy in the treatment of histaminic edema, flare, and pruritus.\r\n\r\nHydroxyzine is not a cortical depressant, so its sedative properties likely occur at the subcortical level of the CNS. These sedative properties allow activity as an anxiolytic. Antiemetic efficacy is likely secondary to activity at off-targets.","Histamine H1 receptor inverse agonist; Potassium voltage-gated channel subfamily H member 2 inhibitor","Therapeutic strategy associated"]
[191,"DB00559","approved; investigational","small molecule","Bosentan","4-(1,1-Dimethylethyl)-N-(6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-(2,2'-bipyrimidin)-4-yl) benzenesulfornamide; bosentan anhydrous; p-tert-Butyl-N-(6-(2-hydroxyethoxy)-5-(o-methoxyphenoxy)-2-(2-pyrimidinyl)-4-pyrimidinyl)benzenesulfonamide","C27H29N5O6S","COC1=CC=CC=C1OC1=C(NS(=O)(=O)C2=CC=C(C=C2)C(C)(C)C)N=C(N=C1OCCO)C1=NC=CC=N1","Bosentan is a dual endothelin receptor antagonist marketed under the trade name Tracleer by Actelion Pharmaceuticals. Bosentan is used to treat pulmonary hypertension by blocking the action of endothelin molecules that would otherwise promote narrowing of the blood vessels and lead to high blood pressure.","147536-97-8","551.614","Used in the treatment of pulmonary arterial hypertension (PAH), to improve exercise ability and to decrease the rate of clinical worsening (in patients with WHO Class III or IV symptoms).","Bosentan belongs to a class of drugs known as endothelin receptor antagonists (ERAs). Patients with PAH have elevated levels of endothelin, a potent blood vessel constrictor, in their plasma and lung tissue. Bosentan blocks the binding of endothelin to its receptors, thereby negating endothelin's deleterious effects.","Endothelin-1 (ET-1) is a neurohormone, the effects of which are mediated by binding to ET<sub>A</sub> and ET<sub>B</sub> receptors in the endothelium and vascular smooth muscle. It displays a slightly higher affinity towards ET<sub>A</sub> receptors than ET<sub>B</sub> receptors. ET-1 concentrations are elevated in plasma and lung tissue of patients with pulmonary arterial hypertension, suggesting a pathogenic role for ET-1 in this disease. Bosentan is a specific and competitive antagonist at endothelin receptor types ET<sub>A</sub> and ET<sub>B</sub>.","Endothelin-1 receptor antagonist; Endothelin B receptor antagonist","Indication associated"]
[192,"DB00560","approved","small molecule","Tigecycline","(4S,4aS,5aR,12aS)-9-(2-(tert-butylamino)acetamido)-4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide","C29H39N5O8","[H][C@@]12CC3=C(C(O)=C(NC(=O)CNC(C)(C)C)C=C3N(C)C)C(=O)C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@]1([H])C2","Tigecycline is a glycylcycline antibiotic developed and marketed by Wyeth under the brand name Tygacil. It was developed in response to the growing prevalence of antibiotic resistance in bacteria such as Staphylococcus aureus. It was granted fast-track approval by the U.S. Food and Drug Administration (FDA) on June 17, 2005.","220620-09-7","585.6487","For the treatment of infections caused by susceptible strains of the designated microorganisms in the following conditions: Complicated skin and skin structure infections caused by <i>Escherichia coli</i>, <i>Enterococcus faecalis</i> (vancomycin-susceptible isolates only), <i>Staphylococcus aureus</i> (methicillin-susceptible and -resistant isolates), <i>Streptococcus agalactiae</i>, <i>Streptococcus anginosus</i> grp. (includes <i>S. anginosus</i>, <i>S. intermedius</i>, and <i>S. constellatus</i>), <i>Streptococcus pyogenes</i> and <i>Bacteroides fragilis</i>. Complicated intra-abdominal infections caused by <i>Citrobacter freundii</i>, <i>Enterobacter cloacae</i>, <i>Escherichia coli</i>, <i>Klebsiella oxytoca</i>, <i>Klebsiella pneumoniae</i>, <i>Enterococcus faecalis</i> (vancomycin-susceptible isolates only), <i>Staphylococcus aureus</i> (methicillin-susceptible isolates only), <i>Streptococcus anginosus</i> grp. (includes <i>S. anginosus</i>, <i>S. intermedius</i>, and <i>S. constellatus</i>), <i>Bacteroides fragilis</i>, <i>Bacteroides thetaiotaomicron</i>, <i>Bacteroides uniformis</i>, <i>Bacteroides vulgatus</i>, <i>Clostridium perfringens</i>, and <i>Peptostreptococcus micros</i>.","Tigecycline is the first clinically-available drug in a new class of antibiotics called the glycylcyclines. Glycylcyclines are a new class of antibiotics derived from tetracycline. These tetracycline analogues are specifically designed to overcome two common mechanisms of tetracycline resistance, namely resistance mediated by acquired efflux pumps and/or ribosomal protection. Glycylcycline antibiotics have a similar mechanism of action as tetracycline antibiotics. Both classes of antibiotics bind to the 30S ribosomal subunit to prevent the amino-acyl tRNA from binding to the A site of the ribosome. However, the glycylcyclines appear to bind more effectively than the tetracyclines.","Tigecycline, a glycylcycline, inhibits protein translation in bacteria by binding to the 30S ribosomal subunit and blocking entry of amino-acyl tRNA molecules into the A site of the ribosome. This prevents incorporation of amino acid residues into elongating peptide chains. Tigecycline carries a glycylamido moiety attached to the 9-position of minocycline. The substitution pattern is not present in any naturally occurring or semisynthetic tetracycline and imparts certain microbiologic properties to tigecycline. Tigecycline is not affected by the two major tetracycline resistance mechanisms, ribosomal protection and efflux. Accordingly, tigecycline has demonstrated in vitro and in vivo activity against a broad spectrum of bacterial pathogens. There has been no cross resistance observed between tigecycline and other antibiotics. Tigecycline is not affected by resistance mechanisms such as beta-lactamases (including extended spectrum beta-lactamases), target site modifications, macrolide efflux pumps or enzyme target changes (e.g. gyrase/topoisomerase). In vitro studies have not demonstrated antagonism between tigecycline and other commonly used antibacterial drugs. In general, tigecycline is considered bacteriostatic.","16S ribosomal RNA binder; 30S ribosomal protein S9 binder; 30S ribosomal protein S12 binder; 30S ribosomal protein S13 binder; 30S ribosomal protein S14 binder; 30S ribosomal protein S19 binder","Indication associated"]
[193,"DB00562","approved","small molecule","Benzthiazide","3-((benzylthio)methyl)-6-chloro-7-sulfamoyl-2H-benzo-1,2,4-thiadiazine 1,1-dioxide; 3-benzylthiomethyl-6-chloro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide; 3-benzylthiomethyl-6-chloro-7-sulfamoyl-1,2,4-benzothiadiazine 1,1-dioxide; 6-chloro-1,1-dioxo-3-(phenylmethylsulfanylmethyl)-4H-benzo[e][1,2,4]thiadiazine-7-sulfonamide; 6-chloro-7-sulfamoyl-3-benzylthiomethyl-2H-1,2,4-benzothiadiazine 1,1-dioxide; Benzthiazide","C15H14ClN3O4S3","NS(=O)(=O)C1=CC2=C(C=C1Cl)N=C(CSCC1=CC=CC=C1)NS2(=O)=O","Benzthiazide is used to treat hypertension and edema. Like other thiazides, benzthiazide promotes water loss from the body (diuretics). They inhibit Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue.","91-33-8","431.937","For the treatment of high blood pressure and management of edema.","Benzthiazide is used to treat hypertension and edema. Like other thiazides, benzthiazide promotes water loss from the body (diuretics). They inhibit Na<sup>+</sup>/Cl<sup>-</sup> reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue.","As a diuretic, benzthiazide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like benzthiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of benzthiazide is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle.","Solute carrier family 12 member 3 inhibitor; Carbonic anhydrase 1 inhibitor; Carbonic anhydrase 2 inhibitor; Carbonic anhydrase 4 inhibitor; Carbonic anhydrase 9 inhibitor; Carbonic anhydrase 12 inhibitor; Carbonic anhydrase inhibitor","Therapeutic strategy associated"]
[194,"DB00563","approved","small molecule","Methotrexate","4-amino-10-methylfolic acid; 4-amino-N(10)-methylpteroylglutamic acid; Amethopterin; Methotrexate; MTX; N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamic acid","C20H22N8O5","CN(CC1=CN=C2N=C(N)N=C(N)C2=N1)C1=CC=C(C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O","Methotrexate is a folate derivative that inhibits several enzymes responsible for nucleotide synthesis. This inhibition leads to suppression of inflammation as well as prevention of cell division. Because of these effects, methotrexate is often used to treat inflammation caused by arthritis or to control cell division in neoplastic diseases such as breast cancer and non-Hodgkin's lymphoma.\r\n\r\nDue to the toxic effects of methotrexate, it is indicated for treatment of some forms of arthritis and severe psoriasis only if first line treatment has failed or patients are intolerant of those treatments.\r\n\r\nMethotrexate was granted FDA approval on 7 December 1953.","59-05-2","454.4393","Methotrexate oral solution is indicated for pediatric acute lymphoblastic leukemia and pediatric polyarticular juvenile idiopathic arthritis. Methotrexate injections for subcutaneous use are indicated for severe active rheumatoid arthritis, polyarticular juvenile idiopathic arthritis and severe, recalcitrant, disabling psoriasis.\r\n\r\nOther formulations are indicated to treat gestational choriocarcinoma, chorioadenoma destruens, hydatiform mole, breast cancer, epidermoid cancer of the head and neck, advanced mycosis fungoides, lung cancer, and advanced non-Hodgkin's lymphoma. It is also used in the maintenance of acute lymphocytic leukemia. Methotrexate is also given before treatment with leucovorin to prolong relapse-free survival following surgical removal of a tumour in non-metastatic osteosarcoma.","Methotrexate inhibits enzymes responsible for nucleotide synthesis which prevents cell division and leads to anti-inflammatory actions. It has a long duration of action and is generally given to patients once weekly. Methotrexate has a narrow therapeutic index.\r\n\r\nDo not take methotrexate daily.","Methotrexate enters tissues and is converted to a methotrexate polyglutamate by folylpolyglutamate.\r\n\r\nMethotrexate's mechanism of action is due to its inhibition of enzymes responsible for nucleotide synthesis including  dihydrofolate reductase, thymidylate synthase, aminoimidazole caboxamide ribonucleotide transformylase (AICART), and amido phosphoribosyltransferase. Inhibtion of nucleotide synthesis prevents cell division.\r\n\r\nIn rheumatoid arthritis, methotrexate polyglutamates inhibit AICART more than methotrexate. This inhibition leads to accumulation of AICART ribonucleotide, which inhibits adenosine deaminase, leading to an accumulation of adenosine triphosphate and adenosine in the extracellular space, stimulating adenosine receptors, leading to anti-inflammatory action.","Dihydrofolate reductase inhibitor; Thymidylate synthase inhibitor; Bifunctional purine biosynthesis protein PURH inhibitor","Therapeutic strategy associated"]
[195,"DB00569","approved; investigational","small molecule","Fondaparinux","Natural heparin pentasaccharide","C31H53N3O49S8","CO[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](O[C@@H]2O[C@H]([C@@H](O[C@H]3O[C@H](COS(O)(=O)=O)[C@@H](O[C@@H]4O[C@@H]([C@@H](O[C@H]5O[C@H](COS(O)(=O)=O)[C@@H](O)[C@H](O)[C@H]5NS(O)(=O)=O)[C@H](O)[C@H]4O)C(O)=O)[C@H](OS(O)(=O)=O)[C@H]3NS(O)(=O)=O)[C@H](O)[C@H]2OS(O)(=O)=O)C(O)=O)[C@H](O)[C@H]1NS(O)(=O)=O","Fondaparinux (Arixtra) is a synthetic anticoagulant agent consisting of five monomeric sugar units and a O-methyl group at the reducing end of the molecule. It is structurally similar to polymeric glycosaminoglycan heparin and heparan sulfate (HS) when they are cleaved into monomeric units. The monomeric sequence in heparin and HS is thought to form the high affinity binding site for the natural anti-coagulant factor, antithrombin III (ATIII). Once bound to heparin or HS, the anticoagulant activity of ATIII is potentiated by 1000-fold. Fondaparinux potentiates the neutralizing action of ATIII on activated Factor X 300-fold. Fondaparinux may be used: to prevent venous thromboembolism in patients who have undergone orthopedic surgery of the lower limbs (e.g. hip fracture, hip replacement and knee surgery); to prevent VTE in patients undergoing abdominal surgery who are are at high risk of thromboembolic complications; in the treatment of deep vein thrombosis (DVT) and pumonary embolism (PE); in the management of unstable angina (UA) and non-ST segment elevation myocardial infarction (NSTEMI); and in the management of ST segment elevation myocardial infarction (STEMI).","104993-28-4","1508.263","Approved for: (1) prophylaxis of VTE for up to one month post surgery in patients undergoing orthopedic surgery of the lower limbs such as hip fracture, hip replacement and knee surgery; (2) prophylaxis of VTE patients undergoing abdominal surgery who are at high risk of thromboembolic complications (e.g. patients undergoing abdominal cancer surgery); (3) treatment of acute DVT and PE; (4) management of UA and NSTEMI for the prevention of death and subsequent myocardial infarction (MI); and (5) management of STEMI for the prevention of death and myocardial reinfarction in patients who are managed with thrombolytics or who are initially to receive no form of reperfusion therapy. Fondaparinux should not be used as the sole anticoagulant during percutaneous coronary intervention (PCI) due to an increased risk of guiding catheter thrombosis.","Fondaparinux binds specifically to the natural anticoagulant factor, ATIII. Binding to ATIII potentiates the neutralizing action of ATIII on Factor Xa 300-times. Neutralization of Factor Xa decreases the conversion of prothrombin to thrombin, which subsequently decreases the conversion of fibrinogen to fibrin (loose meshwork). The decrease in thrombin also decreases the activation of Factor XIII, which decreases the conversion of fibrin in its loose meshwork form to its stabilized meshwork form. Disruption of the coagulation cascade effectively decreases the formation of blood clots. Fondaparinux does not inactivate thrombin (activated Factor II). According to the manufacturer, fondaparinux has no known effect on platelet function. In studies comparing fondaparinux to enoxaparin, decreases in platelet levels were observed in similar numbers of patients from both groups (2-5%) . At the recommended dose, Fondaparinux does not affect fibrinolytic activity or bleeding time. There is no antidote for fondaparinux. Monitoring of the anticoagulant activity of fondaparinux is not generally required. The anti-factor Xa assay may be used to monitor therapy in special populations such as those with renal impairment or who are pregnant. Complete blood count (CBC) and kidney function should be monitored during treatment.","The antithrombotic activity of fondaparinux is the result of ATIII-mediated selective inhibition of Factor Xa. By selectively binding to ATIII, Fondaparinux potentiates (about 300 times) the neutralization of Factor Xa by ATIII. Neutralization of Factor Xa interrupts the blood coagulation cascade and thus inhibits thrombin formation and thrombus development. It is thought that fondaparinux is unlikely to induce thrombocytopenia via a heparin-induced thrombocytopenia (HIT)-like mechanism given its chemical structure . As a result, fondaparinux has been used as an alternative anticoagulant in heparin-induced thrombocytopenia (HIT) patients . However, it is important to note that rare cases of HIT have been reported in patients treated with fondaparinux .","Antithrombin-III potentiator; Coagulation factor X inhibitor","Indication associated"]
[196,"DB00571","approved; investigational","small molecule","Propranolol","1-((1-Methylethyl)amino)-3-(1-naphthalenyloxy)-2-propanol; 1-(isopropylamino)-3-(1-naphthyloxy)propan-2-ol; beta-Propranolol; Propanalol; Propanolol; β-Propranolol","C16H21NO2","CC(C)NCC(O)COC1=CC=CC2=C1C=CC=C2","Propranolol is a racemic mixture of 2 enantiomers where the S(-)-enantiomer has approximately 100 times the binding affinity for beta adrenergic receptors. Propranolol is used to treat a number of conditions but most commonly is used for hypertension. \r\n\r\nPropranolol was granted FDA approval on 13 November 1967.","525-66-6","259.3434","Propranolol is indicated to treat hypertension. Propranolol is also indicated to treat angina pectoris due to coronary atherosclerosis, atrial fibrillation, myocardial infarction, migraine, essential tremor, hypertrophic subaortic stenosis, pheochromocytoma, and proliferating infantile hemangioma.","Propranolol is a beta-adrenergic receptor antagonist used to treat hypertension. Propranolol has a long duration of action as it is given once or twice daily depending on the indication. When patients abruptly stop taking propranolol, they may experience exacerbations of angina and myocardial infarctions.","Propranolol is a nonselective β-adrenergic receptor antagonist. Blocking of these receptors leads to vasoconstriction, inhibition of angiogenic factors like vascular endothelial growth factor (VEGF) and basic growth factor of fibroblasts (bFGF), induction of apoptosis of endothelial cells, as well as down regulation of the renin-angiotensin-aldosterone system.","Beta-1 adrenergic receptor antagonist; Beta-2 adrenergic receptor antagonist; Beta-3 adrenergic receptor antagonist; 5-hydroxytryptamine receptor 1A other/unknown; 5-hydroxytryptamine receptor 1B other/unknown","Therapeutic strategy associated"]
[197,"DB00573","approved","small molecule","Fenoprofen","(+/-)-fenoprofen; (+/-)-m-phenoxyhydratropic acid; (±)-2-(3-phenoxyphenyl)propionic acid; 2-(3-phenoxyphenyl)propionic acid; 2-(m-phenoxyphenyl)propionic acid; 3-phenoxyhydratropic acid; DL-2-(3-phenoxyphenyl)propionic acid; Fenoprofen; α-(m-phenoxyphenyl)propionic acid; α-methyl-3-phenoxybenzeneacetic acid","C15H14O3","CC(C(O)=O)C1=CC(OC2=CC=CC=C2)=CC=C1","An anti-inflammatory analgesic and antipyretic highly bound to plasma proteins. It is pharmacologically similar to aspirin, but causes less gastrointestinal bleeding.","29679-58-1","242.2699","For relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis. Also for the relief of mild to moderate pain.","Fenoprofen is a propionic acid derivative with analgesic, antiinflammatory and antipyretic properties. Fenoprofen inhibits prostaglandin synthesis by decreasing the enzyme needed for biosynthesis. In patients with rheumatoid arthritis, the anti-inflammatory action of fenoprofen has been evidenced by relief of pain, increase in grip strength, and reductions in joint swelling, duration of morning stiffness, and disease activity (as assessed by both the investigator and the patient). In patients with osteoarthritis, the anti-inflammatory and analgesic effects of fenoprofen have been demonstrated by reduction in tenderness as a response to pressure and reductions in night pain, stiffness, swelling, and overall disease activity (as assessed by both the patient and the investigator). These effects have also been demonstrated by relief of pain with motion and at rest and increased range of motion in involved joints. In patients with rheumatoid arthritis and osteoarthritis, clinical studies have shown fenoprofen to be comparable to aspirin in controlling the aforementioned measures of disease activity, but mild gastrointestinal reactions (nausea, dyspepsia) and tinnitus occurred less frequently in patients treated with fenoprofen than in aspirin-treated patients. It is not known whether fenoprofen causes less peptic ulceration than does aspirin. In patients with pain, the analgesic action of fenoprofen has produced a reduction in pain intensity, an increase in pain relief, improvement in total analgesia scores, and a sustained analgesic effect.","Fenoprofen's exact mode of action is unknown, but it is thought that prostaglandin synthetase inhibition is involved. Fenoprofen has been shown to inhibit prostaglandin synthetase isolated from bovine seminal vesicles.","Prostaglandin G/H synthase 2 inhibitor; Prostaglandin G/H synthase 1 inhibitor; Peroxisome proliferator-activated receptor alpha activator; Peroxisome proliferator-activated receptor gamma","Target associated"]
[198,"DB00574","approved; illicit; investigational; withdrawn","small molecule","Fenfluramine","(±)-fenfluramine; 1-(m-trifluoromethyl-phenyl)-2-ethylaminopropane; DL-Fenfluramine; Fenfluramina; Fenfluramine","C12H16F3N","CCNC(C)CC1=CC=CC(=C1)C(F)(F)F","Dravet syndrome is a pediatric encephalopathy that typically manifests within the first year of life following exposure to elevated temperatures. It is characterized by recurrent pharmacoresistant seizures, which increase in frequency and severity with disease progression. Concomitantly with these seizures, patients typically display delayed development and neurocognitive impairment. Fenfluramine is a serotonergic phenethylamine originally used as an appetite suppressant until concerns regarding cardiotoxicity in obese patients lead to its withdrawal from the market in 1997. Through its ability to modulate neurotransmission, fenfluramine has reemerged as an effective therapy against pharmacoresistant seizures, such as those involved in Dravet syndrome.\r\n\r\nFenfluramine was granted initial FDA approval in 1973 prior to its withdrawal; it was granted a new FDA approval on June 25, 2020, for treatment of Dravet syndrome patients through the restricted FINTEPLA REMS program. It is currently sold under the name FINTEPLA® by Zogenix INC.","458-24-2","231.2573","Fenfluramine is indicated for the treatment of seizures in Dravet syndrome patients aged two years and older.","Fenfluramine increases extracellular serotonin levels, and also acts as both a serotonergic 5-HT<sub>2</sub> receptor agonist and σ1 receptor antagonist. These activities, through an incompletely understood mechanism, lead to anti-epileptiform activity and therapeutic benefit. This modulation has other effects such as decreased appetite, weight loss, sedation, lethargy, increased blood pressure, and mood alteration including possible suicidal ideation. There is a risk of glaucoma and potentially fatal serotonin syndrome. Fenfluramine should be gradually withdrawn following treatment alteration or cessation.","Dravet syndrome is a complex pediatric encephalopathy characterized by recurrent pharmacoresistant seizures of variable type, delayed development, and in many cases, impairment in speech, language, gait, and other neurocognitive functions. Despite substantial variation in presentation and severity, roughly 80% of patients with Dravet syndrome have mutations in the _SCN1A_ gene, which encodes the alpha subunit of a voltage-gated sodium channel (Na<sub>v</sub>1.1). This channel is predominantly localized in inhibitory GABAergic interneurons as well as in excitatory pyramidal neurons; it is thought that dysfunction of neurotransmission regulation results in the seizures and other corresponding symptoms of Dravet syndrome.\r\n\r\nVarious _in vitro_ and _in vivo_ studies have demonstrated that fenfluramine is capable of acting as an agonist of multiple serotonin receptors including 5-HT<sub>1A</sub>, 5-HT<sub>1D</sub>, 5-HT<sub>2A</sub>, 5-HT<sub>2B</sub>, and 5-HT<sub>2C</sub>, as well as a σ1 receptor antagonist. This is at least partly because fenfluramine, as well as its active metabolite norfenfluramine, can act on sodium-dependent serotonin transporters (SERTs) to reverse transport direction and thereby increase extracellular serotonin levels. However, work in animal models of Dravet syndrome suggest that only the modulation of 5-HT<sub>1D</sub>, 5-HT<sub>2C</sub>, σ1, and possibly 5-HT<sub>2A</sub> receptors of fenfluramine result in the anti-epileptiform activity. Interestingly, 5-HT<sub>2B</sub> receptor agonism, which had previously been associated with cardiac valvulopathy, is not anticipated to have any therapeutic value in Dravet syndrome.\r\n\r\nAlthough the exact mechanism by which stimulation/inhibition of various receptors leads to the observed therapeutic benefit is unclear, it is hypothesized to be two-fold. Stimulation of 5-HT<sub>1D</sub> and 5-HT<sub>2C</sub> may result in increased GABAergic neurotransmission, while σ1 receptor antagonism may help to modulate responses to _N_-methyl-D-aspartate (NMDA).","Sodium-dependent serotonin transporter substrate&inhibitor; 5-hydroxytryptamine receptor 1D agonist; 5-hydroxytryptamine receptor 2C agonist; Sigma non-opioid intracellular receptor 1 antagonist; 5-hydroxytryptamine receptor 2A agonist; 5-hydroxytryptamine receptor 2B agonist; 5-hydroxytryptamine receptor 1A agonist","Therapeutic strategy associated"]
[199,"DB00575","approved","small molecule","Clonidine","2-((2,6-Dichlorophenyl)imino)imidazolidine; 2,6-Dichloro-N-2-imidazolidinylidenebenzenamine; Chlofazoline","C9H9Cl2N3","ClC1=CC=CC(Cl)=C1NC1=NCCN1","Clonidine is an imidazole derivate that acts as an agonist of alpha-2 adrenoceptors. This activity is useful for the treatment of hypertension, severe pain, and ADHD.\r\n\r\nClonidine was granted FDA approval on 3 September 1974.","4205-90-7","230.094","Clonidine tablets and transdermal systems are indicated for the treatment of hypertension alone or in combination with other medications. A clonidine injection is indicated for use with opiates in the treatment of severe cancer pain where opiates alone are insufficient. An extended release tablet of clonidine is indicated for the treatment of ADHD either alone or in combination with other medications.\r\n\r\nClonidine is also used for the diagnosis of pheochromocytoma, treatment of nicotine dependance, and opiate withdrawal.","Clonidine functions through agonism of alpha-2 adrenoceptors which have effects such as lowering blood pressure, sedation, and hyperpolarization of nerves. It has a long duration of action as it is given twice daily and the therapeutic window is between 0.1mg and 2.4mg daily.","Clonidine is primarily an alpha-2 adrenoceptor agonist which causes central hypotensive and anti-arrhythmogenic effects. The alpha-2 adrenoceptor is coupled to the G-proteins G<sub>o</sub> and G<sub>i</sub>. G<sub>i</sub> inhibits adenylyl cyclase and activates opening of a potassium channel that causes hyperpolarization. Clonidine binding to the alpha-2 adrenoceptor causes structural changes in the alpha subunit of the G-protein, reducing its affinity for GDP. Magnesium catalyzes the replacement of GDP with GTP. The alpha subunit dissociates from the other subunits and associates with an effector.\r\n\r\nThe stimulation of alpha-2 adrenoceptors in the locus coeruleus may be responsible for the hypnotic effects of clonidine as this region of the brain helps regulate wakefulness. Clonidine can also decrease transmission of pain signals at the spine. Finally clonidine can affect regulators of blood pressure in the ventromedial and rostral-ventrolateral areas of the medulla.","Alpha-2A adrenergic receptor agonist; Alpha-2B adrenergic receptor agonist; Alpha-2C adrenergic receptor agonist; Alpha-1A adrenergic receptor agonist; Alpha-1B adrenergic receptor agonist; Alpha-1D adrenergic receptor agonist","Indication associated"]
[200,"DB00580","approved; investigational; withdrawn","small molecule","Valdecoxib",null,"C16H14N2O3S","CC1=C(C(=NO1)C1=CC=CC=C1)C1=CC=C(C=C1)S(N)(=O)=O","Valdecoxib was removed from the Canadian, U.S., and E.U. markets in 2005 due to concerns about a possible increased risk of heart attack and stroke.","181695-72-7","314.359","For the treatment of osteoarthritis and dysmenorrhoea","Valdecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is classified as a nonsteroidal anti-inflammatory drug (NSAID). Valdecoxib is used for its anti-inflammatory, analgesic, and antipyretic activities in the management of osteoarthritis (OA) and for the treatment of dysmenorrhea or acute pain. Unlike celecoxib, valdecoxib lacks a sulfonamide chain and does not require CYP450 enzymes for metabolism.","Both COX-1 and COX-2 catalyze the conversion of arachidonic acid to prostaglandin (PG) H2, the precursor of PGs and thromboxane. Valdecoxib selectively inhibits the cyclooxygenase-2 (COX-2) enzyme, important for the mediation of inflammation and pain. Unlike non-selective NSAIDs, valdecoxib does not inhibit platelet aggregation.","Prostaglandin G/H synthase 2 inhibitor; Carbonic anhydrase 2 inhibitor; Carbonic anhydrase 3 inhibitor","Therapeutic strategy associated"]
[201,"DB00584","approved; vet_approved","small molecule","Enalapril","(S)-1-(N-(1-(ethoxycarbonyl)-3-phenylpropyl)-L-alanyl)-L-proline; (S)-1-{(S)-2-[1-((S)-Ethoxycarbonyl)-3-phenyl-propylamino]-propionyl}-pyrrolidine-2-carboxylic acid; 1-(N-((S)-1-carboxy-3-phenylpropyl)-L-alanyl)-L-proline 1'-ethyl ester; Enalapril","C20H28N2O5","CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O","Enalapril is a prodrug belonging to the angiotensin-converting enzyme (ACE) inhibitor drug class that works on the renin-angiotensin-aldosterone system, which is responsible for the regulation of blood pressure and fluid and electrolyte homeostasis. Enalapril is an orally-active and long-acting nonsulphydryl antihypertensive agent that suppresses the renin-angiotensin-aldosterone system to lower blood pressure. It was developed from a targeted research programmed using molecular modelling. Being a prodrug, enalapril is rapidly biotransformed into its active metabolite, , which is responsible for the pharmacological actions of enalapril. The active metabolite of enalapril competitively inhibits the ACE to hinder the production of angiotensin II, a key component of the renin-angiotensin-aldosterone system that promotes vasoconstriction and renal reabsorption of sodium ions in the kidneys. Ultimately, enalaprilat works to reduce blood pressure and blood fluid volume.\r\n\r\nCommonly marketed under the trade name Vasotec, enalapril was first approved by the FDA in 1985 for the management of hypertension, heart failure, and asymptomatic left ventricular dysfunction. It is also found in a combination product containing  that is used for the management of hypertension. The active metabolite enalaprilat is also available in oral tablets and intravenous formulations for injection.","75847-73-3","376.4467","Indicated for the management of essential or renovascular hypertension  as monotherapy or in combination with other antihypertensive agents, such as thiazide diuretics, for an additive effect.\r\n\r\nIndicated for the treatment of symptomatic congestive heart failure, usually in combination with diuretics and digitalis.\r\n\r\nIndicated for the management of asymptomatic left ventricular dysfunction in patients with an ejection fraction of ≤ to 35 percent to decrease the rate of development of overt heart failure and the incidence of hospitalization for heart failure.","Enalapril is an antihypertensive agent that exhibits natriuretic and uricosuric properties. Enalapril lowers blood pressure in all grades of essential and renovascular hypertension, and peripheral vascular resistance without causing an increase in heart rate. Individuals with low-renin hypertensive population were still responsive to enalapril. The duration of hypertensive effect in the systolic and diastolic blood pressure persists for at least 24 hours following initial administration of a single oral dose, and repeated daily administration of enalapril confers an additional reduction in blood pressure and a steady-state antihypertensive response may take several weeks. In patients with severe congestive heart failure and inadequate clinical response to conventional antihypertensive therapies, treatment with enalapril resulted in improvements in cardiac performance as observed by a reduction in both preload and afterload, and improved clinical status long-term. Furthermore, enalapril was shown to increase cardiac output and stroke volume while decreasing pulmonary capillary wedge pressure in patients with congestive heart failure refractory to conventional treatment with digitalis and diuretics. In clinical studies, enalapril reduced left ventricular mass, and did not affect cardiac function or myocardial perfusion during exercise. Enalapril is not highly associated with the risk of bradycardia unlike most diuretics and beta-blockers  and it does not produce rebound hypertension upon discontinuation of therapy. \r\n\r\nEnalapril is not reported to produce hypokalaemia, hyperglycaemia, hyperuricaemia or hypercholesterolaemia. In the kidneys, enalapril was shown to increase renal blood flow and decrease renal vascular resistance. It also augmented the glomerular filtration rate in patients with a glomerular filtration rate less than 80 mL/min. When used in combination, enalapril was shown to attenuate the extent of drug-induced hypokalemia caused by hydrochlorothiazide  and the antihypertensive effects of both drugs were potentiated.","The renin-angiotensin-aldosterone system (RAAS) is a signaling pathway that works in synergism with the sympathetic system to regulate blood pressure and fluid and electrolyte homeostasis. Activation of this system upon stimulation by different factors, such as low blood pressure and nerve impulses, leads to increased release of norepinephrine (NE) from sympathetic nerve terminals and effects on the vascular growth, vasoconstriction, and salt retention in the kidneys. Renin is released from \r\nRenin acts on the precursor prottein angiotensinogen, which is a plasma globulin synthesized from the liver, to produce cleaved peptide hormone angiotensin I. Angiotensin I then can be further cleaved by ACE to produce angiotensin II, a vasoconstrictive peptide hormone. Present in different isoforms, angiotensin converting enzyme (ACE) is peptidyl dipeptidase enzyme expressed in various tissues, including the vascular tissues, such as the heart, brain, and kidneys. ACE also plays a role in inactivation of bradykinin, a potent vasodepressor peptide. Angiotensin II mediates various actions on the body by working on its G-protein coupled receptors, AT1 and AT2. It causes direct vasoconstriction of precapillary arterioles and postcapillary venules, inhibits the reuptake of NE thereby increasing available levels, stimulates the release of catecholamines from the adrenal medulla, reduces urinary excretion of sodium ions and water by promoting proximal tubular reabsorption, stimulates synthesis and release of aldosterone from the adrenal cortex, and stimulates hypertrophy of both vascular smooth muscle cells and cardiac myocytes.\r\n\r\nEnalapril is a pharmacologically inactive prodrug that requires hepatic biotransformation to form , its active metabolite that works on the RAAS to inhibit ACE. Biotransformation is critial for the therapeutic actions of the drug, as enalapril itself is only a weak inhibitor of ACE. ACE inhibition results in reduced production and plasma levels of angiotensin II, increased plasma renin activity due to the loss of feedback inhibition by angiotensin II, and decreased aldosterone secretion. However, plasma aldosterone levels usually return to normal during long-term administration of enalapril. Decreased levels of angiotensin II subsequently leads to the dilatation of peripheral vessles and reduced vascular resistance which in turn lower blood pressure. While inhibition of ACE leading to suppression of RAAS is thought to be the primary mechanism of action of enalapril, the drug was shown to still exert antihypertensive effects on individuals with low-renin hypertension. It is suggested that enalapril may mediate its pharmacological actions via other modes of action that are not fully understood. As ACE is structurally similar to kininase I, which is a carboxypeptidase that degrades bradykinin, whether increased levels of bradykinin play a role in the therapeutic effects of enalapril remains to be elucidated.","Angiotensin-converting enzyme inhibitor","Therapeutic strategy associated"]
[202,"DB00586","approved; vet_approved","small molecule","Diclofenac","[2-(2,6-dichloroanilino)phenyl]acetic acid; 2-((2,6-dichlorophenyl)amino)benzeneacetic acid; Diclofenac; Diclofenac acid","C14H11Cl2NO2","OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl","Diclofenac is a phenylacetic acid derivative and non-steroidal anti-inflammatory drug (NSAID). NSAIDs inhibit cyclooxygenase (COX)-1 and-2 which are the enzyme responsible for producing prostaglandins (PGs). PGs contribute to inflammation and pain signalling. Diclofenac, like other NSAIDs, is often used as first line therapy for acute and chronic pain and inflammation from a variety of causes. Diclofenac was the product of rational drug design based on the structures of , , and . The addition of two chlorine groups in the ortho position of the phenyl ring locks the ring in maximal torsion which appears to be related to increased potency. It is often used in combination with  to prevent NSAID-induced gastric ulcers. Diclofenac was first approved by the FDA in July 1988 under the trade name Voltaren, marketed by Novartis (previously Ciba-Geigy).","15307-86-5","296.149","Diclofenac is indicated for use in the treatment of pain and inflammation from varying sources including inflammatory conditions such as osteoarthritis, rheumatoid arthritis, and akylosing spondylitis, as well as injury-related inflammation due to surgery and physical trauma. It is often used in combination with  as a gastro-protective agent in patients with high risk of developing NSAID-induced ulcers.","Diclofenac reduces inflammation and by extension reduces nociceptive pain and combats fever. It also increases the risk of developing a gastrointestinal ulcer by inhibiting the production of protective mucus in the stomach.","Diclofenac inhibits cyclooxygenase-1 and -2, the enzymes responsible for production of prostaglandin (PG) G<sub>2</sub> which is the precursor to other PGs. These molecules have broad activity in pain and inflammation and the inhibition of their production is the common mechanism linking each effect of diclofenac.\r\n\r\nPGE<sub>2</sub> is the primary PG involved in modulation of nociception. It mediates peripheral sensitization through a variety of effects. PGE<sub>2</sub> activates the G<sub>q</sub>-coupled EP<sub>1</sub> receptor leading to increased activity of the inositol trisphosphate/phospholipase C pathway. Activation of this pathway releases intracellular stores of calcium which directly reduces action potential threshold and activates protein kinase C (PKC) which contributes to several indirect mechanisms. PGE<sub>2</sub> also activates the EP<sub>4</sub> receptor, coupled to G<sub>s</sub>, which activates the adenylyl cyclase/protein kinase A (AC/PKA) signaling pathway. PKA and PKC both contribute to the potentiation of transient receptor potential cation channel subfamily V member 1 (TRPV1) potentiation, which increases sensitivity to heat stimuli. They also activate tetrodotoxin-resistant sodium channels and inhibit inward potassium currents. PKA further contributes to the activation of the P2X3 purine receptor and sensitization of T-type calcium channels. The activation and sensitization of depolarizing ion channels and inhibition of inward potassium currents serve to reduce the intensity of stimulus necessary to generate action potentials in nociceptive sensory afferents. PGE<sub>2</sub> act via EP<sub>3</sub> to increase sensitivity to bradykinin and via EP<sub>2</sub> to further increase heat sensitivity. Central sensitization occurs in the dorsal horn of the spinal cord and is mediated by the EP<sub>2</sub> receptor which couples to G<sub>s</sub>. Pre-synaptically, this receptor increases the release of pro-nociceptive neurotransmitters glutamate, CGRP, and substance P. Post-synaptically it increases the activity of AMPA and NMDA receptors and produces inhibition of inhibitory glycinergic neurons. Together these lead to a reduced threshold of activating, allowing low intensity stimuli to generate pain signals. PGI<sub>2</sub> is known to play a role via its G<sub>s</sub>-coupled IP receptor although the magnitude of its contribution varies. It has been proposed to be of greater importance in painful inflammatory conditions such as arthritis. By limiting sensitization, both peripheral and central, via these pathways NSAIDs can effectively reduce inflammatory pain.\r\n\r\nPGI<sub>2</sub> and PGE<sub>2</sub> contribute to acute inflammation via their IP and EP<sub>2</sub> receptors. Similarly to β adrenergic receptors these are G<sub>s</sub>-coupled and mediate vasodilation through the AC/PKA pathway. PGE<sub>2</sub> also contributes by increasing leukocyte adhesion to the endothelium and attracts the cells to the site of injury. PGD<sub>2</sub> plays a role in the activation of endothelial cell release of cytokines through its DP<sub>1</sub> receptor. PGI<sub>2</sub> and PGE<sub>2</sub> modulate T-helper cell activation and differentiation through IP, EP<sub>2</sub>, and EP<sub>4</sub> receptors which is believed to be an important activity in the pathology of arthritic conditions. By limiting the production of these PGs at the site of injury, NSAIDs can reduce inflammation.\r\n\r\nPGE<sub>2</sub> can cross the blood-brain barrier and act on excitatory G<sub>q</sub> EP<sub>3</sub> receptors on thermoregulatory neurons in the hypothalamus. This activation triggers an increase in heat-generation and a reduction in heat-loss to produce a fever. NSAIDs prevent the generation of PGE<sub>2</sub> thereby reducing the activity of these neurons.\r","Prostaglandin G/H synthase 2 inhibitor; Prostaglandin G/H synthase 1 inhibitor","Therapeutic strategy associated"]
[203,"DB00587","experimental","small molecule","Cinalukast","3'-((E)-2-(4-cyclobutyl-2-thiazolyl)vinyl)-2,2-diethylsuccinanilic acid; Cinalukast","C23H28N2O3S","CCC(CC)(CC(=O)NC1=CC(\\C=C\\C2=NC(=CS2)C2CCC2)=CC=C1)C(O)=O","Used in the treatment of asthma, cinalukast selectively antagonizes leukotriene D4 (LTD4) at the cysteinyl leukotriene receptor, CysLT1, in the human airway. Cinalukast inhibits the actions of LTD4 at the CysLT1 receptor, preventing airway edema, smooth muscle contraction, and enhanced secretion of thick, viscous mucus.","128312-51-6","412.545","For Protection against second- phase inflamation in exercise-induced bronchoconstriction and Asthma.","Used in the treatment of asthma, cinalukast selectively antagonizes leukotriene D4 (LTD<sub>4</sub>) at the cysteinyl leukotriene receptor, CysLT1, in the human airway. Cinalukast inhibits the actions of LTD<sub>4</sub> at the CysLT1 receptor, preventing airway edema, smooth muscle contraction, and enhanced secretion of thick, viscous mucus.","Binds to the cysteinyl leukotriene receptor. The cysteinyl leukotrienes (LTC4, LTD<sub>4</sub>, LTE4) are products of arachidonic acid metabolism and are released from various cells, including mast cells and eosinophils. These eicosanoids bind to cysteinyl leukotriene receptors (CysLT) found in the human airway. Cysteinyl leukotrienes and leukotriene receptor occupation have been correlated with the pathophysiology of asthma, including airway edema, smooth muscle contraction, and altered cellular activity associated with the inflammatory process, which contribute to the signs and symptoms of asthma.","Cysteinyl leukotriene receptor 1 antagonist","Therapeutic strategy associated"]
[204,"DB00590","approved","small molecule","Doxazosin","1-(4-Amino-6,7-dimethoxy-2-chinazolinyl)-4-(2,3-dihydro-1,4-benzodioxixin-2-ylcarbonyl)piperazin; 1-(4-Amino-6,7-Dimethoxy-2-quinazolinyl)-4-(1,4-benzodioxan-2-ylcarbonyl)piperazin; Doxazosin","C23H25N5O5","COC1=C(OC)C=C2C(N)=NC(=NC2=C1)N1CCN(CC1)C(=O)C1COC2=CC=CC=C2O1","Doxazosin is an alpha-1 antagonist used for the treatment of benign prostatic hypertrophy (BPH) symptoms and hypertension. Other members of this drug class include , , , and .  Because of its long-lasting effects, doxazosin can be administered once a day. It is marketed by Pfizer and was initially approved by the FDA in 1990.","74191-85-8","451.4751","Doxazosin is indicated to treat the symptoms of benign prostatic hypertrophy, which may include urinary frequency, urgency, and nocturia, among other symptoms. In addition, doxazosin is indicated alone or in combination with various antihypertensive agents for the management of hypertension. Off-label uses of doxazosin include the treatment of pediatric hypertension and the treatment of ureteric calculi.","Doxazosin decreases standing and supine blood pressure and relieves the symptoms of benign prostatic hypertrophy through the inhibition of alpha-1 receptors.\r\nDoxazosin may cause hypotension due to its pharmacological actions. This frequently occurs in the upright position, leading to a feeling of dizziness or lightheadedness. The first dose of doxazosin may lead to such effects, however, subsequent doses may also cause them. The risk of these effects is particularly high when dose adjustments occur or there are long intervals between doxazosin doses. Treatment should be started with the 1 mg dose of doxazosin, followed by slow titration to the appropriate dose. Patients must be advised of this risk and to avoid situations in which syncope and dizziness could be hazardous following the ingestion of doxazosin. Interestingly doxazosin exerts beneficial effects on plasma lipids. It reduces LDL (low-density lipoprotein) cholesterol and triglyceride levels and increases HDL (high-density lipoprotein) cholesterol levels.\r\n\r\nA note on priapism risk\r\n\r\nIn rare cases, doxazosin and other alpha-1 blockers may cause priapism, a painful occurrence of persistent and unrelievable penile erection that can lead to impotence if medical attention is not sought as soon as possible. Patients must be advised of the priapism risk associated with doxazosin and to seek medical attention immediately if it is suspected.","Doxazosin selectively inhibits the postsynaptic alpha-1 receptors on vascular smooth muscle by nonselectively blocking the alpha-1a, alpha-1b, and alpha-1d subtypes. This action on blood vessels decreases systemic peripheral vascular resistance, reducing blood pressure, exerting minimal effects on the heart rate due to its receptor selectivity. Norepinephrine-activated alpha-1 receptors located on the prostate gland and bladder neck normally cause contraction of regional muscular tissue, obstructing urinary flow and contributing to the symptoms of benign prostatic hypertrophy.  Alpha-1 antagonism causes smooth muscle relaxation in the prostate and bladder, effectively relieving urinary frequency, urgency, weak urinary stream, and other unpleasant effects of BPH. Recently, doxazosin was found to cause apoptosis of hERG potassium channels in an in vitro setting, possibly contributing to a risk of heart failure with doxazosin use.","Alpha-1A adrenergic receptor antagonist; Alpha-1D adrenergic receptor antagonist; HERG human cardiac K+ channel inhibitor; Alpha-1B adrenergic receptor","Therapeutic strategy associated"]
[205,"DB00591","approved; investigational; vet_approved","small molecule","Fluocinolone acetonide","6alpha-fluorotriamcinolone acetonide; 6alpha,9alpha-difluoro-16alpha-hydroxyprednisolone 16,17-acetonide; 6α-fluorotriamcinolone acetonide; 6α,9α-difluoro-16α-hydroxyprednisolone 16,17-acetonide; fluocinolone 16,17-acetonide; Fluocinolone acetonide","C24H30F2O6","[H][C@@]12C[C@@]3([H])[C@]4([H])C[C@H](F)C5=CC(=O)C=C[C@]5(C)[C@@]4(F)[C@@H](O)C[C@]3(C)[C@@]1(OC(C)(C)O2)C(=O)CO","Fluocinolone acetonide, with the formula 6-alpha, 9-alpha-difluoro-16-alpha, 17 alpha-acetonide, is a corticosteroid that presents a high lipophilicity. It has been used extensively in dermatological preparations and it has also been investigated thoroughly for its use in implantable corticosteroid devices. This type of device containing fluocinolone acetonide was developed by Taro Pharmaceuticals and approved by FDA in May 2016.","67-73-2","452.4882","Fluocinolone acetonide has been used extensively in different medical areas.\r\n\r\n-In dermatology, it is extensively used for the relief of inflammatory dermatosis, dermatitis, psoriasis, hypertrophic tissues, keloid tissues and atopic dermatitis.\r\n\r\n-It has been used in shampoo products as a low to medium potency corticosteroid for the treatment of seborrheic dermatitis of the scalp.\r\n\r\n-In ear drops, it is used as a low to medium potency corticosteroid for the treatment of chronic eczematous external otitis in adults and pediatric patients 2 years and older.\r\n\r\n-As an intravitreal implant, it is indicated for the treatment of diabetic macular edema with patients that have been previously treated with a course of corticosteroids and no clinically significant rise in intraocular pressure.\r\n\r\n-Fluocinolone acetonide was announced on October 15, 2018 to be FDA approved for the treatment of chronic non-infectious uveitis affecting the posterior segment of the eye.\r\n\r\n-Some reports have indicated the use of fluocinolone acetonide as a vasoprotective agent and for its use in the treatment of first-degree hemorrhoids.","Fluocinolone acetonide is a synthetic anti-inflammatory corticosteroid and thus, the effect of its interaction with the body produces vasoconstriction and suppression of membrane permeability, mitotic activity, immune response and release of inflammatory mediators.\r\n\r\nFor its ophthalmic indications, fluocinolone acetonide is administered as intravitreal micro-insert. This preparation was observed in clinical trials to reduce the recurrence of uveitis flares by 2 fold when compared with the non treated patients even after six months after initial administration. As well the intraocular pressure seemed to increase slightly with the presence of the fluocinolone implant but it is important to monitor intraocular pressure.","Fluocinolone acetonide is a corticosteroid and thus, it can be inferred that it acts by inhibiting the edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, collagen deposition, and scar formation. \r\n\r\nSome reports have indicated that fluocinolone acetonide presents a high binding affinity for the glucocorticoid receptor. After binding the receptor, the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements in the promoter region of the target genes. This effect promotes the induction of phospholipase A2 inhibitory proteins (lipocortins). Through this mechanism of action, it is thought that fluocinolone induces mainly one of the lipocortins, annexin 1, which will later mediate the synthesis of inflammatory mediators such as prostaglandins and leukotrienes by inhibiting the release of arachidonic acid which is the precursor of all these inflammatory mediators. Hence, the induction of these proteins will prevent the release of arachidonic acid by phospholipase A2.","Glucocorticoid receptor agonist; Annexin A1 inducer; Annexin A2 inducer; Annexin A3 inducer; Annexin A4 inducer; Annexin A5 inducer","Therapeutic strategy associated"]
[206,"DB00594","approved","small molecule","Amiloride","3,5-diamino-N-carbamimidoyl-6-chloropyrazine-2-carboxamide; Amiloride; Amipramidin; Amipramidine; Amyloride; N-amidino-3,5-diamino-6-chloropyrazinecarboxamide","C6H8ClN7O","NC(=N)NC(=O)C1=NC(Cl)=C(N)N=C1N","A pyrazine compound inhibiting sodium reabsorption through sodium channels in renal epithelial cells. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with diuretics to spare potassium loss. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p705)","2609-46-3","229.627","For use as adjunctive treatment with thiazide diuretics or other kaliuretic-diuretic agents in congestive heart failure or hypertension.","Amiloride, an antikaliuretic-diuretic agent, is a pyrazine-carbonyl-guanidine that is unrelated chemically to other known antikaliuretic or diuretic agents. It is an antihypertensive, potassium-sparing diuretic that was first approved for use in 1967 and helps to treat hypertension and congestive heart failure. The drug is often used in conjunction with thiazide or loop diuretics. Due to its potassium-sparing capacities, hyperkalemia (high blood potassium levels) are occasionally observed in patients taking amiloride. The risk is high in concurrent use of ACE inhibitors or spironolactone. Patients are also advised not to use potassium-containing salt replacements.","Amiloride works by inhibiting sodium reabsorption in the distal convoluted tubules and collecting ducts in the kidneys by binding to the amiloride-sensitive sodium channels. This promotes the loss of sodium and water from the body, but without depleting potassium. Amiloride exerts its potassium sparing effect through the inhibition of sodium reabsorption at the distal convoluted tubule, cortical collecting tubule and collecting duct; this decreases the net negative potential of the tubular lumen and reduces both potassium and hydrogen secretion and their subsequent excretion. Amiloride is not an aldosterone antagonist and its effects are seen even in the absence of aldosterone.","Amiloride-sensitive sodium channel subunit alpha inhibitor; Amiloride-sensitive sodium channel subunit beta inhibitor; Amiloride-sensitive sodium channel subunit gamma inhibitor; Amiloride-sensitive sodium channel subunit delta inhibitor; Amiloride-sensitive amine oxidase [copper-containing] inhibitor; Acid-sensing ion channel 2 inhibitor; Acid-sensing ion channel 1 inhibitor; Sodium/hydrogen exchanger 1 inhibitor; Urokinase-type plasminogen activator inhibitor","Therapeutic strategy associated"]
[207,"DB00595","approved; investigational; vet_approved","small molecule","Oxytetracycline","5-Hydroxytetracycline; Embryostat; Hydroxytetracyclinum; Mepatar; Oxyterracin; Oxyterracine; Oxytetracycline; Oxytetracycline (anhydrous); Oxytetracycline amphoteric","C22H24N2O9","[H][C@@]12[C@@H](O)[C@@]3([H])C(C(=O)C4=C(C=CC=C4O)[C@@]3(C)O)=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@H]2N(C)C","A tetracycline analog isolated from the actinomycete streptomyces rimosus and used in a wide variety of clinical conditions.","79-57-2","460.434","Oxytetracycline is indicated for treatment of infections caused by a variety of Gram positive and Gram negative microorganisms including <i>Mycoplasma pneumoniae, Pasteurella pestis, Escherichia coli, Haemophilus influenzae</i> (respiratory infections), and <i>Diplococcus pneumoniae</i>.","Oxytetracycline is known as a broad-spectrum antibiotic due to its activity against such a wide range of infections. It was the second of the tetracyclines to be discovered. Oxytetracycline, like other tetracyclines, is used to treat many infections common and rare. Its better absorption profile makes it preferable to tetracycline for moderately severe acne, but alternatives sould be sought if no improvement occurs by 3 months.","Oxytetracycline inhibits cell growth by inhibiting translation. It binds to the 30S ribosomal subunit and prevents the amino-acyl tRNA from binding to the A site of the ribosome. The binding is reversible in nature. Oxytetracycline is lipophilic and can easily pass through the cell membrane or passively diffuses through porin channels in the bacterial membrane.","30S ribosomal protein S9 inhibitor; 30S ribosomal protein S4 inhibitor; 16S ribosomal RNA inhibitor","Indication associated"]
[208,"DB00596","approved","small molecule","Ulobetasol","21-chloro diflorasone; Halobetasol; Ulobetasol","C22H27ClF2O4","[H][C@@]12C[C@H](C)[C@](O)(C(=O)CCl)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])C[C@H](F)C2=CC(=O)C=C[C@]12C","Ulobetasol is a highly potent corticosteroid. It is structurally related to . Due to its high potency, it is mainly prescribed in the treatment of severe plaque psoriasis and corticosteroid responsive dermatoses.\r\n\r\nUlobetasol was granted FDA approval on 17 December 1990.","98651-66-2","428.9","Ulobetasol cream and ointment are indicated in the treatment of inflammatory and pruritic corticosteroid responsive dermatoses. Ulobetasol lotion is indicated in the treatment of plaque psoriasis.","Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals. Ulobetasol has a moderate duration of action as it is applied once or twice daily. Corticosteroids have a wide therapeutic window as patients may require doses that are multiples of what the body naturally produces. Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.","The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.\r\n\r\nGlucocorticoids inhibit phospholipase 2 and neutrophil apoptosis and demargination, resulting in decreased formation of arachidonic acid derivatives. They also inhibit NF-Kappa B and other inflammatory transcription factors while promoting anti-inflammatory genes like interleukin-10.\r\n\r\nLower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.","Glucocorticoid receptor agonist","Therapeutic strategy associated"]
[209,"DB00598","approved","small molecule","Labetalol","3-Carboxamido-4-hydroxy-alpha-((1-methyl-3-phenylpropylamino)methyl)benzyl alcohol; 5-(1-Hydroxy-2-(1-methyl-3-phenylpropylamino)ethyl)salicylamide; Labetolol","C19H24N2O3","CC(CCC1=CC=CC=C1)NCC(O)C1=CC(C(N)=O)=C(O)C=C1","Labetalol is a racemic mixture of 2 diastereoisomers where dilevalol, the R,R' stereoisomer, makes up 25% of the mixture. Labetalol is formulated as an injection or tablets to treat hypertension.\r\n\r\nLabetalol was granted FDA approval on 1 August 1984.","36894-69-6","328.4055","Labetalol injections are indicated to control blood pressure in severe hypertension. Labetalol tablets are indicated alone or in combination with antihypertensives like thiazides and loop diuretics to manage hypertension.","Labetalol antagonizes various adrenergic receptors to decrease blood pressure. The duration of action is long as it is generally given twice daily, and the therapeutic window is wide as patients usually take 200-400mg twice daily. Patients susceptible to bronchospasms should not use labetalol unless they are unresponsive to or intolerant of other antihypertensives.","Labetalol non-selectively antagonizes beta-adrenergic receptors, and selectively antagonizes alpha-1-adrenergic receptors. Following oral administration, labetalol has 3 times the beta-blocking ability than alpha-blocking ability. This increases to 6.9 times following intravenous administration. Antagonism of alpha-1-adrenergic receptors leads to vasodilation and decreased vascular resistance. This leads to a decrease in blood pressure that is most pronounced while standing. Antagonism of beta-1-adrenergic receptors leads to a slight decrease in heart rate. Antagonism of beta-2-adrenergic receptors leads to some of the side effects of labetalol such as bronchospasms, however this may be slightly attenuated by alpha-1-adrenergic antagonism. Labetalol leads to sustained vasodilation over the long term without a significant decrease in cardiac output or stroke volume, and a minimal decrease in heart rate.","Beta-1 adrenergic receptor antagonist; Beta-2 adrenergic receptor antagonist; Alpha-1 adrenergic receptors antagonist","Therapeutic strategy associated"]
[210,"DB00601","approved; investigational","small molecule","Linezolid","N-(((S)-3-(3-Fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl)methyl)acetamide","C16H20FN3O4","CC(=O)NC[C@H]1CN(C(=O)O1)C1=CC(F)=C(C=C1)N1CCOCC1","Linezolid is a synthetic antibiotic which is used for the treatment of infections caused by aerobic Gram-positive bacteria. Its effects are bacteriostatic against both enterococci and staphylococci and bactericidal against most isolates of streptococci. Linezolid exerts its antibacterial activity by inhibiting the initiation of bacterial protein synthesis - more specifically, it binds to the 23S ribosomal RNA of the 50S subunit and, in doing so, prevents the formation of the 70S initiation complex which is essential for bacterial reproduction.\r\n\r\nLinezolid was initially approved in 2000 and was the first member of the oxazolidinone antibiotic class. A second member of this class, , was approved by the FDA in 2014 and is considered generally more effective and tolerable than its predecessor.","165800-03-3","337.3461","Linezolid is indicated in adults and children for the treatment of infections caused by susceptible Gram-positive bacteria, including nosocomial pneumonia, community-acquired pneumonia, skin and skin structure infections, and vancomycin-resistant _Enterococcus faecium_ infections. Examples of susceptible bacteria include _Staphylococcus aureus_, _Streptococcus pneumoniae_, _Streptococcus pyogenes_, and _Streptococcus agalactiae_.\r\n\r\nLinezolid is not indicated for the treatment of Gram-negative infections, nor has it been evaluated for use longer than 28 days.","Linezolid is an oxazolidinone antibacterial agent effective against most strains of aerobic Gram-positive bacteria and mycobacteria. It appears to be bacteriostatic against both staphylococci and enterococci and bactericidal against most isolates of streptococci. Linezolid has shown some _in vitro_ activity against Gram-negative and anaerobic bacteria but is not considered efficacious against these organisms.\r\n\r\nLinezolid is a reversible and non-selective inhibitor of monoamine oxidase (MAO) enzymes and can therefore contribute to the development of serotonin syndrome when administered alongside serotonergic agents such as selective serotonin re-uptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs). Linezolid should not be used for the treatment of catheter-related bloodstream infections or catheter-site infections, as the risk of therapy appears to outweigh its benefits under these circumstances.","Linezolid exerts its antibacterial effects by interfering with bacterial protein translation. It binds to a site on the bacterial 23S ribosomal RNA of the 50S subunit and prevents the formation of a functional 70S initiation complex, which is essential for bacterial reproduction, thereby preventing bacteria from dividing.\r\n\r\nPoint mutations in the bacterial 23S rRNA can lead to linezolid resistance, and the development of linezolid-resistant _Enterococcus faecium_ and _Staphylococcus aureus_ have been documented during its clinical use. As antimicrobial susceptibility patterns are geographically distinct, local antibiograms should be consulted to ensure adequate coverage of relevant pathogens prior to use.","23S ribosomal RNA inhibitor","Indication associated"]
[211,"DB00603","approved; investigational","small molecule","Medroxyprogesterone acetate","(6α)-17-(Acetyloxy)-6-methylpreg-4-ene-3,20-dione; 17-Acetoxy-6α-methylprogesterone; 17α-hydroxy-6α-methylprogesterone acetate; 6-alpha-Methyl-17-alpha-acetoxyprogesterone; 6-alpha-Methyl-17-alpha-hydroxyprogesterone acetate; 6α-Methyl-17-acetoxy progesterone; 6α-Methyl-17α-hydroxyprogesterone acetate; 6α-Methyl-4-pregnene-3,20-dion-17α-ol acetate; Medroxyacetate progesterone; Medroxyprogesterone 17-acetate; Medroxyprogesterone acetate; Methylacetoxyprogesterone; Metigestrona; MPA","C24H34O4","[H][C@@]12CC[C@](OC(C)=O)(C(C)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])C[C@H](C)C2=CC(=O)CC[C@]12C","Medroxyprogesterone acetate (MPA) is a  derivative that is more resistant to metabolism for improved pharmacokinetic properties. MPA can be use to treat secondary amenorrhea, endometrial hyperplasia, abnormal uterine bleeding, osteoporosis, vasomotor symptoms in menopause, vulvar and vaginal atrophy, prevent pregnancy, manage pain in endometriosis, prevent pregnancy, and is also used in palliative care for endometrial and renal carcinoma.\r\n\r\nMedroxyprogesterone acetate was granted FDA approval on 18 June 1959.","71-58-9","386.5244","Medroxyprogesterone acetate (MPA) oral tablets are indicated to treat secondary amenorrhea, reduce the incidence of endometrial hyperplasia in postmenopausal women, and to treat abnormal uterine bleeding due to hormonal imbalance, not organic pathology. Oral tablets containing MPA and conjugated estrogens are indicated to prevent postmenopausal osteoporosis and to treat moderate to severe menopausal symptoms such as vasomotor symptoms, vulvar atrophy, and vaginal atrophy. Subcutaneous MPA is indicated to prevent pregnancy and manage pain associated with endometriosis. Intramuscular MPA is indicated to prevent pregnancy, and at higher concentrations for palliative treatment of endometrial or renal carcinoma.","Medroxyprogesterone acetate (MPA) inhibits gonadotropin production, reduces nuclear estrogen receptors and DNA synthesis in epithelial cells of the endometrium, and induces p53 dependant apoptosis in cancer cell lines. MPA oral tablets have a half life of 40-60 hours and other formulations can have half lives that are considerably longer, so the duration of action is long. The therapeutic window is wide as patients may take doses ranging from 5mg orally daily to 1000mg as a depo injection weekly. Long term use of MPA is associated with a reduction in bone density and patients who taking MPA during adolescence may have lower peak bone mass than untreated patients, which can also increase the risk of osteoporosis and fractures in the future.","Medroxyprogesterone acetate (MPA) inhibits the production of gonadotropin, preventing follicular maturation and ovulation, which is responsible for it’s ability to prevent pregnancy. This action also thins the endometrium. MPA reduces nuclear estrogen receptors and DNA synthesis in epithelial cells of the endometrium. MPA can also induce p53 dependant apoptosis in certain cancer cell lines, and inhibit GABA-A receptors.","Progesterone receptor agonist; Estrogen receptor alpha agonist; P-glycoprotein 1 inhibitor; GABA(A) Receptor inhibitor","Therapeutic strategy associated"]
[212,"DB00605","approved; investigational","small molecule","Sulindac","(Z)-5-Fluoro-2-methyl-1-((p-(methylsulfinyl)phenyl)methylene)-1H-indene-3-acetic acid; cis-5-Fluoro-2-methyl-1-((4-(methylsulfinyl)phenyl)methylene)-1H-indene-3-acetic acid; cis-5-Fluoro-2-methyl-1-((p-methylsulfinyl)benzylidene)indene-3-acetic acid","C20H17FO3S","CC1=C(CC(O)=O)C2=CC(F)=CC=C2\\C1=C/C1=CC=C(C=C1)S(C)=O","Sulindac is a nonsteroidal anti-inflammatory drug (NSAID) of the arylalkanoic acid class that is marketed by Merck under the brand name Clinoril. Like other NSAIDs, it may be used in the treatment of acute or chronic inflammatory conditions. Sulindac is a prodrug, derived from sulfinylindene, that is converted _in vivo_ to an active sulfide compound by liver enzymes. There is evidence from some studies that sulindac may be associated with fewer gastrointestinal side effects than other NSAIDs, except for the cyclooxygenase-2 (COX-2) inhibitor drug class. This may be due to the sulfide metabolite undergoing enterohepatic circulation thus maintaining constant blood levels of the compound without inducing gastrointestinal effects, where the drug is excreted in the bile and then reabsorbed from the intestines. While its full mechanism of action is not fully understood, sulindac is thought to primarily mediate its action by inhibiting prostaglandin synthesis by inhibiting COX-1 and COX-2.","38194-50-2","356.411","For acute or long-term use in the relief of signs and symptoms of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute painful shoulder (acute subacromial bursitis/supraspinatus tendinitis), and acute gouty arthritis.","Sulindac is a non-steroidal anti-inflammatory indene derivative, also possessing analgesic and antipyretic activities.","Sulindac's exact mechanism of action is unknown. Its antiinflammatory effects are believed to be due to inhibition of both COX-1 and COX-2 which leads to the inhibition of prostaglandin synthesis. Antipyretic effects may be due to action on the hypothalamus, resulting in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation.","Prostaglandin G/H synthase 2 inhibitor; Prostaglandin G/H synthase 1 inhibitor; Aldose reductase inhibitor; Mitogen-activated protein kinase 3 inhibitor; Peroxisome proliferator-activated receptor delta negative modulator; Prostaglandin D2 receptor 2 antagonist; Aldo-keto reductase family 1 member B10 inhibitor","Therapeutic strategy associated"]
[213,"DB00606","approved","small molecule","Cyclothiazide","6-chloro-3-(2-norbornen-5-yl)-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine 1,1-dioxide; 6-chloro-3,4-dihydro-3-(2-norbornen-5-yl)-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide; 6-chloro-3,4-dihydro-3-(2-norbornen-5-yl)-7-sulfamoyl-1,2,4-benzothiadiazine 1,1-dioxide; 6-chloro-3,4-dihydro-3-(5-norbornen-2-yl)-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide; Cyclothiazide","C14H16ClN3O4S2","NS(=O)(=O)C1=C(Cl)C=C2NC(NS(=O)(=O)C2=C1)C1CC2CC1C=C2","As a diuretic, cyclothiazide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like cyclothiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of cyclothiazide is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle. Cyclothiazide is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. It is also indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe forms of hypertension.","2259-96-3","389.878","Cyclothiazide is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. It is also indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe forms of hypertension.","Like other thiazides, cyclothiazide promotes water loss from the body (diuretics). It inhibits Na<sup>+</sup>/Cl<sup>-</sup> reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue. Cyclothiazide affects the distal renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosages, all thiazides are approximately equal in their diuretic efficacy. Cyclothiazide increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate.","Hydrochlorothiazide, a thiazide diuretic, inhibits water reabsorption in the nephron by inhibiting the sodium-chloride symporter (SLC12A3) in the distal convoluted tubule, which is responsible for 5% of total sodium reabsorption. Normally, the sodium-chloride symporter transports sodium and chloride from the lumen into the epithelial cell lining the distal convoluted tubule. The energy for this is provided by a sodium gradient established by sodium-potassium ATPases on the basolateral membrane. Once sodium has entered the cell, it is transported out into the basolateral interstitium via the sodium-potassium ATPase, causing an increase in the osmolarity of the interstitium, thereby establishing an osmotic gradient for water reabsorption. By blocking the sodium-chloride symporter, hydrochlorothiazide effectively reduces the osmotic gradient and water reabsorption throughout the nephron.Hydrochlorothiazide, a thiazide diuretic, inhibits water reabsorption in the nephron by inhibiting the sodium-chloride symporter (SLC12A3) in the distal convoluted tubule, which is responsible for 5% of total sodium reabsorption. Normally, the sodium-chloride symporter transports sodium and chloride from the lumen into the epithelial cell lining the distal convoluted tubule. The energy for this is provided by a sodium gradient established by sodium-potassium ATPases on the basolateral membrane. Once sodium has entered the cell, it is transported out into the basolateral interstitium via the sodium-potassium ATPase, causing an increase in the osmolarity of the interstitium, thereby establishing an osmotic gradient for water reabsorption. By blocking the sodium-chloride symporter, hydrochlorothiazide effectively reduces the osmotic gradient and water reabsorption throughout the nephron.","Sodium/potassium-transporting ATPase subunit gamma inhibitor; Carbonic anhydrase 1 inhibitor; Carbonic anhydrase 2 inhibitor; Secreted frizzled-related protein 4 inhibitor; Carbonic anhydrase inhibitor","Indication associated"]
[214,"DB00608","approved; investigational; vet_approved","small molecule","Chloroquine","Chloraquine; Chloroquina; Chloroquinium; N4-(7-chloro-4-quinolinyl)-N1,N1-diethyl-1,4-pentanediamine","C18H26ClN3","CCN(CC)CCCC(C)NC1=CC=NC2=CC(Cl)=CC=C12","Chloroquine is an aminoquinolone derivative first developed in the 1940s for the treatment of malaria. It was the drug of choice to treat malaria until the development of newer antimalarials such as , , and . Chloroquine and its derivative  have since been repurposed for the treatment of a number of other conditions including HIV, systemic lupus erythematosus, and rheumatoid arthritis.\r\n\r\n**The FDA emergency use authorization for  and chloroquine in the treatment of COVID-19 was revoked on 15 June 2020.**\r\n\r\nChloroquine was granted FDA Approval on 31 October 1949.","54-05-7","319.872","Chloroquine is indicated to treat infections of _P. vivax_, _P. malariae_, _P. ovale_, and susceptible strains of _P. falciparum_. It is also used to treat extraintestinal amebiasis.\r\n\r\nChloroquine is also used off label for the treatment of rheumatic diseases, as well as treatment and prophylaxis of Zika virus. Chloroquine is currently undergoing clinical trials for the treatment of COVID-19.","Chloroquine inhibits the action of heme polymerase, which causes the buildup of toxic heme in _Plasmodium_ species. It has a long duration of action as the half life is 20-60 days. Patients should be counselled regarding the risk of retinopathy with long term usage or high dosage, muscle weakness, and toxicity in children.","Chloroquine inhibits the action of heme polymerase in malarial trophozoites, preventing the conversion of heme to hemazoin. _Plasmodium_ species continue to accumulate toxic heme, killing the parasite.\r\n\r\nChloroquine passively diffuses through cell membranes and into endosomes, lysosomes, and Golgi vesicles; where it becomes protonated, trapping the chloroquine in the organelle and raising the surrounding pH. The raised pH in endosomes, prevent virus particles from utilizing their activity for fusion and entry into the cell.\r\n\r\nChloroquine does not affect the level of ACE2 expression on cell surfaces, but inhibits terminal glycosylation of ACE2, the receptor that SARS-CoV and SARS-CoV-2 target for cell entry. ACE2 that is not in the glycosylated state may less efficiently interact with the SARS-CoV-2 spike protein, further inhibiting viral entry.","Glutathione S-transferase A2 inhibitor; Tumor necrosis factor inhibitor; Toll-like receptor 9 inhibitor; Glutathione S-transferase inhibitor; High mobility group protein B1 inhibitor; Glutathione S-transferase Mu 1 inhibitor; Angiotensin-converting enzyme 2 modulator","Target associated"]
[215,"DB00612","approved","small molecule","Bisoprolol","(+-)-1-((alpha-(2-Isopropoxyethoxy)-p-tolyl)oxy)-3-(isopropylamino)-2-propanol; (RS)-1-(4-(2-Isopropoxyethoxymethyl)phenoxy)-3-(isopropylamino)-2-propanol","C18H31NO4","CC(C)NCC(O)COC1=CC=C(COCCOC(C)C)C=C1","Bisoprolol is a cardioselective β1-adrenergic blocking agent used to treat high blood pressure. It is considered a potent drug with a long-half life that can be used once daily to reduce the need for multiple doses of antihypertensive drugs. Bisoprolol is generally well tolerated, likely due to its β1-adrenergic receptor selectivity and is a useful alternative to non-selective β-blocker drugs in the treatment of hypertension such as  and . It may be used alone or in combination with other drugs to manage hypertension and can be useful in patients with chronic obstructive pulmonary disease (COPD) due to its receptor selectivity.","66722-44-9","325.443","Bisoprolol is indicated for the treatment of mild to moderate hypertension. It may be used off-label to treat heart failure, atrial fibrillation, and angina pectoris.","Bisoprolol decreases heart rate (chronotropy), decreases contractility (inotropy), and reduces blood pressure. The results of various clinical studies indicate that bisoprolol reduces cardiovascular mortality and all-cause mortality in patients with heart failure and decreased cardiac ejection fraction (EF).","Though the mechanism of action of bisoprolol has not been fully elucidated in hypertension, it is thought that therapeutic effects are achieved through the antagonism of β-1adrenoceptors to result in lower cardiac output. Bisoprolol is a competitive, cardioselective β1-adrenergic antagonist. When β1-receptors (located mainly in the heart) are activated by adrenergic neurotransmitters such as epinephrine, both the blood pressure and heart rate increase, leading to greater cardiovascular work, increasing the demand for oxygen.  Bisoprolol reduces cardiac workload by decreasing contractility and the need for oxygen through competitive inhibition of β1-adrenergic receptors.\r\n\r\nBisoprolol is also thought to reduce the output of renin in the kidneys, which normally increases blood pressure. Additionally, some central nervous system effects of bisoprolol may include diminishing sympathetic nervous system output from the brain, decreasing blood pressure and heart rate.","Beta-1 adrenergic receptor antagonist; Beta-2 adrenergic receptor antagonist","Indication associated"]
[216,"DB00613","approved; investigational","small molecule","Amodiaquine","Amodiaquine","C20H22ClN3O","CCN(CC)CC1=C(O)C=CC(NC2=C3C=CC(Cl)=CC3=NC=C2)=C1","A 4-aminoquinoquinoline compound with anti-inflammatory properties.","86-42-0","355.861","For treatment of acute malarial attacks in non-immune subjects.","Amodiaquine, a 4-aminoquinoline similar to chloroquine in structure and activity, has been used as both an antimalarial and an anti-inflammatory agent for more than 40 years. Amodiaquine is at least as effective as chloroquine, and is effective against some chloroquine-resistant strains, although resistance to amodiaquine has been reported. The mode of action of amodiaquine has not yet been determined. 4-Aminoquinolines depress cardiac muscle, impair cardiac conductivity, and produce vasodilatation with resultant hypotension. They depress respiration and cause diplopia, dizziness and nausea.","The mechanism of plasmodicidal action of amodiaquine is not completely certain. Like other quinoline derivatives, it is thought to inhibit heme polymerase activity. This results in accumulation of free heme, which is toxic to the parasites. The drug binds the free heme preventing the parasite from converting it to a form less toxic. This drug-heme complex is toxic and disrupts membrane function.","Fe(II)-protoporphyrin IX binder; Histamine N-methyltransferase inhibitor","Therapeutic strategy associated"]
[217,"DB00618","approved","small molecule","Demeclocycline","[4S-(4α,4aα,5aα,6β,12aα)]-7-chloro-4-(dimethylamino)1,4,4a,5,5a,6,11,12a-octahydro-3,6,10,12,12a-pentahydroxy-1,11-dioxo-2-naphthacenecarboxamide; 6-demethyl-7-chlorotetracycline; 7-chloro-6-demethyltetracycline; Demeclocycline; Demethylchlortetracyclin; Demethylchlortetracycline; DMCT; DMCTC","C21H21ClN2O8","[H][C@]12C[C@@]3([H])[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]3(O)C(O)=C1C(=O)C1=C([C@H]2O)C(Cl)=CC=C1O","A tetracycline analog having a 7-chloro and a 6-methyl. Because it is excreted more slowly than tetracycline, it maintains effective blood levels for longer periods of time.","127-33-3","464.853","Used primarily to treat Lyme disease, acne, and bronchitis. Also indicated (but rarely used) to treat urinary tract infections, gum disease, malaria, and other bacterial infections such as gonorrhea and chlamydia. One of its other registered uses is the treatment of hyponatremia (low blood sodium concentration) due to the syndrome of inappropriate antidiuretic hormone (SIADH) where fluid restriction alone has been ineffective.","Demeclocycline is a tetracycline antibiotic active against the following microorganisms: <i>Rickettsiae</i> (Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsial pox, tick fevers), <i>Mycoplasma pneumoniae</i> (PPLO, Eaton agent), agents of psittacosis and ornithosis, agents of lymphogranulomavenereum and granuloma inguinale, the spirochetal agent of relapsing fever (<i>Borrelia recurrentis</i>), <i>Haemophilus ducreyi</i> (chancroid), <i>Yersinia pestis</i>, <i>Pasteurella pestis</i> and <i>Pasteurella tularensis</i>, <i>Bartonella bacilliformis</i>, <i>Bacteroides species</i>, <i>Vibrio comma</i> and <i>Vibrio fetus</i>, and <i>Brucella species</i> (in conjunction with streptomycin). Demeclocycline inhibits cell growth by inhibiting translation. Demeclocycline is lipophilic and can easily pass through the cell membrane or passively diffuses through porin channels in the bacterial membrane. Demeclocycline is not a direct bactericidal agent; rather, it is a bacteriostatic drug that impairs bacterial growth. Because it is excreted more slowly than tetracycline, it maintains effective blood levels for longer periods of time.","Demeclocycline inhibits cell growth by inhibiting translation. It binds (reversibly) to the 30S and 50S ribosomal subunit and prevents the amino-acyl tRNA from binding to the A site of the ribosome, which impairs protein synthesis by bacteria. The binding is reversible in nature. The use in SIADH actually relies on a side-effect of tetracycline antibiotics; many may cause diabetes insipidus (dehydration due to the inability to concentrate urine). It is not completely understood why demeclocycline impairs the action of antidiuretic hormone, but it is thought that it blocks the binding of the hormone to its receptor.","30S ribosomal protein inhibitor; Vasopressin V2 receptor inhibitor","Indication associated"]
[218,"DB00619","approved","small molecule","Imatinib","α-(4-methyl-1-piperazinyl)-3'-((4-(3-pyridyl)-2-pyrimidinyl)amino)-p-toluidide","C29H31N7O","CN1CCN(CC2=CC=C(C=C2)C(=O)NC2=CC(NC3=NC=CC(=N3)C3=CN=CC=C3)=C(C)C=C2)CC1","Imatinib is a small molecule kinase inhibitor used to treat certain types of cancer. It is currently marketed by Novartis as Gleevec (USA) or Glivec (Europe/Australia) as its mesylate salt, imatinib mesilate (INN). It is occasionally referred to as CGP57148B or STI571 (especially in older publications). It is used in treating chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GISTs) and a number of other malignancies.\r\n\r\nIt is the first member of a new class of agents that act by inhibiting particular tyrosine kinase enzymes, instead of non-specifically inhibiting rapidly dividing cells.","152459-95-5","493.6027","For the treatment of Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML), Ph+ acute lymphoblastic leukaemia, myelodysplastic/myeloproliferative diseases, aggressive systemic mastocytosis, hypereosinophilic syndrome and/or chronic eosinophilic leukemia (CEL), dermatofibrosarcoma protuberans, and malignant gastrointestinal stromal tumors (GIST).","Imatinib is an antineoplastic agent and a 2-phenylaminopyrimidine derivative that is used to treat chronic myelogenous leukemia. It works as a specific inhibitor of a number of tyrosine kinase enzymes. Chronic myelogenous leukemia is associated with the Philadelphia chromosome promoting the generation of BCR-ABL mutation, which results from the combination of two genes, known as BCR and ABL. BCR-ABL generates a fusion protein that acts as a constitutively active tyrosine kinase and imatinib works to inhibit this constitutive enzymatic activity.","Imatinib mesylate is a protein-tyrosine kinase inhibitor that inhibits the Bcr-Abl tyrosine kinase, the constitutive abnormal tyrosine kinase created by the Philadelphia chromosome abnormality in chronic myeloid leukemia (CML). It inhibits proliferation and induces apoptosis in Bcr-Abl positive cell lines as well as fresh leukemic cells from Philadelphia chromosome positive chronic myeloid leukemia. Imatinib also inhibits the receptor tyrosine kinases for platelet derived growth factor (PDGF) and stem cell factor (SCF) - called c-kit. Imatinib was identified in the late 1990s by Dr Brian J. Druker. Its development is an excellent example of rational drug design. Soon after identification of the bcr-abl target, the search for an inhibitor began. Chemists used a high-throughput screen of chemical libraries to identify the molecule 2-phenylaminopyrimidine. This lead compound was then tested and modified by the introduction of methyl and benzamide groups to give it enhanced binding properties, resulting in imatinib.","Breakpoint cluster region protein inhibitor; Mast/stem cell growth factor receptor Kit antagonist; RET proto-oncogene inhibitor; High affinity nerve growth factor receptor antagonist; Macrophage colony-stimulating factor 1 receptor antagonist; Platelet-derived growth factor receptor alpha antagonist; Epithelial discoidin domain-containing receptor 1 antagonist; Tyrosine-protein kinase ABL1 inhibitor; Platelet-derived growth factor receptor beta antagonist","Therapeutic strategy associated"]
[219,"DB00620","approved; vet_approved","small molecule","Triamcinolone","11β,16α,17α,21-tetrahydroxy-9α-fluoro-1,4-pregnadiene-3,20-dione; 9-fluoro-11β,16α,17,21-tetrahydroxypregna-1,4-diene-3,20-dione; 9α-fluoro-11β,16α,17,21-tetrahydroxypregna-1,4-diene-3,20-dione; 9α-fluoro-11β,16α,17α,21-tetrahydroxypregna-1,4-diene-3,20-dione; 9α-fluoro-16α-hydroxyprednisolone; Fluoxyprednisolone","C21H27FO6","[H][C@@]12C[C@@H](O)[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])CCC2=CC(=O)C=C[C@]12C","Triamcinolone is a corticosteroid used to treat various inflammatory conditions in the body from allergic rhinitis to acute exacerbations of multiple sclerosis. Triamcinolone can be used as a one time adjunct treatment of osteoarthritic knee pain, or first line as a topical treatment of corticosteroid responsive dermatoses. Triamcinolone is more commonly seen in the forms triamcinolone hexacetonide, triamcinolone acetonide, and triamcinolone diacetate.\r\n\r\nTriamcinolone was granted FDA approval on 3 December 1957. In October 2021, a suspension of triamcinolone acetonide was approved for suprachoroidal injection - the first suprachoroidal injection to receive FDA approval - for the treatment of patients with macular edema associated with uveitis.","124-94-7","394.4339","Triamcinolone hexacetonide injections are indicated for intralesional administration in alopecia areata, discoid lupus erythematosus, keloids, and necrobiosis lipoidica diabeticorum. This formulation can also be used for localized hypertrophic infiltrated inflammatory lesions of granuloma annulare, lichen planus, lichen simplex chronicus, and psoriatic plaques.\r\n\r\nTriamcinolone acetonide spray and cream are indicated for the treatment of inflammatory and pruritic manifestations of corticosteroid responsive dermatoses. A triamcinolone acetonide 10mg/mL or 40mg/mL injection is indicated intra-articularly for acute gouty arthritis, acute and subacute bursitis, acute nonspecific tenosynovitis, epicondylitis, rheumatoid arthritis, and synovitis of osteoarthritis. The same 10mg/mL injection is indicated by the intralesional route for the treatment of alopecia areata, discoid lupus erythematosus, keloids, necrobiosis lipoidica diabeticorum, and tumors of an aponeurosis or tendon. This formulation can also be used for localized hypertrophic infiltrated inflammatory lesions of granuloma annulare, lichen planus, lichen simplex chronicus, and psoriatic plaques. The 40mg/mL injection is indicated intramuscularly for controlling severe allergic conditions such as asthma, atopic dermatitis, contact dermatitis, drug hypersensitivity, perennial or seasonal allergic rhinitis, serum sickness, and transfusion reactions; treatment of bullous dermatitis herpetiformis, exfoliative erythroderma, mycosis fungoides, pemphigus, Stevens-Johnson syndrome, congenital adrenal hyperplasia, hypercalcemia in\r\ncancer, nonsuppurative thyroiditis, autoimmune hemolytic anemia, Diamond-Blackfan anemia, pure red cell aplasia, secondary thrombocytopenia, trichinosis, tuberculous meningitis, acute exacerbations of multiple sclerosis or cerebral edema, sympathetic ophthalmia, temporal arteritis, uveitis, ocular inflammation, berylliosis, idiopathic eosinophilic pneumonias, symptomatic sarcoidosis, dermatomyositis, polymyositis, and systemic lupus erythematosus; adjunct treatment of adrenocortical insufficiency, regional enteritis, ulcerative colitis, fulminating or disseminated pulmonary tuberculosis, acute gouty arthritis, acute rheumatic carditis, ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis; palliative management of leukemia and lymphoma; induction of diuresis or remission of proteinuria in idiopathic nephrotic syndrome or lupus erythematosus. A triamcinolone intravitreal injection is indicated for the treatment of sympathetic ophthalmia, temporal arteritis, uveitis, and ocular inflammatory conditions. The intravitreal injection is also used for visualization during vitrectomy. An extended release suspension is indicated intra-articularly for management of pain in osteoarthritis of the knee.\r\n\r\nA triamcinolone acetonide suspension for injection into the suprachoroidal space is indicated for the treatment of macular edema associated with uveitis.","Triamcinolone is a corticosteroid with anti-inflammatory properties. These properties are used to treat inflammation in conditions that affect various organs and tissues. Triamcinolone should not be administered as an epidural injection.","Corticosteroids like triamcinolone inhibit phospholipase A2 on cell membranes, preventing the breakdown of lysosomal membranes of leukocytes, which in turn prevent the formation of arachidonic acid, which decrease expression of cyclooxygenase and lipoxygenase, inhibiting synthesis of prostaglandins and leukotrienes. Anti-inflammatory activity occurs via reversal of vascular dilation and reducing permeability, which prevents macrophage and leukocyte migration. Triamcinolone also inhibits nuclear factor kappa-B, which decreases the production of pro-inflammatory signals such as interleukin-6, interleukin-8, and monocyte chemoattractant protein-1.","Glucocorticoid receptor agonist","Therapeutic strategy associated"]
[220,"DB00621","approved; investigational","small molecule","Oxandrolone",null,"C19H30O3","[H][C@@]12CC[C@](C)(O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC[C@@]2([H])CC(=O)OC[C@]12C","A synthetic hormone with anabolic and androgenic properties.","53-39-4","306.4397","Use to promote weight gain after weight loss following extensive surgery.","Oxandrolone is an anabolic steroids indicated as adjunctive therapy to promote weight gain after weight loss following extensive surgery, chronic infections, or severe trauma, and in some patients who without definite pathophysiologic reasons fail to gain or to maintain normal weight, to offset the protein catabolism associated with prolonged administration of corticosteroids, and for the relief of the bone pain frequently accompanying osteoporosis. Anabolic steroids are synthetic derivatives of testosterone.","Oxandrolones interact with androgen receptors in target tissues.","Androgen receptor agonist","Therapeutic strategy associated"]
[221,"DB00622","approved; investigational","small molecule","Nicardipine","Nicardipine","C26H29N3O6","COC(=O)C1=C(C)NC(C)=C(C1C1=CC(=CC=C1)[N+]([O-])=O)C(=O)OCCN(C)CC1=CC=CC=C1","A potent calcium channel blockader with marked vasodilator action. It has antihypertensive properties and is effective in the treatment of angina and coronary spasms without showing cardiodepressant effects. It has also been used in the treatment of asthma and enhances the action of specific antineoplastic agents.","55985-32-5","479.525","Used for the management of patients with chronic stable angina and for the treatment of hypertension.","Nicardipine, a dihydropyridine calcium-channel blocker, is used alone or with an angiotensin-converting enzyme inhibitor, to treat hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina. Nicardipine is similar to other peripheral vasodilators. Nicardipine inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.","By deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, nicardipine inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.","Voltage-dependent L-type calcium channel subunit alpha-1C inhibitor; Voltage-dependent L-type calcium channel subunit beta-2 inhibitor; Voltage-dependent calcium channel subunit alpha-2/delta-1 inhibitor; Voltage-dependent L-type calcium channel subunit alpha-1D inhibitor; Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A inhibitor; Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B inhibitor; Alpha-1A adrenergic receptor antagonist; Alpha-1B adrenergic receptor antagonist; Alpha-1D adrenergic receptor antagonist; Muscarinic acetylcholine receptor M1 antagonist; Muscarinic acetylcholine receptor M2 antagonist; Muscarinic acetylcholine receptor M3 antagonist; Muscarinic acetylcholine receptor M4 antagonist; Muscarinic acetylcholine receptor M5 antagonist; Calmodulin other/unknown","Indication associated"]
[222,"DB00626","approved; vet_approved","small molecule","Bacitracin","Bacitracin; Bacitracin A","C66H103N17O16S","CC[C@H](C)[C@H](N)C1=N[C@@H](CS1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H]1CCCCNC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](CC(O)=O)NC(=O)[C@H](CC2=CNC=N2)NC(=O)[C@@H](CC2=CC=CC=C2)NC(=O)[C@@H](NC(=O)[C@@H](CCCN)NC1=O)[C@@H](C)CC","Bacitracin is a combination of at least 9 bacitracins. 60-80% of commercially prepared bacitracin is bacitracin A. The bacillus that produces bacitracin was first isolated from a knee scrape in 1945 from the knee wound of a child named Margaret Tracy.\r\n\r\nBacitracin was granted FDA approval on 29 July 1948.","1405-87-4","1422.693","Bacitracin is indicated in topical formulations for acute and chronic localized skin infections. Occasionally, it is also used intramuscularly for infantile streptococcal pneumonia and empyema. Bacitracin is also formulated as an ointment with neomycin and polymyxin B for over the counter use. A bacitracin ointment formulated with neomycin and polymyxin B along with hydrocortisone is indicated for the treatment of corticosteroid responsive dermatoses with secondary infection.","Bacitracin is a mixture of polypeptides that prevent the formation of the bacterial cell wall and oxidatively cleave DNA. It has a short duration of action as it must be given every 3 to 4 hours topically. Bacitracin is nephrotoxic when given intramuscularly and may lead to renal failure.","Bacitracin binds to a divalent metal ion such as Mn(II), Co(II), Ni(II), Cu(II), or Zn(II). These complexes bind C<sub>55</sub>-isoprenyl pyrophosphate, preventing the hydrolysis of a lipid dolichol pyrophosphate, which finally inhibits cell wall synthesis. Bacitracin metal complexes also bind and oxidatively cleave DNA.","C55-isoprenyl pyrophosphate antagonist; Insulin-degrading enzyme inhibitor; Alpha-2-macroglobulin inhibitor","Indication associated"]
[223,"DB00630","approved","small molecule","Alendronic acid","(4-amino-1-hydroxybutane-1,1-diyl)bis(phosphonic acid); (4-amino-1-hydroxybutylidene)bisphosphonic acid; 4-amino-1-hydroxybutane-1,1-diphosphonic acid; ABDP; Alendronate; Alendronic acid","C4H13NO7P2","NCCCC(O)(P(O)(O)=O)P(O)(O)=O","Alendronic acid is a second generation bisphosphonate that is used for the treatment of some forms of osteoperosis and Paget's disease. It functions by preventing resorption of bone.","66376-36-1","249.096","Alendronic acid is indicated for the treatment and prevention of osteoporosis in men and postmenopausal women, treatment of glucocorticoid-induced osteoporosis, and Paget's disease of bone. However, alendronic acid is not indicated for use in pediatric populations or patients with a creatinine clearance <35mL/min.","Alendronic acid tablets have a very low oral bioavialability. After administration it distributes into soft tissue and bone or is excreted in the urine. Alendronic acid does not undergo metabolism.","Alendronic acid binds to bone hydroxyapatite. Bone resorption causes local acidification, releasing alendronic acid which is that taken into osteoclasts by fluid-phase endocytosis. Endocytic vesicles are acidified, releasing alendronic acid to the cytosol of osteoclasts where they induce apoptosis. Inhibition of osteoclasts results in decreased bone resorption which is shown through decreased urinary calcium, deoxypyridinoline and cross-linked N-telopeptidases of type I collagen.","Farnesyl pyrophosphate synthase inhibitor; Hydroxylapatite antagonist; Tyrosine-protein phosphatase non-receptor type 4 inhibitor; Receptor-type tyrosine-protein phosphatase S inhibitor; Receptor-type tyrosine-protein phosphatase epsilon inhibitor; V-type proton ATPase catalytic subunit A inhibitor","Therapeutic strategy associated"]
[224,"DB00631","approved; investigational","small molecule","Clofarabine","(2R,3R,4S,5R)-5-(6-amino-2-chloropurin-9-yl)-4-fluoro-2-(hydroxymethyl)oxolan-3-ol; 2-chloro-9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)adenine; 2-chloro-9-(2'-deoxy-2'-fluoro-β-D-arabinofuranosyl)adenine; CAFdA; Cl-F-Ara-A","C10H11ClFN5O3","[H][C@]1(F)[C@H](O)[C@@H](CO)O[C@H]1N1C=NC2=C(N)N=C(Cl)N=C12","Clofarabine is a purine nucleoside antimetabolite that is being studied in the treatment of cancer. It is marketed as Clolar in the U.S. and Canada, or Evoltra in Europe, Australia, and New Zealand. Clofarabine is used in paediatrics to treat a type of leukaemia called relapsed or refractory acute lymphoblastic leukaemia (ALL), only after at least two other types of treatment have failed. It is not known if the drug extends life expectancy. Its potential use in acute myeloid leukaemia (AML) and juvenile myelomonocytic leukaemia (JMML) has been investigated.","123318-82-1","303.677","For the treatment of pediatric patients 1 to 21 years old with relapsed or refractory acute lymphocytic (lymphoblastic) leukemia after at least two prior regimens. It is designated as an orphan drug by the FDA for this use.","Clofarabine is a purine nucleoside antimetabolite that differs from other puring nucleoside analogs by the presence of a chlorine in the purine ring and a flourine in the ribose moiety. Clofarabine seems to interfere with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected by clofarabine, other effects also occur. Clofarabine prevents cells from making DNA and RNA by interfering with the synthesis of nucleic acids, thus stopping the growth of cancer cells.","Clofarabine is metabolized intracellularly to the active 5'-monophosphate metabolite by deoxycytidine kinase and 5'-triphosphate metabolite by mono- and di-phospho-kinases. This metabolite inhibits DNA synthesis through an inhibitory action on ribonucleotide reductase, and by terminating DNA chain elongation and inhibiting repair through competitive inhibition of DNA polymerases. This leads to the depletion of the intracellular deoxynucleotide triphosphate pool and the self-potentiation of clofarabine triphosphate incorporation into DNA, thereby intensifying the effectiveness of DNA synthesis inhibition. The affinity of clofarabine triphosphate for these enzymes is similar to or greater than that of deoxyadenosine triphosphate. In preclinical models, clofarabine has demonstrated the ability to inhibit DNA repair by incorporation into the DNA chain during the repair process. Clofarabine 5'-triphosphate also disrupts the integrity of mitochondrial membrane, leading to the release of the pro-apoptotic mitochondrial proteins, cytochrome C and apoptosis-inducing factor, leading to programmed cell death.","DNA polymerase alpha catalytic subunit inhibitor; Ribonucleoside-diphosphate reductase large subunit inhibitor; DNA other/unknown","Therapeutic strategy associated"]
[225,"DB00635","approved; vet_approved","small molecule","Prednisone","1,2-Dehydrocortisone; 1,4-Pregnadiene-17α,21-diol-3,11,20-trione; 17,21-Dihydroxypregna-1,4-diene-3,11,20-trione; Dehydrocortisone; Prednisone","C21H26O5","[H][C@@]12CC[C@](O)(C(=O)CO)[C@@]1(C)CC(=O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)C=C[C@]12C","A synthetic anti-inflammatory glucocorticoid derived from . It is biologically inert and converted to  in the liver.\r\n\r\nPrednisone was granted FDA approval on 21 February 1955.","53-03-2","358.4281","Prednisone is indicated as an anti-inflammatory or immunosuppressive drug for allergic, dermatologic, gastrointestinal, hematologic, ophthalmologic, nervous system, renal, respiratory, rheumatologic, infectious, endocrine, or neoplastic conditions as well as in organ transplant.","Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals. Prednisone has a short duration of action as the half life is 2-3 hours. Corticosteroids have a wide therapeutic window as patients make require doses that are multiples of what the body naturally produces. Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.","Prednisone is first metabolized in the liver to its active form, prednisolone, a glucocorticoid agonist corticosteroid.\r\n\r\nThe short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.\r\n\r\nGlucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10.\r\n\r\nLower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.","Glucocorticoid receptor agonist","Therapeutic strategy associated"]
[226,"DB00636","approved; investigational","small molecule","Clofibrate","2-(4-Chlorophenoxy)-2-methylpropanoic acid ethyl ester; 2-(p-Chlorophenoxy)-2-methylpropionic acid ethyl ester; alpha-(p-Chlorophenoxy)isobutyric acid, ethyl ester; alpha-p-Chlorophenoxyisobutyryl ethyl ester; Clofibrate; EPIB; Ethyl 2-(p-chlorophenoxy)isobutyrate; Ethyl chlorophenoxyisobutyrate; Ethyl clofibrate; Liprin","C12H15ClO3","CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1","A fibric acid derivative used in the treatment of hyperlipoproteinemia type III and severe hypertriglyceridemia. (From Martindale, The Extra Pharmacopoeia, 30th ed, p986)","637-07-0","242.699","For Primary Dysbetalipoproteinemia (Type III hyperlipidemia) that does not respond adequately to diet. This helps control high cholesterol and high triglyceride levels.","Clofibrate is an antilipidemic agent similar to gemfibrozil. It acts to lower elevated serum lipids by reducing the very low-density lipoprotein fraction (S<sub>f</sub> 20-400) rich in triglycerides. Serum cholesterol may be decreased, particularly in those patients whose cholesterol elevation is due to the presence of IDL as a result of Type III hyperlipoproteinemia. Several investigators have observed in their studies that clofibrate may produce a decrease in cholesterol linoleate but an increase in palmitoleate and oleate, the latter being considered atherogenic in experimental animals. The significance of this finding is unknown at this time. Reduction of triglycerides in some patients treated with clofibrate or certain of its chemically and clinically similar analogs may be associated with an increase in LDL cholesterol. Increase in LDL cholesterol has been observed in patients whose cholesterol is initially normal. Animal studies suggest that clofibrate interrupts cholesterol biosynthesis prior to mevalonate formation.","Clofibrate increases the activity of extrahepatic lipoprotein lipase (LL), thereby increasing lipoprotein triglyceride lipolysis. Chylomicrons are degraded, VLDLs are converted to LDLs, and LDLs are converted to HDL. This is accompanied by a slight increase in secretion of lipids into the bile and ultimately the intestine. Clofibrate also inhibits the synthesis and increases the clearance of apolipoprotein B, a carrier molecule for VLDL. Also, as a fibrate, Clofibrate is an agonist of the PPAR-α receptor in muscle, liver, and other tissues. This agonism ultimately leads to modification in gene expression resulting in increased beta-oxidation, decreased triglyceride secretion, increased HDL, increased lipoprotein lipase activity.","Peroxisome proliferator-activated receptor alpha agonist","Target associated"]
[227,"DB00641","approved","small molecule","Simvastatin","2,2-dimethylbutyric acid, 8-ester with (4R,6R)-6-(2-((1S,2S,6R,8S,8aR)-1,2,6,7,8,8a-hexahydro-8-hydroxy-2,6-dimethyl-1-naphthyl)ethyl)tetrahydro-4-hydroxy-2H-pyran-2-one; Simvastatin","C25H38O5","[H][C@]12[C@H](C[C@@H](C)C=C1C=C[C@H](C)[C@@H]2CC[C@@H]1C[C@@H](O)CC(=O)O1)OC(=O)C(C)(C)CC","Simvastatin, also known as the brand name product Zocor, is a lipid-lowering drug derived synthetically from a fermentation product of _Aspergillus terreus_. It belongs to the statin class of medications, which are used to lower the risk of cardiovascular disease and manage abnormal lipid levels by inhibiting the endogenous production of cholesterol in the liver. More specifically, statin medications competitively inhibit the enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) Reductase, which catalyzes the conversion of HMG-CoA to mevalonic acid and is the third step in a sequence of metabolic reactions involved in the production of several compounds involved in lipid metabolism and transport including cholesterol, low-density lipoprotein (LDL) (sometimes referred to as \"bad cholesterol\"), and very low-density lipoprotein (VLDL). Prescribing of statin medications is considered standard practice following any cardiovascular events and for people with a moderate to high risk of development of CVD, such as those with Type 2 Diabetes. The clear evidence of the benefit of statin use coupled with very minimal side effects or long term effects has resulted in this class becoming one of the most widely prescribed medications in North America.\r\n\r\nSimvastatin and other drugs from the statin class of medications including , , , , and  are considered first-line options for the treatment of dyslipidemia. Increasing use of the statin class of drugs is largely due to the fact that cardiovascular disease (CVD), which includes heart attack, atherosclerosis, angina, peripheral artery disease, and stroke, has become a leading cause of death in high-income countries and a major cause of morbidity around the world. Elevated cholesterol levels, and in particular, elevated low-density lipoprotein (LDL) levels, are an important risk factor for the development of CVD. Use of statins to target and reduce LDL levels has been shown in a number of landmark studies to significantly reduce the risk of development of CVD and all-cause mortality. Statins are considered a cost-effective treatment option for CVD due to their evidence of reducing all-cause mortality including fatal and non-fatal CVD as well as the need for surgical revascularization or angioplasty following a heart attack. Evidence has shown that even for low-risk individuals (with <10% risk of a major vascular event occurring within 5 years) statins cause a 20%-22% relative reduction in major cardiovascular events (heart attack, stroke, coronary revascularization, and coronary death) for every 1 mmol/L reduction in LDL without any significant side effects or risks.\r\n\r\nWhile all statin medications are considered equally effective from a clinical standpoint,  is considered the most potent; doses of 10 to 40mg  per day were found in clinical studies to result in a 45.8% to 54.6% decrease in LDL cholesterol levels, while simvastatin has been found to have an average decrease in LDL-C of ~35%. Potency is thought to correlate to tissue permeability as the more lipophilic statins such as simvastatin are thought to enter endothelial cells by passive diffusion, as opposed to hydrophilic statins such as  and  which are taken up into hepatocytes through OATP1B1 (organic anion transporter protein 1B1)-mediated transport. Despite these differences in potency, several trials have demonstrated only minimal differences in terms of clinical outcomes between statins.","79902-63-9","418.5662","Simvastatin is indicated for the treatment of hyperlipidemia to reduce elevated total cholesterol (total-C), low-density lipoprotein cholesterol (LDL‑C), apolipoprotein B (Apo B), and triglycerides (TG), and to increase high-density lipoprotein cholesterol (HDL-C).\r\n\r\nThis includes the treatment of primary hyperlipidemia (Fredrickson type IIa, heterozygous familial and nonfamilial), mixed dyslipidemia (Fredrickson type IIb), hypertriglyceridemia (Fredrickson type IV hyperlipidemia), primary dysbetalipoproteinemia (Fredrickson type III hyperlipidemia), homozygous familial hypercholesterolemia (HoFH) as an adjunct to other lipid-lowering treatments, as well as adolescent patients with Heterozygous Familial Hypercholesterolemia (HeFH).\r\n\r\nSimvastatin is also indicated to reduce the risk of cardiovascular morbidity and mortality including myocardial infarction, stroke, and the need for revascularization procedures. It is primarily used in patients at high risk of coronary events because of existing coronary heart disease, diabetes, peripheral vessel disease, history of stroke or other cerebrovascular disease.\r\n\r\nPrescribing of statin medications is considered standard practice following any cardiovascular events and for people with a moderate to high risk of development of CVD. Statin-indicated conditions include diabetes mellitus, clinical atherosclerosis (including myocardial infarction, acute coronary syndromes, stable angina, documented coronary artery disease, stroke, trans ischemic attack (TIA), documented carotid disease, peripheral artery disease, and claudication), abdominal aortic aneurysm, chronic kidney disease, and severely elevated LDL-C levels.","Simvastatin is an oral antilipemic agent which inhibits HMG-CoA reductase. It is used to lower total cholesterol, low density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apoB), non-high density lipoprotein-cholesterol (non-HDL-C), and trigleride (TG) plasma concentrations while increasing HDL-C concentrations. High LDL-C, low HDL-C and high TG concentrations in the plasma are associated with increased risk of atherosclerosis and cardiovascular disease. The total cholesterol to HDL-C ratio is a strong predictor of coronary artery disease and high ratios are associated with higher risk of disease. Increased levels of HDL-C are associated with lower cardiovascular risk. By decreasing LDL-C and TG and increasing HDL-C, rosuvastatin reduces the risk of cardiovascular morbidity and mortality.\r\n\r\nElevated cholesterol levels, and in particular, elevated low-density lipoprotein (LDL) levels, are an important risk factor for the development of CVD. Use of statins to target and reduce LDL levels has been shown in a number of landmark studies to significantly reduce the risk of development of CVD and all-cause mortality. Statins are considered a cost-effective treatment option for CVD due to their evidence of reducing all-cause mortality including fatal and non-fatal CVD as well as the need for surgical revascularization or angioplasty following a heart attack. Evidence has shown that even for low-risk individuals (with <10% risk of a major vascular event occurring within 5 years) statins cause a 20%-22% relative reduction in major cardiovascular events (heart attack, stroke, coronary revascularization, and coronary death) for every 1 mmol/L reduction in LDL without any significant side effects or risks.\r\n\r\n**Skeletal Muscle Effects**\r\n\r\nSimvastatin occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase (CK) above ten times the upper limit of normal (ULN). Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred. Predisposing factors for myopathy include advanced age (≥65 years), female gender, uncontrolled hypothyroidism, and renal impairment. Chinese patients may also be at increased risk for myopathy. In most cases, muscle symptoms and CK increases resolved when treatment was promptly discontinued.\r\n\r\nIn a clinical trial database of 41,413 patients, the incidence of myopathy was approximately 0.03% and 0.08% at 20 and 40 mg/day, respectively, while the risk of myopathy with simvastatin 80 mg (0.61%) was disproportionately higher than that observed at the lower doses. It's therefore recommended that the 80mg dose of simvastatin should be used only in patients who have been taking simvastatin 80 mg chronically (e.g., for 12 months or more) without evidence of muscle toxicity. As well, patients already stabilized on simvastatin 80mg should be monitored closely for evidence of muscle toxicity; if they need to be initiated on an interacting drug that is contraindicated or is associated with a dose cap for simvastatin, that patient should be switched to an alternative statin with less potential for the drug-drug interaction.\r\n\r\nThe risk of myopathy during treatment with simvastatin may be increased with concurrent administration of interacting drugs such as , , , , and strong inhibitors of the CYP3A4 enzyme.  Cases of myopathy, including rhabdomyolysis, have been reported with HMG-CoA reductase inhibitors coadministered with , and caution should therefore be exercised when prescribing these two medications together.\r\n\r\n**Liver Enzyme Abnormalities**\r\n\r\nPersistent increases (to more than 3X the ULN) in serum transaminases have occurred in approximately 1% of patients who received simvastatin in clinical studies. When drug treatment was interrupted or discontinued in these patients, the transaminase levels usually fell slowly to pretreatment levels. The increases were not associated with jaundice or other clinical signs or symptoms. \r\n\r\nIn the Scandinavian Simvastatin Survival Study (4S), the number of patients with more than one transaminase elevation to >3 times the ULN, over the course of the study, was not significantly different between the simvastatin and placebo groups (14  vs. 12 ). The frequency of single elevations of ALT to 3 times the ULN was significantly higher in the simvastatin group in the first year of the study (20 vs. 8, p=0.023), but not thereafter. In the HPS (Heart Protection Study), in which 20,536 patients were randomized to receive simvastatin 40 mg/day or placebo, the incidences of elevated transaminases (>3X ULN confirmed by repeat test) were 0.21% (n=21) for patients treated with simvastatin and 0.09% (n=9) for patients treated with placebo. \r\n\r\n**Endocrine Effects**\r\n\r\nIncreases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including simvastatin.\r\n\r\nAlthough cholesterol is the precursor of all steroid hormones, studies with simvastatin have suggested that this agent has no clinical effect on steroidogenesis. Simvastatin caused no increase in biliary lithogenicity and, therefore, would not be expected to increase the incidence of gallstones.","Simvastatin is a prodrug in which the 6-membered lactone ring of simvastatin is hydrolyzed <i>in vivo</i> to generate the beta,delta-dihydroxy acid, an active metabolite structurally similar to HMG-CoA (hydroxymethylglutaryl CoA). Once hydrolyzed, simvastatin competes with HMG-CoA for HMG-CoA reductase, a hepatic microsomal enzyme, which catalyzes the conversion of HMG-CoA to mevalonate, an early rate-limiting step in cholesterol biosynthesis. Simvastatin acts primarily in the liver, where decreased hepatic cholesterol concentrations stimulate the upregulation of hepatic low density lipoprotein (LDL) receptors which increases hepatic uptake of LDL. Simvastatin also inhibits hepatic synthesis of very low density lipoprotein (VLDL). The overall effect is a decrease in plasma LDL and VLDL. \r\n\r\nAt therapeutic doses, the HMG-CoA enzyme is not completely blocked by simvastatin activity, thereby allowing biologically necessary amounts of mevalonate to remain available. As mevalonate is an early step in the biosynthetic pathway for cholesterol, therapy with simvastatin would also not be expected to cause any accumulation of potentially toxic sterols. In addition, HMG-CoA is metabolized readily back to acetyl-CoA, which participates in many biosynthetic processes in the body.\r\n\r\nIn vitro and in vivo animal studies also demonstrate that simvastatin exerts vasculoprotective effects independent of its lipid-lowering properties, also known as the pleiotropic effects of statins. This includes improvement in endothelial function, enhanced stability of atherosclerotic plaques, reduced oxidative stress and inflammation, and inhibition of the thrombogenic response.\r\n\r\nStatins have also been found to bind allosterically to β2 integrin function-associated antigen-1 (LFA-1), which plays an important role in leukocyte trafficking and in T cell activation.","3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor; Integrin alpha-L inhibitory allosteric modulator; Histone deacetylase 2 inhibitor","Therapeutic strategy associated"]
[228,"DB00650","approved","small molecule","Leucovorin","(5-formyl-5,6,7,8-tetrahydropteroyl)glutamate; 10-Formyl-7,8-dihydrofolic acid; 5-Formyl-5,6,7,8-tetrahydrofolic acid; 5-Formyl-5,6,7,8-tetrahydropteroyl-L-glutamic acid; 5-Formyltetrahydrofolate; 5-formyltetrahydrofolic acid; Folinate; Folinic acid; L(-)-5-Formyl-5,6,7,8-tetrahydrofolic acid; N-(5-formyl-5,6,7,8-tetrahydropteroyl)-L-glutamic acid; N5-Formyl-5,6,7,8-tetrahydrofolic acid; N5-Formyltetrahydrofolic acid","C20H23N7O7","[H]C(=O)N1C(CNC2=CC=C(C=C2)C(=O)N[C@@H](CCC(O)=O)C(O)=O)CNC2=C1C(=O)NC(N)=N2","Folinic Acid (also known as 5-formyl tetrahydrofolic acid or leucovorin) is the 5-formyl derivative of tetrahydrofolic acid, a necessary co-factor in the body. Commercially available leucovorin is composed of a 1:1 racemic mixture of the dextrorotary and levorotary isomers, while levoleucovorin contains only the pharmacologically active levo-isomer. In vitro, the levo-isomer has been shown to be rapidly converted to the biologically available methyl-tetrahydrofolate form while the dextro form is slowly excreted by the kidneys. Despite this difference in activity, the two commercially available forms have been shown to be pharmacokinetically identical and may be used interchangeably with limited differences in efficacy or side effects (Kovoor et al, 2009). \r\n\r\nAs folate analogs, leucovorin and levoleucovorin are both used to counteract the toxic effects of folic acid antagonists, such as methotrexate, which act by inhibiting the enzyme dihydrofolate reductase (DHFR). They are indicated for use as rescue therapy following use of high-dose methotrexate in the treatment of osteosarcoma or for diminishing the toxicity associated with inadvertent overdosage of folic acid antagonists. Injectable forms are also indicated for use in the treatment of megaloblastic anemias due to folic acid deficiency when oral therapy is not feasible and for use in combination with 5-fluorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer. \r\n\r\nFolic acid is an essential B vitamin required by the body for the synthesis of purines, pyrimidines, and methionine before incorporation into DNA or protein. However, in order to function in this role, it must first be reduced by the enzyme dihydrofolate reductase (DHFR) into the cofactors dihydrofolate (DHF) and tetrahydrofolate (THF). This important pathway, which is required for de novo synthesis of nucleic acids and amino acids, is disrupted when high-dose methotrexate is used for cancer therapy. As methotrexate functions as a DHFR inhibitor to prevent DNA synthesis in rapidly dividing cells, it also prevents the formation of DHF and THF. This results in a deficiency of coenzymes and a resultant buildup of toxic substances that are responsible for numerous adverse side effects associated with methotrexate therapy. As levoleucovorin and leucovorin are analogs of tetrahydrofolate (THF), they are able to bypass DHFR reduction and act as a cellular replacement for the co-factor THF, thereby preventing these toxic side effects.","58-05-9","473.446","For the treatment of osteosarcoma (after high dose methotrexate therapy). Used to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages of folic acid antagonists, and to treat megaloblastic anemias due to folic acid deficiency. Also used in combination with 5-fluorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer.","Leucovorin is one of several active, chemically reduced derivatives of folic acid. It is useful as an antidote to drugs which act as folic acid antagonists. Leucovorin is a mixture of the diastereoisomers of the 5-formyl derivative of tetrahydrofolic acid (THF). The biologically active compound of the mixture is the (-)-l-isomer, known as Citrovorum factor or (-)-folinic acid. Leucovorin does not require reduction by the enzyme dihydrofolate reductase in order to participate in reactions utilizing folates as a source of &ldquo;one-carbon&rdquo; moieties. Administration of leucovorin can counteract the therapeutic and toxic effects of folic acid antagonists such as methotrexate, which act by inhibiting dihydrofolate reductase. Leucovorin has also been used to enhance the activity of fluorouracil.","As leucovorin is a derivative of folic acid, it can be used to increase levels of folic acid under conditions favoring folic acid inhibition (following treatment of folic acid antagonists such as methotrexate). Leucovorin enhances the activity of fluorouracil by stabilizing the bond of the active metabolite (5-FdUMP) to the enzyme thymidylate synthetase.",null,"Indication associated"]
[229,"DB00654","approved; investigational","small molecule","Latanoprost","isopropyl (Z)-7-((1R,2R,3R,5S)-3,5-dihydroxy-2-((3R)-3-hydroxy-5-phenylpentyl)cyclopentyl)-5-heptenoate; propan-2-yl (5Z)-7-{(1R,2R,3R,5S)-3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl]cyclopentyl}hept-5-enoate","C26H40O5","CC(C)OC(=O)CCC\\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1CC[C@@H](O)CCC1=CC=CC=C1","Latanoprost is a prodrug analog of prostaglandin F2 alpha that is used to treat elevated intraocular pressure (IOP). It was initially approved by the FDA in 1998. Latanoprost is the first topical prostaglandin F2 alpha analog used for glaucoma treatment. It has been found to be well-tolerated and its use does not normally result in systemic adverse effects like other drugs used to treat elevated intraocular pressure, such as . Another benefit latanoprost is that it can be administered once a day.","130209-82-4","432.5928","Latanoprost is indicated for the reduction of elevated intraocular pressure in patients who have been diagnosed with open-angle glaucoma or ocular hypertension. Latanoprost may be combined in a product with , a rho kinase inhibitor, for the same indications. In addition to the above indications, the Canadian monograph for this drug also approves latanoprost for the treatment of elevated intraocular pressure as a result of angle-closure glaucoma that has been treated with peripheral iridotomy or laser iridoplasty.","Latanoprost effectively decreases intraocular pressure by increasing uveoscleral outflow. A decrease in intraocular pressure has been measured within 3–4 hours post-administration, reaches a maximum decrease at 8–12 hours, and can be maintained for a period of 24 hours. \r\n\r\n**A note on eye and periorbital changes** \r\n\r\nBetween 3 to 10% of patients taking latanoprost have experienced iris pigmentation after about 3-4 months of latanoprost use. Patients should be notified of this risk before initiating treatment.  It may occur in both patients with light-colored irides (green-brown or blue/grey-brown) or dark-colored (brown) irides, but is less pronounced in the latter group. This drug may also cause other ocular effects including infrequent conjunctival hyperemia, pigmentation of periocular tissues, eyelash changes, hypertrichosis, and ocular irritation.","Elevated intraocular pressure leads to an increased risk of glaucomatous visual field loss. The higher the intraocular pressure, the higher the risk of damage to the optic nerve and loss of visual field. Latanoprost selectively stimulates the prostaglandin F2 alpha receptor and this results in a decreased intraocular pressure (IOP) via the increased outflow of aqueous humor, which is often implicated in cases of elevated intraocular pressure. Possible specific mechanisms of the abovementioned increased aqueous outflow are the remodeling of the extracellular matrix and regulation of matrix metalloproteinases. These actions result in higher tissue permeability related to humor outflow pathways, which likely change outflow resistance and/or outflow rates.\r","Prostaglandin F2-alpha receptor agonist","Indication associated"]
[230,"DB00657","approved; investigational","small molecule","Mecamylamine","Mecamylamine","C11H21N","CNC1(C)C2CCC(C2)C1(C)C","A nicotinic antagonist that is well absorbed from the gastrointestinal tract and crosses the blood-brain barrier. Mecamylamine has been used as a ganglionic blocker in treating hypertension, but, like most ganglionic blockers, is more often used now as a research tool.","60-40-2","167.2911","For the treatment of moderately severe to severe essential hypertension and in uncomplicated cases of malignant hypertension","Mecamylamine is a potent, oral antihypertensive agent and ganglion blocker, and is a secondary amine. Mecamylamine is indicated for the management of moderately severe to severe essential hypertension and in uncomplicated cases of malignant hypertension. Mecamylamine reduces blood pressure in both normotensive and hypertensive individuals. A small oral dosage often produces a smooth and predictable reduction of blood pressure. Although this antihypertensive effect is predominantly orthostatic, the supine blood pressure is also significantly reduced. Mecamylamine crosses the blood-brain and placental barriers.","Mecamylamine is a ganglionic blocker which prevents stimulation of postsynaptic receptors by acetylcholine released from presynaptic nerve endings. The hypotensive effect of Mecamylamine is attributed to reduction in sympathetic tone, vasodilation, and reduced cardiac output, and is primarily postural.","Neuronal acetylcholine receptor subunit alpha-2 antagonist; Neuronal acetylcholine receptor subunit alpha-7; Neuronal acetylcholine receptor subunit alpha-4; Neuronal acetylcholine receptor subunit beta-2","Therapeutic strategy associated"]
[231,"DB00661","approved","small molecule","Verapamil","Iproveratril; Verapamil","C27H38N2O4","COC1=C(OC)C=C(CCN(C)CCCC(C#N)(C(C)C)C2=CC(OC)=C(OC)C=C2)C=C1","Verapamil is a phenylalkylamine calcium channel blocker used in the treatment of high blood pressure, heart arrhythmias, and angina, and was the first calcium channel antagonist to be introduced into therapy in the early 1960s. It is a member of the non-dihydropyridine class of calcium channel blockers, which includes drugs like  and , but is chemically unrelated to other cardioactive medications. Verapamil is administered as a racemic mixture containing equal amounts of the S- and R-enantiomer, each of which is pharmacologically distinct - the S-enantiomer carries approximately 20-fold greater potency than the R-enantiomer, but is metabolized at a higher rate.","52-53-9","454.6016","Verapamil is indicated in the treatment of vasopastic (i.e. Prinzmetal's) angina, unstable angina, and chronic stable angina. It is also indicated to treat hypertension, for the prophylaxis of repetitive paroxysmal supraventricular tachycardia, and in combination with digoxin to control ventricular rate in patients with atrial fibrillation or atrial flutter. Given intravenously, it is indicated for the treatment of various supraventricular tachyarrhythmias, including rapid conversion to sinus rhythm in patients with supraventricular tachycardia and for temporary control of ventricular rate in patients with atrial fibrillation or atrial flutter.\r\n\r\nVerapamil is commonly used off-label for prophylaxis of cluster headaches.","Verapamil is an L-type calcium channel blocker with antiarrhythmic, antianginal, and antihypertensive activity. Immediate-release verapamil has a relatively short duration of action, requiring dosing 3 to 4 times daily, but extended-release formulations are available that allow for once-daily dosing. As verapamil is a negative inotropic medication (i.e. it decreases the strength of myocardial contraction), it should not be used in patients with severe left ventricular dysfunction or hypertrophic cardiomyopathy as the decrease in contractility caused by verapamil may increase the risk of exacerbating these pre-existing conditions.","Verapamil inhibits L-type calcium channels by binding to a specific area of their alpha-1 subunit,Cav1.2, which is highly expressed on L-type calcium channels in vascular smooth muscle and myocardial tissue where these channels are responsible for the control of peripheral vascular resistance and heart contractility. Calcium influx through these channels allows for the propagation of action potentials necessary for the contraction of muscle tissue and the heart's electrical pacemaker activity. Verapamil binds to these channels in a voltage- and frequency-dependent manner, meaning affinity is increased 1) as vascular smooth muscle membrane potential is reduced, and 2) with excessive depolarizing stimulus. \r\n\r\nVerapamil's mechanism of action in the treatment of angina and hypertension is likely due to the mechanism described above. Inhibition of calcium influx prevents the contraction of vascular smooth muscle, causing relaxation/dilation of blood vessels throughout the peripheral circulation - this lowers systemic vascular resistance (i.e. afterload) and thus blood pressure. This reduction in vascular resistance also reduces the force against which the heart must push, decreasing myocardial energy consumption and oxygen requirements and thus alleviating angina.\r\n\r\nElectrical activity through the AV node is responsible for determining heart rate, and this activity is dependent upon calcium influx through L-type calcium channels. By inhibiting these channels and decreasing the influx of calcium, verapamil prolongs the refractory period of the AV node and slows conduction, thereby slowing and controlling the heart rate in patients with arrhythmia.\r\n\r\nVerapamil's mechanism of action in the treatment of cluster headaches is unclear, but is thought to result from an effect on other calcium channels (e.g. N-, P-, Q-, or T-type).\r\n\r\nVerapamil is known to interact with other targets, including other calcium channels, potassium channels, and adrenergic receptors.","Voltage-dependent L-type calcium channel subunit alpha-1C inhibitor; Voltage-dependent N-type calcium channel subunit alpha-1B inhibitor; Voltage-dependent P/Q-type calcium channel subunit alpha-1A inhibitor; ATP-sensitive inward rectifier potassium channel 11 inhibitor; Voltage-dependent T-type calcium channel subunit alpha-1G inhibitor; Voltage-dependent T-type calcium channel subunit alpha-1H inhibitor; Potassium voltage-gated channel subfamily H member 2 inhibitor; Sodium-dependent serotonin transporter unknown; Alpha-1A adrenergic receptor antagonist; Alpha-1B adrenergic receptor antagonist; Alpha-1D adrenergic receptor antagonist","Therapeutic strategy associated"]
[232,"DB00663","approved; vet_approved","small molecule","Flumethasone","6alpha,9-Difluoro-11beta,17,21-trihydroxy-16alpha-methylpregna-1,4-diene-3,20-dione; Flumetasone; Flumethasone","C22H28F2O5","[H][C@@]12C[C@@H](C)[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])C[C@H](F)C2=CC(=O)C=C[C@]12C","Flumethasone is a moderately potent difluorinated corticosteroid ester with anti-inflammatory, antipruritic and vasoconstrictive properties. As it is a privalate salt, its anti-inflammatory action is concentrated at the site of application. This local effect on diseased areas results in a prompt decrease in inflammation, exudation and itching.","2135-17-3","410.458","For the treatment of contact dermatitis, atopic dermatitis, exczema, psoriasis, diaper rash and other skin conditions","Flumethasone pivalate is a moderately potent difluorinated corticosteroid ester with anti-inflammatory, antipruritic and vasoconstrictive properties. As it is a privalate salt, its anti-inflammatory action is concentrated at the site of application. This local effect on diseased areas results in a prompt decrease in inflammation, exudation and itching.","Flumethasone is a glucocorticoid receptor agonist. This complex binds to the nucleus causing a variety of genetic activation and repressions. The antiinflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. The immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding. Flumethasone binds to plasma transcortin, and it becomes active when it is not bound to transcortin.","Glucocorticoid receptor agonist","Therapeutic strategy associated"]
[233,"DB00668","approved; vet_approved","small molecule","Epinephrine","(−)-(R)-epinephrine; (−)-3,4-dihydroxy-α-((methylamino)methyl)benzyl alcohol; (−)-adrenaline; (R)-(-)-Adnephrine; (R)-(-)-Adrenaline; (R)-(-)-Epinephrine; (R)-(-)-Epirenamine; (R)-(−)-adrenaline; 4-[(1R)-1-Hydroxy-2-(methylamino)ethyl]-1,2-benzenediol; Adrenaline; Epinephrine; L-Adrenaline; Levoepinephrine","C9H13NO3","CNC[C@H](O)C1=CC(O)=C(O)C=C1","Epinephrine, also known as _adrenaline_, is a hormone and neurotransmitter and produced by the adrenal glands that can also be used as a drug due to its various important functions. Though it has long been used in the treatment of hypersensitivity reactions, epinephrine in the auto-injector form (EpiPen) has been available since 1987 in the USA. Many new products/biosimilars and dosage routes have been approved under various names over the last several decades , , .  On August 16, 2018, Teva Pharmaceuticals USA gained approval to market its generic epinephrine auto-injector in 0.3 mg and 0.15 mg strengths . Dosage delivery routes for epinephrine include intravenous, inhalation, nebulization, intramuscular injection, and subcutaneous injection.\r\n\r\nIn general, the most common uses of parenteral epinephrine are to relieve respiratory distress due to bronchospasm, to provide rapid relief of hypersensitivity (anaphylactic or anaphylactoid) reactions to drugs, animal serums and other allergens, and to prolong the action of infiltration anesthetics . In addition to the above functions, epinephrine is the primary drug administered during cardiopulmonary resuscitation (CPR) to reverse cardiac arrest , .  It can be used in severe cases of croup .","51-43-4","183.2044","Epinephrine injection is indicated in the emergency treatment of allergic reactions (Type I) including anaphylaxis to stinging insects (e.g., order Hymenoptera, which include bees, wasps, hornets, yellow jackets and fire ants) and biting insects (e.g., triatoma, mosquitos), allergen immunotherapy, foods, drugs, diagnostic testing substances (e.g., radiocontrast media) and other allergens, as well as idiopathic anaphylaxis or exercise-induced anaphylaxis. Injectable epinephrine is intended for immediate/urgent administration in patients, who are found to be at increased risk for anaphylaxis, including individuals with a history of anaphylaxis. Selection of the appropriate dosage strength is determined according to body weight . \r\n\r\nEpinephrine's cardiac effects may be of use in restoring cardiac rhythm in cardiac arrest due to various causes but is not used in cardiac failure or in hemorrhagic, traumatic, or cardiogenic shock .\r\n\r\nEpinephrine is used as a hemostatic agent. It is also used in treating mucosal congestion of hay fever, rhinitis, and acute sinusitis; to relieve bronchial asthmatic paroxysms; in syncope due to complete heart block or carotid sinus hypersensitivity; for symptomatic relief of serum sickness, urticaria, angioneurotic edema; for resuscitation in cardiac arrest following anesthetic accidents; in simple (open angle) glaucoma; for relaxation of uterine musculature and to inhibit uterine contractions. Epinephrine injection can be utilized to prolong the action of local anesthetics .\r\n\r\nIn addition to the above, epinephrine is used as an over the counter (OTC) agent for the intermittent symptoms of asthma, such as wheezing, tightness of chest and shortness of breath .  It is also used for the maintenance of mydriasis during intraocular surgery .","Epinephrine is a sympathomimetic drug. It causes an adrenergic receptive mechanism on effector cells and mimics all actions of the sympathetic nervous system except those on the facial arteries and sweat glands . \r\n\r\nImportant effects of epinephrine include increased heart rate, myocardial contractility, and renin release via beta-1 receptors. Beta-2 effects produce bronchodilation which may be useful as an adjunct treatment of asthma exacerbations as well as vasodilation, tocolysis, and increased aqueous humor production . In croup, nebulized epinephrine is associated with both clinically and statistically significant transient reduction of croup symptoms 30 minutes post-treatment . Epinephrine also alleviates pruritus, urticaria, and angioedema and may be helpful in relieving gastrointestinal and genitourinary symptoms associated with anaphylaxis because of its relaxing effects on the smooth muscle of the stomach, intestine, uterus, and urinary bladder .","Epinephrine acts on alpha and beta-adrenergic receptors. Epinephrine acts on alpha and beta receptors and is the strongest alpha receptor activator . Through its action on alpha-adrenergic receptors, epinephrine minimizes the vasodilation and increased the vascular permeability that occurs during anaphylaxis, which can cause the loss of intravascular fluid volume as well as hypotension.  Epinephrine relaxes the smooth muscle of the bronchi and iris and is a histamine antagonist, rendering it useful in treating the manifestations of allergic reactions and associated conditions . This drug also produces an increase in blood sugar and increases glycogenolysis in the liver . Through its action on beta-adrenergic receptors, epinephrine leads to bronchial smooth muscle relaxation that helps to relieve bronchospasm, wheezing, and dyspnea that may occur during anaphylaxis .","Alpha-1A adrenergic receptor agonist; Alpha-1B adrenergic receptor agonist; Beta-1 adrenergic receptor agonist; Beta-2 adrenergic receptor agonist; Alpha-2A adrenergic receptor agonist; Alpha-2B adrenergic receptor agonist; Alpha-1D adrenergic receptor antagonist; Tumor necrosis factor antagonist&agonist","Target associated"]
[234,"DB00669","approved; investigational","small molecule","Sumatriptan","(3-[2-(dimethylamino)ethyl]-1H-indol-5-yl)-N-methylmethanesulfonamide; 1-[3-(2-dimethylaminoethyl)-1H-indol-5-yl]-N-methyl-methanesulfonamide; 3-(2-(dimethylamino)ethyl)-N-methyl-1H-indole-5-methanesulfonamide; 3-[2-(dimethylamino)ethyl]-N-methylindole-5-methanesulfonamide","C14H21N3O2S","CNS(=O)(=O)CC1=CC=C2NC=C(CCN(C)C)C2=C1","Sumatriptan is a serotonin receptor agonist commonly used to treat migraines and sometimes cluster headaches. Sumatriptan is the first of the triptans and was made available in Europe in 1991 to treat migraines. Sumatriptan was granted FDA approval on 28 December 1992.","103628-46-2","295.4","A combination sumatriptan and  tablet is indicated for the treatment of migraines with or without auras in patients 12 years of age and older. Sumatriptan nasal powder, nasal spray, subcutaneous injection, and tablets are indicated to treat migraines with or without auras in adults. One of the subcutaneous formulations of sumatriptan is also indicated to treat cluster headaches in adults, while the other subcutaneous formulation is not.","Sumatriptan constricts cranial blood vessels and prevents the release of vasoactive peptides. The dose of sumatriptan varies widely by route of administration and in most cases, no more than 2 doses should be given daily. Medication overuse headaches may occur in patients who use sumatriptan frequently.","Sumatriptan is an agonist of 5-HT<sub>1B</sub> and 5-HT<sub>1D</sub>. This agonism leads to constriction of cranial blood vessels and inhibits the release of pro-inflammatory neuropeptides. Sumatriptan decreases carotid arterial blood flow, but increases blood flow velocity in the internal carotid artery and middle cerebral artery.","5-hydroxytryptamine receptor 1D agonist; 5-hydroxytryptamine receptor 1B agonist; 5-hydroxytryptamine receptor 1F agonist; 5-hydroxytryptamine receptor 1A agonist","Therapeutic strategy associated"]
[235,"DB00671","approved; investigational","small molecule","Cefixime","(−)-cefixim; Cefixime; Cefixime anhydrous","C16H15N5O7S2","[H][C@]12SCC(C=C)=C(N1C(=O)[C@H]2NC(=O)C(=N/OCC(O)=O)\\C1=CSC(N)=N1)C(O)=O","Cefixime, an antibiotic, is a third-generation cephalosporin like ceftriaxone and cefotaxime. Cefixime is highly stable in the presence of beta-lactamase enzymes. As a result, many organisms resistant to penicillins and some cephalosporins due to the presence of beta-lactamases, may be susceptible to cefixime. The antibacterial effect of cefixime results from inhibition of mucopeptide synthesis in the bacterial cell wall.","79350-37-1","453.45","For use in the treatment of the following infections when caused by susceptible strains of the designated microorganisms: (1) uncomplicated urinary tract infections caused by <i>Escherichia coli</i> and <i>Proteus mirabilis</i>, (2) otitis media caused by <i>Haemophilus influenzae</i> (beta-lactamase positive and negative strains), <i>Moraxella catarrhalis</i> (most of which are beta-lactamase positive), and <i>S. pyogenes</i>, (3) pharyngitis and tonsillitis caused by <i>S. pyogenes</i>, (4) acute bronchitis and acute exacerbations of chronic bronchitis caused by <i>Streptococcus pneumoniae</i> and <i>Haemophilus influenzae</i> (beta-lactamase positive and negative strains), and (5) uncomplicated gonorrhea (cervical/urethral) caused by <i>Neisseria gonorrhoeae</i> (penicillinase- and non-penicillinase-producing strains).","Cefixime, an antibiotic, is a third-generation cephalosporin like ceftriaxone and cefotaxime. Cefixime is highly stable in the presence of beta-lactamase enzymes. As a result, many organisms resistant to penicillins and some cephalosporins due to the presence of beta-lactamases, may be susceptible to cefixime. The antibacterial effect of cefixime results from inhibition of mucopeptide synthesis in the bacterial cell wall.","Like all beta-lactam antibiotics, cefixime binds to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, causing the inhibition of the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that cefixime interferes with an autolysin inhibitor.","Penicillin-binding protein 2 inhibitor","Indication associated"]
[236,"DB00675","approved","small molecule","Tamoxifen","(Z)-2-(4-(1,2-Diphenyl-1-butenyl)phenoxy)-N,N-dimethylethanamine; (Z)-2-(para-(1,2-Diphenyl-1-butenyl)phenoxy)-N,N-dimethylamine; 1-p-beta-Dimethylaminoethoxyphenyl-trans-1,2-diphenylbut-1-ene; 1-para-beta-Dimethylaminoethoxyphenyl-trans-1,2-diphenylbut-1-ene; trans-Tamoxifen","C26H29NO","CC\\C(=C(/C1=CC=CC=C1)C1=CC=C(OCCN(C)C)C=C1)C1=CC=CC=C1","Tamoxifen is a non-steroidal antiestrogen used to treat estrogen receptor positive breast cancers as well as prevent the incidence of breast cancer in high risk populations. Tamoxifen is used alone or as an adjuvant in these treatments. Tamoxifen may no longer be the preferred treatment for these types of cancers as patients generally have better survival, side effect profiles, and compliance with .\r\n\r\nTamoxifen was granted FDA approval on 30 December 1977.","10540-29-1","371.5146","Tamoxifen is indicated to treat estrogen receptor positive metastatic breast cancer in adults, as an adjuvant in the treatment of early stage estrogen receptor positive breast cancer in adults, to reduce the risk of invasive breast cancer after surgery and radiation in adult women with ductal carcinoma in situ.","Tamoxifen is a selective estrogen receptor modulator that inhibits growth and promotes apoptosis in estrogen receptor positive tumors. It has a long duration of action as the active metabolite N-desmethyltamoxifen has a half life of approximately 2 weeks. It has a narrow therapeutic index as higher doses can lead to breathing difficulty or convulsions. Tamoxifen administration is also associated with an increased incidence of uterine malignancies.","Tamoxifen competitively inhibits estrogen binding to its receptor, which is critical for it's activity in breast cancer cells. Tamoxifen leads to a decrease in tumor growth factor α and insulin-like growth factor 1, and an increase in sex hormone binding globulin. The increase in sex hormon binding globulin limits the amount of freely available estradiol. These changes reduce levels of factors that stimulate tumor growth.\r\n\r\nTamoxifen has also been shown to induce apoptosis in estrogen receptor positive cells. This action is thought to be the result of inhibition of protein kinase C, which prevents DNA synthesis. Alternate theories for the apoptotic effect of tamoxifen comes from the approximately 3 fold increase in intracellular and mitochondrial calcium ion levels after administration or the induction of tumor growth factor β.","Estrogen receptor alpha antagonist&agonist; Estrogen receptor beta antagonist&agonist; 3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase inhibitor; Protein kinase C inhibitor; Androgen receptor; Potassium voltage-gated channel subfamily H member 2 inhibitor; Nuclear receptor subfamily 1 group I member 2; Estrogen-related receptor gamma; Sex hormone-binding globulin inducer; Mitogen-activated protein kinase 8 modulator","Therapeutic strategy associated"]
[237,"DB00682","approved","small molecule","Warfarin","4-Hydroxy-3-(3-oxo-1-phenylbutyl)coumarin; Warfarin; Zoocoumarin","C19H16O4","CC(=O)CC(C1=CC=CC=C1)C1=C(O)C2=C(OC1=O)C=CC=C2","Warfarin is an anticoagulant drug normally used to prevent blood clot formation as well as migration. Although originally marketed as a pesticide (d-Con, Rodex, among others), Warfarin has since become the most frequently prescribed oral anticoagulant in North America. Warfarin has several properties that should be noted when used medicinally, including its ability to cross the placental barrier during pregnancy which can result in fetal bleeding, spontaneous abortion, preterm birth, stillbirth, and neonatal death. Additional adverse effects such as necrosis, purple toe syndrome, osteoporosis, valve and artery calcification, and drug interactions have also been documented with warfarin use. Warfarin does not actually affect blood viscosity, rather, it inhibits vitamin-k dependent synthesis of biologically active forms of various clotting factors in addition to several regulatory factors.","81-81-2","308.3279","**Indicated** for:\r\n\r\n1) Prophylaxis and treatment of venous thromboembolism and related pulmonary embolism.\r\n\r\n2) Prophylaxis and treatment of thromboembolism associated with atrial fibrillation.\r\n\r\n3) Prophylaxis and treatment of thromboembolism associated with cardiac valve replacement.\r\n\r\n4) Use as adjunct therapy to reduce mortality, recurrent myocardial infarction, and thromboembolic events post myocardial infarction.\r\n\r\n**Off-label** uses include:\r\n\r\n1) Secondary prevention of stroke and transient ischemic attacks in patients with rheumatic mitral valve disease but without atrial fibrillation.","Warfarin is an anticoagulant, as such it disrupts the coagulation cascade to reduce frequency and extent of thrombus formation. In patients with deep vein thrombosis or atrial fibrillation there is an increased risk of thrombus formation due to the reduced movement of blood. For patients with cardiac valve disease or valve replacements this increased coagulability is due to tissue damage. Thrombi due to venous thrombosis can travel to the lungs and become pulmonary emboli, blocking circulation to a portion of lung tissue. Thrombi which form in the heart can travel to the brain and cause ischemic strokes. Prevention of these events is the primary goal of warfarin therapy.\r\n\r\nLimitation of thrombus formation is also a source of adverse effects. In patients with atheroscelotic plaques rupture typically results in thrombus formation. When these patients are anticoagulated plaque rupture can allow the escape of cholesterol from the lipid core in the form of atheroemboli or cholesterol microemboli. These emboli are smaller than thrombi and block smaller vessels, usually less than 200 μm in diameter. The consequences of this are varied and depend on the location of the blockage. Effects include visual disturbances, acute kidney injury or worsening of chronic kidney disease, central nervous system ischemia, and purple or blue toe syndrome. Blue toe syndrome can be reversed if it has not progressed to tissue necrosis but the other effects of microemboli are often permanent.\r\n\r\nAntocoagulation appears to mediate warfarin-related nephropathy, a seemingly spontaneous kidney injury or worsening of chronic kidney disease associated with warfarin therapy. Nephropathy in this case appears to be due to increased passage of red blood cells through the glomerulus and subsequent blockage of renal tubules with red blood cell casts. This is worsened or possibly triggered by pre-existing kidney damage. Increased risk of warfarin-related nephropathy occurs at INRs over 3.0 but risk does not increase as a function of INR beyond this point.\r\n\r\nWarfarin has been linked to the development of calciphylaxis. This is thought to be due to warfarin's inhibition of (VKA) recycling as VKA is needed for the carboxylation of matrix Gla protein. This protein is an anti-calcification factor and its inhibition through preventing the carboxylation step in its production leads to a shift in calcification balance in favor of calciphylaxis. \r\n\r\nTissue necrosis can occur early on in warfarin therapy. This is attributable to half lives of the clotting factors impacted by inhibition of vitamin K recycling. Proteins C and S are anticoagulation factors with half lives of 8 and 24 hours respectively. The coagulation factors IX, X, VII, and thrombin (factor II) have half lives of 24, 36, 6, and 50 hours respectively. This means proteins C and S are inactivated sooner than pro-coagulation proteins, with the exception of factor VII, resulting in a pro-thrombotic state for the first few days of therapy. Thrombi which form in this time period can occlude arterioles in various locations, blocking blood flow and causing tissue necrosis due to ischemia.","Warfarin is a  antagonist which acts to inhibit the production of vitamin K by vitamin K epoxide reductase. The reduced form of vitamin K, vitamin KH<sub>2</sub> is a cofactor used in the γ-carboxylation of coagulation factors VII, IX, X, and thrombin. Carboxylation induces a conformational change allowing the factors to bind Ca<sup>2+</sup> and to phospholipid surfaces. Uncarboxylated factors VII, IX, X, and thrombin are biologically inactive and therefore serve to interrupt the coagulation cascade. The endogenous anticoagulation proteins C and S also require  γ-carboxylation to function. This is particularly true in the case of thrombin which must be activated in order to form a thrombus. vitamin KH<sub>2</sub> is converted to vitamin K epoxide as part of the γ-carboxylation reaction catalyzed by γ-glutamyl carboxylase. Vitamin K epoxide is then converted to vitamin K<sub>1</sub> by vitamin K epoxide reductase then back to vitamin KH<sub>2</sub> by vitamin K reductase. Warfarin binds to vitamin K epoxide reductase complex subunit 1 and irreversibly inhibits the enzyme thereby stopping the recycling of vitamin K by preventing the conversion of vitamin K epoxide to vitamin K<sub>1</sub>. This process creates a hypercoagulable state for a short time as proteins C and S degrade first with half lives of 8 and 24 hours, with the exception of factor VII which has a half life of 6 hours. Factors IX, X, and finally thrombin degrade later with half lives of 24, 36, and 50 hours resulting in a dominant anticoagulation effect. In order to reverse this anticoagulation vitamin K must be supplied, either exogenously or by removal of the vitamin K epoxide reductase inhibition, and time allowed for new coagulation factors to be synthesized. It takes approximately 2 days for new coagulation factors to be synthesized in the liver. Vitamin K<sub>2</sub>, functionally identical to vitamin K<sub>1</sub>, is synthesized by gut bacteria leading to interactions with antibiotics as elimination of these bacteria can reduce vitamin K<sub>2</sub supply and result in a greater anticoagulation effect.","Vitamin K epoxide reductase complex subunit 1 inhibitor; Nuclear receptor subfamily 1 group I member 2","Therapeutic strategy associated"]
[238,"DB00684","approved; investigational","small molecule","Tobramycin","3'-Deoxykanamycin B; Nebramycin 6; O-3-Amino-3-deoxy-alpha-D-glucopyranosyl-(1-4)-O-(2,6-diamino-2,3,6-trideoxy-alpha-D-ribohexopyranosyl-(1-4))-2-deoxy-D-streptamine","C18H37N5O9","NC[C@H]1O[C@H](O[C@@H]2[C@@H](N)C[C@@H](N)[C@H](O[C@H]3O[C@H](CO)[C@@H](O)[C@H](N)[C@H]3O)[C@H]2O)[C@H](N)C[C@@H]1O","Aminoglycosides, many of which are derived directly from _Streptomyces_ spp., are concentration-dependent bactericidal antibiotics with a broad spectrum of activity against Gram-positive and Gram-negative organisms. Inhaled tobramycin is notable for its use in treating chronic _Pseudomonas aeruginosa_ infections in cystic fibrosis patients, as _P. aeruginosa_ is notoriously inherently resistant to many antibiotics. However, tobramycin can also be administered intravenously and topically to treat a variety of infections caused by susceptible bacteria. Its use is limited in some cases by characteristic toxicities such as nephrotoxicity and ototoxicity, yet it remains a valuable option in the face of growing resistance to front-line antibiotics such as β-lactams and cephalosporins.\r\n\r\nTobramycin was approved by the FDA in 1975 and is currently available in a variety of forms for administration by inhalation, injection, and external application to the eye (ophthalmic).","32986-56-4","467.5145","Inhaled tobramycin is indicated for the management of cystic fibrosis patients with _Pseudomonas aeruginosa_, but is not recommended in patients under six years of age, those with forced expiratory volume in 1 second (FEV<sub>1</sub>) <25 or >80% predicted, or in those with _Burkholderia cepacia_.\r\n\r\nTobramycin applied topically to the eyes is indicated for the treatment of external eye (and adjoining structure) infections by susceptible bacteria. \r\n\r\nTobramycin injection is indicated in adult and pediatric patients for the treatment of serious bacterial infections, including septicemia (caused by _P. aeruginosa_, _Escherichia coli_, and _Klebsiella_ spp.), lower respiratory tract infections (caused by _P. aeruginosa_, _Klebsiella_ spp., _Enterobacter_ spp., _Serratia_ spp., _E. coli_, and _Staphylococcus aureus_, both penicillinase and non-penicillinase-producing strains), serious central-nervous-system infections (meningitis, caused by susceptible organisms), intra-abdominal infections including peritonitis (caused by _E. coli_, _Klebsiella_ spp., and _Enterobacter_ spp.), skin, bone, and skin structure infections (caused by _P. aeruginosa_, _Proteus_ spp., _E. coli_, _Klebsiella_ spp., _Enterobacter_ spp., _Serratia_ spp. and _S. aureus_), and complicated and recurrent urinary tract infections (caused by _P. aeruginosa_, _Proteus_ spp., _E. coli_, _Klebsiella_ spp., _Enterobacter_ spp., _Serratia_ spp., _S. aureus_, _Providencia_ spp., and _Citrobacter_ spp.). Aminoglycosides, including tobramycin, should generally not be used in uncomplicated urinary tract infections or staphylococcal infections unless less toxic antibiotics cannot be used and the bacteria in question are known to be sensitive to aminoglycosides.\r\n\r\nAs with all antibiotics, tobramycin use should be limited to cases where bacterial infections are known or strongly suspected to be caused by sensitive organisms, and the possible emergence of resistance should be monitored closely.","Tobramycin is an aminoglycoside antibiotic derived from the actinomycete _Streptomyces tenebrarius_. It has a broad spectrum of activity against Gram-negative bacteria, including _Enterobacteriaceae_, _Escherichia coli_, _Klebsiella pneumoniae_, _Morganella morganii_, _Moraxella lacunata_, _Proteus_ spp., _Haemophilus_ spp., _Acinetobacter_ spp., _Neisseria_ spp., and, importantly, _Pseudomonas aeruginosa_. Aminoglycosides also generally retain activity against the biothreat agents _Yersinia pestis_ and _Francisella tularensis_. In addition, aminoglycosides are active against some Gram-positive bacteria such as _Staphylococcus_ spp., including methicillin-resistant (MRSA) and vancomycin-resistant strains, _Streptococcus_ spp., and _Mycobacterium_ spp.\r\n\r\nLike other aminoglycosides, tobramycin is taken up and retained by proximal tubule and cochlear cells in the kidney and ear, respectively, and hence carries a risk of nephrotoxicity and ototoxicity. There is also a risk of neuromuscular block, which may be more pronounced in patients with preexisting neuromuscular disorders such as myasthenia gravis or Parkinson's disease. Aminoglycosides can cross the placenta, resulting in total, irreversible, bilateral congenital deafness in babies born to mothers who were administered an aminoglycoside during pregnancy. Due to the low systemic absorption of inhaled and topical tobramycin formulations, these effects are more pronounced with injected tobramycin than with other formulations. However, all formulations carry a risk of hypersensitivity reactions, including potentially fatal cutaneous reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis.","Tobramycin is a 4,6-disubstituted 2-deoxystreptamine (DOS) ring-containing aminoglycoside antibiotic with activity against various Gram-negative and some Gram-positive bacteria. The mechanism of action of tobramycin has not been unambiguously elucidated, and some insights into its mechanism rely on results using similar aminoglycosides. In general, like other aminoglycosides, tobramycin is bactericidal and exhibits both immediate and delayed killing, which are attributed to different mechanisms, as outlined below.\r\n\r\nAminoglycosides are polycationic at physiological pH, such that they readily bind to bacterial membranes (\"ionic binding\"); this includes binding to lipopolysaccharide and phospholipids within the outer membrane of Gram-negative bacteria and to teichoic acid and phospholipids within the cell membrane of Gram-positive bacteria. This binding displaces divalent cations and increases membrane permeability, which allows aminoglycoside entry. Additional aminoglycoside entry (\"energy-dependent phase I\") into the cytoplasm requires the proton-motive force, allowing access of the aminoglycoside to its primary intracellular target of the bacterial 30S ribosome. Mistranslated proteins produced as a result of aminoglycoside binding to the ribosome (see below) integrate into and disrupt the cell membrane, which allows more of the aminoglycoside into the cell (\"energy-dependent phase II\"). Hence, tobramycin and other aminoglycosides have both immediate bactericidal effects through membrane disruption and delayed bactericidal effects through impaired protein synthesis; observed experimental data and mathematical modelling support this two-mechanism model.\r\n\r\nInhibition of protein synthesis was the first recognized effect of aminoglycoside antibiotics. Structural and cell biological studies suggest that aminoglycosides bind to the 16S rRNA in helix 44 (h44), near the A site of the 30S ribosomal subunit, altering interactions between h44 and h45. This binding also displaces two important residues, A1492 and A1493, from h44, mimicking normal conformational changes that occur with successful codon-anticodon pairing in the A site. Overall, aminoglycoside binding has several negative effects, including inhibiting translation initiation and elongation and ribosome recycling. Recent evidence suggests that the latter effect is due to a cryptic second binding site situated in h69 of the 23S rRNA of the 50S ribosomal subunit. Also, by stabilizing a conformation that mimics correct codon-anticodon pairing, aminoglycosides promote error-prone translation; mistranslated proteins can incorporate into the cell membrane, inducing the damage discussed above.\r\n\r\nAlthough direct mutation of the 16S rRNA is a rare resistance mechanism, due to the gene being present in numerous copies, posttranscriptional 16S rRNA modification by 16S rRNA methyltransferases (16S-RMTases) at the N7 position of G1405 or the N1 position of A1408 are common resistance mechanisms in aminoglycoside-resistant bacteria. These mutants also further support the proposed mechanism of action of aminoglycosides. Direct modification of the aminoglycoside itself through acetylation, adenylation, and phosphorylation by aminoglycoside-modifying enzymes (AMEs) are also commonly encountered resistance mutations. Finally, due to the requirement for active transport of aminoglycosides across bacterial membranes, they are not active against obligately anaerobic bacteria.","16S ribosomal RNA inhibitor; 23S ribosomal RNA inhibitor; Bacterial outer membrane incorporation into and destabilization; Cytoplasmic membrane incorporation into and destabilization","Indication associated"]
[239,"DB00688","approved; investigational","small molecule","Mycophenolate mofetil","2-morpholinoethyl (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-5-phthalanyl)-4-methyl-4-hexenoate; Mycophenolate mofetil; Mycophenolic acid morpholinoethyl ester","C23H31NO7","COC1=C(C\\C=C(/C)CCC(=O)OCCN2CCOCC2)C(O)=C2C(=O)OCC2=C1C","Mycophenolate mofetil, also known as MMF or CellCept, is a prodrug of mycophenolic acid, and classified as a reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH). This drug is an immunosuppressant combined with drugs such as  and corticosteroids to prevent organ rejection after hepatic, renal, and cardiac transplants. It is marketed by Roche Pharmaceuticals and was granted FDA approval for the prophylaxis of transplant rejection in 1995. In addition to the above uses, mycophenolate mofetil has also been studied for the treatment of nephritis and other complications of autoimmune diseases. Unlike another immunosuppressant class, the calcineurin inhibitors, MMF generally does not cause nephrotoxicity or fibrosis.\r\n\r\nPreviously, mycophenolic acid (MPA) was administered to individuals with autoimmune diseases beginning in the 1970s, but was discontinued due to gastrointestinal effects and concerns over carcinogenicity. The new semi-synthetic 2-morpholinoethyl ester of MPA was synthesized to avoid the gastrointestinal effects associated with the administration of MPA. It demonstrates an increased bioavailability, a higher efficacy, and reduced gastrointestinal effects when compared to MPA.","128794-94-5","433.4947","Mycophenolate mofetil is indicated for the prophylaxis of organ rejection in patients undergoing allogeneic renal, hepatic, or cardiac transplants. It should be used with cyclosporine and corticosteroids. Mycophenolate mofetil may also be used off-label as a second-line treatment for autoimmune hepatitis that has not responded adequately to first-line therapy. Other off-label uses of this drug include lupus-associated nephritis and dermatitis in children.","Mycophenolate mofetil is a prodrug of mycophenolic acid (MPA). The active form of mycophenolate, MPA, prevents the proliferation of immune cells and the formation of antibodies that cause transplant rejection. The above effects lead to higher rates of successful transplantation, avoiding the devastating effects of graft rejection.\r\n\r","The active metabolite of mycophenolate, mycophenolic acid, prevents T-cell and B-cell proliferation and the production of cytotoxic T-cells and antibodies. Lymphocyte and monocyte adhesion to endothelial cells of blood vessels that normally part of inflammation is prevented via the glycosylation of cell adhesion molecules by MPA. MPA inhibits de novo purine biosynthesis (that promotes immune cell proliferation) by inhibiting inosine 5’-monophosphate dehydrogenase enzyme (IMPDH), with a preferential inhibition of IMPDH II. IMPDH normally transforms inosine monophosphate (IMP) to xanthine monophosphate (XMP), a metabolite contributing to the production of guanosine triphosphate (GTP). GTP is an important molecule for the synthesis of ribonucleic acid (RNA), deoxyribonucleic acid (DNA), and protein. As a result of the above cascade of effects, mycophenolate mofetil reduces de-novo production of guanosine nucleotides, interfering with the synthesis of DNA, RNA, and protein required for immune cell production. Further contributing to the above anti-inflammatory effects, MMF depletes tetrahydrobiopterin, causing the decreased function of inducible nitric oxide synthase enzyme, in turn decreasing the production of peroxynitrite, a molecule that promotes inflammation.","Inosine-5'-monophosphate dehydrogenase 1 inhibitor&inducer; Inosine-5'-monophosphate dehydrogenase 2 inhibitor; 6-pyruvoyl tetrahydrobiopterin synthase inhibitor","Therapeutic strategy associated"]
[240,"DB00691","approved","small molecule","Moexipril","Moexipril","C27H34N2O7","CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@@H](C)C(=O)N1CC2=CC(OC)=C(OC)C=C2C[C@H]1C(O)=O","Moexipril is a non-sulfhydryl containing precursor of the active angiotensin-converting enzyme (ACE) inhibitor moexiprilat. It is used to treat high blood pressure (hypertension). It works by relaxing blood vessels, causing them to widen. Lowering high blood pressure helps prevent strokes, heart attacks and kidney problems.","103775-10-6","498.5681","For the treatment of hypertension.","Moexipril is a non-sulfhydryl containing precursor of the active angiotensin-converting enzyme (ACE) inhibitor moexiprilat. It is used to treat high blood pressure (hypertension). It works by relaxing blood vessels, causing them to widen. Lowering high blood pressure helps prevent strokes, heart attacks and kidney problems.","Moexipril is a prodrug for moexiprilat, which inhibits ACE in humans and animals. The mechanism through which moexiprilat lowers blood pressure is believed to be primarily inhibition of ACE activity. ACE is a peptidyl dipeptidase that catalyzes the conversion of the inactive decapeptide angiotensin I to the vasoconstrictor substance angiotensin II. Angiotensin II is a potent peripheral vasoconstrictor that also stimulates aldosterone secretion by the adrenal cortex and provides negative feedback on renin secretion. ACE is identical to kininase II, an enzyme that degrades bradykinin, an endothelium-dependent vasodilator. Moexiprilat is about 1000 times as potent as moexipril in inhibiting ACE and kininase II. Inhibition of ACE results in decreased angiotensin II formation, leading to decreased vasoconstriction, increased plasma renin activity, and decreased aldosterone secretion. The latter results in diuresis and natriuresis and a small increase in serum potassium concentration (mean increases of about 0.25 mEq/L were seen when moexipril was used alone). Whether increased levels of bradykinin, a potent vasodepressor peptide, play a role in the therapeutic effects of moexipril remains to be elucidated. Although the principal mechanism of moexipril in blood pressure reduction is believed to be through the renin-angiotensin-aldosterone system, ACE inhibitors have some effect on blood pressure even in apparent low-renin hypertension.","Angiotensin-converting enzyme inhibitor","Indication associated"]
[241,"DB00692","approved","small molecule","Phentolamine","2-(N-(m-hydroxyphenyl)-p-toluidinomethyl)imidazoline","C17H19N3O","CC1=CC=C(C=C1)N(CC1=NCCN1)C1=CC(O)=CC=C1","A nonselective alpha-adrenergic antagonist. It is used in the treatment of hypertension and hypertensive emergencies, pheochromocytoma, vasospasm of raynaud disease and frostbite, clonidine withdrawal syndrome, impotence, and peripheral vascular disease.","50-60-2","281.3523","Used as an aid for the diagnosis of pheochromocytoma, and may be administered immediately prior to or during pheochromocytomectomy to prevent or control paroxysmal hypertension resulting from anesthesia, stress, or operative manipulation of the tumor. Phentolamine has also been used to treat hypertensive crisis caused by sympathomimetic amines or catecholamine excess by certain foods or drugs in patients taking MAO inhibitors, or by clonidine withdrawal syndrome. Other indications include the prevention of dermal necrosis and sloughing following IV administration or extravasation of norepinephrine, decrease in impedance to left ventricular ejection and the infarct size in patients with MI associated with left ventricular failure, treatment of erectile dysfunction through self-injection of small doses combined with papaverine hydrochloride into the corpus cavernosum, and as an adjunct to the management of cocaine overdose to reverse coronary vasoconstriction following use of oxygen, benzodiazepines,and nitroglycerin.","Phentolamine is indicated for the control of episodes of hypertension and sweating that occur with a disease called pheochromocytoma. If tachycardia is excessive, it may be necessary to use a beta-blocking agent concomitantly. Phentolamine is a long-acting, adrenergic, alpha-receptor blocking agent which can produce and maintain \"chemical sympathectomy\" by oral administration. It increases blood flow to the skin, mucosa and abdominal viscera, and lowers both supine and erect blood pressures. It has no effect on the parasympathetic system. Phentolamine works by blocking alpha receptors in certain parts of the body. Alpha receptors are present in the muscle that lines the walls of blood vessels. When the receptors are blocked by Phentolamine, the muscle relaxes and the blood vessels widen. This widening of the blood vessels results in a lowering of blood pressure.","Phentolamine produces its therapeutic actions by competitively blocking alpha-adrenergic receptors (primarily excitatory responses of smooth muscle and exocrine glands), leading to a muscle relaxation and a widening of the blood vessels. This widening of the blood vessels results in a lowering of blood pressure. The action of phentolamine on the alpha adrenergic receptors is relatively transient and the blocking effect is incomplete. The drug is more effective in antagonizing responses to circulating epinephrine and/or norepinephrine than in antagonizing responses to mediator released at the adrenergic nerve ending. Phentolamine also stimulates β-adrenergic receptors and produces a positive inotropic and chronotropic effect on the heart and increases cardiac output.","Alpha-2A adrenergic receptor antagonist; Alpha-1A adrenergic receptor antagonist; Alpha-1B adrenergic receptor antagonist; Alpha-1D adrenergic receptor antagonist","Indication associated"]
[242,"DB00693","approved","small molecule","Fluorescein","3,6-fluorandiol; 3',6'-dihydroxyfluoran; 9-(o-carboxyphenyl)-6-hydroxy-3-isoxanthenone; 9-(o-carboxyphenyl)-6-hydroxy-3H-xanthen-3-one; C.I. Solvent Yellow 94; D and C Yellow No. 7; D&C Yellow No. 7; Fluorescein; Fluoresceine; Fluoreszein; Japan Yellow 201; Resorcinolphthalein; Solvent Yellow 94; Yellow fluorescein","C20H12O5","OC1=CC=C2C(OC3=CC(O)=CC=C3C22OC(=O)C3=C2C=CC=C3)=C1","A phthalic indicator dye that appears yellow-green in normal tear film and bright green in a more alkaline medium, such as the aqueous humor, and is used therapeutically as a diagnostic aid in corneal injuries and corneal trauma. It has been approved by FDA for use in externally applied drugs and cosmetics. (From Merck Index, 12th ed; American Medical Association Drug Evaluations; 1995, p2275)","2321-07-5","332.3063","For diagnostic imaging. Primarily indicated in diagnostic fluorescein angiography or angioscopy of the fundus and of the iris vasculature.",null,"Fluorescein sodium is used extensively as a diagnostic tool in the field of ophthalmology. Fluorescein is a fluorescent compound or fluorophore having a maximum absorbance of 494 m and an emission maximum of 521 nm. The yellowish-green fluorescence of the compound  can be used to demarcate the vascular area under observation, distinguishing it from adjacent areas. It is applied topically in the form of a drop or it can be injected intravenously to produce a fluorescein angiogram. Topical fluorescein is a useful tool in the diagnosis of corneal abrasions, corneal ulcers, herpetic corneal infections, and dry eye. Fluorescein angiography is used to diagnose and categorize macular degeneration, diabetic retinopathy, inflammatory intraocular conditions, and intraocular tumors.\r\n\r","Ig kappa chain V-II region RPMI 6410 other; DNA other","Therapeutic strategy associated"]
[243,"DB00694","approved","small molecule","Daunorubicin","(+)-Daunomycin; (8S-cis)-8-acetyl-10-((3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyrannosyl)oxy)-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-5,12-napthacenedione; Acetyladriamycin; Daunomycin; Leukaemomycin C; Rubidomycin","C27H29NO10","COC1=CC=CC2=C1C(=O)C1=C(O)C3=C(C[C@](O)(C[C@@H]3O[C@H]3C[C@H](N)[C@H](O)[C@H](C)O3)C(C)=O)C(O)=C1C2=O","A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of leukemia and other neoplasms.","20830-81-3","527.5199","For remission induction in acute nonlymphocytic leukemia (myelogenous, monocytic, erythroid) of adults and for remission induction in acute lymphocytic leukemia of children and adults.\r\n\r\nDaunorubicin is indicated in combination with  for the treatment of newly-diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC) in adults and pediatric patients 1 year and older.","Daunorubicin is an anthracycline antibiotic and antineoplastic agent. It acts by inhibiting cellular reproduction through interference with DNA replication although it may contribute to the induction of cell death by increasing oxidative stress through the generation of reactive oxygen species and free radicals. As an antineoplastic agent, daunorubicin carries significant toxicities including cytopenias, hepatotoxicity, and extravasation reactions. Like other anthracyclines, daunorubicin also exhibits cardiotoxicity in proportion with the cumulative dose received over time.","Daunorubicin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action: Daunorubicin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes.","DNA intercalation; DNA topoisomerase 2-alpha inhibitor; DNA topoisomerase 2-beta inhibitor","Therapeutic strategy associated"]
[244,"DB00695","approved; vet_approved","small molecule","Furosemide","2-Furfurylamino-4-chloro-5-sulfamoylbenzoic acid; 4-Chloro-5-sulfamoyl-N-furfuryl-anthranilic acid; 4-Chloro-N-(2-furylmethyl)-5-sulfamoylanthranilic acid; 4-Chloro-N-furfuryl-5-sulfamoylanthranilic acid; Frusemide; Furosemid; Furosemide","C12H11ClN2O5S","NS(=O)(=O)C1=C(Cl)C=C(NCC2=CC=CO2)C(=C1)C(O)=O","Furosemide is a potent loop diuretic that acts on the kidneys to ultimately increase water loss from the body. It is an anthranilic acid derivative. Furosemide is used for edema secondary to various clinical conditions, such as congestive heart failure exacerbation, liver failure, renal failure, and high blood pressure. It mainly works by inhibiting electrolyte reabsorption from the kidneys and enhancing the excretion of water from the body. Furosemide has a fast onset and short duration of action and has been used safely and effectively in both pediatric and adult patients. The use of furosemide is particularly beneficial in clinical settings that require a drug with a higher diuretic potential. In addition to oral formulations, the solution for intravenous and intramuscular administration is also available, which is typically limited to patients who are unable to take oral medication or for patients in emergency clinical situations.","54-31-9","330.744","Furosemide is indicated for the treatment of edema associated with congestive heart failure, cirrhosis of the liver, and renal disease, including the nephrotic syndrome, in adults and pediatric patients. \r\n\r\nOral furosemide is indicated alone for the management of mild to moderate hypertension or severe hypertension in combination with other antihypertensive medications.\r\n\r\nIntravenous furosemide is indicated as adjunctive therapy in acute pulmonary edema when a rapid onset of diuresis is desired.","Furosemide manages hypertension and edema associated with congestive heart failure, cirrhosis, and renal disease, including the nephrotic syndrome. Furosemide is a potent loop diuretic that works to increase the excretion of Na+ and water by the kidneys by inhibiting their reabsorption from the proximal and distal tubules, as well as the loop of Henle. It works directly acts on the cells of the nephron and indirectly modifies the content of the renal filtrate. Ultimately, furosemide increases the urine output by the kidney. Protein-bound furosemide is delivered to its site of action in the kidneys and secreted via active secretion by nonspecific organic transporters expressed at the luminal site of action. \r\n\r\nFollowing oral administration, the onset of the diuretic effect is about 1 and 1.5 hours , and the peak effect is reached within the first 2 hours. The duration of effect following oral administration is about 4-6 hours but may last up to 8 hours. Following intravenous administration, the onset of effect is within 5 minutes, and the peak effect is reached within 30 minutes. The duration of action following intravenous administration is approximately 2 hours. Following intramuscular administration, the onset of action is somewhat delayed.","Furosemide promotes diuresis by blocking tubular reabsorption of sodium and chloride in the proximal and distal tubules, as well as in the thick ascending loop of Henle. This diuretic effect is achieved through the competitive inhibition of sodium-potassium-chloride cotransporters (NKCC2) expressed along these tubules in the nephron, preventing the transport of sodium ions from the lumenal side into the basolateral side for reabsorption. This inhibition results in increased excretion of water along with sodium, chloride, magnesium, calcium, hydrogen, and potassium ions. As with other loop diuretics, furosemide decreases the excretion of uric acid. \r\n\r\nFurosemide exerts direct vasodilatory effects, which results in its therapeutic effectiveness in the treatment of acute pulmonary edema. Vasodilation leads to reduced responsiveness to vasoconstrictors, such as angiotensin II and noradrenaline, and decreased production of endogenous natriuretic hormones with vasoconstricting properties. It also leads to increased production of prostaglandins with vasodilating properties. Furosemide may also open potassium channels in resistance arteries. The main mechanism of action of furosemide is independent of its inhibitory effect on carbonic anhydrase and aldosterone.","Solute carrier family 12 member 1 inhibitor; Carbonic anhydrase 2 inhibitor; G-protein coupled receptor 35 agonist","Indication associated"]
[245,"DB00696","approved","small molecule","Ergotamine","(5'α)-12'-hydroxy-2'-methyl-5'-(phenylmethyl)ergotoman-3',6',18-trione; 12'-Hydroxy-2'-methyl-5'alpha-(phenylmethyl)ergotaman-3',6',18-trione; 12'-hydroxy-2'-methyl-5'α-(phenylmethyl)ergotaman-3',6',18-trione","C33H35N5O5","[H][C@@]12CCCN1C(=O)[C@H](CC1=CC=CC=C1)N1C(=O)[C@](C)(NC(=O)[C@H]3CN(C)[C@]4([H])CC5=CNC6=CC=CC(=C56)C4=C3)O[C@@]21O","A vasoconstrictor found in ergot of Central Europe. It is an alpha-1 selective adrenergic agonist and is commonly used in the treatment of migraine disorders.","113-15-5","581.6615","For use as therapy to abort or prevent vascular headache, e.g., migraine, migraine variants, or so called \"histaminic cephalalgia\".","Ergotamine is a vasoconstrictor and alpha adrenoreceptor antagonist. The pharmacological properties of ergotamine are extremely complex; some of its actions are unrelated to each other, and even mutually antagonistic. The drug has partial agonist and/or antagonist activity against tryptaminergic, dopaminergic and alpha adrenergic receptors depending upon their site, and it is a highly active uterine stimulant. It causes constriction of peripheral and cranial blood vessels and produces depression of central vasomotor centers. The pain of a migraine attack is believed to be due to greatly increased amplitude of pulsations in the cranial arteries, especially the meningeal branches of the external carotid artery. Ergotamine reduces extracranial blood flow, causes a decline in the amplitude of pulsation in the cranial arteries, and decreases hyperperfusion of the territory of the basilar artery. It does not reduce cerebral hemispheric blood flow.","Ergotamine acts on migraine by one of two proposed mechanisms: 1) activation of 5-HT<sub>1D</sub> receptors located on intracranial blood vessels, including those on arterio-venous anastomoses, leads to vasoconstriction, which correlates with the relief of migraine headache, and 2) activation of 5-HT<sub>1D</sub> receptors on sensory nerve endings of the trigeminal system results in the inhibition of pro-inflammatory neuropeptide release.","5-hydroxytryptamine receptor 1D agonist; 5-hydroxytryptamine receptor 1B agonist; 5-hydroxytryptamine receptor 2A agonist; Dopamine D2 receptor agonist; Alpha-1A adrenergic receptor partial agonist; Alpha-1B adrenergic receptor partial agonist; Alpha-1D adrenergic receptor partial agonist; Alpha-2A adrenergic receptor partial agonist; D(1) dopamine receptor agonist; 5-hydroxytryptamine receptor 1A agonist; 5-hydroxytryptamine receptor 1F agonist; 5-hydroxytryptamine receptor 2C agonist; 5-hydroxytryptamine receptor 2B; Alpha-2C adrenergic receptor","Therapeutic strategy associated"]
[246,"DB00699","approved; investigational","small molecule","Nicergoline","(8β)-10-methoxy-1,6-dimethylergoline-8-methanol 5-bromo-3-pyridinecarboxylate (ester); 10-methoxy-1,6-dimethylergoline-8β-methanol 5-bromonicotinate; Nicergoline","C24H26BrN3O3","[H][C@@]12CC3=CN(C)C4=CC=CC(=C34)[C@]1(C[C@@H](COC(=O)C1=CN=CC(Br)=C1)CN2C)OC","An ergot derivative that has been used as a cerebral vasodilator and in peripheral vascular disease. It has been suggested to ameliorate cognitive deficits in cerebrovascular disease.","27848-84-6","484.386","For the treatment of senile dementia, migraines of vascular origin, transient ischemia, platelet hyper-aggregability, and macular degeneration.","Nicergoline is a potent vasodilator (improves brain blood flow). On the cerebral level it prompts a lowering of vascular resistance, an increase in arterial flow and stimulates the use of oxygen and glucose. Nicergoline also improves blood circulation in the lungs and limbs and has been shown to inhibit blood platelet aggregation.","Nicergoline acts by inhibiting the postsynaptic alpha(1)-adrenoceptors on vascular smooth muscle. This inhibits the vasoconstrictor effect of circulating and locally released catecholamines (epinephrine and norepinephrine), resulting in peripheral vasodilation. Therefore the mechanism of Nicergoline is to increase vascular circulation in the brain, thereby enhancing the transmission of nerve signals across the nerve fibres, which secrete acetylcholine as a neural transmitter.","Alpha-1A adrenergic receptor antagonist","Therapeutic strategy associated"]
[247,"DB00700","approved","small molecule","Eplerenone","Eplerenone; Epoxymexrenone","C24H30O6","[H][C@@]12CC[C@@]3(CCC(=O)O3)[C@@]1(C)C[C@H]1O[C@@]11[C@@]2([H])[C@@H](CC2=CC(=O)CC[C@]12C)C(=O)OC","Eplerenone, an aldosterone receptor antagonist similar to spironolactone, has been shown to produce sustained increases in plasma renin and serum aldosterone, consistent with inhibition of the negative regulatory feedback of aldosterone on renin secretion. The resulting increased plasma renin activity and aldosterone circulating levels do not overcome the effects of eplerenone. Eplerenone selectively binds to recombinant human mineralocorticoid receptors relative to its binding to recombinant human glucocorticoid, progesterone and androgen receptors.","107724-20-9","414.4914","For improvement of survival of stable patients with left ventricular systolic dysfunction (ejection fraction <40%) and clinical evidence of congestive heart failure after an acute myocardial infarction.","Eplerenone, an aldosterone receptor antagonist similar to spironolactone, has been shown to produce sustained increases in plasma renin and serum aldosterone, consistent with inhibition of the negative regulatory feedback of aldosterone on renin secretion. The resulting increased plasma renin activity and aldosterone circulating levels do not overcome the effects of eplerenone. Eplerenone selectively binds to recombinant human mineralocorticoid receptors relative to its binding to recombinant human glucocorticoid, progesterone and androgen receptors.","Eplerenone binds to the mineralocorticoid receptor and thereby blocks the binding of aldosterone (component of the renin-angiotensin-aldosterone-system, or RAAS). Aldosterone synthesis, which occurs primarily in the adrenal gland, is modulated by multiple factors, including angiotensin II and non-RAAS mediators such as adrenocorticotropic hormone (ACTH) and potassium. Aldosterone binds to mineralocorticoid receptors in both epithelial (e.g., kidney) and nonepithelial (e.g., heart, blood vessels, and brain) tissues and increases blood pressure through induction of sodium reabsorption and possibly other mechanisms.","Mineralocorticoid receptor antagonist","Indication associated"]
[248,"DB00702","approved; investigational","small molecule","Icodextrin",{"$nulls":3},"Icodextrin is an iso-osmotic peritoneal dialysis solution containing glucose polymers. It is used primarily for ambulatory peritoneal dialysis (CAPD) of diabetic patients and automated peritoneal dialysis (APD) for patients with end-stage renal disease. It is injected as a solution into the peritoneal cavity. The drug is absorbed via convective transport via peritoneal lymphatic pathways.","337376-15-5",null,"Used for continuous ambulatory peritoneal dialysis (CAPD) of diabetic patients or automated peritoneal dialysis (APD) for the management of end-stage renal disease.","Icodextrin is an iso-osmotic peritoneal dialysis solution containing glucose polymers. It is used primarily for ambulatory peritoneal dialysis (CAPD) of diabetic patients and automated peritoneal dialysis (APD) for patients with end-stage renal disease. It is injected as a solution into the peritoneal cavity. The drug is absorbed via convective transport via peritoneal lymphatic pathways.","Icodextrin is a starch-derived, water-soluble glucose polymer linked by alpha (1-4) and alpha (1-6) glycosidic bonds with an average molecular weight between 13,000 and 19,000 daltons. It functions as a colloid osmotic agent to achieve ultrafiltration during long (12-16 hour) peritoneal dialysis dwells. In other words it helps clean waste out of the body when the kidneys are not functioning properly. Icodectrin acts in the peritoneal cavity by exerting osmotic pressure across small intercellular pores resulting in transcapillary ultrafiltration through the dwell. This is due to the fact that the polymer is minimially absorbed across the peritoneal membrane. Icodextrin achieves superior fluid removal compared with glucose-based dialysates.",null,"Indication associated"]
[249,"DB00710","approved; investigational","small molecule","Ibandronate","Ibandronic acid","C9H23NO7P2","CCCCCN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O","Ibandronate, or BM 21.0955, is a third generation, nitrogen containing bisphosphonate similar to , , and . It is used to prevent and treat postmenopausal osteoporosis. Ibandronate was first described in the literature in 1993 as a treatment for bone loss in dogs.\r\n\r\nIbandronate was granted FDA approval on 16 May 2003.","114084-78-5","319.2289","For the treatment and prevention of osteoporosis in postmenopausal women.","Ibandronate is a nitrogen containing bisphosphonate used to treat and prevent osteoporosis in postmenopausal women. The therapeutic index is wide as overdoses are not especially toxic, and the duration of action is long as the half life can be up to 157 hours. Patients should be counselled regarding the risk of  upper GI adverse reactions, hypocalcemia, musculoskeletal pain, osteonecrosis of the jaw, atypical fractures of the femur, and severe renal impairment.","Bisphosphonates are taken into the bone where they bind to hydroxyapatite. Bone resorption by osteoclasts causes local acidification, releasing the bisphosphonate, which is taken into the osteoclast by fluid-phase endocytosis. Endocytic vesicles become acidified, releasing bisphosphonates into the cytosol of osteoclasts where they act.\r\n\r\nOsteoclasts mediate resorption of bone. When osteoclasts bind to bone they form podosomes, ring structures of F-actin. Disruption of the podosomes causes osteoclasts to detach from bones, preventing bone resorption.\r\n\r\nNitrogen containing bisphosphonates such as ibandronate are known to induce apoptosis of hematopoietic tumor cells by inhibiting the components of the mevalonate pathway farnesyl diphosphate synthase, farnesyl diphosphate, and geranylgeranyl diphosphate. These components are essential for post-translational prenylation of GTP-binding proteins like Rap1. The lack of prenylation of these proteins interferes with their function, and in the case of Rap1, leads to apoptosis. ibandronate also activated caspase-3 which contribute to apoptosis.","Farnesyl pyrophosphate synthase inhibitor; Hydroxylapatite antagonist; Geranylgeranyl pyrophosphate synthase inhibitor","Therapeutic strategy associated"]
[250,"DB00712","approved; investigational","small molecule","Flurbiprofen","(±)-2-fluoro-α-methyl-4-biphenylacetic acid; 2-(2-fluorobiphenyl-4-yl)propanoic acid; 2-fluoro-α-methyl-(1,1'-biphenyl)-4-acetic acid; 3-fluoro-4-phenylhydratropic acid","C15H13FO2","CC(C(O)=O)C1=CC(F)=C(C=C1)C1=CC=CC=C1","Flurbiprofen, a propionic acid derivative, is a nonsteroidal anti-inflammatory agent (NSAIA) with antipyretic and analgesic activity. Oral formulations of flurbiprofen may be used for the symptomatic treatment of rheumatoid arthritis, osteoarthritis and anklylosing spondylitis. Flurbiprofen may also be used topically prior to ocular surgery to prevent or reduce intraoperative miosis. Flurbiprofen is structurally and pharmacologically related to fenoprofen, ibuprofen, and ketoprofen.","5104-49-4","244.2609","Flurbiprofen tablets are indicated for the acute or long-term symptomatic treatment of rheumatoid arthritis, osteorarthritis and anklosing spondylitis. It may also be used to treat pain associated with dysmenorrhea and mild to moderate pain accompanied by inflammation (e.g. bursitis, tendonitis, soft tissue trauma). Topical ophthalmic formulations may be used pre-operatively to prevent intraoperative miosis.","Flurbiprofen, a nonsteroidal anti-inflammatory agent (NSAIA) of the propionic acid class, is structually and pharmacologically related to fenoprofen, ibuprofen, and ketoprofen, and has similar pharmacological actions to other prototypica NSAIAs. Flurbiprofen exhibits antiinflammatory, analgesic, and antipyretic activities. The commercially available flurbiprofen is a racemic mixture of (+)S- and (-) R-enantiomers. The S-enantiomer appears to possess most of the anti-inflammatory, while both enantiomers may possess analgesic activity.","Similar to other NSAIAs, the anti-inflammatory effect of flurbiprofen occurs via reversible inhibition of cyclooxygenase (COX), the enzyme responsible for the conversion of arachidonic acid to prostaglandin G2 (PGG2) and PGG2 to prostaglandin H2 (PGH2) in the prostaglandin synthesis pathway. This effectively decreases the concentration of prostaglandins involved in inflammation, pain, swelling and fever. Flurbiprofen is a non-selective COX inhibitor and inhibits the activity of both COX-1 and -2. It is also one of the most potent NSAIAs in terms of prostaglandin inhibitory activity.","Prostaglandin G/H synthase 1 inhibitor; Prostaglandin G/H synthase 2 inhibitor","Therapeutic strategy associated"]
[251,"DB00715","approved; investigational","small molecule","Paroxetine","(−)-(3S,4R)-4-(p-fluorophenyl)-3-((3,4-(methylenedioxy)phenoxy)methyl)piperidine; (3S-trans)-3-((1,3-benzodioxol-5-yloxy)methyl)-4-(4-fluorophenyl)piperidine; Paroxetine","C19H20FNO3","FC1=CC=C(C=C1)[C@@H]1CCNC[C@H]1COC1=CC2=C(OCO2)C=C1","Paroxetine is a selective serotonin reuptake inhibitor (SSRI) drug commonly known as Paxil. It has a variety of uses, including the treatment of anxiety disorders, major depression, posttraumatic stress disorder, and symptoms of menopause, among others. It was approved by the FDA in the early 1990s and marketed by SmithKline Beecham. A unique feature of this drug is that it is highly potent and selective in its inhibition of serotonin reuptake and has little effect on other neurotransmitters. Because of its potent inhibition of serotonin reuptake, paroxetine is more likely to cause withdrawal effects upon cessation. Paroxetine is well tolerated in most patients with a similar adverse effect profile to other members of its drug class. The controlled release formulation was designed to decrease the likelihood of nausea that is sometimes associated with paroxetine.","61869-08-7","329.3654","Paroxetine is indicated for the management of depression, obsessive-compulsive disorder, panic disorder, social anxiety disorder, generalized anxiety disorder, posttraumatic stress disorder. One form of paroxetine, commercially known as Brisdelle, is used to manage mild to moderate vasomotor symptoms of menopause. Off-label, paroxetine may be used for the treatment of premature ejaculation or irritable bowel syndrome (IBS).","Paroxetine treats the symptoms of depression, various anxiety disorders, posttraumatic stress disorder, obsessive-compulsive disorder, and the vasomotor symptoms of menopause via the inhibition of serotonin reuptake. The onset of action of paroxetine is reported to be approximately 6 weeks.\r\n\r\nDue its serotonergic activity, paroxetine, like other SSRI drugs, may potentiate serotonin syndrome. This risk is especially high when monoamine oxidase (MAO) inhibitors are given within 2 weeks of paroxetine administration. Upon cessation of MAO inhibitors, a 2-week interval before paroxetine administration is recommended. Do not coadminister these agents.","Paroxetine enhances serotonergic activity via the inhibition presynaptic reuptake of serotonin by the serotonin (SERT) receptor. This inhibition raises the level of serotonin in the synaptic cleft, relieving various symptoms. This drug has been demonstrated to be a stronger inhibitor of serotonin reuptake than other members of the same drug class, including , , and . The mechanism of action of paroxetine in relieving the vasomotor symptoms of menopause is unknown, according to the Brisdelle prescribing information, but may occur due to its effects on thermoregulation.\r\n\r\nParoxetine shows a clinically insignificant affinity for adrenergic alpha-1 and alpha-2 receptors and β-adrenergic receptors, dopamine D1 and D2 receptors, histamine H1 receptors and serotonin 5-HT1A, 5-HT2A and 5-HT2C receptors. This drug shows some affinity for muscarinic cholinergic receptors and 5-H2B receptors. The delayed onset of paroxetine therapeutic effects may be explained by the initial paroxetine actions on the 5-HT neurons.  In rats, paroxetine activates 5-HT1A receptors when it is first administered, inhibiting the stimulation of the  5-HT neurons and subsequent release of serotonin at the synaptic cleft.","Sodium-dependent serotonin transporter inhibitor; Sodium-dependent noradrenaline transporter inhibitor; 5-hydroxytryptamine receptor 2A agonist; Alpha-1 adrenergic receptors binder; Alpha-2 adrenergic receptors binder; Beta adrenergic receptor inhibitor; Dopamine D2 receptor other/unknown; Histamine H1 receptor inhibitor; Serotonin Receptors; Muscarinic acetylcholine receptor inhibitor; 5-hydroxytryptamine receptor 2B agonist; D(1) dopamine receptor other/unknown","Indication associated"]
[252,"DB00716","approved; investigational","small molecule","Nedocromil","9-ethyl-6,9-dihydro-4,6-dioxo-10-propyl-4H-pyrano(3,2-g)quinoline-2,8-dicarboxylic acid; Nedocromil","C19H17NO7","CCCC1=C2N(CC)C(=CC(=O)C2=CC2=C1OC(=CC2=O)C(O)=O)C(O)=O","A pyranoquinolone derivative that inhibits activation of inflammatory cells which are associated with asthma, including eosinophils, neutrophils, macrophages, mast cells, monocytes, and platelets.","69049-73-6","371.3408","For the treatment of mild to moderate asthma","Nedocromil is a anti-inflammatory agent and can be administered directly to the bronchial mucosa. It has significant inhibitory effect on allergen-induced early and late asthmatic reactions and on bronchial hyperresponsiveness.","Nedocromil has been shown to inhibit the in vitro activation of, and mediator release from, a variety of inflammatory cell types associated with asthma, including eosinophils, neutrophils, macrophages, mast cells, monocytes, and platelets. Nedocromil inhibits activation and release of inflammatory mediators such as histamine, prostaglandin D2 and leukotrienes c4 from different types of cells in the lumen and mucosa of the bronchial tree. These mediators are derived from arachidonic acid metabolism through the lipoxygenase and cyclo-oxygenase pathways. The mechanism of action of nedocromil may be due partly to inhibition of axon reflexes and release of sensory neuropeptides, such as substance P, neurokinin A, and calcitonin-gene&ntilde;related peptides. The result is inhibition of bradykinin-induced bronchoconstriction. Nedocromil does not posess any bronchodilator, antihistamine, or corticosteroid activity.","Cysteinyl leukotriene receptor 1 antagonist; Cysteinyl leukotriene receptor 2 antagonist; fMet-Leu-Phe receptor antagonist; Prostaglandin D2 receptor unknown; Heat shock protein HSP 90-alpha","Therapeutic strategy associated"]
[253,"DB00717","approved","small molecule","Norethisterone","(17alpha)-17-ethynyl-17-hydroxyestra-4,8(14),9-trien-3-one; 17-hydroxy-19-nor-17-α-pregn-4-en-20-yn-3-one; 17-hydroxy-19-nor-17α-pregn-4-en-20-yn-3-one; 17-α-ethynyl-17-hydroxy-4-estren-3-one; 17-α-ethynyl-19-norandrost-4-en-17-β-ol-3-one; 17-α-ethynyl-19-nortestosterone; 17-α-ethynyl-4-estren-17-ol-3-one; 17-β-hydroxy-19-norpregn-4-en-20-yn-3-one; 17α-ethinyl-19-nortestosterone; 17α-ethinylestra-4-en-17β-ol-3-one; 17α-ethynyl-17-hydroxy-4-estren-3-one; 17α-ethynyl-17β-hydroxy-19-norandrost-4-en-3-one; 17α-ethynyl-19-nor-4-androsten-17β-ol-3-one; 17α-ethynyl-19-norandrost-4-en-17β-ol-3-one; 17α-ethynyl-19-nortestosterone; 17α-ethynyl-4-estren-17-ol-3-one; 17β-hydroxy-19-norpregn-4-en-20-yn-3-one; 19-nor-17-α-ethynyl-17-β-hydroxy-4-androsten-3-one; 19-nor-17-α-ethynylandrosten-17-β-ol-3-one; 19-nor-17-α-ethynyltestosterone; 19-Nor-17alpha-ethynyl-17beta-hydroxy-4-androsten-3-one; 19-nor-17α-ethynyl-17β-hydroxy-4-androsten-3-one; 19-nor-17α-ethynylandrosten-17β-ol-3-one; 19-nor-17α-ethynyltestosterone; 19-nor-ethindrone; 19-norethisterone; 4-estren-17α-ethynyl-17β-ol-3-one; Norethindrone; Norethisterone","C20H26O2","[H][C@@]12CC[C@@](O)(C#C)[C@@]1(C)CC[C@]1([H])[C@@]3([H])CCC(=O)C=C3CC[C@@]21[H]","Norethisterone, also known as norethindrone, is a synthetic progestational hormone belonging to the 19-nortestosterone-derived class of progestins. It is further classified as a second-generation progestin, along with  and its derivatives, and is the active form of several other progestins including  and . Norethisterone mimics the actions of endogenous , albeit with a greater potency, and is used on its own or in combination with estrogen derivatives in a variety of applications including contraception and hormone replacement therapy. First derived in 1951 in Mexico City, norethisterone was originally intended for use as a remedy for irregular menstruation and endometriosis, and was not marketed for use as an oral contraceptive until 1962.","68-22-4","298.4192","Norethisterone is indicated as an oral contraceptive when given as monotherapy or in combination with an estrogen component, such as  or . In combination with an estrogen component, oral norethisterone is also indicated as a hormone replacement therapy in the treatment of postmenopausal osteoporosis and moderate-to-severe vasomotor symptoms arising from menopause. When applied via transdermal patch, the combination of norethisterone and estradiol is indicated for the treatment of hypoestrogenism, vulvovaginal atrophy, and moderate-severe vasomotor symptoms.\r\n\r\nNorethisterone, taken in combination with intramuscular , is also indicated for the symptomatic treatment of endometriosis-related pain.","Norethisterone is a synthetic oral progestin used for contraception or to treat other hormone-related conditions such as menopausal symptoms and endometriosis. As a synthetic progestin, norethisterone acts similarly to endogenous progesterone but with a much higher potency - it acts at the pelvic level to alter cervical and endometrial function, as well as via the inhibition of pituitary hormones that play a role in follicular maturation and ovulation. A small increase in the risk of developing breast cancer has been observed in patients using combined oral contraceptives, with some evidence also implicating progestin-only pills - patients starting hormonal contraception should be advised of this risk and should employ routine breast self-examinations to check for evidence of any developing masses.","On a molecular level, progestins like norethisterone exert their effects on target cells via binding to progesterone receptors that result in downstream changes to target genes. Target cells are found in the reproductive tract, breast, pituitary, hypothalamus, skeletal tissue, and central nervous system. Contraceptive efficacy is derived mainly from changes to the cervical mucus, wherein norethisterone increases the cell content and viscosity of the mucous to impede sperm transport and migration. Norethisterone also induces a variety of changes to the endometrium - including atrophy, irregular secretion, and suppressed proliferation - that make it inhospitable for implantation. Working via a negative feedback loop, norethisterone also acts on both the hypothalamus and anterior pituitary to suppress the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. Suppression of these hormones prevents follicular development, ovulation, and corpus luteum development. \r\n\r\nWhen used as a component of hormone replacement therapy in menopausal women, norethisterone’s value is mainly in suppressing the growth of the endometrium. As estrogen stimulates endometrial growth, the unopposed use of estrogen in postmenopausal women with an intact uterus can lead to endometrial hyperplasia which can increase the risk of endometrial cancer. The addition of a progestin to a hormone replacement therapy in this population protects against this endometrial hyperplasia and, therefore, lowers the risk associated with the use of hormone replacement therapies.\r\n\r\nNorethisterone, along with other progestins and endogenous progesterone, has a low affinity for other steroid receptors, such as the androgen receptor and glucocorticoid receptor. While affinity and agonistic activity at these receptors is minimal, it is thought that androgen receptor agonism is responsible for some of the adverse effects observed with progestin use (e.g. acne, serum lipid changes).","Progesterone receptor agonist; Androgen receptor agonist; Glucocorticoid receptor agonist","Indication associated"]
[254,"DB00724","approved; investigational","small molecule","Imiquimod","1-isobutyl-1H-imidazo[4,5-c]quinolin-4-amine; 4-Amino-1-isobutyl-1H-imidazo(4,5-c)quinoline","C14H16N4","CC(C)CN1C=NC2=C1C1=C(C=CC=C1)N=C2N","Imiquimod is an immune response modifier that acts as a toll-like receptor 7 agonist. Imiquimod is commonly used topically to treat warts on the skin of the genital and anal areas. Imiquimod does not cure warts, and new warts may appear during treatment. Imiquimod does not fight the viruses that cause warts directly, however, it does help to relieve and control wart production. Miquimod is also used to treat a skin condition of the face and scalp called actinic keratoses and certain types of skin cancer called superficial basal cell carcinoma.","99011-02-6","240.3036","For the topical treatment of clinically typical, nonhyperkeratotic, nonhypertrophic actinic keratoses on the face or scalp in immunocompetent adults. Also indicated for the treatment of external genital and perianal warts/condyloma acuminata in individuals 12 years old and above.","Imiquimod is an immune response modifier that acts as a toll-like receptor 7 agonist. Imiquimod is commonly used topically to treat warts on the skin of the genital and anal areas. Imiquimod does not cure warts, and new warts may appear during treatment. Imiquimod does not fight the viruses that cause warts directly, however, it does help to relieve and control wart production. It is not used on warts inside the vagina, penis, or rectum. Imiquimod is also used to treat a skin condition of the face and scalp called actinic keratoses. Imiquimod can also be used to treat certain types of skin cancer called superficial basal cell carcinoma. Imiquimod is particularly useful on areas where surgery or other treatments may be difficult, complicated or otherwise undesirable, especially the face and lower legs.","Imiquimod's mechanism of action is via stimulation of innate and acquired immune responses, which ultimately leads to inflammatory cell infiltration within the field of drug application followed by apoptosis of diseased tissue. Imiquimod does not have direct antiviral activity. Studies of mice show that imiquimod may induce cytokines, including interferon-alpha (IFNA) as well as several IFNA genes (IFNA1, IFNA2, IFNA5, IFNA6, and IFNA8) as well as the IFNB gene. Imiquimod also induced the expression of interleukin (IL)-6, IL-8, and tumor necrosis factor alpha genes. In the treatment of basal cell carcinoma, Imiquimod appears to act as a toll-like receptor-7 agonist, and is thought to exert its anti-tumor effect via modification of the immune response and stimulation of apoptosis in BCC cells. In treating basal cell carcinoma it may increase the infiltration of lymphocytes, dendritic cells, and macrophages into the tumor lesion.","Toll-like receptor 7 agonist; Toll-like receptor 8 agonist","Therapeutic strategy associated"]
[255,"DB00726","approved","small molecule","Trimipramine","10,11-dihydro-N,N,β-trimethyl-5H-dibenz[b,f]azepine-5-propanamine; 5-(γ-dimethylamino-β-methylpropyl)-10,11-dihydro-5H-dibenzo[b,f]azepine; 5-[3-(dimethylamino)-2-methylpropyl]-10,11-dihydro-5H-dibenz[b,f]azepine; beta-Methylimipramine; Trimeprimine; Trimeproprimine; β-methylimipramine","C20H26N2","CC(CN(C)C)CN1C2=CC=CC=C2CCC2=CC=CC=C12","Tricyclic antidepressant similar to imipramine, but with more antihistaminic and sedative properties.","739-71-9","294.4338","For the treatment of depression and depression accompanied by anxiety, agitation or sleep disturbance","Trimipramine is a tricyclic antidepressant. It was thought that tricyclic antidepressants work by inhibiting the re-uptake of the neurotransmitters norepinephrine and serotonin by nerve cells. However, this response occurs immediately, yet mood does not lift for around two weeks. It is now thought that changes occur in receptor sensitivity in the cerebral cortex and hippocampus. The hippocampus is part of the limbic system, a part of the brain involved in emotions. Presynaptic receptors are affected: a1 and b1 receptors are sensitized, a2 receptors are desensitised (leading to increased noradrenaline production). Tricyclics are also known as effective analgesics for different types of pain, especially neuropathic or neuralgic pain. A precise mechanism for their analgesic action is unknown, but it is thought that they modulate anti-pain opioid systems in the CNS via an indirect serotonergic route. They are also effective in migraine prophylaxis, but not in abortion of acute migraine attack. The mechanism of their anti-migraine action is also thought to be serotonergic.","Trimipramine's mechanism of action differs from other tricyclic antidepressants. Trimipramine acts by decreasing the reuptake of norepinephrine and serotonin (5-HT).","Sodium-dependent serotonin transporter inhibitor; Sodium-dependent noradrenaline transporter inhibitor; Sodium-dependent dopamine transporter inhibitor; 5-hydroxytryptamine receptor 2A agonist; 5-hydroxytryptamine receptor 1A antagonist; Alpha-1A adrenergic receptor antagonist; Alpha-1B adrenergic receptor antagonist; Dopamine D2 receptor other/unknown; Alpha-2B adrenergic receptor other/unknown; Histamine H1 receptor antagonist; 5-hydroxytryptamine receptor 2C antagonist; 5-hydroxytryptamine receptor 3A binder; 5-hydroxytryptamine receptor 1D binder; Alpha-2A adrenergic receptor antagonist; D(1) dopamine receptor binder; Beta adrenergic receptor binder; Muscarinic acetylcholine receptor binder; 5-hydroxytryptamine receptor 1C binder","Indication associated"]
[256,"DB00727","approved; investigational","small molecule","Nitroglycerin","1,2,3-propanetrioltrinitrate; 1,2,3-propanetriyl nitrate; Glycerin trinitrate; Glycerol trinitrate; Glycerol, nitric acid triester; Glyceryl trinitrate; NG; Nitroglicerina; Nitroglycerin; Nitroglycerine; Nitroglycerol; Nitromed; Propane-1,2,3-triyl trinitrate; Trinitroglycerin; Trinitroglycerol","C3H5N3O9","[O-][N+](=O)OCC(CO[N+]([O-])=O)O[N+]([O-])=O","Nitroglycerin is a vasodilator drug used for the treatment of chest pain and high blood pressure. It was first approved in 2000 and is currently marketed by Pfizer, and other companies, depending on the dosage form. Nitroglycerin is available in various forms, including a spray form, sublingual tablet form, intravenous form, extended-release tablet form, and transdermal form.  A less commonly known fact is that in addition to treating angina, nitroglycerin is also used in an ointment to treat the pain that accompanies anal fissures. The rectal ointment form of nitroglycerin was approved by the FDA in 1955.","55-63-0","227.0865","Nitroglycerin is indicated for various purposes. It is indicated to prevent and treat angina or chest pain due to cardiovascular disease, as well as to treat peri-operative hypertension or induce intra-operative hypotension. It is also indicated to treat acute heart failure in patients with myocardial infarction. In the ointment form, nitroglycerin is indicated to treat pain caused by anal fissures. The transdermal form is applied directly to the skin to prevent acute anginal attacks. \r\n\r\nThe intravenous form is used off-label in emergency settings and is commonly used to treat acute coronary spasm caused by cocaine, hypertensive emergencies, as well as acute congestive heart failure exacerbations. Some other off-label uses of nitroglycerin include management of variceal hemorrhage, management of esophageal spasticity, and induction of uterine relaxation.","Nitroglycerin causes the relaxation of vascular smooth muscles, causing arteriolar and venous dilatation. It reduces cardiac preload and afterload and reduces coronary artery spasm, decreasing systemic vascular resistance as well as systolic and diastolic blood pressure. The reduction of cardiac work by nitroglycerin is thought to cause the most relief of anginal symptoms, with some contributions from arteriolar dilatation effects.","Nitroglycerin is converted by mitochondrial aldehyde dehydrogenase (mtALDH) to nitric oxide (NO), an active substance which then activates the enzyme guanylate cyclase. The activation of this enzyme is followed by the synthesis of cyclic guanosine 3',5'-monophosphate (cGMP), activating a cascade of protein kinase-dependent phosphorylation events in smooth muscles. This process eventually leads to the dephosphorylation of the myosin light chain of smooth muscles, causing relaxation and increased blood flow in veins, arteries and cardiac tissue.. The above processes lead to decreased work of the heart decreased blood pressure, relief of anginal symptoms, and increased blood flow to the myocardium.One in vitro study using mouse aorta suggests that nitric oxide (an activated metabolite of nitroglycerin) targets the natriuretic peptide receptors.","Atrial natriuretic peptide receptor 1 agonist","Indication associated"]
[257,"DB00731","approved; investigational","small molecule","Nateglinide","Nateglinide","C19H27NO3","CC(C)[C@H]1CC[C@@H](CC1)C(=O)N[C@H](CC1=CC=CC=C1)C(O)=O","Nateglinide is an oral antihyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus (NIDDM). It belongs to the meglitinide class of short-acting insulin secretagogues, which act by binding to β cells of the pancreas to stimulate insulin release. Nateglinide is an amino acid derivative that induces an early insulin response to meals decreasing postprandial blood glucose levels. It should only be taken with meals and meal-time doses should be skipped with any skipped meal. Approximately one month of therapy is required before a decrease in fasting blood glucose is seen. Meglitnides may have a neutral effect on weight or cause a slight increase in weight. The average weight gain caused by meglitinides appears to be lower than that caused by sulfonylureas and insulin and appears to occur only in those naïve to oral antidiabetic agents. Due to their mechanism of action, meglitinides may cause hypoglycemia although the risk is thought to be lower than that of sulfonylureas since their action is dependent on the presence of glucose. In addition to reducing postprandial and fasting blood glucose, meglitnides have been shown to decrease glycosylated hemoglobin (HbA1c) levels, which are reflective of the last 8-10 weeks of glucose control. Meglitinides appear to be more effective at lowering postprandial blood glucose than metformin, sulfonylureas and thiazolidinediones. Nateglinide is extensively metabolized in the liver and excreted in urine (83%) and feces (10%). The major metabolites possess less activity than the parent compound. One minor metabolite, the isoprene, has the same potency as its parent compound.","105816-04-4","317.429","For the treatment of non-insulin dependent-diabetes mellitus in conjunction with diet and exercise.","Insulin secretion by pancreatic β cells is partly controlled by cellular membrane potential. Membrane potential is regulated through an inverse relationship between the activity of cell membrane ATP-sensitive potassium channels (ABCC8) and extracellular glucose concentrations. Extracellular glucose enters the cell via GLUT2 (SLC2A2) transporters. Once inside the cell, glucose is metabolized to produce ATP. High concentrations of ATP inhibit ATP-sensitive potassium channels causing membrane depolarization. When extracellular glucose concentrations are low, ATP-sensitive potassium channels open causing membrane repolarization. High glucose concentrations cause ATP-sensitive potassium channels to close resulting in membrane depolarization and opening of L-type calcium channels. The influx of calcium ions stimulates calcium-dependent exocytosis of insulin granules. Nateglinide increases insulin release by inhibiting ATP-sensitive potassium channels in a glucose-dependent manner.","Nateglinide activity is dependent on the presence functioning β cells and glucose. In contrast to sulfonylurea insulin secretatogogues, nateglinide has no effect on insulin release in the absence of glucose. Rather, it potentiates the effect of extracellular glucose on ATP-sensitive potassium channel and has little effect on insulin levels between meals and overnight. As such, nateglinide is more effective at reducing postprandial blood glucose levels than fasting blood glucose levels and requires a longer duration of therapy (approximately one month) before decreases in fasting blood glucose are observed. The insulinotropic effects of nateglinide are highest at intermediate glucose levels (3 to 10 mmol/L) and it does not increase insulin release already stimulated by high glucose concentrations (greater than 15 mmol/L). Nateglinide appears to be selective for pancreatic β cells and does not appear to affect skeletal or cardiac muscle or thyroid tissue.","ATP-binding cassette sub-family C member 8 inhibitor; Peroxisome proliferator-activated receptor gamma agonist","Target associated"]
[258,"DB00734","approved; investigational","small molecule","Risperidone","Risperidone","C23H27FN4O2","CC1=C(CCN2CCC(CC2)C2=NOC3=C2C=CC(F)=C3)C(=O)N2CCCCC2=N1","Risperidone is a second-generation antipsychotic (SGA) medication used in the treatment of a number of mood and mental health conditions including schizophrenia and bipolar disorder. It is one of the most widely used SGAs. , another commonly used SGA, is the primary active metabolite of risperidone (i.e. 9-hydroxyrisperidone).\r\n\r\nSchizophrenia and various mood disorders are thought to be caused by an excess of dopaminergic D2 and serotonergic 5-HT2A activity, resulting in overactivity of central mesolimbic pathways and mesocortical pathways, respectively. Risperidone is thought to reduce this overactivity through inhibition of dopaminergic D2 receptors and serotonergic 5-HT2A receptors in the brain.\r\n\r\nRisperidone binds with a very high affinity to 5-HT2A receptors, approximately 10-20 fold greater than the drug's binding affinity to D2 receptors, and carries lesser activity at several off-targets which may responsible for some of its undesirable effects.","106266-06-2","410.4845","Risperidone is indicated for the treatment of schizophrenia and irritability associated with autistic disorder. It is also indicated as monotherapy, or adjunctly with lithium or valproic acid, for the treatment of acute mania or mixed episodes associated with bipolar I disorder.\r\n\r\nRisperidone is additionally indicated in Canada for the short-term symptomatic management of aggression or psychotic symptoms in patients with severe dementia of the Alzheimer type unresponsive to nonpharmacological approaches.\r\n\r\nRisperidone is also used off-label for a number of conditions including as an adjunct to antidepressants in treatment-resistant depression.","The primary action of risperidone is to decrease dopaminergic and serotonergic pathway activity in the brain, therefore decreasing symptoms of schizophrenia and mood disorders.\r\n\r\nRisperidone has a high binding affinity for serotonergic 5-HT2A receptors when compared to dopaminergic D2 receptors in the brain. Risperidone binds to D2 receptors with a lower affinity than first-generation antipsychotic drugs, which bind with very high affinity. A reduction in extrapyramidal symptoms with risperidone, when compared to its predecessors, is likely a result of its moderate affinity for dopaminergic D2 receptors.","Though its precise mechanism of action is not fully understood, current focus is on the ability of risperidone to inhibit the D2 dopaminergic receptors and 5-HT2A serotonergic receptors in the brain. Schizophrenia is thought to result from an excess of dopaminergic D2 and serotonergic 5-HT2A activity, resulting in overactivity of central mesolimbic pathways and mesocortical pathways, respectively.\r\n\r\nD2 dopaminergic receptors are transiently inhibited by risperidone, reducing dopaminergic neurotransmission, therefore decreasing positive symptoms of schizophrenia, such as delusions and hallucinations. Risperidone binds transiently and with loose affinity to the dopaminergic D2 receptor, with an ideal receptor occupancy of 60-70% for optimal effect. Rapid dissociation of risperidone from the D2 receptors contributes to decreased risk of extrapyramidal symptoms (EPS), which occur with permanent and high occupancy blockade of D2 dopaminergic receptors. Low-affinity binding and rapid dissociation from the D2 receptor distinguish risperidone from the traditional antipsychotic drugs. A higher occupancy rate of D2 receptors is said to increase the risk of extrapyramidal symptoms and is therefore to be avoided. \r\n \r\nIncreased serotonergic mesocortical activity in schizophrenia results in negative symptoms, such as depression and decreased motivation. The high-affinity binding of risperidone to 5-HT2A receptors leads to a decrease in serotonergic activity. In addition, 5-HT2A receptor blockade results in decreased risk of extrapyramidal symptoms, likely by increasing dopamine release from the frontal cortex, and not the nigrostriatal tract. Dopamine level is therefore not completely inhibited. Through the above mechanisms, both serotonergic and D2 blockade by risperidone are thought to synergistically work to decrease the risk of extrapyramidal symptoms. \r\n \r\nRisperidone has also been said to be an antagonist of alpha-1 (α1), alpha-2 (α2), and histamine (H1) receptors. Blockade of these receptors is thought to improve symptoms of schizophrenia, however the exact mechanism of action on these receptors is not fully understood at this time.","5-hydroxytryptamine receptor 2A antagonist; Dopamine D2 receptor antagonist; Alpha-1B adrenergic receptor antagonist; Alpha-2B adrenergic receptor antagonist; Alpha-1A adrenergic receptor antagonist; Alpha-2C adrenergic receptor antagonist; Histamine H1 receptor antagonist; 5-hydroxytryptamine receptor 2C antagonist; 5-hydroxytryptamine receptor 1D antagonist; 5-hydroxytryptamine receptor 1A antagonist; 5-hydroxytryptamine receptor 7 antagonist; D(2L) dopamine receptor antagonist; Dopamine D1 receptor antagonist","Indication associated"]
[259,"DB00738","approved; investigational","small molecule","Pentamidine","1,5-bis(4-amidinophenoxy)pentane; 4,4'-(1,5-pentanediylbis(oxy))bis-benzenecarboximidamide; 4,4'-(pentamethylenedioxy)dibenzamidine; 4,4'-Diamidinodiphenoxypentane; p,p'-(pentamethylenedioxy)dibenzamidine","C19H24N4O2","NC(=N)C1=CC=C(OCCCCCOC2=CC=C(C=C2)C(N)=N)C=C1","Antiprotozoal agent effective in trypanosomiasis, leishmaniasis, and some fungal infections; used in treatment of pneumocystis pneumonia in HIV-infected patients. It may cause diabetes mellitus, central nervous system damage, and other toxic effects.","100-33-4","340.4195","For the treatment of pneumonia due to <i>Pneumocystis carinii</i>.","Pentamidine is an antiprotozoal agent. It is an aromatic diamidine, and is known to have activity against <i>Pneumocystis carinii</i>. The exact nature of its antiprotozoal action is unknown. <i>in vitro</i> studies with mammalian tissues and the protozoan <i>Crithidia oncopelti</i> indicate that the drug interferes with nuclear metabolism producing inhibition of the synthesis of DNA, RNA, phospholipids and proteins. Little is known about the drug's pharmacokinetics. The medication is also useful in Leishmaniasis and in prophylaxis against sleeping sickness caused by <i>Trypanosoma brucei gambiense</i>. Hydration before treatment lessens the incidence and severity of side effects, which include liver or kidney dysfunction, hypertension, hypotension, hypoglycemia, hypocalemia, leukopenia, thrombcytopenia, anemia, and allergic reaction. It is generally well-tolerated.","The mode of action of pentamidine is not fully understood. It is thought that the drug interferes with nuclear metabolism producing inhibition of the synthesis of DNA, RNA, phospholipids, and proteins.","DNA intercalation; tRNA (cytosine(38)-C(5))-methyltransferase other","Indication associated"]
[260,"DB00739","approved; vet_approved; withdrawn","small molecule","Hetacillin","(2S,5R,6R)-6-[(4R)-2,2-dimethyl-5-oxo-4-phenylimidazolidin-1-yl]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; 6β-[(4R)-2,2-dimethyl-5-oxo-4-phenylimidazolidin-1-yl]penicillanic acid; Hetacillin","C19H23N3O4S","[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2N1C(=O)[C@H](NC1(C)C)C1=CC=CC=C1)C(O)=O","Hetacillin is a penicillin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. The name \"penicillin\" can either refer to several variants of penicillin available, or to the group of antibiotics derived from the penicillins. Hetacillin has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of Hetacillin results from the inhibition of cell wall synthesis and is mediated through Hetacillin binding to penicillin binding proteins (PBPs). Hetacillin has been withdrawn from the market since it has been discovered that it has no therapeutic advantage compared to non-ester derivatives like ampicillin.","3511-16-8","389.469","Hetacillin is a beta-lactam antibiotic prodrug used to treat bacterial infections. In the body it gets converted to ampicillin.","Hetacillin is a penicillin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. The name \"penicillin\" can either refer to several variants of penicillin available, or to the group of antibiotics derived from the penicillins. Hetacillin has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of Hetacillin results from the inhibition of cell wall synthesis and is mediated through Hetacillin binding to penicillin binding proteins (PBPs).","Hetacillin is a semisynthetic penicillin prodrug which itself has no antibacterial activity, but is converted in the body to ampicillin and has actions and uses similar to those of ampicillin. Hetacillin is prepared by reacting ampicillin with acetone. Ampicillin rapidly decomposes because of the intramolecular attack of the side chain amino group on the lactam ring. _In vitro_ studies have shown that hetacillin is resistant to beta lactamase activity. However, this effect is transient, as the hydrolysis product, ampicillin, is readily inactivated by beta lactamase. Hetacillin locks up the offending amino group and prevents the decomposition of Hetacillin. Once hydrolyzed to ampicillin (and acetone), ampicillin binds to the penicillin binding proteins found in susceptible bacteria. This inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins.","Penicillin-binding protein 2a inhibitor; Penicillin-binding protein 1b inhibitor; Penicillin-binding protein 3 inhibitor; Penicillin-binding protein 1A inhibitor; Penicillin-binding protein 2B inhibitor","Indication associated"]
[261,"DB00741","approved; vet_approved","small molecule","Hydrocortisone","(11β)-11,17,21-trihydroxypregn-4-ene-3,20-dione; 11beta-hydrocortisone; 11beta,17alpha,21-Trihydroxy-4-pregnene-3,20-dione; 11β-hydrocortisone; 17-Hydroxycorticosterone; 4-pregnen-11β,17α,21-triol-3,20-dione; Cortisol; Hydrocortisone; Kendall's compound F; Reichstein's substance M","C21H30O5","[H][C@@]12CC[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C","Hydrocortisone, or cortisol, is a glucocorticoid secreted by the adrenal cortex. Hydrocortisone is used to treat immune, inflammatory, and neoplastic conditions. It was discovered in the 1930s by Edward Kendall and named Compound F, or 17-hydroxycorticosterone.\r\n\r\nHydrocortisone was granted FDA approval on 5 August 1952.","50-23-7","362.4599","Otic solutions are indicated for infections of the external auditory canal caused by susceptible organisms and with inflammation. Hydrocortisone tablets are indicated for certain endocrine, rheumatic, collagen, allergic, ophthalmic, respiratory, hematologic, neoplastic, edematous, gastrointestinal, and other conditions. A hydrocortisone enema is indicated for ulcerative colitis, a topical ointment with antibiotics is indicated for corticosteroid responsive dermatoses with infections, and a topical cream with  is indicated to treat cold sores. Oral granules of hydrocortisone are used as a replacement therapy for Adrenocortical Insufficiency (AI) in children under 17 years of age.","Hydrocortisone binds to the glucocorticoid receptor leading to downstream effects such as inhibition of phospholipase A2, NF-kappa B, other inflammatory transcription factors, and the promotion of anti-inflammatory genes. Hydrocortisone has a wide therapeutic index and a moderate duration of action. Patients should stop taking the medication if irritation or sensitization occurs.","The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.\r\n\r\nGlucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10.\r\n\r\nLower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.","Glucocorticoid receptor agonist; Annexin A1 agonist","Therapeutic strategy associated"]
[262,"DB00742","approved; investigational","small molecule","Mannitol","(2R,3R,4R,5R)-hexane-1,2,3,4,5,6-hexaol; (2R,3R,4R,5R)-hexane-1,2,3,4,5,6-hexol; D-(-)-Mannitol; D-Mannitol; Manna Sugar; Mannit; Mannite","C6H14O6","OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO","Mannitol is an osmotic diuretic that is metabolically inert in humans and occurs naturally, as a sugar or sugar alcohol, in fruits and vegetables. Mannitol elevates blood plasma osmolality, resulting in enhanced flow of water from tissues, including the brain and cerebrospinal fluid, into interstitial fluid and plasma. As a result, cerebral edema, elevated intracranial pressure, and cerebrospinal fluid volume and pressure may be reduced. Mannitol may also be used for the promotion of diuresis before irreversible renal failure becomes established; the promotion of urinary excretion of toxic substances; as an Antiglaucoma agent; and as a renal function diagnostic aid.\r\n\r\nOn October 30, 2020, mannitol was approved by the FDA as add-on maintenance therapy for the control of pulmonary symptoms associated with cystic fibrosis in adult patients and is currently marketed for this indication under the name BRONCHITOL® by Chiesi USA Inc.","69-65-8","182.1718","Used for the promotion of diuresis before irreversible renal failure becomes established, the reduction of intracranial pressure, the treatment of cerebral edema, and the promotion of urinary excretion of toxic substances.\r\n\r\nMannitol is also indicated as add-on maintenance therapy for improving pulmonary function in cystic fibrosis patients aged 18 and over who have passed the BRONCHITOL tolerance test (BTT). It is recommended that patients take an orally inhaled short-acting bronchodilator 5-15 minutes prior to every inhaled mannitol dose.","Chemically, mannitol is an alcohol and a sugar, or a polyol; it is similar to xylitol or sorbitol. However, mannitol has a tendency to lose a hydrogen ion in aqueous solutions, which causes the solution to become acidic. For this reason, it is not uncommon to add a substance to adjust its pH, such as sodium bicarbonate. Mannitol is commonly used to increase urine production (diuretic). It is also used to treat or prevent medical conditions that are caused by an increase in body fluids/water (e.g., cerebral edema, glaucoma, kidney failure). Mannitol is frequently given along with other diuretics (e.g., furosemide, chlorothiazide) and/or IV fluid replacement.\r\n\r\nInhaled mannitol has the possibility to cause bronchospasm and hemoptysis; the occurrence of either should lead to discontinuation of inhaled mannitol.","Mannitol is an osmotic diuretic that is metabolically inert in humans and occurs naturally, as a sugar or sugar alcohol, in fruits and vegetables. Mannitol elevates blood plasma osmolality, resulting in enhanced flow of water from tissues, including the brain and cerebrospinal fluid, into interstitial fluid and plasma. As a result, cerebral edema, elevated intracranial pressure, and cerebrospinal fluid volume and pressure may be reduced. As a diurectic mannitol induces diuresis because it is not reabsorbed in the renal tubule, thereby increasing the osmolality of the glomerular filtrate, facilitating excretion of water, and inhibiting the renal tubular reabsorption of sodium, chloride, and other solutes. Mannitol promotes the urinary excretion of toxic materials and protects against nephrotoxicity by preventing the concentration of toxic substances in the tubular fluid. As an Antiglaucoma agent mannitol levates blood plasma osmolarity, resulting in enhanced flow of water from the eye into plasma and a consequent reduction in intraocular pressure. As a renal function diagnostic aid mannitol is freely filtered by the glomeruli with less than 10% tubular reabsorption. Therefore, its urinary excretion rate may serve as a measurement of glomerular filtration rate (GFR).\r\n\r\nThe exact mechanism of action of inhaled mannitol in the symptomatic maintenance treatment of cystic fibrosis remains unclear. It is hypothesized that mannitol produces an osmotic gradient across the airway epithelium that draws fluid into the extracellular space and alters the properties of the airway surface mucus layer, allowing easier mucociliary clearance.",null,"Therapeutic strategy associated"]
[263,"DB00744","approved; investigational; withdrawn","small molecule","Zileuton","(±)-1-(1-Benzo[b]thien-2-ylethyl)-1-hydroxyurea; Leutrol; N-(1-Benzo(b)thien-2-ylethyl)-N-hydroxyurea; N-[1-(benzo[b]thiophen-2-yl)ethyl]-N-hydroxyurea","C11H12N2O2S","CC(N(O)C(N)=O)C1=CC2=CC=CC=C2S1","Leukotrienes are substances that induce numerous biological effects including augmentation of neutrophil and eosinophil migration, neutrophil and monocyte aggregation, leukocyte adhesion, increased capillary permeability, and smooth muscle contraction. These effects contribute to inflammation, edema, mucus secretion, and bronchoconstriction in the airways of asthmatic patients. Zileuton relieves such symptoms through its selective inhibition of 5-lipoxygenase, the enzyme that catalyzes the formation of leukotrienes from arachidonic acid. Specifically, it inhibits leukotriene LTB4, LTC4, LTD4, and LTE4 formation. Both the R(+) and S(-) enantiomers are pharmacologically active as 5-lipoxygenase inhibitors in in vitro systems. The immediate release tablet of Zileuton has been withdrawn from the US market.","111406-87-2","236.29","For the prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older.","Zileuton is an asthma drug that differs chemically and pharmacologically from other antiasthmatic agents. It blocks leukotriene synthesis by inhibiting 5-lipoxygenase, an enzyme of the eicosanoid synthesis pathway. Current data indicates that asthma is a chronic inflammatory disorder of the airways involving the production and activity of several endogenous inflammatory mediators, including leukotrienes. Sulfido-peptide leukotrienes (LTC4, LTD4, LTE4, also known as the slow-releasing substances of anaphylaxis) and LTB4, a chemoattractant for neutrophils and eosinophils, are derived from the initial unstable product of arachidonic acid metabolism, leukotriene A4 (LTA4), and can be measured in a number of biological fluids including bronchoalveolar lavage fluid (BALF) from asthmatic patients. In humans, pretreatment with zileuton attenuated bronchoconstriction caused by cold air challenge in patients with asthma.","Leukotrienes are substances that induce numerous biological effects including augmentation of neutrophil and eosinophil migration, neutrophil and monocyte aggregation, leukocyte adhesion, increased capillary permeability, and smooth muscle contraction. These effects contribute to inflammation, edema, mucus secretion, and bronchoconstriction in the airways of asthmatic patients. Zileuton relieves such symptoms through its selective inhibition of 5-lipoxygenase, the enzyme that catalyzes the formation of leukotrienes from arachidonic acid. Specifically, it inhibits leukotriene LTB4, LTC4, LTD4, and LTE4 formation. Both the R(+) and S(-) enantiomers are pharmacologically active as 5-lipoxygenase inhibitors in <i>in vitro</i> systems. Due to the role of leukotrienes in the pathogenesis of asthma, modulation of leukotriene formation by interruption of 5-lipoxygenase activity may reduce airway symptoms, decrease bronchial smooth muscle tone, and improve asthma control.","Arachidonate 5-lipoxygenase inhibitor","Therapeutic strategy associated"]
[264,"DB00749","approved; investigational; vet_approved","small molecule","Etodolac","(±)-1,8-diethyl-1,3,4,9-tetrahydropyrano(3,4-b)indole-1-acetic acid; (1,8-Diethyl-1,3,4,9-tetrahydro-pyrano[3,4-b]indol-1-yl)-acetic acid; 1,3,4,9-tetrahydro-1,8-diethylpyrano(3,4-b)indole-1-acetic acid; 1,8-diethyl-1,3,4,9-tetrahydropyrano(3,4-b)indole-1-acetic acid; 1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-ylacetic acid; Etodolac; Etodolic acid","C17H21NO3","CCC1=C2NC3=C(CCOC3(CC)CC(O)=O)C2=CC=C1","Etodolac is a non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic and antipyretic properties. Its therapeutic effects are due to its ability to inhibit prostaglandin synthesis. It is indicated for relief of signs and symptoms of rheumatoid arthritis and osteoarthritis.","41340-25-4","287.3535","For acute and long-term management of signs and symptoms of osteoarthritis and rheumatoid arthritis, as well as for the management of pain.","Etodolac is an anti-inflammatory agent with analgesic and antipyretic properties. It is used to treat osteoarthritis, rheumatoid arthritis and control acute pain. The therapeutic effects of etodolac are achieved via inhibition of the synthesis of prostaglandins involved in fever, pain, swelling and inflammation. Etodolac is administered as a racemate. As with other NSAIDs, the S-form has been shown to be active while the R-form is inactive. Both enantiomers are stable and there is no evidence of R- to S- conversion _in vivo_.","Similar to other NSAIDs, the anti-inflammatory effects of etodolac result from inhibition of the enzyme cycooxygenase (COX). This decreases the synthesis of peripheral prostaglandins involved in mediating inflammation. Etodolac binds to the upper portion of the COX enzyme active site and prevents its substrate, arachidonic acid, from entering the active site. Etodolac was previously thought to be a non-selective COX inhibitor, but it is now known to be 5 – 50 times more selective for COX-2 than COX-1. Antipyresis may occur by central action on the hypothalamus, resulting in peripheral dilation, increased cutaneous blood flow, and subsequent heat loss.","Prostaglandin G/H synthase 2 inhibitor; Prostaglandin G/H synthase 1 inhibitor; Retinoic acid receptor RXR-alpha other","Therapeutic strategy associated"]
[265,"DB00751","approved; investigational","small molecule","Epinastine","(±)-epinastine; 3-amino-9,13b-dihydro-1H-dibenz(c,f)imidazo(1,5-a)azepine; Epinastine","C16H15N3","NC1=NCC2N1C1=CC=CC=C1CC1=CC=CC=C21","Epinastine is used for the prevention of itching associated with allergic conjunctivitis. It has a multi-action effect that inhibits the allergic response in 3 ways: 1. stabilizes mast cells by preventing mast cell degranulation to control the allergic response, 2. prevents histamine binding to both the H1- and H2-receptors to stop itching and provide lasting protection, and 3. prevents the release of proinflammatory chemical mediators from the blood vessel to halt progression of the allergic response.","80012-43-7","249.3104","For the prevention of itching associated with allergic conjunctivitis.","Epinastine is an antihistamine and an inhibitor of histamine release from the mast cell for topical administration to the eyes. Epinastine is indicated for the prevention of itching associated with allergic conjunctivitis. Epinastine is a topically active, direct H<sub>1</sub>-receptor antagonist and an inhibitor of the release of histamine from the mast cell. Epinastine is selective for the histamine H<sub>1</sub>-receptor and has affinity for the histamine H2 receptor. Epinastine also possesses affinity for the a1-, a2-, and 5-HT<sub>2</sub> -receptors. Epinastine does not penetrate the blood/brain barrier and, therefore, is not expected to induce side effects of the central nervous system.","Epinastine has a multiaction effect that inhibits the allergic response in 3 ways: 1. stabilizes mast cells by preventing mast cell degranulation to control the allergic response, 2. prevents histamine binding to both the H1- and H<sub>2</sub>-receptors to stop itching and provide lasting protection, and 3. prevents the release of proinflammatory chemical mediators from the blood vessel to halt progression of the allergic response.","Histamine H1 receptor antagonist; Histamine H2 receptor antagonist; Alpha-1A adrenergic receptor unknown; Alpha-2A adrenergic receptor unknown; 5-hydroxytryptamine receptor 2A antagonist; 5-hydroxytryptamine receptor 7 antagonist","Therapeutic strategy associated"]
[266,"DB00758","approved","small molecule","Clopidogrel","(+)-Clopidogrel","C16H16ClNO2S","[H][C@@](N1CCC2=C(C1)C=CS2)(C(=O)OC)C1=CC=CC=C1Cl","Clopidogrel is a prodrug of a platelet inhibitor used to reduce the risk of myocardial infarction and stroke. Clopidogrel is indicated to reduce the risk of myocardial infarction for patients with non-ST elevated acute coronary syndrome (ACS), patients with ST-elevated myocardial infarction, and in recent MI, stroke, or established peripheral arterial disease,\r\n\r\nIt has been shown to be superior to  in reducing cardiovascular outcomes in patients with cardiovascular disease and provides additional benefit to patients with acute coronary syndromes already taking aspirin.\r\n\r\nClopidogrel was granted FDA approval on 17 November 1997.","113665-84-2","321.822","Clopidogrel is indicated to reduce the risk of myocardial infarction for patients with non-ST elevated acute coronary syndrome (ACS), patients with ST-elevated myocardial infarction, and in recent MI, stroke, or established peripheral arterial disease,","Clopidogrel is a prodrug of a platelet inhibitor used to reduce the risk of myocardial infarction and stroke. It has a long duration of action as it is taken once daily and a large therapeutic window as it is given in doses of 75-300mg daily.","Clopidogrel is metabolized to its active form by carboxylesterase-1. The active form is a platelet inhibitor that irreversibly binds to P2Y<sub>12</sub> ADP receptors on platelets. This binding prevents ADP binding to P2Y<sub>12</sub> receptors, activation of the glycoprotein GPIIb/IIIa complex, and platelet aggregation.","P2Y purinoceptor 12 antagonist","Therapeutic strategy associated"]
[267,"DB00759","approved; vet_approved","small molecule","Tetracycline","(4S,4aS,5aS,12aS)-4-(Dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,6,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-2-naphthacenecarboxamide; Abramycin; Anhydrotetracycline; Deschlorobiomycin; Tetracycline; Tsiklomitsin","C22H24N2O8","[H][C@@]12C[C@@]3([H])C(=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@H]2N(C)C)C(=O)C1=C(O)C=CC=C1[C@@]3(C)O","Tetracycline is a broad spectrum polyketide antibiotic produced by the Streptomyces genus of Actinobacteria. It exerts a bacteriostatic effect on bacteria by binding reversible to the bacterial 30S ribosomal subunit and blocking incoming aminoacyl tRNA from binding to the ribosome acceptor site. It also binds to some extent to the bacterial 50S ribosomal subunit and may alter the cytoplasmic membrane causing intracellular components to leak from bacterial cells.","60-54-8","444.4346","Used to treat bacterial infections such as Rocky Mountain spotted fever, typhus fever, tick fevers, Q fever, rickettsialpox and Brill-Zinsser disease. May be used to treat infections caused by Chlamydiae spp., B. burgdorferi (Lyme disease), and upper respiratory infections caused by typical (S. pneumoniae, H. influenzae, and M. catarrhalis) and atypical organisms (C. pneumoniae, M. pneumoniae, L. pneumophila). May also be used to treat acne. Tetracycline may be an alternative drug for people who are allergic to penicillin.","Tetracycline is a short-acting antibiotic that  inhibits bacterial growth by inhibiting translation. It binds to the 30S ribosomal subunit and prevents the amino-acyl tRNA from binding to the A site of the ribosome. It also binds to some extent to the 50S ribosomal subunit. This binding is reversible in nature. Additionally tetracycline may alter the cytoplasmic membrane of bacteria causing leakage of intracellular contents, such as nucleotides, from the cell.","Tetracycline passively diffuses through porin channels in the bacterial membrane and reversibly binds to the 30S ribosomal subunit, preventing binding of tRNA to the mRNA-ribosome complex, and thus interfering with protein synthesis.","30S ribosomal protein S7 inhibitor; 30S ribosomal protein S14 inhibitor; 30S ribosomal protein S3 inhibitor; 30S ribosomal protein S8 inhibitor; 30S ribosomal protein S19 inhibitor; 16S ribosomal RNA inhibitor; Major prion protein inhibitor; Multidrug translocase MdfA; Protein-arginine deiminase type-4","Indication associated"]
[268,"DB00760","approved; investigational","small molecule","Meropenem","(4R,5S,6S)-3-{[(3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-yl]thio}-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; Meropenem anhydrous","C17H25N3O5S","[H][C@]1([C@@H](C)O)C(=O)N2C(C(O)=O)=C(S[C@@H]3CN[C@@H](C3)C(=O)N(C)C)[C@H](C)[C@]12[H]","Meropenem is a broad-spectrum carbapenem antibiotic. It is active against Gram-positive and Gram-negative bacteria. Meropenem exerts its action by penetrating bacterial cells readily and interfering with the synthesis of vital cell wall components, which leads to cell death.\r\n\r\nIn August 2017, a combination antibacterial therapy under the market name vabomere was approved for treatment of adult patients with complicated urinary tract infections (cUTI). Vabomere consists of meropenem and  and is intravenously admininstered. The treatment aims to resolve infection-related symptoms and achieve negative urine culture, where the infections are proven or strongly suspected to be caused by susceptible bacteria.","96036-03-2","383.463","For use as single agent therapy for the treatment of the following infections when caused by susceptible isolates of the designated microorganisms: <b>complicated skin and skin structure infections</b> due to <i>Staphylococcus aureus</i> (b-lactamase and non-b-lactamase producing, methicillin-susceptible isolates only), <i>Streptococcus pyogenes</i>, <i>Streptococcus agalactiae</i>, viridans group streptococci, <i>Enterococcus faecalis</i> (excluding vancomycin-resistant isolates), <i>Pseudomonas aeruginosa</i>, <i>Escherichia coli</i>, <i>Proteus mirabilis</i>, <i>Bacteroides fragilis</i> and <i>Peptostreptococcus</i> species; <b>complicated appendicitis and peritonitis</b> caused by viridans group streptococci, <i>Escherichia coli</i>, <i>Klebsiella pneumoniae</i>, <i>Pseudomonas aeruginosa</i>, <i>Bacteroides fragilis</i>, <i>B. thetaiotaomicron</i>, and <i>Peptostreptococcus</i> species. Also for use in the treatment of bacterial meningitis caused by <i>Streptococcus pneumoniae</i>, <i>Haemophilus influenzae</i> (b-lactamase and non-b-lactamase-producing isolates), and <i>Neisseria meningitidis</i>.","Meropenem is a broad-spectrum carbapenem antibiotic. It is active against Gram-positive and Gram-negative bacteria. Meropenem exerts its action by penetrating bacterial cells readily and interfering with the synthesis of vital cell wall components, which leads to cell death.","The bactericidal activity of meropenem results from the inhibition of cell wall synthesis. Meropenem readily penetrates the cell wall of most Gram-positive and Gram-negative bacteria to reach penicillin-binding- protein (PBP) targets. Its strongest affinities are toward PBPs 2, 3 and 4 of <i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i>; and PBPs 1, 2 and 4 of <i>Staphylococcus aureus</i>.","D-alanyl-D-alanine carboxypeptidase DacB inhibitor","Indication associated"]
[269,"DB00762","approved; investigational","small molecule","Irinotecan","(+)-Irinotecan; Irinotecan; Irinotecan lactone","C33H38N4O6","CCC1=C2CN3C(=CC4=C(COC(=O)[C@]4(O)CC)C3=O)C2=NC2=CC=C(OC(=O)N3CCC(CC3)N3CCCCC3)C=C12","Irinotecan is an antineoplastic enzyme inhibitor primarily used in the treatment of colorectal cancer. It is a derivative of camptothecin that inhibits the action of topoisomerase I. Irinotecan prevents religation of the DNA strand by binding to topoisomerase I-DNA complex, and causes double-strand DNA breakage and cell death. It is a derivative of camptothecin. Irinotecan was approved for the treatment of advanced pancreatic cancer in October, 2015 (irinotecan liposome injection, trade name Onivyde).","97682-44-5","586.678","For the treatment of metastatic colorectal cancer (first-line therapy when administered with 5-fluorouracil and leucovorin). Also used in combination with cisplatin for the treatment of extensive small cell lung cancer. Irinotecan is currently under investigation for the treatment of metastatic or recurrent cervical cancer. Also used in combination with fluorouracil and leucovorin for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy.","Irinotecan is an antineoplastic enzyme inhibitor primarily used in the treatment of colorectal cancer. Irinotecan is a semisynthetic derivative of camptothecin. Camptothecins interact specifically with topoisomerase I, an enzyme in the cell nucleus that regulates DNA topology and facilitates nuclear processes such as DNA replication, recombination, and repair. During these processes, topoisomerase I relieves torsional strain in DNA by inducing reversible single-strand breaks, allowing single DNA strands to pass through the break. The 3'-DNA terminus of the broken DNA strands bind covalently with the topoisomerase enzyme to form a catalytic intermediate called a cleavable complex. After the DNA is sufficiently relaxed and the strand passage reaction is complete, DNA topoisomerase reattaches the broken DNA strands to form the chemically unaltered topoisomers that allow transcription to proceed. Irinotecan and its active metabolite SN-38 bind to the topoisomerase I-DNA complex and prevent religation of these single-strand breaks. Current research suggests that the cytotoxicity of irinotecan is due to double-strand DNA damage produced during DNA synthesis when replication enzymes interact with the ternary complex formed by topoisomerase I, DNA, and either Irinotecan or SN-38. Mammalian cells cannot efficiently repair these double-strand breaks. The precise contribution of SN-38 to the activity of irinotecan in humans is not known. Irinotecan is cell cycle phase-specific (S-phase).","Irinotecan inhibits the action of topoisomerase I. Irinotecan prevents religation of the DNA strand by binding to topoisomerase I-DNA complex. The formation of this ternary complex interferes with the moving replication fork, which induces replication arrest and lethal double-stranded breaks in DNA. As a result, DNA damage is not efficiently repaired and apoptosis (programmed cell death) occurs.","DNA topoisomerase 1 inhibitor; DNA topoisomerase I, mitochondrial inhibitor","Therapeutic strategy associated"]
[270,"DB00764","experimental","small molecule","Mometasone","(+)-Mometasone; Mometasone","C22H28Cl2O4","[H][C@@]12C[C@@H](C)[C@](O)(C(=O)CCl)[C@@]1(C)C[C@H](O)[C@@]1(Cl)[C@@]2([H])CCC2=CC(=O)C=C[C@]12C","Mometasone is a corticosteroid not currently used in medical products.  however, is still in use.","105102-22-5","427.361","The inhaler is indicated for the maintenance treatment of asthma as prophylactic therapy. The nasal spray is indicated for the treatment of the nasal symptoms of seasonal allergic and perennial allergic rhinitis.","Mometasone is a medium-potency synthetic corticosteroid with antiinflammatory, antipruritic, and vasoconstrictive properties. Studies in asthmatic patients have demonstrated that mometasone provides a favorable ratio of topical to systemic activity due to its primary local effect along with the extensive hepatic metabolism and the lack of active metabolites. Though effective for the treatment of asthma, glucocorticoids do not affect asthma symptoms immediately. Maximum improvement in symptoms following inhaled administration of mometasone furoate may not be achieved for 1 to 2 weeks or longer after starting treatment. When glucocorticoids are discontinued, asthma stability may persist for several days or longer. Mometasone has been shown in vitro to exhibit a binding affinity for the human glucocorticoid receptor which is approximately 12 times that of dexamethasone, 7 times that of triamcinolone acetonide, 5 times that of budesonide, and 1.5 times that of fluticasone. The clinical significance of these findings is unknown.","Unbound corticosteroids cross cell membranes and bind with high affinity to specific cytoplasmic receptors. Inflammation is decreased by diminishing the release of leukocytic acid hydrolases, prevention of macrophage accumulation at inflamed sites, interference with leukocyte adhesion to the capillary wall, reduction of capillary membrane permeability, reduction of complement components, inhibition of histamine and kinin release, and interference with the formation of scar tissue. The antiinflammatory actions of corticosteroids are thought to involve phospholipase A<sub>2</sub> inhibitory proteins, lipocortins, which control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes. Mometasone furoate has been shown in vitro to exhibit a binding affinity for the human glucocorticoid receptor which is approximately 12 times that of dexamethasone, 7 times that of triamcinolone acetonide, 5 times that of budesonide, and 1.5 times that of fluticasone.","Glucocorticoid receptor agonist; Progesterone receptor agonist","Therapeutic strategy associated"]
[271,"DB00765","approved","small molecule","Metyrosine","(-)-alpha-Methyl-L-tyrosine; (–)-α-methyl-L-tyrosine; (S)-alpha-Methyltyrosine; Methyltyrosine; Metirosine; Metyrosine; α-methyl-L-p-tyrosine; α-methyl-p-tyrosine; α-methyl-para-tyrosine; α-MPT","C10H13NO3","C[C@](N)(CC1=CC=C(O)C=C1)C(O)=O","An inhibitor of the enzyme tyrosine 3-monooxygenase, and consequently of the synthesis of catecholamines. It is used to control the symptoms of excessive sympathetic stimulation in patients with pheochromocytoma. (Martindale, The Extra Pharmacopoeia, 30th ed)","672-87-7","195.2151","For use in the treatment of patients with pheochromocytoma, for preoperative preparation of patients for surgery, management of patients when surgery is contraindicated, and chronic treatment of patients with malignant pheochromocytoma.","In patients with pheochromocytoma, who produce excessive amounts of norepinephrine and epinephrine, administration of one to four grams of metyrosine per day has reduced catecholamine biosynthesis from about 35 to 80 percent as measured by the total excretion of catecholamines and their metabolites (metanephrine and vanillylmandelic acid). The maximum biochemical effect usually occurs within two to three days, and the urinary concentration of catecholamines and their metabolites usually returns to pretreatment levels within three to four days after metyrosine is discontinued. Most patients with pheochromocytoma treated with metyrosine experience decreased frequency and severity of hypertensive attacks with their associated headache, nausea, sweating, and tachycardia. In patients who respond, blood pressure decreases progressively during the first two days of therapy with metyrosine; after withdrawal, blood pressure usually increases gradually to pretreatment values within two to three days.","Metyrosine inhibits tyrosine hydroxylase, which catalyzes the first transformation in catecholamine biosynthesis, i.e., the conversion of tyrosine to dihydroxyphenylalanine (DOPA). Because the first step is also the rate-limiting step, blockade of tyrosine hydroxylase activity results in decreased endogenous levels of catecholamines and their synthesis. This consequently, depletes the levels of the catecholamines dopamine, adrenaline and noradrenaline in the body,usually measured as decreased urinary excretion of catecholamines and their metabolites. One main end result of the catecholamine depletion is a decrease in blood presure.","Tyrosine 3-monooxygenase binder","Therapeutic strategy associated"]
[272,"DB00768","approved","small molecule","Olopatadine",null,"C21H23NO3","CN(C)CC\\C=C1\\C2=CC=CC=C2COC2=C1C=C(CC(O)=O)C=C2","Olopatadine is a selective histamine H1 antagonist and mast cell stabilizer that works by attenuating inflammatory and allergic reactions. It is a structural analog of , which has a minimal anti-allergic activity. Olopatadine works by blocking the effects of histamine, which is a primary inflammatory mediator that causes inflammatory and allergic reactions. An ophthalmic solution of olopatadine was approved by the FDA and European Union for the treatment of seasonal and perennial allergic conjunctivitis in 1996 and 2002, respectively. In comparison to other anti-allergenic ophthalmic medications, olopatadine displays a good comfort and tolerability profile since it does not cause perturbation of cell membranes. Olopatadine is used for the symptomatic treatment of ocular itching associated with allergic conjunctivitis in ophthalmic formulations and seasonal allergic rhinitis in intranasal formulations. It is currently marketed under several brand names, including Pazeo, Patanase, and Opatanol.","113806-05-6","337.4122","Olopatadine is indicated for the symptomatic treatment of ocular itching associated with allergic conjunctivitis as ophthalmic solution.\r\n\r\nIn nasal spray, olopatadine is indicated for the symptomatic relief of seasonal allergic rhinitis in patients 12 years of age and older.","Inflammatory reactions in response to various stimuli are mediated by endogenous mediators and other pro-inflammatory factors. Histamine receptor activation and mast cell degranulation are primary mechanisms that cause inflammatory reactions such as ocular itching, hyperemia, chemosis, eyelid swelling, and tearing of seasonal allergic conjunctivitis. Olopatadine is an anti-allergenic molecule and mast cell stabilizer that inhibits the _in vivo_ type 1 immediate hypersensitivity reaction. By blocking the effects of histamine, olopatadine works to reduce the symptoms of allergies and inflammation at various sites of administration, including the eyes and nose. It has shown to exert antihistaminic effects in isolated tissues, animal models, and humans. Olopatadine also demonstrated dose-dependent inhibition of immunologically-stimulated release of histamine from rat basophilic leukemia cells and human conjunctival mast cells _in vitro_. Olopatadine has a relatively rapid onset of action and prolonged duration, where it was shown to mediate anti-histaminic effects at 5 minutes to 24 hours post-administration.\r\n\r\nWhile olopatadine is a non-sedating antihistamine agent, there have been reports of somnolence in some patients taking nasal olopatadine during clinical trials. Temporary blurred vision or other visual disturbances were observed following ophthalmic administration. Olopatadine has negligible effects on alpha-adrenergic, dopamine, muscarinic type 1 and 2, and serotonin receptors. In clinical trials, there was no evidence of any effect of olopatadine on QT prolongation was observed following intranasal administration.","Histamine is a biogenic vasoactive amine that binds to its receptors, which are G-protein coupled receptors. Signaling through the histamine H1 receptor is thought to primarily promote the activation of inflammatory reactions, such as allergy, asthma, and autoimmune diseases. H1 receptor signaling activates the intracellular transcription factors, such as IP3, PLC, PKC, DAG, and intracellular calcium ions, which all work to activate further downstream cascades. Activated downstream cascades lead to the production of cytokines, the release of mast cell inflammatory mediators, synthesis of prostacyclins, activation of platelet factor, as well as the synthesis of nitric oxide, arachidonic acid, and thromboxane, which all contribute to inflammatory reactions. \r\n\r\nOlopatadine is an anti-allergic molecule that works via several mechanisms. As a mast cell stabilizer, it stabilizes rodent basophils and human conjunctival mast cells and inhibits the immunologically-stimulated release of histamine. Olopatadine acts as an antagonist at the histamine H1 receptors with high selectivity, which is explained by a unique receptor binding pocket that consists of the aspartate residue in the third transmembrane helix and other sites in the H1 receptor. Upon binding, olopatadine blocks the H1 receptor signaling pathway, inhibiting the release of inflammatory mediators, such as tryptase, prostaglandin D2, TNF-alpha, as well as pro-inflammatory cytokines. It also decreases chemotaxis and inhibits eosinophil activation. _In vitro_, olopatadine was shown to inhibit epithelial cell intercellular adhesion molecule-1 (ICAM-1), which promotes the recruitment of migrating pro-inflammatory mediators.","Histamine H1 receptor antagonist; Histamine H2 receptor antagonist; Histamine H3 receptor antagonist; Protein S100-A1 antagonist; Protein S100-A12 antagonist; Protein S100-B other/unknown; Protein S100-A13 other/unknown; Protein S100-A2 antagonist","Therapeutic strategy associated"]
[273,"DB00769","approved","small molecule","Hydrocortamate","17-Hydroxycorticosterone, 21-(diethylamino)acetate; Hydrocortamate","C27H41NO6","[H][C@@]12CC[C@](O)(C(=O)COC(=O)CN(CC)CC)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C","Hydrocortamate is a synthetic glucocorticoid used for its anti-inflammatory or immunosuppressive properties to treat inflammation due to corticosteroid-responsive dermatoses. Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger a variety of important cardiovascular, metabolic, immunologic and homeostatic effects.","76-47-1","475.6175","Used topically as an antiinflammatory in the treatment of steroid-responsive dermatoses","Hydrocortamate is a synthetic glucocorticoid used for its anti-inflammatory or immunosuppressive properties to treat inflammation due to corticosteroid-responsive dermatoses. Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger a variety of important cardiovascular, metabolic, immunologic and homeostatic effects. Glucocorticoids are distinguished from mineralocorticoids and sex steroids by having different receptors, target cells, and effects. Technically, the term corticosteroid refers to both glucocorticoids and mineralocorticoids, but is often used as a synonym for glucocorticoid. Glucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-alpha, the most important of which is the IL-2. Reduced cytokine production limits T cell proliferation. Glucocorticoids also suppress humoral immunity, causing B cells to express lower amounts of IL-2 and IL-2 receptors. This diminishes both B cell clonal expansion and antibody synthesis. The diminished amounts of IL-2 also leads to fewer T lymphocyte cells being activated.","Hydrocortamate binds to the cytosolic glucocorticoid receptor. After binding the receptor the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes. The anti-inflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. The immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding.","Glucocorticoid receptor agonist","Therapeutic strategy associated"]
[274,"DB00771","approved","small molecule","Clidinium","3-(2-Hydroxy-2,2-diphenyl-acetoxy)-1-methyl-1-azonia-bicyclo[2.2.2]octane; 3-hydroxy-1-methylquinuclidinium benzilate ester; N-methyl quinuclidinyl benzilate","C22H26NO3","C[N@@+]12CC[C@@H](CC1)C(C2)OC(=O)C(O)(C1=CC=CC=C1)C1=CC=CC=C1","Clidinium is a synthetic anticholinergic agent which has been shown in experimental and clinical studies to have a pronounced antispasmodic and antisecretory effect on the gastrointestinal tract. It inhibits muscarinic actions of acetylcholine at postganglionic parasympathetic neuroeffector sites. It is used for the treatment of peptic ulcer disease and also to help relieve abdominal or stomach spasms or cramps due to colicky abdominal pain, diverticulitis, and irritable bowel syndrome.","7020-55-5","352.4467","For the treatment of peptic ulcer disease and also to help relieve abdominal or stomach spasms or cramps due to colicky abdominal pain, diverticulitis, and irritable bowel syndrome.","Clidinium is a synthetic anticholinergic agent which has been shown in experimental and clinical studies to have a pronounced antispasmodic and antisecretory effect on the gastrointestinal tract.","Inhibits muscarinic actions of acetylcholine at postganglionic parasympathetic neuroeffector sites primarily by inhibiting the M1 muscarinic receptors.","Muscarinic acetylcholine receptor M1 antagonist","Indication associated"]
[275,"DB00773","approved","small molecule","Etoposide","(−)-etoposide; 4-demethylepipodophyllotoxin β-D-ethylideneglucoside; 4'-Demethylepipodophyllotoxin 9-(4,6-O-(R)-ethylidene-beta-D-glucopyranoside); 9-((4,6-O-Ethylidine-beta-D-glucopyranosyl)oxy)-5,8,8a,9-tetrahydro-5-(4-hydroxy-3,4-dimethyloxyphenyl)furo(3',4'':6,7)naptho-(2,3-d)-1,3-dioxol-6(5aH)-one; Etoposide; trans-Etoposide","C29H32O13","[H][C@]12COC(=O)[C@]1([H])[C@H](C1=CC(OC)=C(O)C(OC)=C1)C1=CC3=C(OCO3)C=C1[C@H]2O[C@@H]1O[C@]2([H])CO[C@@H](C)O[C@@]2([H])[C@H](O)[C@H]1O","A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.","33419-42-0","588.5566","For use in combination with other chemotherapeutic agents in the treatment of refractory testicular tumors and as first line treatment in patients with small cell lung cancer. Also used to treat other malignancies such as lymphoma, non-lymphocytic leukemia, and glioblastoma multiforme.","Etoposide is an antineoplastic agent and an epipodophyllotoxin (a semisynthetic derivative of the podophyllotoxins). It inhibits DNA topoisomerase II, thereby ultimately inhibiting DNA synthesis. Etoposide is cell cycle dependent and phase specific, affecting mainly the S and G2 phases. Two different dose-dependent responses are seen. At high concentrations (10 &micro;g/mL or more), lysis of cells entering mitosis is observed. At low concentrations (0.3 to 10 &micro;g/mL), cells are inhibited from entering prophase. It does not interfere with microtubular assembly. The predominant macromolecular effect of etoposide appears to be the induction of DNA strand breaks by an interaction with DNA-topoisomerase II or the formation of free radicals.","Etoposide inhibits DNA topoisomerase II, thereby inhibiting DNA re-ligation. This causes critical errors in DNA synthesis at the premitotic stage of cell division and can lead to apoptosis of the cancer cell. Etoposide is cell cycle dependent and phase specific, affecting mainly the S and G2 phases of cell division. Inhibition of the topoisomerase II alpha isoform results in the anti-tumour activity of etoposide. The drug is also capable of inhibiting the beta isoform but inhibition of this target is not associated with the anti-tumour activity. It is instead associated with the carcinogenic effect.","DNA topoisomerase 2-alpha inhibitor; DNA topoisomerase 2-beta inhibitor","Therapeutic strategy associated"]
[276,"DB00774","approved; investigational; withdrawn","small molecule","Hydroflumethiazide","Dihydroflumethazide; Hydroflumethiazide; Idroflumetiazide; Metforylthiadiazin","C8H8F3N3O4S2","NS(=O)(=O)C1=CC2=C(NCNS2(=O)=O)C=C1C(F)(F)F","A thiazide diuretic with actions and uses similar to those of hydrochlorothiazide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p822)","135-09-1","331.292","Used as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. Also used in the management of hypertension either as the sole therapeutic agent or to enhance the effect of other antihypertensive drugs in the more severe forms of hypertension.","Hydroflumethiazide is an oral thiazide used to treat hypertension and edema. High blood pressure adds to the workload of the heart and arteries. If it continues for a long time, the heart and arteries may not function properly. This can damage the blood vessels of the brain, heart, and kidneys, resulting in a stroke, heart failure, or kidney failure. High blood pressure may also increase the risk of heart attacks. Like other thiazides, Hydroflumethiazide promotes water loss from the body (diuretics). Thiazides inhibit Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue.","Hydroflumethiazide is a thiazide diuretic that inhibits water reabsorption in the nephron by inhibiting the sodium-chloride symporter (SLC12A3) in the distal convoluted tubule, which is responsible for 5% of total sodium reabsorption. Normally, the sodium-chloride symporter transports sodium and chloride from the lumen into the epithelial cell lining the distal convoluted tubule. The energy for this is provided by a sodium gradient established by sodium-potassium ATPases on the basolateral membrane. Once sodium has entered the cell, it is transported out into the basolateral interstitium via the sodium-potassium ATPase, causing an increase in the osmolarity of the interstitium, thereby establishing an osmotic gradient for water reabsorption. By blocking the sodium-chloride symporter, Hydroflumethiazide effectively reduces the osmotic gradient and water reabsorption throughout the nephron.","Carbonic anhydrase 7 inhibitor; Carbonic anhydrase 9 inhibitor; Solute carrier family 12 member 1 inhibitor; Sodium/potassium-transporting ATPase subunit alpha-1 inducer; Calcium-activated potassium channel subunit alpha-1 inducer; Carbonic anhydrase 1 inhibitor; Carbonic anhydrase 2 inhibitor; Carbonic anhydrase 4 inhibitor; Carbonic anhydrase 12 inhibitor","Indication associated"]
[277,"DB00775","approved","small molecule","Tirofiban","(2S)-2-(butylsulfonylamino)-3-[4-(4-piperidin-4-ylbutoxy)phenyl]propanoic acid; N-(Butylsulfonyl)-O-(4-(4-piperidyl)butyl)-L-tyrosine","C22H36N2O5S","CCCCS(=O)(=O)N[C@@H](CC1=CC=C(OCCCCC2CCNCC2)C=C1)C(O)=O","Tirofiban prevents the blood from clotting during episodes of chest pain or a heart attack, or while the patient is undergoing a procedure to treat a blocked coronary artery. It is a non-peptide reversible antagonist of the platelet glycoprotein (GP) IIb/IIIa receptor, and inhibits platelet aggregation.","144494-65-5","440.597","For treatment, in combination with heparin, of acute coronary syndrome, including patients who are to be managed medically and those undergoing PTCA or atherectomy.","Tirofiban prevents the blood from clotting during episodes of chest pain or a heart attack, or while the patient is undergoing a procedure to treat a blocked coronary artery. It is a non-peptide antagonist of the platelet glycoprotein (GP) IIb/IIIa receptor, and inhibits platelet aggregation. When administered intravenously, tirofiban inhibits ex vivo platelet aggregation in a dose- and concentration-dependent manner. When given according to the recommended regimen, >90% inhibition is attained by the end of the 30-minute infusion. Tirofiban has been recently shown in patients with unstable angina to reduce ischemic events at 48 hours following infusion when compared to standard heparin therapy.","Tirofiban is a reversible antagonist of fibrinogen binding to the GP IIb/IIIa receptor, the major platelet surface receptor involved in platelet aggregation. Platelet aggregation inhibition is reversible following cessation of the infusion of tirofiban.","Integrin alpha-IIb antagonist; Integrin beta-3 antagonist","Therapeutic strategy associated"]
[278,"DB00780","approved","small molecule","Phenelzine","Phenelzine","C8H12N2","NNCCC1=CC=CC=C1","Phenelzine, with the formula β-phenylethylhydrazine, is a monoamine oxidase inhibiting antidepressant that is effective in the treatment of panic disorder and social anxiety disorder. It was developed by Parke Davis and originally FDA approved on June 9th, 1961. It is currently approved under prescription by the name of Nardil.","51-71-8","136.1943","Phenelzine is indicated for the treatment of nonendogenous, neurotic or atypical depression for patients that do not tolerate other forms of therapy. \r\n\r\nAtypical depression has a high prevalence rate, starts in early life, tends to last longer, is more likely to occur in people with bipolar disorder, has a high comorbidity with anxiety disorder and carries more risk of suicidal behavior. It is important to specify the atypical feature to predict the clinical course of depression and hence generate the best treatment and service. The featuring symptoms of the atypical feature include mood reactivity, two or more of this symptoms: 1) increased appetite, 2) increased sleep, 3) leaden paralysis and 4) interpersonal rejection sensitivity and should not have melancholic or catatonic features of depression.\r\n\r\nNeurotic depression is a depression of an emotionally unstable person. It is a secondary condition to major personality disorder, neuroses and drug use disorders. Likewise, a primary depression with a family history of depression spectrum disease would fit in this category.\r\n\r\nA nonendogenous depression is characterized by a disturbance in mood and general outlook. The physical symptoms tend to be less severe and it often occurs in response to stressful life events that keep occurring over a large period of time generating a continuous stress in the daily living.","The elimination of monoamine oxidase by phenelzine results in the elevation of brain amines such as 2-phenylethylamine which is a metabolite of phenelzine. These amines have then marked effects on the uptake and release of catecholamines and serotonin in nerve endings. Phenelzine is shown to elevate brain levels of the gamma-aminobutyric acid (GABA) and alanine (ALA) as well as to inhibit the activity of the transaminases that normally metabolize these amino acids. In preclinical studies, it has been shown to be neuroprotective in cerebral ischemia.","The basic mechanism of action of phenelzine acts as an inhibitor and substrate of monoamine oxidase which subsequently causes an elevation in brain levels of catecholamines and serotonin. It also presents a similar structure to amphetamine which explains the effect on the uptake and release of dopamine, noradrenaline, and serotonin. Phenelzine has been reported to inhibit tyrosine aminotransferase, aromatic amino acid decarboxylase, and dopamine B-hydroxylase.","Amine oxidase [flavin-containing] A antagonist; Amine oxidase [flavin-containing] B antagonist; Membrane primary amine oxidase inhibitor; 4-aminobutyrate aminotransferase, mitochondrial inhibitor; Alanine aminotransferase 1 inhibitor; Alanine aminotransferase 2 inhibitor; Glutamic acid decarboxylase inhibitor","Indication associated"]
[279,"DB00784","approved","small molecule","Mefenamic acid","Mefenamic acid; N-(2,3-xylyl)-2-aminobenzoic acid; N-2,3-xylylanthranilic acid","C15H15NO2","CC1=C(C)C(NC2=CC=CC=C2C(O)=O)=CC=C1","A non-steroidal anti-inflammatory agent with analgesic, anti-inflammatory, and antipyretic properties. It is an inhibitor of cyclooxygenase.","61-68-7","241.2851","For the treatment of rheumatoid arthritis, osteoarthritis, dysmenorrhea, and mild to moderate pain, inflammation, and fever.","Mefenamic acid, an anthranilic acid derivative, is a member of the fenamate group of nonsteroidal anti-inflammatory drugs (NSAIDs). It exhibits anti-inflammatory, analgesic, and antipyretic activities. Similar to other NSAIDs, mefenamic acid inhibits prostaglandin synthetase.","Mefenamic acid binds the prostaglandin synthetase receptors COX-1 and COX-2, inhibiting the action of prostaglandin synthetase. As these receptors have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity, the symptoms of pain are temporarily reduced.","Prostaglandin G/H synthase 2 inhibitor; Prostaglandin G/H synthase 1 inhibitor","Therapeutic strategy associated"]
[280,"DB00785","approved","small molecule","Cryptenamine",{"$nulls":3},"Cryptenamine is a mixture of closely related hypotensive alkaloids from Veratrum album (Liliaceae). It has been used in the treatment of hypertension but has largely been replaced by drugs with fewer adverse effects. Cryptenamine has a marked and re-producible depressor effect when given intravenously to hypertensive patients, however the mechanism of action is not known.","1356-18-9",null,"For the treatment of hypertension.","Cryptenamine is a mixture of closely related hypotensive alkaloids from <i>Veratrum album</i> (Liliaceae). It has been used in the treatment of hypertension but has largely been replaced by drugs with fewer adverse effects.","Cryptenamine has a marked and re-producible depressor effect when given intravenously to hypertensive patients, however the mechanism of action is not known. Some evidence has suggested that cryptenamine acts in a similar fashion to atropine, which lowers the \"rest and digest\" activity of all muscles and glands regulated by the parasympathetic nervous system. This occurs because atropine is a competitive inhibitor of the muscarinic acetylcholine receptors (acetylcholine is the neurotransmitter used by the parasympathetic nervous system). Therefore muscarinic acetylcholine receptors will be listed as experimental targets for cryptenamine.","Muscarinic acetylcholine receptor M2 antagonist; Beta adrenergic receptor inhibitor&potentiator","Therapeutic strategy associated"]
[281,"DB00788","approved; vet_approved","small molecule","Naproxen","(+)-(S)-6-Methoxy-α-methyl-2-naphthaleneacetic acid; (+)-(S)-Naproxen; (+)-2-(6-Methoxy-2-naphthyl)propionic acid; (+)-2-(Methoxy-2-naphthyl)-propionic acid; (+)-Naproxen; (S)-(+)-2-(6-Methoxy-2-naphthyl)propionic acid; (S)-(+)-Naproxen; (S)-2-(6-Methoxy-2-naphthyl)propanoic acid; (S)-2-(6-Methoxy-2-naphthyl)propionic acid; (S)-6-Methoxy-alpha-methyl-2-naphthaleneacetic acid; (S)-Naproxen; Naprolag","C14H14O3","COC1=CC2=C(C=C1)C=C(C=C2)[C@H](C)C(O)=O","Naproxen is classified as a nonsteroidal anti-inflammatory dug (NSAID) and was initially approved for prescription use in 1976 and then for over-the-counter (OTC) use in 1994. It can effectively manage acute pain as well as pain related to rheumatic diseases, and has a well studied adverse effect profile. Given its overall tolerability and effectiveness, naproxen can be considered a first line treatment for a variety of clinical situations requiring analgesia. Naproxen is available in both immediate and delayed release formulations, in combination with sumatriptan to treat migraines, and in combination with esomeprazole to lower the risk of developing gastric ulcers.","22204-53-1","230.2592","Naproxen is indicated for the management of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, polyarticular juvenile idiopathic arthritis, tendinitis, bursitis, acute gout, primary dysmenorrhea, and for the relief of mild to moderate pain. Further, it is first-line therapy for osteoarthritis, acute gouty arthritis, dysmenorrhea, and musculoskeletal inflammation and pain.","Naproxen is an established non-selective NSAID and is useful as an analgesic, anti-inflammatory and antipyretic. Similar to other NSAIDs, the pharmacological activity of naproxen can be attributed to the inhibition of cyclo-oxygenase, which in turn reduces prostaglandin synthesis in various tissues and fluids including the synovial fluid, gastric mucosa, and the blood. \r\n\r\nAlthough naproxen is an effective analgesic, it can have unintended deleterious effects in the patient. For instance, naproxen can adversely affect blood pressure control. A study found that use of naproxen induced an increase in blood pressure, although the increase was not as significant as that found with ibuprofen use.\r\n\r\nFurther, studies have found that the risk of upper gastrointestinal bleeding is on average four-fold higher for individuals taking NSAIDs. Other factors that increase the risk of upper gastrointestinal bleeding include concurrent use of corticosteroids or anticoagulants, and a history of gastrointestinal ulcers.","As with other non-selective NSAIDs, naproxen exerts it's clinical effects by blocking COX-1 and COX-2 enzymes leading to decreased prostaglandin synthesis. Although both enzymes contribute to prostaglandin production, they have unique functional differences. The COX-1 enzymes is constitutively active and can be found in normal tissues such as the stomach lining, while the COX-2 enzyme is inducible and produces prostaglandins that mediate pain, fever and inflammation. The COX-2 enzyme mediates the desired antipyretic, analgesic and anti-inflammatory properties offered by Naproxen, while undesired adverse effects such as gastrointestinal upset and renal toxicities are linked to the COX-1 enzyme.","Prostaglandin G/H synthase 1 inhibitor; Peptostreptococcal albumin-binding protein; Prostaglandin G/H synthase 2 inhibitor","Therapeutic strategy associated"]
[282,"DB00795","approved","small molecule","Sulfasalazine","2-Hydroxy-5-((4-((2-pyridinylamino)sulfonyl)phenyl)azo)benzoic acid; 2-Hydroxy-5-[4-(pyridin-2-ylsulfamoyl)-phenylazo]-benzoic acid; 4-(Pyridyl-2-amidosulfonyl)-3'-carboxy-4'-hydroxyazobenzene; 5-((p-(2-Pyridylsulfamoyl)phenyl)azo)salicylic acid; 5-(4-(2-Pyridylsulfamoyl)phenylazo)-2-hydroxybenzoic acid; 5-(p-(2-Pyridylsulfamyl)phenylazo)salicylic acid; Azopyrin; Salazosulfapyridine; Salicylazosulfapyridine; Sulfasalazine","C18H14N4O5S","OC(=O)C1=CC(=CC=C1O)\\N=N\\C1=CC=C(C=C1)S(=O)(=O)NC1=NC=CC=C1","A drug that is used in the management of inflammatory bowel diseases. Its activity is generally considered to lie in its metabolic breakdown product, 5-aminosalicylic acid (see mesalamine) released in the colon. (From Martindale, The Extra Pharmacopoeia, 30th ed, p907)","599-79-1","398.393","For the treatment of Crohn's disease and rheumatoid arthritis as a second-line agent.","Sulfasalazine is an anti-inflammatory indicated for the treatment of ulcerative colitis and rheumatoid arthritis.","The mode of action of Sulfasalazine or its metabolites, 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP), is still under investigation, but may be related to the anti-inflammatory and/or immunomodulatory properties that have been observed in animal and <i>in vitro</i> models, to its affinity for connective tissue, and/or to the relatively high concentration it reaches in serous fluids, the liver and intestinal walls, as demonstrated in autoradiographic studies in animals. In ulcerative colitis, clinical studies utilizing rectal administration of Sulfasalazine, SP and 5-ASA have indicated that the major therapeutic action may reside in the 5-ASA moiety. The relative contribution of the parent drug and the major metabolites in rheumatoid arthritis is unknown.","Arachidonate 5-lipoxygenase inhibitor; Prostaglandin G/H synthase 2 inhibitor; Prostaglandin G/H synthase 1 inhibitor; Peroxisome proliferator-activated receptor gamma agonist; Inhibitor of nuclear factor kappa-B kinase subunit alpha inhibitor; Inhibitor of nuclear factor kappa-B kinase subunit beta inhibitor; Cystine/glutamate transporter inhibitor; Acetyl-CoA acetyltransferase, mitochondrial inhibitor; Thromboxane-A synthase antagonist; Phospholipase A2 antagonist","Therapeutic strategy associated"]
[283,"DB00796","approved","small molecule","Candesartan cilexetil","Candesartan cilexetil","C33H34N6O6","CCOC1=NC2=C(N1CC1=CC=C(C=C1)C1=CC=CC=C1C1=NN=NN1)C(=CC=C2)C(=O)OC(C)OC(=O)OC1CCCCC1","Candesartan is an angiotensin-receptor blocker (ARB) that may be used alone or with other agents to treat hypertension. It is administered orally as the prodrug, candesartan cilexetil, which is rapidly converted to its active metabolite, candesartan, during absorption in the gastrointestinal tract. Candesartan lowers blood pressure by antagonizing the renin-angiotensin-aldosterone system (RAAS); it competes with angiotensin II for binding to the type-1 angiotensin II receptor (AT1) subtype and prevents the blood pressure increasing effects of angiotensin II. Unlike angiotensin-converting enzyme (ACE) inhibitors, ARBs do not have the adverse effect of dry cough. Candesartan may be used to treat hypertension, isolated systolic hypertension, left ventricular hypertrophy and diabetic nephropathy. It may also be used as an alternative agent for the treatment of heart failure, systolic dysfunction, myocardial infarction and coronary artery disease.","145040-37-5","610.671","May be used as a first line agent to treat uncomplicated hypertension, isolated systolic hypertension and left ventricular hypertrophy. May be used as a first line agent to delay progression of diabetic nephropathy. Candesartan may be also used as a second line agent in the treatment of congestive heart failure, systolic dysfunction, myocardial infarction and coronary artery disease in those intolerant of ACE inhibitors.","Candesartan cilexetil is an ARB prodrug that is rapidly converted to candesartan, its active metabolite, during absorption from the gastrointestinal tract. Candesartan confers blood pressure lowering effects by antagonizing the hypertensive effects of angiotensin II via the RAAS. RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from granular cells of the juxtaglomerular apparatus in the kidneys. Renin cleaves circulating angiotensinogen to angiotensin I, which is cleaved by angiotensin converting enzyme (ACE) to angiotensin II. Angiotensin II increases blood pressure by increasing total peripheral resistance, increasing sodium and water reabsorption in the kidneys via aldosterone secretion, and altering cardiovascular structure. Angiotensin II binds to two receptors: type-1 angiotensin II receptor (AT1) and type-2 angiotensin II receptor (AT2). AT1 is a G-protein coupled receptor (GPCR) that mediates the vasoconstrictive and aldosterone-secreting effects of angiotensin II. Studies performed in recent years suggest that AT2 antagonizes AT1-mediated effects and directly affects long-term blood pressure control by inducing vasorelaxation and increasing urinary sodium excretion. Angiotensin receptor blockers (ARBs) are non-peptide competitive inhibitors of AT1. ARBs block the ability of angiotensin II to stimulate pressor and cell proliferative effects. Unlike ACE inhibitors, ARBs do not affect bradykinin-induced vasodilation. The overall effect of ARBs is a decrease in blood pressure.","Candesartan selectively blocks the binding of angiotensin II to AT1 in many tissues including vascular smooth muscle and the adrenal glands. This inhibits the AT1-mediated vasoconstrictive and aldosterone-secreting effects of angiotensin II and results in an overall decrease in blood pressure. Candesartan is greater than 10,000 times more selective for AT1 than AT2. Inhibition of aldosterone secretion may increase sodium and water excretion while decreasing potassium excretion.","Type-1 angiotensin II receptor antagonist","Target associated"]
[284,"DB00800","approved","small molecule","Fenoldopam",null,"C16H16ClNO3","OC1=CC=C(C=C1)C1CNCCC2=C(Cl)C(O)=C(O)C=C12","A dopamine D1 receptor agonist that is used as an antihypertensive agent. It lowers blood pressure through arteriolar vasodilation.","67227-56-9","305.756","For the in-hospital, short-term (up to 48 hours) management of severe hypertension when rapid, but quickly reversible, emergency reduction of blood pressure is clinically indicated, including malignant hypertension with deteriorating end-organ function.","Fenoldopam is an agonist at D<sub>1</sub>-like dopamine receptors, binds to &alpha;<sub>2</sub>-adrenoceptors, increasing renal blood flow.","Fenoldopam is a rapid-acting vasodilator. It is an agonist for D<sub>1</sub>-like dopamine receptors and binds with moderate affinity to &alpha;<sub>2</sub>-adrenoceptors. It has no significant affinity for D<sub>2</sub>-like receptors, &alpha;<sub>1</sub> and &beta;-adrenoceptors, 5<sub>HT1</sub> and 5<sub>HT2</sub> receptors, or muscarinic receptors. Fenoldopam is a racemic mixture with the R-isomer responsible for the biological activity. The R-isomer has approximately 250-fold higher affinity for D<sub>1</sub>-like receptors than does the S-isomer. In non-clinical studies, fenoldopam had no agonist effect on presynaptic D<sub>2</sub>-like dopamine receptors, or &alpha; or &beta; -adrenoceptors, nor did it affect angiotensin-converting enzyme activity. Fenoldopam may increase norepinephrine plasma concentration.","Dopamine D5 receptor agonist; Dopamine D1 receptor agonist; Alpha-2B adrenergic receptor antagonist; Alpha-2C adrenergic receptor antagonist; Alpha-2A adrenergic receptor antagonist; Alpha-1B adrenergic receptor inhibitor; Alpha-1D adrenergic receptor inhibitor; Alpha-1A adrenergic receptor inhibitor","Indication associated"]
[285,"DB00803","approved","small molecule","Colistin","Colimycin; Kolimycin; Polymyxin E","C52H98N16O13","CCC(C)CCCC(=O)N[C@@H](CCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)C(NC(=O)[C@@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC1=O)[C@@H](C)O","Cyclic polypeptide antibiotic from Bacillus colistinus. It is composed of Polymyxins E1 and E2 (or Colistins A, B, and C) which act as detergents on cell membranes. Colistin is less toxic than Polymyxin B, but otherwise similar; the methanesulfonate is used orally.","1066-17-7","1155.455","For the treatment of acute or chronic infections due to sensitive strains of certain gram-negative bacilli, particularly <i>Pseudomonas aeruginosa</i>.","Colistin is a polymyxin antibiotic agent. Polymyxins are cationic polypeptides that disrupt the bacterial cell membrane through a detergentlike mechanism. With the development of less toxic agents, such as extended-spectrum penicillins and cephalosporins, parenteral polymyxin use was largely abandoned, except for the treatment of multidrug-resistant pulmonary infections in patients with cystic fibrosis. More recently, however, the emergence of multidrug-resistant gram-negative bacteria, such as <i>Pseudomonas aeruginosa</i> and <i>Acinetobacter baumannii</i>, and the lack of new antimicrobial agents have led to the revived use of the polymyxins.","Colistin is a surface active agent which penetrates into and disrupts the bacterial cell membrane. Colistin is polycationic and has both hydrophobic and lipophilic moieties. It interacts with the bacterial cytoplasmic membrane, changing its permeability. This effect is bactericidal. There is also evidence that polymyxins enter the cell and precipitate cytoplasmic components, primarily ribosomes.","Bacterial outer membrane incorporation into and destabilization","Therapeutic strategy associated"]
[286,"DB00804","approved","small molecule","Dicyclomine","2-(diethylamino)ethyl 1-cyclohexylcyclohexanecarboxylate; Bicyclohexyl-1-carboxylic acid 2-diethylamino-ethyl ester; Dicyclomine; Dicycloverin; Dicycloverine","C19H35NO2","CCN(CC)CCOC(=O)C1(CCCCC1)C1CCCCC1","Dicyclomine is a muscarinic M1, M3, and M2 receptor antagonist as well as a non-competitive inhibitor of histamine and bradykinin used to treat spasms of the intestines seen in functional bowel disorder and irritable bowel syndrome. Though it is commonly prescribed, its recommendation may have been based on a small amount of evidence and so its prescription is becoming less favourable.\r\n\r\nDicyclomine was granted FDA approval on 11 May 1950.","77-19-0","309.4867","Dicyclomine is indicated for the treatment of functional bowel disorder and irritable bowel syndrome.","Dicyclomine is an anticholinergic drug used to relax the smooth muscles of the intestines. It's duration of action is not especially long as it is usually taken 4 times daily with individual doses of 20-40mg orally or 10-20mg by intramuscular injection. Dicyclomine should not be administered intravenously.","Dicyclomine achieves its action partially through direct antimuscarinic activity of the M1, M3, and M2 receptors; and partially through antagonism of bradykinin and histamine. Dicyclomine non-competitively inhibits the action of bradykinin and histamine, resulting in direct action on the smooth muscle, and decreased strength of contractions seen in spasms of the ileum.","Muscarinic acetylcholine receptor M1 antagonist; Muscarinic acetylcholine receptor M3 antagonist; Muscarinic acetylcholine receptor M2 antagonist","Indication associated"]
[287,"DB00805","approved","small molecule","Minaprine","4-(2-((4-Methyl-6-phenyl-3-pyridazinyl)amino)ethyl)morpholine; 4-Methyl-3-(2-morpholinoethylamino)-6-phenylpyridazin; Minaprine; N-(4-Methyl-6-phenyl-3-pyridazinyl)-4-morpholineethanamine","C17H22N4O","CC1=CC(=NN=C1NCCN1CCOCC1)C1=CC=CC=C1","Minaprine is a psychotropic drug which has proved to be effective in the treatment of various depressive states. Like most antidepressants minaprine antagonizes behavioral despair. Minaprine  is an amino-phenylpyridazine antidepressant reported to be relatively free of cardiotoxicity, drowsiness, and weight gain.","25905-77-5","298.3828","For the treatment of depression","Minaprine is an amino-phenylpyridazine antidepressant reported to be relatively free of cardiotoxicity, drowsiness, and weight gain. Similar to other antidepressant treatments, minaprine attenuates the beta-adrenergic receptor function. Studies have also shown that minaprine improves memory consolidation and that repeated drug administration leads to potentiation of this effect. Moreover, the effects of minaprine on memory consolidation are related to its dopaminergic action.","Minaprine binds to serotonin type 2 receptors and to dopamine D1 and D2 type receptors. It also binds to the serotonin reuptake pump. Therefore, minaprine blocks the reuptake of both dopamine and serotonin. It is also, to a slight degree, cholinomimetic. Thus it may exhibit both mood-brightening and nootropic properties. It also acts as a reversible inhibitor of MAO-A (RIMA).It has also been found to inhibit acetylcholinesterase.","Amine oxidase [flavin-containing] A inhibitor; 5-hydroxytryptamine receptor 2B antagonist; 5-hydroxytryptamine receptor 2A antagonist; 5-hydroxytryptamine receptor 2C antagonist; Acetylcholinesterase inhibitor; Sodium-dependent serotonin transporter inhibitor; Dopamine D1 receptor agonist; Dopamine D2 receptor agonist; Muscarinic acetylcholine receptor M1 agonist","Indication associated"]
[288,"DB00808","approved","small molecule","Indapamide","Metindamide","C16H16ClN3O3S","CC1CC2=CC=CC=C2N1NC(=O)C1=CC(=C(Cl)C=C1)S(N)(=O)=O","The most significant modifiable risk factor for cardiovascular disease and the most prominent contributor to all-cause mortality is hypertension. Characterized by an office blood pressure of ≥140/90, hypertension is pervasive and impacts an estimated 25% of adults globally. Treatment for hypertension should include a number of lifestyle changes (ie. reduced sodium intake) along with pharmacotherapy - it should be noted that treatment with several antihypertensive agents may be required in order to achieve blood pressure targets.\r\n\r\nThiazide-like diuretics such as indapamide are a valuable tool for the treatment of hypertension and continue to grow in popularity, falling behind only ACE inhibitors in terms of prescription frequency. When compared to  (another commonly prescribed diuretic), indapamide has been shown to be superior at lowering systolic blood pressure, reducing left ventricular mass index, lowering oxidative stress, inhibiting platelet aggregation, and reducing microalbuminuria associated with diabetes. Interestingly, unlike thiazide diuretics, several sources suggest that indapamide is not associated with glucose or lipid disturbances. \r\n\r\nIndapamide is characterized by both a methylindoline and a sulfamoyl chlorobenzamide functional group, with the former being largely responsible for the molecule’s lipid solubility.","26807-65-8","365.835","Indapamide is a diuretic indicated for use as monotherapy or in combination with other blood pressure-lowering agents to treat hypertension. It may also be used to treat fluid and salt retention associated with congestive heart failure.\r","Classified as a sulfonamide diuretic, indapamide is an effective antihypertensive agent and by extension, has shown efficacy in the prevention of target organ damage.\r\nAdministration of indapamide produces water and electrolyte loss, with higher doses associated with increased diuresis. Severe and clinically significant electrolyte disturbances may occur with indapamide use - for example, hypokalemia resulting from renal potassium loss may lead to QTc prolongation. Further electrolyte imbalances may occur due to renal excretion of sodium, chloride, and magnesium. \r\n\r\nOther indapamide induced changes include increases in plasma renin and aldosterone, and reduced calcium excretion in the urine. In many studies investigating the effects of indapamide in both non-diabetic and diabetic hypertensive patients, glucose tolerance was not significantly altered. However, additional studies are necessary to assess the long term metabolic impacts of indapamide, since thiazide related impaired glucose tolerance can take several years to develop in non-diabetic patients.","Indapamide acts on the nephron, specifically at the proximal segment of the distal convoluted tubule where it inhibits the Na+/Cl- cotransporter, leading to reduced sodium reabsorption. As a result, sodium and water are retained in the lumen of the nephron for urinary excretion. The effects that follow include reduced plasma volume, reduced venous return, lower cardiac output, and ultimately decreased blood pressure.\r\n\r\nInterestingly, it is likely that thiazide-like diuretics such as indapamide have additional blood pressure lowering mechanisms that are unrelated to diuresis. This is exemplified by the observation that the antihypertensive effects of thiazides are sustained 4-6 weeks after initiation of therapy, despite recovering plasma and extracellular fluid volumes. \r\n\r\nSome studies have suggested that indapamide may decrease responsiveness to pressor agents while others have suggested it can decrease peripheral resistance. Although it is clear that diuresis contributes to the antihypertensive effects of indapamide, further studies are needed to investigate the medication’s ability to decrease peripheral vascular resistance and relax vascular smooth muscle.","Solute carrier family 12 member 3 inhibitor","Therapeutic strategy associated"]
[289,"DB00811","approved","small molecule","Ribavirin","1-beta-D-Ribofuranosyl-1,2,4-triazole-3-carboxamide; 1-beta-D-Ribofuranosyl-1H-1,2,4-triazole-3-carboxamide; RBV; Tribavirin","C8H12N4O5","NC(=O)C1=NN(C=N1)[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O","Producing a broad-spectrum activity against several RNA and DNA viruses, Ribavirin is a synthetic guanosine nucleoside and antiviral agent that interferes with the synthesis of viral mRNA. It is primarily indicated for use in treating hepatitis C and viral hemorrhagic fevers. HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients . It is reported that ribavirin might be only effective in early stages of viral hemorrhagic fevers including Lasser fever, Crimean-Congo hemorrhagic fever, Venezuelan hemorrhagic fever, and Hantavirus infection. Ribavirin is a prodrug that is metabolized into nucleoside analogs that blocks viral RNA synthesis and viral mRNA capping. Before the development of newer drugs, ribavirin and / dual therapy was considered the first-generation and standard antiviral treatment . The dual therapy was administered for 48 weeks in patients with genotype 1, 4, 5, and 6, and 24 weeks in patients with genotype 2 and 3 . Newer drugs developed as Hepatitis C viral infection treatments can be used to reduce or eliminate the use of ribavirin, which are associated with serious adverse effects. They also improve therapeutic efficacy in patients with failed / and ribavirin-based therapy. The potential use of ribavirin as a treatment for acute myeloid leukemia is currently under investigation.\r\n\r\nAccording to 2017 American Association for the Study of Liver Diseases (AASLD) and 2015 consensus guidelines from the Canadian Association for the Study of the Liver (CASL), ribavirin is typically used as an adjunct therapy to various first-line and second-line combination therapies recommended for each genotypes. Ribavirin is added to decrease relapse rates by accelerating viral clearance early in the treatment course . When used to treat Hepatitis C virus (HCV) infections, it is always used as a part of combination therapies as ribavirin monotherapy is not efficacious in the treatment of chronic hepatitis C infection . Additionally, including ribavirin in the regimen can increase the risk of anemia. \r\n\r\nIn HCV genotye 1/2/3/4/5/6 patients, ribavirin can be used in combination therapy involving  and , Eplusa (, ), Harvoni (, ),  and , Viekira Pak (, , , ), Technivie (, , ) and Zepatier (, ). Addition of weight-based ribavirin to Technivie therapy increased sustained virologic response after 12 weeks of daily therapy (SVR12) from 90% to 97% in patients with HCV genotype 1a and 90.9% to 100% in HCV genotype 4 patients . Zepatier therapy along with ribavirin improved SVR in HCV genotype 5 patients. Combination therapy of ribavirin and  results in the SVR of 44% in patients with genotype 1 infection and 70% in patients with genotype 2-6. The inclusion of ribavirin in the combination therapies depend on individual patient's profile, for example if HCV genotype 3 patient has a Y93H genetic variant and compensated cirrhosis.","36791-04-5","244.2047","Indicated for the treatment of chronic Hepatitis C virus (HCV) infection in combination with other antiviral agents with the intent to cure or achieve a sustained virologic response (SVR). Typically added to improve SVR and reduce relapse rates .\r\n\r\nThe addition of ribavirin in Technivie therapy indicated for treating HCV genotype 1a and 4 infections is recommended in patients with or without cirrhosis. \r\n\r\nResistance: viral genetic determinants resulting in variable response to ribavirin therapy has not been yet determined.","Ribavirin mediates direct antiviral activity against a number of DNA and RNA viruses by increasing the mutation frequency in the genomes of several RNA viruses. It is a member of the nucleoside antimetabolite drugs that interfere with duplication of the viral genetic material. The drug inhibits the activity of the enzyme RNA dependent RNA polymerase, due to its resemblence to building blocks of the RNA molecules.","Ribavirin is reported to have several mechanism of actions that lead to inhibition of viral RNA and protein synthesis. \r\nAfter activation by adenosine kinase to ribavirin mono-, di-, and triphosphate metabolites. Ribavirin triphosphate (RTP) is the predominant metabolite which directly inhibits viral mRNA polymerase by binding to the nucleotide binding site of the enzyme. This prevents the binding of the correct nucleotides, leading to a reduction in viral replication or to the production of defective virions . RTP also demonstrates an inhibitory action on viral mRNA guanylyltransferase and mRNA 2′-O-methyltransferase of dengue virus. Inhibition of these enzymes disrupts the posttranslational capping of the 5′ end of viral mRNA through ribavirin being incorporated at the 5′ end in place of guanosine and preventing the cap methylation step. \r\n\r\nInhibition of host inosine monophosphate dehydrogenase (IMPDH) and subsequent depletion of GTP pool is proposed to be another mechanism of action of ribavirin. IMPDH catalyzes the rate-limiting step where inosine 5′-monophosphate is converted to xanthine monophosphate during guanosine monophosphate (GMP) synthesis. GMP is later converted to guanosine triphoshpate (GTP). Ribavirin monophosphate mimics inosine 5′-monophosphate and acts as a competitive inhibitor of IMPDH. Inhibited de novo synthesis of guanine nucleotides and decreased intracellular GTP pools leads to a decline in viral protein synthesis and limit replication of viral genomes .\r\n\r\nRibavirin acts as a mutagen in the target virus to cause an 'error catastrophe' due to increased viral mutations. RTP pairs with cytidine triphosphate or uridine triphosphate with equal efficiency and to block HCV RNA elongation. It causes premature termination of nascent HCV RNA and increases mutagenesis by producing defective virions .\r\n\r\nRibavirin also exerts an immunomodulatory action of the host to the virus by shifting a Th2 response in favor of a Th1 phenotype. Th2 response and production of type 2 cytokines such as IL-4, IL-5, and IL-10 stimulates the humoral response which enhances immunity toward the virus . Ribavirin enhanced induction of interferon-related genes, including the interferon-α receptor, and down-regulation of genes involved in interferon inhibition, apoptosis, and hepatic stellate cell activation in vitro .","Inosine-5'-monophosphate dehydrogenase 1 inhibitor; Inosine-5'-monophosphate dehydrogenase 2; RNA-directed RNA polymerase L antagonist; RNA-directed RNA polymerase catalytic subunit inhibitor; Genome polyprotein inhibitor","Therapeutic strategy associated"]
[290,"DB00812","approved; vet_approved","small molecule","Phenylbutazone","3,5-Dioxo-1,2-diphenyl-4-n-butylpyrazolidine; 4-butyl-1,2-diphenyl-pyrazolidine-3,5-dione; 4-n-Butyl-1,2-diphenyl-3,5-pyrazolidinedione; Phenbutazone; Phenylbutazone","C19H20N2O2","CCCCC1C(=O)N(N(C1=O)C1=CC=CC=C1)C1=CC=CC=C1","A drug that has anti-inflammatory, antipyretic, and analgesic activities. It is especially effective in the treatment of ankylosing spondylitis. It also is useful in rheumatoid arthritis and Reiter&#39;s syndrome (investigational indication). Although phenylbutazone is effective in gouty arthritis, risk/benefit considerations indicate that this drug should not be employed for this disease. (From AMA Drug Evaluations Annual, 1994, p1822)","50-33-9","308.3743","For the treatment of backache and ankylosing spondylitis","Phenylbutazone is a synthetic, pyrazolone derivative. It is a nonhormonal anti-inflammatory, antipyretic compound useful in the management of inflammatory conditions. The apparent analgesic effect is probably related mainly to the compound's anti-inflammatory properties and arise from its ability to reduce production of prostaglandin H and prostacyclin. Prostaglandins act on a variety of cells such as vascular smooth muscle cells causing constriction or dilation, on platelets causing aggregation or disaggregation and on spinal neurons causing pain. Prostacylcin causes vascular constriction platelet disaggregation","Phenylbutazone binds to and inactivates prostaglandin H synthase and prostacyclin synthase through peroxide (H2O2) mediated deactivation. The reduced production of prostaglandin leads to reduced inflammation of the surrounding tissues.","Prostaglandin G/H synthase 2 inhibitor; Prostacyclin synthase inhibitor; Prostaglandin G/H synthase 1 inhibitor","Therapeutic strategy associated"]
[291,"DB00814","approved; vet_approved","small molecule","Meloxicam",null,"C14H13N3O4S2","CN1C(C(=O)NC2=NC=C(C)S2)=C(O)C2=C(C=CC=C2)S1(=O)=O","Meloxicam is a nonsteroidal anti-inflammatory drug (NSAID) used to relieve various types of pain, including pain caused by musculoskeletal conditions, osteoarthritis, and rheumatoid arthritis. With a longer half-life than most other NSAIDS, it is a favorable option for those who require once-daily dosing. Meloxicam is available in oral, transdermal, and intravenous formulations. It is a preferential COX-2 inhibitor, purportedly reducing the risk of adverse gastrointestinal tract effects, however, this is a topic of controversy.","71125-38-7","351.401","Meloxicam is indicated for the symptomatic treatment of arthritis and osteoarthritis.  In addition, it is indicated for the pauciarticular and polyarticular course of Juvenile Rheumatoid Arthritis (JRA) in patients aged 2 years old or above. Off-label uses include  the treatment of dental or post-surgical pain. In addition to the above, meloxicam has also been studied in the treatment of neuropathic pain. \r\n\r\nMeloxicam, together with the local anesthetic , is indicated for the production of postsurgical analgesia in adult patients for up to 72 hours following bunionectomy, open inguinal herniorrhaphy or total knee arthroplasty.","Meloxicam is an anti-inflammatory, analgesic analgesic with antipyretic effects in fever. Prostaglandins are substances that contribute to inflammation. This drug also exerts preferential actions against COX-2, which may reduce the possible gastrointestinal effects of this drug.  \r\n\r\nIn humans, meloxicam has demonstrated the ability to decrease erythrocyte sedimentation rate(ESR) in patients with rheumatoid arthritis, and to decrease ESR, C-reactive protein (CRP), as well as  aquaporin-1 expression. As with other NSAIDS, prolonged use of meloxicum can result in renal or cardiovascular impairment or thrombotic cardiovascular events.\r\n\r\nA note on gastrointestinal effects\r\n\r\nAs meloxicam preferentially inhibits COX-2, it is thought to cause less gastrointestinal irritation compared to other NSAIDS. Despite this, it still carries a risk of gastric inflammation, bleeding and ulceration.   In one study, patients on meloxicam suffered from gastrointestinal symptoms at a rate of 13% compared to 19% of those on . GI events were found to be less severe in the meloxicam-treated patients.","Meloxicam inhibits prostaglandin synthetase (cylooxygenase 1 and 2) enzymes leading to a decreased synthesis of prostaglandins, which normally mediate painful inflammatory symptoms. As prostaglandins sensitize neuronal pain receptors, inhibition of their synthesis leads to analgesic and inflammatory effects. Meloxicam preferentially inhibits COX-2, but also exerts some activity against COX-1, causing gastrointestinal irritation.","Prostaglandin G/H synthase 2 inhibitor; Prostaglandin G/H synthase 1 inhibitor","Therapeutic strategy associated"]
[292,"DB00817","approved; investigational","small molecule","Rosoxacin","1-ethyl-1,4-dihydro-4-oxo-7-(4-pyridyl)-3-quinolinecarboxylic acid; Acrosoxacin","C17H14N2O3","CCN1C=C(C(O)=O)C(=O)C2=C1C=C(C=C2)C1=CC=NC=C1","Rosoxacin is a quinolone derivative antibiotic for the treatment of bacterial infection of respiratory tract, urinary tract, GI, CNS and immuno compromised patients. Rosoxacin is known to be effective against penicillin resistant strains and is a single dose orally administered drug, which avoids all complications of parenteral administration seen with penicillin, especially anaphylactic shock.","40034-42-2","294.3047","For the treatment of bacterial infection of respiratory tract, urinary tract, GI, CNS and immuno compromised patients.","Rosoxacin is a nonfluorinated quinolone antibiotic. Its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase, which allows the untwisting required to replicate one DNA double helix into two. Rosoxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria.","Rosoxacin binds to and inhibits the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, and recombination.","DNA gyrase subunit B inhibitor; DNA topoisomerase 4 subunit A inhibitor","Indication associated"]
[293,"DB00820","approved; investigational","small molecule","Tadalafil","(6R-trans)-6-(1,3-Benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydro-2-methyl-pyrazino(1',2':1,6)pyrido(3,4-b)indole-1,4-dione; (6R,12aR)-2,3,6,7,12,12a-Hexahydro-2-methyl-6-(3,4-(methylenedioxy)phenyl) pyrazino(1',2':1,6)pyrido(3,4-b)indole-1,4-dione; Tadalafil","C22H19N3O4","[H][C@]12CC3=C(NC4=CC=CC=C34)[C@H](N1C(=O)CN(C)C2=O)C1=CC2=C(OCO2)C=C1","Tadalafil is a selective phosphodiesterase-5 inhibitor that is used in the treatment of erectile dysfunction (ED), pulmonary arterial hypertension (PAH), and benign prostatic hypertrophy. It was first approved in 2003 by the FDA for use in ED and later in 2009 for PAH. In contrast to other PDE5 inhibitors like , tadalafil has greater selectivity for PDE5 and a longer half-life which has made it a more suitable option for chronic once-daily dosing in the treatment of PAH.","171596-29-5","389.404","Tadalafil is indicated for the treatment of erectile dysfunction (ED) and either alone or in combination with  for the treatment of benign prostatic hypertrophy (BPH). It is also indicated for the treatment of pulmonary arterial hypertension (PAH) both alone and in combination with  or other endothelin-1 antagonists.","Tadalafil exerts a therapeutic effect in ED by increasing sexual stimulation-dependant smooth muscle relaxation in the penis, allowing the corpus cavernosum to fill with blood to produce an erection. Smooth muscle relaxation in the pulmonary vasculature helps to produce vasodilation in PAH which reduces blood pressure in the pulmonary arteries. In BPH, tadalafil may contribute to decreased smooth muscle cell proliferation which may reduce the size of the prostate and relieve the anatomical obstruction which produces urinary symptoms of BPH. The decreased affinity of tadalafil for PDE6 compared to other PDE5 inhibitors may explain the reduced incidence of visual side effects.","Tadalafil is a selective phosphodiesterase-5 (PDE5) inhibitor that produces several downstream effects with the most common therapeutic effect being smooth muscle relaxation.  Patients may experience ED due to a variety of causes including psychogenic, neurogenic, vasculogenic, iatrogenic, or endocrine.  These causes result in dysfunction of penile smooth muscle relaxation through either disrupted neuronal signaling or direct influence on smooth muscle cells. During sexual arousal, non-adrenergic non-cholinergic (NANC) neurons release nitric oxide (NO). Nitric oxide stimulates guanylate cyclase which converts guanosine triphosphate to cyclic guanosine monophosphate (cGMP). cGMP activates the cGMP-dependent kinase (PKG) in a signal cascade which activates K+ channels leading to inhibition of Ca2+ channels, inhibits platelet activation, and inhibits smooth muscle cell proliferation while inducing apoptosis. This signal cascade is attenuated by PDE5 which breaks the phosphodiester bond of cGMP, converting it to GMP. Inhibition of PDE5 by tadalafil increases signaling via the PKG cascade which supports penile smooth muscle relaxation during sexual arousal by decreasing Ca2+ entry into smooth muscle cells. This smooth muscle relaxation allows blood to fill the corpus cavernosum thereby producing an erection.\r\n\r\nIn PAH, blood pressure in the pulmonary arteries is raised due to a variety of mechanisms stemming from endothelial dysfunction. Decreased production of NO and prostacyclin reduce vasodilatory signaling while overproduction of endothelin-1 and thromboxane increase vasoconstriction. Inflammation, thromboses, and hypoxia later contribute to vascular remodeling which further reduces luminal size. The resultant increase in blood pressure reduces the capacity for gas exchange and increases afterload at the right ventricle, producing symptoms of dyspnea, fatigue, and dizziness as well as leading to right-sided heart failure. Tadalafil exerts its therapeutic effect in PAH through boosting NO-cGMP signaling to contribute to smooth muscle relaxation as with ED.\r\n\r\nLastly, tadalafil is used to treat BPH. BPH produces urinary dysfunction through hyperproliferation of the epithelial and smooth muscle layers of the prostate. The increased size of the prostate blocks urine flow through the urethra resulting in higher residual volumes due to incomplete emptying. Tadalafil does not appear to exert its benefit via smooth muscle relaxation of the prostate. It may instead exert its effect through a mix of increased oxygenation and decreased inflammation, which decreases tissue remodeling, and inhibition of cell proliferation through the cGMP cascade.\r\n\r\nThe decreased affinity for PDE6 compared to other PDE5 inhibitors may explain the decreased incidence of visual side effects as PDE6 is present in the eye and contributes to color vision.","cGMP-specific 3',5'-cyclic phosphodiesterase inhibitor; Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A inhibitor; Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma inhibitor","Therapeutic strategy associated"]
[294,"DB00821","approved; vet_approved; withdrawn","small molecule","Carprofen","(+/-)-2-(3-chloro-9H-carbazol-7-yl)propanoic acid; (±)-6-chloro-α-methylcarbazole-2-acetic acid; 2-(6-Chloro-9H-carbazol-2-yl)-propionic acid; 6-chloro-α-methyl-9H-carbazole-2-acetic acid","C15H12ClNO2","CC(C(O)=O)C1=CC2=C(C=C1)C1=C(N2)C=CC(Cl)=C1","Carprofen is a non-steroidal anti-inflammatory drug (NSAID) that is used by veterinarians as a supportive treatment for the relief of arthritic symptoms in geriatric dogs. Carprofen was previously used in human medicine for over 10 years (1985-1995). It was generally well tolerated, with the majority of adverse effects being mild, such as gastro-intestinal pain and nausea, similar to those recorded with aspirin and other non-steroidal anti-inflammatory drugs. It is no longer marketed for human usage, after being withdrawn on commercial grounds.","53716-49-7","273.714","For use as a pain reliever in the treatment of joint pain and post-surgical pain.","Carprofen is a non-steroidal anti-inflammatory drug (NSAID) of the propionic acid class that includes ibuprofen, naproxen, and ketoprofen. It is no longer used in the clinical setting, but is approved for use in dogs. Carprofen is non-narcotic and has characteristic analgesic and antipyretic activity approximately equipotent to indomethacin in animal models.","The mechanism of action of carprofen, like that of other NSAIDs, is believed to be associated with the inhibition of cyclooxygenase activity. Two unique cyclooxygenases have been described in mammals. The constitutive cyclooxygenase, COX-1, synthesizes prostaglandins necessary for normal gastrointestinal and renal function. The inducible cyclooxygenase, COX-2, generates prostaglandins involved in inflammation. Inhibition of COX-1 is thought to be associated with gastrointestinal and renal toxicity while inhibition of COX-2 provides anti-inflammatory activity. In an <i>in vitro</i> study using canine cell cultures, carprofen demonstrated selective inhibition of COX-2 versus COX-1.","Prostaglandin G/H synthase 2 inhibitor; Prostaglandin G/H synthase 1 inhibitor","Therapeutic strategy associated"]
[295,"DB00824","approved; experimental","small molecule","Enprofylline","3-n-propylxanthine; 3-Propyl-3,7-dihydro-purine-2,6-dione; 3-propylxanthine; 3,7-dihydro-3-propyl-1H-purine-2,6-dione; Enprofylline","C8H10N4O2","CCCN1C2=C(NC=N2)C(=O)NC1=O","Enprofylline is a derivative of theophylline which shares bronchodilator properties. Enprofylline is used in asthma, chronic obstructive pulmonary disease, and in the management of cerebrovascular insufficiency, sickle cell disease, and diabetic neuropathy. Long-term enprofylline administration may be associated with elevation in liver enzyme levels and unpredictable blood levels.","41078-02-8","194.1906","Used in the management of symptoms of asthma. Also used in the treatment of peripheral vascular diseases and in the management of cerebrovascular insufficiency, sickle cell disease, and diabetic neuropathy.","Enprofylline is a synthetic dimethylxanthine derivative structurally related to theophylline and caffeine. It antagonizes erythrocyte phosphodiesterase, increasing cAMP activity.","Enprofylline inhibits erythrocyte phosphodiesterase, resulting in an increase in erythrocyte cAMP activity. Subsequently, the erythrocyte membrane becomes more resistant to deformity. Along with erythrocyte activity, enprofylline also decreases blood viscosity by reducing plasma fibrinogen concentrations and increasing fibrinolytic activity.","cAMP-specific 3',5'-cyclic phosphodiesterase 4A inhibitor; cAMP-specific 3',5'-cyclic phosphodiesterase 4B inhibitor; Adenosine receptor A2b antagonist; Adenosine receptor A1 inhibitor; Adenosine receptor A2a inhibitor; Adenosine receptor A3 inhibitor","Indication associated"]
[296,"DB00827","approved; investigational; withdrawn","small molecule","Cinoxacin","1-ethyl-6,7-methylenedioxy-4(1H)-oxocinnoline-3-carboxylic acid; 5-Ethyl-8-oxo-5,8-dihydro-1,3-dioxa-5,6-diaza-cyclopenta[b]naphthalene-7-carboxylic acid","C12H10N2O5","CCN1N=C(C(O)=O)C(=O)C2=CC3=C(OCO3)C=C12","Synthetic antimicrobial related to oxolinic acid and nalidixic acid and used in urinary tract infections.","28657-80-9","262.2182","For the treatment of initial and recurrent urinary tract infections in adults caused by the following susceptible microorganisms: <i>Escherichia coli</i>, <i>Proteus mirabilis</i>, <i>Proteus vulgaris</i>, <i>Klebsiella</i> species (including <i>K. pneumoniae</i>), and <i>Enterobacter</i> species.","Cinoxacin is a synthetic antibacterial agent with <i>in vitro</i> activity against many gram-negative aerobic bacteria, particularly strains of the Enterobacteriaceae family. Cinoxacin inhibits bacterial deoxyribonucleic acid (DNA) synthesis, is bactericidal, and is active over the entire urinary pH range. Cross resistance with nalidixic acid has been demonstrated.","Evidence exists that cinoxacin binds strongly, but reversibly, to DNA, interfering with synthesis of RNA and, consequently, with protein synthesis. It appears to also inhibit DNA gyrase. This enzyme is necessary for proper replicated DNA separation. By inhibiting this enzyme, DNA replication and cell division is inhibited.","DNA gyrase subunit A inhibitor; DNA intercalation","Indication associated"]
[297,"DB00828","approved","small molecule","Fosfomycin","(-)-(1R,2S)-(1,2-Epoxypropyl)phosphonic acid; (1R,2S)-epoxypropylphosphonic acid; (2R-cis)-(3-Methyloxiranyl)phosphonic acid; 1R-cis-(1,2-epoxypropyl)phosphonic acid; cis-(1R,2S)-epoxypropylphosphonic acid; FCM; Fosfocina; Fosfomycin; L-cis-1,2-epoxypropylphosphonic acid; Phosphomycin; Phosphonemycin; Phosphonomycin","C3H7O4P","C[C@@H]1O[C@@H]1P(O)(O)=O","Fosfomycin was discovered in 1969 by scientists at the Spanish Penicillin and Antibiotics Company and is produced by _Streptomyces fradiae_. It may also be produced synthetically and is commercially available as the disodium salt for intravenous administration and as the calcium or trometamol salt for oral administration. In terms of chemical structure, fosfomycin is a phosphoenolpyruvate analog and contains a phosphonic group and an epoxide ring.\r\n\r\nDue to its ease of administration as a single 3-gram oral dose and desirable safety profile, fosfomycin has largely become a first-line therapeutic option for the treatment of uncomplicated urinary tract infections (UTIs) in females. Despite being FDA approved only for urinary tract infections, fosfomycin actually has a broad spectrum of activity and is active against both gram-positive and gram-negative bacteria. As such there is great interest in exploring the usefulness of fosfomycin for indications beyond the treatment of UTIs.","23155-02-4","138.059","Fosfomycin is indicated for the treatment of uncomplicated cases of cystitis caused by susceptible strains of _Escherichia coli_ and _Enterococcus faecalis_. Fosfomycin is not officially indicated for the treatment of pyelonephritis or perinephric abscess, although there have been reported cases of off-label usage in these situations.","Although used primarily to treat urinary tract infections, fosfomycin has been shown to act synergistically with other antibiotics against clinically relevant bacteria. There is also growing interest in the potential of fosfomycin to treat more complex infections since it has retained activity against many difficult-to-treat strains of bacteria including methicillin-resistant _Staphylococcus aureus_ (MRSA) and multidrug-resistant enterobacteria. Further, since fosfomycin has a unique and singular mechanism of action, the risk of cross-resistance with other antibiotics is low.\r\n\r\nFosfomycin also demonstrates immunomodulating properties. For example, the antibiotic may influence components of the acute inflammatory cytokine response and enhances neutrophil phagocytic destruction of pathogens.\r\n\r\nFosfomycin penetrates biofilms effectively and is capable of not only reducing or eliminating microorganisms in biofilms but can also alter the biofilm structure.","Fosfomycin exerts its bactericidal effects by binding covalently to a cysteine in the active site of the UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) enzyme, rendering it inactive. By preventing MurA from catalyzing the condensation of phosphoenolpyruvate (PEP) with UDP-N-acetylglucosamine (UNAG), fosfomycin inhibits the production of the peptidoglycan precursor UDP N-acetylmuramic acid (UDP-MurNAc). Ultimately, the first step of bacterial cell wall synthesis is disrupted.\r\n\r\nIn _Escherichia coli_, fosfomycin gains entry into bacterial cells via two mechanisms: the L-alpha-glycerophosphate system and the hexose-6-phosphate transporter system.\r\n\r\nFosfomycin also has important effects on cell adhesion. For example, the adhesion of bacterial cells to urinary epithelial cells is reduced in the presence of fosfomycin. The adhesion of _Streptococcus pneumoniae_ and _Haemophilus influenzae_ to respiratory epithelial cells is also reduced","UDP-N-acetylglucosamine 1-carboxyvinyltransferase inhibitor","Therapeutic strategy associated"]
[298,"DB00830","approved; illicit","small molecule","Phenmetrazine","2-phenyl-3-methylmorpholine; Fenmetrazin; Phenmetrazin; Phenmetrazine","C11H15NO","CC1NCCOC1C1=CC=CC=C1","A sympathomimetic drug used primarily as an appetite depressant. Its actions and mechanisms are similar to dextroamphetamine.","134-49-6","177.2429","Used as an anorectic in the treatment of obesity.","Phenmetrazine is a sympathomimetic drug used primarily as an appetite depressant. Its actions and mechanisms are similar to dextroamphetamine. Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. Phenmetrazine was originally sold under the tradename Preludin as an anorectic. It has since been removed from the market. It is by some considered to have a greater potential for addiction than the amphetamines, and has been abused in many countries, for example Sweden.","Phenmetrazine is thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron leading to an increase in the release of these monoamines into the extraneuronal space. Dopamine integrates incoming sensory stimuli, initiates and controls fine movement (nigro-neostriatal pathway), controls emotional behavior (midbrain mesolimbic-forebrain system) and controls hypothalamic-pituitary endocrine system (tubero-infundibular system). It is this latter effect on the tubero-infundibular systm that seems to lead to reduced food intake. Phenmetrazine also acts as a monoamine oxidase inhibitor.","Sodium-dependent noradrenaline transporter inhibitor; Sodium-dependent dopamine transporter inhibitor","Indication associated"]
[299,"DB00833","approved","small molecule","Cefaclor","3-Chloro-7-D-(2-phenylglycinamido)-3-cephem-4-carboxylic acid; CCL; Cefaclor anhydrous; Cephaclor","C15H14ClN3O4S","[H][C@]12SCC(Cl)=C(N1C(=O)[C@H]2NC(=O)[C@H](N)C1=CC=CC=C1)C(O)=O","Semisynthetic, broad-spectrum antibiotic derivative of cephalexin.","53994-73-3","367.807","For the treatment of certain infections caused by bacteria such as pneumonia and ear, lung, skin, throat, and urinary tract infections.","Cefaclor is a second generation cephalosporin antibiotic with a spectrum resembling first-generation cephalosporins. <i>In vitro</i> tests demonstrate that the bactericidal action of the cephalosporins results from inhibition of cell-wall synthesis. As indicated by _in vitro_ and _in vivo_ clinical studies, cefaclor was shown to be effective against most strains of Gram positive aerobes - Staphylococci (including coagulase-positive, coagulase-negative, and penicillinase-producing strains), <i>Streptococcus pneumoniae</i>, <i>Streptococcus pyogenes</i> (group A &szlig;-hemolytic streptococci), as well as Gram-negative aerobes - <i>Escherichia coli</i>, <i>Haemophilus influenzae</i> (including &szlig;-lactamase-producing ampicillin-resistant strains), <i>Klebsiella sp</i>, and <i>Proteus mirabilis</i>.","Cefaclor, like the penicillins, is a beta-lactam antibiotic. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins. It is possible that cefaclor interferes with an autolysin inhibitor.","Penicillin-binding protein 3 inhibitor; Penicillin-binding protein 1A inhibitor","Indication associated"]
[300,"DB00834","approved; investigational","small molecule","Mifepristone","Mifepristone","C29H35NO2","[H][C@@]12CC[C@@](O)(C#CC)[C@@]1(C)C[C@H](C1=CC=C(C=C1)N(C)C)C1=C3CCC(=O)C=C3CC[C@@]21[H]","Mifepristone is a progestational and glucocorticoid hormone antagonist. Its inhibition of progesterone induces bleeding during the luteal phase and in early pregnancy by releasing endogenous prostaglandins from the endometrium or decidua. As a glucocorticoid receptor antagonist, the drug has been used to treat hypercortisolism in patients with nonpituitary cushing syndrome. The two marketed forms of mifepristone are Mifeprex® (mifepristone 200mg) and Korlym™ (mifepristone 300mg). Currently under investigation for use in psychotic depression (phase 3 trials).","84371-65-3","429.5937","For the medical termination of intrauterine pregnancy through 49 days' pregnancy. Also indicated to control hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing's syndrome who have type 2 diabetes mellitus or glucose intolerance and are not candidates for surgery or have had unsuccessful surgery.","Mifepristone is a synthetic steroid with antiprogestational effects indicated for the medical termination of intrauterine pregnancy through 49 days' pregnancy. Doses of 1 mg/kg or greater of mifepristone have been shown to antagonize the endometrial and myometrial effects of progesterone in women. During pregnancy, the compound sensitizes the myometrium to the contraction-inducing activity of prostaglandins. Mifepristone also exhibits antiglucocorticoid and weak antiandrogenic activity. The activity of the glucocorticoid dexamethasone in rats was inhibited following doses of 10 to 25 mg/kg of mifepristone. Doses of 4.5 mg/kg or greater in human beings resulted in a compensatory elevation of adrenocorticotropic hormone (ACTH) and cortisol.","The anti-progestational activity of mifepristone results from competitive interaction with progesterone at progesterone-receptor sites. Based on studies with various oral doses in several animal species (mouse, rat, rabbit and monkey), the compound inhibits the activity of endogenous or exogenous progesterone. The termination of pregnancy results.\r\n\r\nIn the treatment of Cushing's syndrome, Mifepristone blocks the binding of cortisol to its receptor. It does not decrease cortisol production but reduces the effects of excess cortisol, such as high blood sugar levels.","Progesterone receptor antagonist; Glucocorticoid receptor antagonist; Prostate-specific antigen; Nuclear receptor subfamily 1 group I member 2","Indication associated"]
[301,"DB00836","approved","small molecule","Loperamide","Loperamide","C29H33ClN2O2","CN(C)C(=O)C(CCN1CCC(O)(CC1)C1=CC=C(Cl)C=C1)(C1=CC=CC=C1)C1=CC=CC=C1","One of the long-acting synthetic antidiarrheals; it is not significantly absorbed from the gut, and has no effect on the adrenergic system or central nervous system, but may antagonize histamine and interfere with acetylcholine release locally.","53179-11-6","477.038","For the control and symptomatic relief of acute nonspecific diarrhea and of chronic diarrhea associated with inflammatory bowel disease or gastroenteritis. Also used for reducing the volume of discharge from ileostomies.","Loperamide is a synthetic anti-diarrheal indicated for the control and symptomatic relief of acute nonspecific diarrhea and of chronic diarrhea associated with inflammatory bowel disease. Loperamide is also indicated for reducing the volume of discharge from ileostomies. In man, Loperamide prolongs the transit time of the intestinal contents. It reduces the daily fecal volume, increases the viscosity and bulk density, and diminishes the loss of fluid and electrolytes. Tolerance to the antidiarrheal effect has not been observed. Loperamide is an opioid receptor agonist and acts on the mu opioid receptors in the myenteric plexus large intestines; it does not affect the central nervous system like other opioids. It works specifically by decreasing the activity of the myenteric plexus which decreases the motility of the circular and longitudinal smooth muscles of the intestinal wall. This increases the amount of time substances stay in the intestine, allowing for more water to be absorbed out of the fecal matter. Loperamide also decreases colonic mass movements and suppresses the gastrocolic reflex.","<i>In vitro</i> and animal studies show that Loperamide acts by slowing intestinal motility and by affecting water and electrolyte movement through the bowel. Loperamide inhibits peristaltic activity by a direct effect on the circular and longitudinal muscles of the intestinal wall. It is a non-selective calcium channel blocker and binds to opioid mu-receptors. Evidence also suggests that at higher concentrations it binds to calmodulin.","Mu-type opioid receptor agonist; Delta-type opioid receptor agonist; Kappa-type opioid receptor agonist; Voltage-dependent P/Q-type calcium channel subunit alpha-1A inhibitor; Pro-opiomelanocortin modulator; Calmodulin inhibitor; Nuclear receptor subfamily 1 group I member 3","Therapeutic strategy associated"]
[302,"DB00838","approved","small molecule","Clocortolone","9-chloro-6alpha-Fluoro-11beta,21-dihydroxy-16alpha-methyl-1,4-pregnadien-3,20-dione; 9-chloro-6alpha-Fluoro-16alpha-methyl-1,4-pregnadiene-11beta,21-diol-3,20-dione","C22H28ClFO4","[H][C@@]12C[C@@H](C)[C@H](C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1(Cl)[C@@]2([H])C[C@H](F)C2=CC(=O)C=C[C@]12C","Clocortolone is a medium potency corticosteroid that is often used as a topical cream for the relief of inflammatory oand pruritic (itching) arising from steroid-responsive dermatoses of the scalp.","4828-27-7","410.907","For short-term topical treatment of the inflammatory and pruritic manifestations of moderate to severe corticosteroid-responsive dermatoses of the scalp.","Like other topical corticosteroids, clocortolone has anti-inflammatory, antipruritic, and vasoconstrictive properties. Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Clocortolone is a moderate potency topical corticosteroid that should not be used with occlusive dressings. It is recommended that treatment should be limited to 2 consecutive weeks and therapy should be discontinued when adequate results have been achieved.","The precise mechanism of the antiinflammatory activity of topical steroids in the treatment of steroid-responsive dermatoses, in general, is uncertain. However, corticosteroids are thought to act by the induction of phospholipase A<sub>2</sub> inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A<sub>2</sub>. These enzyme transcriptional changes are mediated by the drug binding first to the glucocorticoid receptor. This complex can migrate to the cell nucleus which then binds to DNA initiating genetic activation and repression of various genes.","Glucocorticoid receptor agonist","Therapeutic strategy associated"]
[303,"DB00839","approved; investigational","small molecule","Tolazamide","1-(Hexahydro-1-azepinyl)-3-p-tolylsulfonylurea; 1-(Hexahydro-1H-azepin-1-yl)-3-(p-tolylsulfonyl)urea; 4-(p-Tolylsulfonyl)-1,1-hexamethylenesemicarbazide; N-(p-Toluenesulfonyl)-N'-hexamethyleniminourea","C14H21N3O3S","CC1=CC=C(C=C1)S(=O)(=O)NC(=O)NN1CCCCCC1","A sulphonylurea hypoglycemic agent with actions and uses similar to those of chlorpropamide.","1156-19-0","311.4","For use as an adjunct to diet to lower the blood glucose in patients with non-insulin dependent diabetes mellitus (Type II) whose hyperglycemia cannot be satisfactorily controlled by diet alone.","Tolazamide is an oral blood glucose lowering drug of the sulfonylurea class. Tolazamide appears to lower the blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. The mechanism by which tolazamide lowers blood glucose during long-term administration has not been clearly established. With chronic administration in Type II diabetic patients, the blood glucose lowering effect persists despite a gradual decline in the insulin secretory response to the drug. Extrapancreatic effects may be involved in the mechanism of action of oral sulfonylurea hypoglycemic drugs. Some patients who are initially responsive to oral hypoglycemic drugs, including tolazamide, may become unresponsive or poorly responsive over time. Alternatively, tolazamide may be effective in some patients who have become unresponsive to one or more other sulfonylurea drugs. In addition to its blood glucose lowering actions, tolazamide produces a mild diuresis by enhancement of renal free water clearance.","Sulfonylureas likely bind to ATP-sensitive potassium-channel receptors on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Depolarization stimulates calcium ion influx through voltage-sensitive calcium channels, raising intracellular concentrations of calcium ions, which induces the secretion, or exocytosis, of insulin.","Sulfonylurea receptor 1, Kir6.2 blocker","Indication associated"]
[304,"DB00841","approved","small molecule","Dobutamine","(±)-4-(2-((3-(p-hydroxyphenyl)-1-methylpropyl)amino)ethyl)pyrocatechol; 3,4-dihydroxy-N-[3-(4-hydroxyphenyl)-1-methylpropyl]-β-phenylethylamine; 4-{2-[3-(4-Hydroxy-phenyl)-1-methyl-propylamino]-ethyl}-benzene-1,2-diol; DL-dobutamine; rac-dobutamine; racemic-dobutamine","C18H23NO3","CC(CCC1=CC=C(O)C=C1)NCCC1=CC(O)=C(O)C=C1","A beta-1 agonist catecholamine that has cardiac stimulant action without evoking vasoconstriction or tachycardia. It is proposed as a cardiotonic after myocardial infarction or open heart surgery.","34368-04-2","301.3801","Indicated when parenteral therapy is necessary for inotropic support in the short-term treatment of patients with cardiac decompensation due to depressed contractility resulting either from organic heart disease or from cardiac surgical procedures.","Dobutamine is a direct-acting inotropic agent whose primary activity results from stimulation of the beta-adrenoceptors of the heart while producing comparatively mild chronotropic, hypertensive, arrhythmogenic, and vasodilative effects. Dobutamine acts primarily on beta-1 adrenergic receptors, with negligible effects on beta-2 or alpha receptors. It does not cause the release of endogenous norepinephrine, as does dopamine.","Dobutamine directly stimulates beta-1 receptors of the heart to increase myocardial contractility and stroke volume, resulting in increased cardiac output.","Beta-1 adrenergic receptor agonist; Beta-2 adrenergic receptor agonist; Alpha-1 adrenergic receptors agonist; Estrogen receptor alpha","Therapeutic strategy associated"]
[305,"DB00843","approved","small molecule","Donepezil","Domepezil","C24H29NO3","COC1=C(OC)C=C2C(=O)C(CC3CCN(CC4=CC=CC=C4)CC3)CC2=C1","In 2016, the global burden of dementia was estimated to be 43.8 million, demonstrating a significant increase from a global prevalence of 20.2 million in 1990. Donepezil, also known as Aricept, is a piperidine derivative acetylcholinesterase inhibitor used in the management of the dementia of Alzheimer's Disease, and in some cases, is used to manage other types of dementia. \r\n\r\nDonepezil was first approved by the FDA in 1996, and its extended-release form was approved in combination with  in 2014 to manage moderate and severe forms of Alzheimer's dementia. Though it does not alter the progression of Alzheimer's disease, donepezil is effective in managing the symptoms of its associated dementia.","120014-06-4","379.492","Donepezil is indicated for the management of mild to moderate Alzheimer’s Disease at doses of 5 mg or 10 mg. It is also indicated for the management of moderate to severe Alzheimer’s Disease in a higher dose of 10 mg or 23 mg administered once daily. Off-label uses include the management of vascular dementia, Parkinson's Disease-associated dementia, and Lewy body dementia, among others. When combined with memantine, the extended-release form of donepezil is indicated to treat the symptoms of moderate to severe dementia.","By inhibiting the acetylcholinesterase enzyme, donepezil improves the cognitive and behavioral signs and symptoms of Alzheimer's Disease, which may include apathy, aggression, confusion, and psychosis.","\r\nThe commonly accepted cholinergic hypothesis proposes that a portion of the cognitive and behavioral decline associated with Alzheimer's are the result of decreased cholinergic transmission in the central nervous system. Donepezil selectively and reversibly inhibits the acetylcholinesterase enzyme, which normally breaks down acetylcholine. The main pharmacological actions of this drug are believed to occur as the result of this enzyme inhibition, enhancing cholinergic transmission, which relieves the symptoms of Alzheimer's dementia. In addition to the above, other mechanisms of action of donepezil are possible, including the opposition of glutamate-induced excitatory transmission via downregulation of NMDA receptors and the regulation of amyloid proteins, which have demonstrated significant effects on the disease process of Alzheimer's. Other possible targets for donepezil may also include the inhibition various inflammatory signaling pathways, exerting neuroprotective effects.","Acetylcholinesterase inhibitor; 5-hydroxytryptamine receptor 2A inducer; Cholinesterase inducer; Nitric oxide synthase, brain inhibitor&inducer; Tumor necrosis factor-inducible gene 6 protein inhibitor; Interleukin-1 beta inhibitor&inducer; Nuclear factor NF-kappa-B inhibitor; NMDA receptor downregulator","Therapeutic strategy associated"]
[306,"DB00845","approved; investigational","small molecule","Clofazimine","Riminophenazine","C27H22Cl2N4","CC(C)N=C1C=C2N(C3=CC=C(Cl)C=C3)C3=C(C=CC=C3)N=C2C=C1NC1=CC=C(Cl)C=C1","Clofazimine is a highly lipophilic antimicrobial riminophenazine dye used in combination with other agents, such as , for the treatment of leprosy. It was originally described in 1957 and was the prototypical riminophenazine dye - a bright-red dye that, in its clinical use, results in long-lasting discoloration of the skin and bodily fluids. Although it carries _in vitro_ activity against other mycobacterium, such as _Mycobacterium tuberculosis_, it is generally considered an ineffective treatment in comparison to classic tuberculosis treatments such as  and .","2030-63-9","473.396","Clofazimine is indicated for the treatment of lepromatous leprosy, including dapsone-resistant lepromatous leprosy and lepromatous leprosy complicated by erythema nodosum leprosum. To prevent the development of drug resistance, it should be used only in combination with other antimycobacterial leprosy treatments.","Clofazimine exerts a slow bactericidal effect on <i>Mycobacterium leprae</i> (Hansen's bacillus) due primarily to its action on the bacterial outer membrane, though there is some evidence that activity on the bacterial respiratory chain and ion transporters may play a role. It also exerts anti-inflammatory properties due to the suppression of T-lymphocyte activity. Clofazimine has a relatively long duration of action owing to its long residence time in the body, but is still administered daily.\r\n\r\nApproximately 75-100% of patients receiving clofazimine will experience an orange-pink to brownish-black discoloration of the skin, conjunctivae, and bodily fluids. Skin discoloration may take several months or years to reverse following the cessation of therapy. Clofazimine has also been implicated in abdominal obstruction, in some cases fatal, due to the deposition of drug and formation of crystals in the intestinal mucosa - complaints of abdominal pain and nausea/vomiting should be investigated promptly, and the doses of clofazimine should be lowered or discontinued if it is found to be the culprit.\r\n\r\nIts use should be avoided in patients with hepatic dysfunction.","Although the precise mechanism(s) of action of clofazimine have not been elucidated, its antimicrobial activity appears to be membrane-directed. It was previously thought that, due to its lipophilicity, clofazimine participated in the generation of intracellular reactive oxygen species (ROS) via redox cycling, specifically H<sub>2</sub>O<sub>2</sub> and superoxide, which then exerted an antimicrobial effect. A more recent and compelling theory involves clofazimine interacting with bacterial membrane phospholipids to generate antimicrobial lysophospholipids - bactericidal efficacy may, then, arise from the combined membrane-destabilizing effects of both clofazimine and lysophospholipids, which interfere with K+ uptake and, ultimately, ATP production.\r\n\r\nThe anti-inflammatory activity of clofazimine is the result of its inhibition of T-lymphocyte activation and proliferation. Several mechanisms have been proposed, including direct antagonism of T-cell Kv 1.3 potassium channels and indirect action by promoting the release of E-series prostaglandins and reactive oxygen species from bystander neutrophils and monocytes.","Peroxisome proliferator-activated receptor gamma modulator; Potassium voltage-gated channel subfamily A member 3 antagonist","Therapeutic strategy associated"]
[307,"DB00846","approved","small molecule","Flurandrenolide","Fludroxicortide; Flurandrenolide; Flurandrenolone","C24H33FO6","CC1(C)O[C@@H]2C[C@H]3[C@@H]4C[C@H](F)C5=CC(=O)CC[C@]5(C)[C@H]4[C@@H](O)C[C@]3(C)[C@@]2(O1)C(=O)CO","A corticosteroid used topically in the treatment of various skin disorders. It is usually employed as a cream or an ointment, and is also used as a polyethylene tape with an adhesive. (From Martindale, The Extra Pharmacopoeia, 30th ed, p733)","1524-88-5","436.5136","For relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses, particularly dry, scaling localized lesions","Flurandrenolide is primarily effective because of its anti-inflammatory, antipruritic, and vasoconstrictive actions.","Flurandrenolide is a topical corticosteroid.  It is normally applied to a plastic tape called Cordran.  Cordran is primarily effective because of its anti-inflammatory, antipruritic, and vasoconstrictive actions. Flurandrenolide, which is slowly released from the Cordran tape, binds to the cytosolic glucocorticoid receptor. After binding the receptor the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes. The anti-inflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. Specifically glucocorticoids induce lipocortin-1 (annexin-1) synthesis, which then binds to cell membranes preventing the phospholipase A2 from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. Cyclooxygenase (both COX-1 and COX-2) expression is also suppressed, potentiating the effect. In another words, the two main products in inflammation Prostaglandins and Leukotrienes are inhibited by the action of Glucocorticoids. Glucocorticoids also stimulate the lipocortin-1 escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines etc.) from neutrophils, macrophages and mastocytes. Additionally the immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding.  Like other glucocorticoid agents Fluocinolone acetonide acts as a physiological antagonist to insulin by decreasing glycogenesis (formation of glycogen).  It also promotes the breakdown of lipids (lipolysis), and proteins, leading to the mobilization of extrahepatic amino acids and ketone bodies. This leads to increased circulating glucose concentrations (in the blood). There is also decreased glycogen formation in the liver.\r\n\r","Glucocorticoid receptor agonist","Therapeutic strategy associated"]
[308,"DB00852","approved","small molecule","Pseudoephedrine","(+) threo-2-(methylamino)-1-phenyl-1-propanol; (+)-(1S,2S)-Pseudoephedrine; (+)-Pseudoephedrine; (+)-psi-Ephedrine; (+)-threo-Ephedrine; d-Isoephedrine; d-Pseudoephedrine; d-psi-2-Methylamino-1-phenyl-1-propanol; d-psi-Ephedrine; Isoephedrine; L-(+)-Pseudoephedrine; L(+)-psi-Ephedrine; Pseudoephedrine; Pseudoephedrine D-form; Psi-ephedrin; Psi-ephedrine; trans-Ephedrine; ψ-ephedrine","C10H15NO","CN[C@@H](C)[C@@H](O)C1=CC=CC=C1","Pseudoephedrine is structurally related to  but exerts a weaker effect on the sympathetic nervous system. Both drugs naturally occur in in ephedra plant which have a history of use in traditional Eastern medicine and were first researched in the west in 1889. The decongestant effect of pseudoephedrine was described in dogs in 1927.","90-82-4","165.2322","Pseudoephedrine is a sympathomimetic amine used for its decongestant activity.","Pseudoephedrine causes vasoconstriction which leads to a decongestant effect. It has a short duration of action unless formulated as an extended release product. Patients should be counselled regarding the risk of central nervous system stimulation.","Pseudoephedrine acts mainly as an agonist of alpha adrenergic receptors and less strongly as an agonist of beta adrenergic receptors. This agonism of adrenergic receptors produces vasoconstriction which is used as a decongestant and as a treatment of priapism. Pseudoephedrine is also an inhibitor of norepinephrine, dopamine, and serotonin transporters.\r\n\r\nThe sympathomimetic effects of pseudoephedrine include an increase in mean arterial pressure, heart rate, and chronotropic response of the right atria. Pseudoephedrine is also a partial agonist of the anococcygeal muscle. Pseudoephedrine also inhibits NF-kappa-B, NFAT, and AP-1.","Sodium-dependent noradrenaline transporter inhibitor; Sodium-dependent dopamine transporter inhibitor; Alpha-1A adrenergic receptor agonist; Alpha-2A adrenergic receptor agonist; Sodium-dependent serotonin transporter inhibitor; Beta-2 adrenergic receptor partial agonist; Beta-1 adrenergic receptor agonist&partial agonist; Nuclear factor of activated T-cells, cytoplasmic 1 inhibitor; Tumor necrosis factor inhibitor; Nuclear factor NF-kappa-B p105 subunit inhibitor; activator protein 1 inhibitor; Interleukin-2 inhibitor","Target associated"]
[309,"DB00853","approved; investigational","small molecule","Temozolomide","3-methyl-4-oxo-3,4-dihydroimidazo(5,1-d)(1,2,3,5)tetrazine-8-carboxamide; 3,4-dihydro-3-methyl-4-oxoimidazo(5,1-d)-1,2,3,5-tetrazine-8-carboxamide; 3,4-dihydro-3-methyl-4-oxoimidazo(5,1-d)-as-tetrazine-8-carboxamide; 8-carbamoyl-3-methylimidazo(5,1-d)-1,2,3,5-tetrazin-4(3H)-one; Methazolastone; Temozolomide","C6H6N6O2","CN1N=NC2=C(N=CN2C1=O)C(N)=O","Refractory anaplastic astrocytoma (WHO grade III) and Glioblastoma multiforme (WHO grade IV) are primary malignant brain tumours with poor prognosis and limited treatment options. Despite considerable genetic heterogeneity, these tumours often have impaired DNA repair systems, rendering them initially sensitive to alkylating agents, although they invariably develop resistance to these agents over time. Temozolomide is an imidazotetrazine prodrug that is stable at acidic pH but undergoes spontaneous nonenzymatic hydrolysis at neutral or slightly basic pH; these properties allow for both oral and intravenous administration. Following initial hydrolysis, further reactions liberate a highly reactive methyl diazonium cation capable of methylating various residues on adenosine and guanine bases leading to DNA lesions and eventual apoptosis. Temozomolide as an adjunct to radiotherapy followed by maintenance dosing remains the standard of care for both Glioblastoma and refractory anaplastic astrocytoma.\r\n\r\nTemozolomide was granted FDA approval on August 11, 1999, as an oral capsule and subsequently on February 27, 2009, as an intravenous injection. It is currently marketed under the trademark TEMODAR® by Merck.","85622-93-1","194.1508","Temozolomide is indicated in adult patients for the treatment of newly diagnosed glioblastoma concomitantly with radiotherapy and for use as maintenance treatment thereafter. It is also indicated for the treatment of refractory anaplastic astrocytoma in adult patients who have experienced disease progression on a drug regimen containing nitrosourea and procarbazine.","Temozolomide is a prodrug of the imidazotetrazine class that requires nonenzymatic hydrolysis at physiological pH _in vivo_ to perform alkylation of adenine/guanine residues, leading to DNA damage through futile repair cycles and eventual cell death. Temozolomide treatment is associated with myelosuppression, which is likely to be more severe in females and geriatric patients. Patients must have an ANC of ≥1.5 x 10<sup>9</sup>/L and a platelet count of ≥100 x 10<sup>9</sup>/L before starting therapy and must be monitored weekly during the concomitant radiotherapy phase, on days one and 22 of maintenance cycles, and weekly at any point where the ANC/platelet count falls below the specified values until recovery. Cases of myelodysplastic syndrome and secondary malignancies, including myeloid leukemia, have been observed following temozolomide administration. Pneumocystis pneumonia may occur in patients undergoing treatment, and prophylaxis should be provided for patients in the concomitant phase of therapy with monitoring at all stages. Severe hepatotoxicity has also been reported, and liver testing should be performed at baseline, midway through the first cycle, before each subsequent cycle, and approximately two to four weeks after the last dose. Animal studies suggest that temozolomide has significant embryo-fetal toxicity; male and female patients should practice contraception up to three and six months following the last dose of temozolomide, respectively.","Glioblastoma (glioblastoma multiforme) is the most common and aggressive adult primary brain tumour, accounting for 45.6% of all primary malignant brain tumours. Primarily defined histopathologically by necrosis and microvascular proliferation (WHO grade IV classification), glioblastomas are commonly treated through radiotherapy and concomitant alkylation-based chemotherapy with temozolomide. Temozolomide (TMZ) is a small (194 Da) lipophilic alkylating agent of the imidazotetrazine class that is stable at acidic pH, allowing for both oral and intravenous dosing, and can cross the blood-brain barrier to affect CNS tumours. After absorption, TMZ undergoes spontaneous nonenzymatic breakdown at physiological pH to form 5-(3-methyltriazen-1-yl) imidazole-4-carboxamide (MTIC), which then reacts with water to produce 5-aminoimidazole-4-carboxamide (AIC) and a highly reactive methyl diazonium cation. Brain tumours such as glioblastoma typically possess a more alkaline pH than healthy tissue, favouring TMZ activation within tumour tissue.\r\n\r\nThe methyl diazonium cation is highly reactive and methylates DNA at the N7 position of guanine (N7-MeG, 70%), the N3 position of adenine (N3-MeA, 9%), and the O6 position of guanine (O6-MeG, 6%). Although more prevalent, N7-MeG and N3-MeA are rapidly repaired by the base excision repair pathway and are not primary mediators of temozolomide toxicity, although N3-MeA lesions are lethal if not repaired. By comparison, repair of O6-MeG requires action by the suicide enzyme methylguanine-DNA methyltransferase (MGMT), which removes the methyl group to restore guanine. If not repaired by MGMT, O6-MeG mispairs with thymine, activating the DNA mismatch repair (MMR) pathway that removes the thymine (not the O6-MeG), resulting in futile cycles of repair and eventual DNA strand breaks leading to apoptosis. As MMR activity is crucial for temozolomide cytotoxicity, cells that have reduced or absent MGMT function and an intact MMR pathway are the most sensitive to temozolomide treatment. Glioblastomas that upregulate MGMT downregulate MMR or alter both are resistant to TMZ, leading to treatment failure.\r\n\r\nMore recently, increased interest has also been shown in the immunomodulatory effects of TMZ, related to its myelosuppressive effects. Counterintuitively, lymphodepletion may enhance the antitumour effects of cellular immunotherapy and improve the dynamics of memory cells by altering tumour-specific versus tumour-tolerant populations. The depletion of tumour-localized immunosuppressive T<sub>reg</sub> cells may contribute to an improved response to immunotherapy. Hence, TMZ treatment may also form the backbone of immunotherapy strategies against glioblastoma in the future.","DNA cross-linking/alkylation","Therapeutic strategy associated"]
[310,"DB00859","approved","small molecule","Penicillamine","(−)-penicillamine; (S)-2-amino-3-mercapto-3-methylbutanoic acid; (S)-3,3-dimethylcysteine; 3-mercapto-D-valine; D-(−)-penicillamine; D-penicillamine; D-β,β-dimethylcysteine; Penicillamine","C5H11NO2S","[H][C@](N)(C(O)=O)C(C)(C)S","Penicillamine is a pharmaceutical of the chelator class. The pharmaceutical form is D-penicillamine, as L-penicillamine is toxic (it inhibits the action of pyridoxine). It is an α-amino acid metabolite of penicillin, although it has no antibiotic properties.","52-67-5","149.211","For treatment of Wilson's disease, cystinuria and active rheumatoid arthritis.","Penicillamine is a chelating agent used in the treatment of Wilson's disease. It is also used to reduce cystine excretion in cystinuria and to treat patients with severe, active rheumatoid arthritis unresponsive to conventional therapy. Penicillamine is used as a form of immunosuppression to treat rheumatoid arthritis. Penicillamine inhibits macrophages, decreases IL-1 and the number of T-lymphocytes, and prevents collagen cross linkage. In Wilson's disease it binds copper, allowing it to be eliminated in the urine.","Penicillamine is a chelating agent recommended for the removal of excess copper in patients with Wilson's disease. From in vitro studies which indicate that one atom of copper combines with two molecules of penicillamine. Penicillamine also reduces excess cystine excretion in cystinuria. This is done, at least in part, by disulfide interchange between penicillamine and cystine, resulting in formation of penicillamine-cysteine disulfide, a substance that is much more soluble than cystine and is excreted readily. Penicillamine interferes with the formation of cross-links between tropocollagen molecules and cleaves them when newly formed. The mechanism of action of penicillamine in rheumatoid arthritis is unknown although it appears to suppress disease activity. Unlike cytotoxic immunosuppressants, penicillamine markedly lowers IgM rheumatoid factor but produces no significant depression in absolute levels of serum immunoglobulins. Also unlike cytotoxic immunosuppressants which act on both, penicillamine in vitro depresses T-cell activity but not B-cell activity.","Copper chelator","Indication associated"]
[311,"DB00860","approved; vet_approved","small molecule","Prednisolone","(11β)-11,17,21-trihydroxypregna-1,4-diene-3,20-dione; 1,4-pregnadiene-11β,17α,21-triol-3,20-dione; 1,4-pregnadiene-3,20-dione-11β,17α,21-triol; 3,20-dioxo-11β,17α,21-trihydroxy-1,4-pregnadiene; delta-dehydrocortisol; delta-dehydrohydrocortisone; delta-hydrocortisone; delta(1)-Dehydrocortisol; delta(1)-Dehydrohydrocortisone; delta(1)-Hydrocortisone; Hydroretrocortine; Metacortandralone; PRDL; Prednisolone","C21H28O5","[H][C@@]12CC[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)C=C[C@]12C","Prednisolone is a glucocorticoid similar to  used for its anti-inflammatory, immunosuppressive, anti-neoplastic, and vasoconstrictive effects.\r\n\r\nPrednisolone was granted FDA approval on 21 June 1955.","50-24-8","360.444","Prednisolone is indicated to treat endocrine, rheumatic, and hematologic disorders; collagen, dermatologic, ophthalmic, respiratory, and gastrointestinal diseases; allergic and edematous states; and other conditions like tuberculous meningitis.","Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals. Prednisolone has a short duration of action as the half life is 2.1-3.5 hours. Corticosteroids have a wide therapeutic window as patients make require doses that are multiples of what the body naturally produces. Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.","The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.\r\n\r\nGlucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10.\r\n\r\nLower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.","Glucocorticoid receptor agonist","Therapeutic strategy associated"]
[312,"DB00861","approved; investigational","small molecule","Diflunisal","2-(hydroxy)-5-(2,4-difluorophenyl)benzoic acid; 2',4'-difluoro-4-hydroxy-3-biphenylcarboxylic acid; 5-(2,4-difluorophenyl)salicylic acid","C13H8F2O3","OC(=O)C1=C(O)C=CC(=C1)C1=C(F)C=C(F)C=C1","Diflunisal, a salicylate derivative, is a nonsteroidal anti-inflammatory agent (NSAIA) with pharmacologic actions similar to other prototypical NSAIAs. Diflunisal possesses anti-inflammatory, analgesic and antipyretic activity. Though its mechanism of action has not been clearly established, most of its actions appear to be associated with inhibition of prostaglandin synthesis via the arachidonic acid pathway. Diflunisal is used to relieve pain accompanied with inflammation and in the symptomatic treatment of rheumatoid arthritis and osteoarthritis.","22494-42-4","250.1976","For symptomatic treatment of mild to moderate pain accompanied by inflammation (e.g. musculoskeletal trauma, post-dental extraction, post-episiotomy), osteoarthritis, and rheumatoid arthritis.","Diflunisal is a nonsteroidal drug with analgesic, anti-inflammatory and antipyretic properties. It is a peripherally-acting non-narcotic analgesic drug. Habituation, tolerance and addiction have not been reported. Diflunisal is a difluorophenyl derivative of salicylic acid. Chemically, diflunisal differs from aspirin (acetylsalicylic acid) in two respects. The first of these two is the presence of a difluorophenyl substituent at carbon 1. The second difference is the removal of the 0-acetyl group from the carbon 4 position. Diflunisal is not metabolized to salicylic acid, and the fluorine atoms are not displaced from the difluorophenyl ring structure.","The precise mechanism of the analgesic and anti-inflammatory actions of diflunisal is not known. Diflunisal is a prostaglandin synthetase inhibitor. In animals, prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain. Since prostaglandins are known to be among the mediators of pain and inflammation, the mode of action of diflunisal may be due to a decrease of prostaglandins in peripheral tissues.","Prostaglandin G/H synthase 2 inhibitor; Prostaglandin G/H synthase 1 inhibitor","Therapeutic strategy associated"]
[313,"DB00865","approved; illicit","small molecule","Benzphetamine","(+)-benzphetamine; (+)-N-benzyl-N,α-dimethylphenethylamine; (+)-N,α-dimethyl-N-(phenylmethyl)-benzeneethanamine; (S)-(+)-benzphetamine; (S)-(+)-N-benzyl-N,α-dimethylphenethylamine; (S)-benzphetamine; (αS)-N,α-dimethylphenethylamine; Benzaphetamine; Benzfetamine; Benzphetamine; Benzylamphetamine; d-N-methyl-N-benzyl-β-phenylisopropylamine; N-methyl-1-phenyl-N-(phenylmethyl)propan-2-amine","C17H21N","C[C@@H](CC1=CC=CC=C1)N(C)CC1=CC=CC=C1","A sympathomimetic agent with properties similar to dextroamphetamine. It is used in the treatment of obesity. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1222)","156-08-1","239.3553","For the management of exogenous obesity as a short term adjunct (a few weeks) in a regimen of weight reduction based on caloric restriction","Benzphetamine, a phenylalkylamin, is related to amphetamine both chemically and pharmacologically. It is an anorectic agent indicated in the management of exogenous obesity as a short term adjunct (a few weeks) in a regimen of weight reduction based on caloric restriction. Benzphetamine is a sympathomimetic amine with pharmacologic activity similar to the prototype drugs of this class used in obesity, the amphetamines. Actions include central nervous system stimulation and elevation of blood pressure. Tachyphylaxis and tolerance have been demonstrated with all drugs of this class in which these phenomena have been looked for.","The mechanism of action of these drugs is not fully understood, however it may be similar to that of amphetamines. Amphetamines stimulate noepinephrine and dopamine release in nerve endings in the lateral hypothalamic feeding centre, decreasing appetite. This release is mediated by the binding of benzphetamine to centrally located adrenergic receptors.","Synaptic vesicular amine transporter inducer; Alpha-2A adrenergic receptor agonist; Alpha-1A adrenergic receptor agonist; Sodium-dependent dopamine transporter inhibitor","Therapeutic strategy associated"]
[314,"DB00866","experimental; withdrawn","small molecule","Alprenolol","(RS)-1-(2-allylphenoxy)-3-(isopropylamino)propan-2-ol; 1-(2-Allylphenoxy)-3-isopropylamino-2-propanol; 1-(o-Allylphenoxy)-3-(isopropylamino)-2-propanol; Aprenololo","C15H23NO2","CC(C)NCC(O)COC1=CC=CC=C1CC=C","One of the adrenergic beta-antagonists used as an antihypertensive, anti-anginal, and anti-arrhythmic agent. Alprenolol is no longer marketed by AstraZeneca, but may still be available in generic varieties.","13655-52-2","249.3486","For the treatment of hypertension, angina, and arrhythmia","Alprenolol is a non-selective beta-blocker used in the treatment of hypertension, edema, ventricular tachycardias, and atrial fibrillation. Alprenolol impairs AV node conduction and decreases sinus rate and may also increase plasma triglycerides and decrease HDL-cholesterol levels. Alprenolol is nonpolar and hydrophobic, with low to moderate lipid solubility. Alprenolol has little to no intrinsic sympathomimetic activity and, unlike some other beta-adrenergic blocking agents, alprenolol has little direct myocardial depressant activity and does not have an anesthetic-like membrane-stabilizing action.","Alprenolol non-selectively blocks beta-1 adrenergic receptors mainly in the heart, inhibiting the effects of epinephrine and norepinephrine resulting in a decrease in heart rate and blood pressure. Also, with a more minor effect, by binding beta-2 receptors in the juxtaglomerular apparatus, alprenolol inhibits the production of renin, thereby inhibiting angiotensin II and aldosterone production and therefore inhibits the vasoconstriction and water retention due to angiotensin II and aldosterone, respectively.","Beta-1 adrenergic receptor antagonist; Beta-2 adrenergic receptor antagonist; 5-hydroxytryptamine receptor 1A antagonist; Beta-3 adrenergic receptor antagonist","Indication associated"]
[315,"DB00869","approved","small molecule","Dorzolamide","(4S,6S)-4-ethylamino-6-methyl-7,7-dioxo-4,5,6,7-tetrahydro-7lambda*6*-thieno[2,3-b]thiopyran-2-sulfonic acid amide; (4S,trans)-4-(ethylamino)-6-methyl-5,6-dihydro-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide; 4-Ethylamino-6-methyl-7,7-dioxo-4,5,6,7-tetrahydro-7lambda*6*-thieno[2,3-b]thiopyran-2-sulfonic acid amide; 4-ethylamino-6-methyl-7,7-dioxo-4,5,6,7-tetrahydro-7lambda6-thieno[2,3-b]thiopyran-2-sulfonic acid amide; 4S,6S-dorzolamide","C10H16N2O4S3","CCN[C@H]1C[C@H](C)S(=O)(=O)C2=C1C=C(S2)S(N)(=O)=O","Dorzolamide is a non-bacteriostatic sulfonamide derivative  and topical carbonic anhydrase (CA) inhibitor that treats elevated intraocular pressure (IOP) associated with open-angle glaucoma and ocular hypertension. It works by blocking an enzyme in the ciliary process that regulates ion balance and fluid pressure in the eyes. Unlike oral CA inhibitors, dorzolamide has negligible effects of acid-base or electrolyte disturbances and other systemic adverse effects. First marketed in 1995, dorzolamide is available in ophthalmic solutions as monotherapy marketed as Trusopt  or in combination with  as Cosopt PF.","120279-96-1","324.44","Dorzolamide is indicated for the management of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma. It can also be used in combination with  for the same indication in patients who are insufficiently responsive to ophthalmic beta-blockers.\r\n\r\nIts pre-operative use was also investigated to prevent elevated intraocular pressure after neodynium yttrium aluminum garnet laser posterior capsulotomy.","Dorzolamide is a carbonic anhydrase inhibitor that reduces elevated intraocular pressure in open-angle glaucoma or ocular hypertension. When used in combination with topic beta-adrenergic antagonists, dorzolamide has an additive effect of lowering intraocular pressure. The peak ocular hypotensive effect of dorzolamide is observed at about 2 hours following ophthalmic administration.","Elevated intraocular pressure is a characteristic manifestation of ocular hypertension or open-angle glaucoma. The level of intraocular pressure (IOP) is governed by the balance between the production of aqueous humour (by ocular ciliary processes) and its outflow from the anterior segment of the eye via trabecular (conventional) or uveoscleral (unconventional) pathways. When there is an increase in the resistance to the trabecular outflow of aqueous humour, the intraocular pressure is elevated. Subsequently, optic nerve damage can occur from blood flow restrictions and mechanical distortion of ocular structures. Optic nerve damage can further result in optic disc cupping and progressive visual field loss (and blindness in some cases). \r\n\r\nCarbonic anhydrase (CA) is a ubiquitous enzyme that catalyzes the reversible hydration of carbon dioxide to bicarbonate ions and dehydration of carbonic acid. In the ocular ciliary processes, the local production of bicarbonate by CAs promotes sodium and fluid transport. CA-II is a key isoenzyme found primarily in red blood cells (RBCs) that regulates aqueous humour production. Dorzolamide is a highly specific CA-II inhibitor, where it displays a 4000-fold higher affinity for carbonic anhydrase II than carbonic anhydrase I. The inhibition of CA-II in the ciliary process disrupts the formation of bicarbonate ions and reduces sodium and fluid transport, which leads to decreased aqueous humour secretion and reduced intraocular pressure.","Carbonic anhydrase 2 inhibitor; Carbonic anhydrase 4 inhibitor; Carbonic anhydrase 1 inhibitor; Carbonic anhydrase 3 inhibitor","Indication associated"]
[316,"DB00870","approved; withdrawn","small molecule","Suprofen","(±)-2-(p-(2-thenoyl)phenyl)propionic acid; 2-[4-(Thiophene-2-carbonyl)-phenyl]-propionic acid; p-2-thenoylhydratropic acid; Suprofen; Sutoprofen; α-methyl-4-(2-thienylcarbonyl)benzeneacetic acid","C14H12O3S","CC(C(O)=O)C1=CC=C(C=C1)C(=O)C1=CC=CS1","An ibuprofen-type anti-inflammatory analgesic and antipyretic. It inhibits prostaglandin synthesis and has been proposed as an anti-arthritic. It is no longer approved for use in the United States.","40828-46-4","260.308","Used as eye drops to inhibit the miosis (pupil constriction) that may occur during ocular surgery.","Suprofen is a non-steroidal anti-inflammatory analgesic and antipyretic. Ophthalmic anti-inflammatory medicines are used in the eye to lessen problems that can occur during or after some kinds of eye surgery. Sometimes, the pupil of the eye gets smaller during an operation (pupil constriction), making it more difficult for the surgeon to reach some areas of the eye. Suprofen is used to help prevent this.","Suprofen binds to the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isoenzymes, preventing the synthesis of prostaglandins and reducing the inflammatory response. Cyclooxygenase catalyses the formation of prostaglandins and thromboxane from arachidonic acid (itself derived from the cellular phospholipid bilayer by phospholipase A<sub>2</sub>). Prostaglandins act (among other things) as messenger molecules in the process of inflammation. The overall result is a reduction in pain and inflammation in the eyes and the prevention of pupil constriction during surgery. Normally trauma to the anterior segment of the eye (especially the iris) increases endogenous prostaglandin synthesis which leads to constriction of the iris sphincter.","Prostaglandin G/H synthase 1 inhibitor; Prostaglandin G/H synthase 2 inhibitor","Therapeutic strategy associated"]
[317,"DB00872","approved; investigational","small molecule","Conivaptan","4'-((4,5-dihydro-2-methylimidazo(4,5-d)(1)benzazepin-6(1H)-yl)carbonyl)-2-biphenylcarboxanilide; Conivaptan","C32H26N4O2","CC1=NC2=C(CCN(C(=O)C3=CC=C(NC(=O)C4=CC=CC=C4C4=CC=CC=C4)C=C3)C3=CC=CC=C23)N1","Conivaptan is a non-peptide inhibitor of antidiuretic hormone (vasopressin). It was approved in 2004 for hyponatremia (low blood sodium levels) caused by syndrome of inappropriate antidiuretic hormone (SIADH). Conivaptan inhibits both isotypes of the vasopressin receptor (V1a and V2).","210101-16-9","498.5744","For the treatment of euvolemic or hypervolemic hyponatremia (e.g. the syndrome of inappropriate secretion of antidiuretic hormone, or in the setting of hypothyroidism, adrenal insufficiency, pulmonary disorders, etc.) in hospitalized patients.","Conivaptan is a nonpeptide, dual antagonist of arginine vasopressin (AVP) V<sub>1A</sub> and V<sub>2</sub> receptors. The level of AVP in circulating blood is critical for the regulation of water and electrolyte balance and is usually elevated in both euvolemic and hypervolemic hyponatremia. The AVP effect is mediated through V<sub>2</sub> receptors, which are functionally coupled to aquaporin channels in the apical membrane of the collecting ducts of the kidney. These receptors help to maintain plasma osmolality within the normal range by increasing permeability of the renal collecting ducts to water. Vasopressin also causes vasoconstriction through its actions on vascular <sub>1A</sub> receptors. The predominant pharmacodynamic effect of conivaptan in the treatment of hyponatremia is through its V<sub>2</sub> antagonism of AVP in the renal collecting ducts, an effect that results in aquaresis, or excretion of free water. Conivaptan's antagonist activity on V<sub>1A</sub> receptors may also cause splanchnic vasodilation, resulting in possible hypotension or variceal bleeding in patients with cirrhosis. The pharmacodynamic effects of conivaptan include increased free water excretion (i.e., effective water clearance ) generally accompanied by increased net fluid loss, increased urine output, and decreased urine osmolality.","Conivaptan is a dual AVP antagonist with nanomolar affinity for human arginine vasopressin V<sub>1A</sub> and V<sub>2</sub> receptors <i>in vitro</i>. This antagonism occurs in the renal collecting ducts, resulting in aquaresis, or excretion of free water.","Vasopressin V1a receptor antagonist; Vasopressin V2 receptor antagonist","Indication associated"]
[318,"DB14596","approved","small molecule","Loteprednol etabonate","Loteprednol etabonate","C24H31ClO7","[H][C@@]12CC[C@](OC(=O)OCC)(C(=O)OCCl)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)C=C[C@]12C","Loteprednol Etabonate (LE) is a topical corticoid anti-inflammatory. It is used in ophthalmic solution for the treatment of steroid responsive inflammatory conditions of the eye such as allergic conjunctivitis, uveitis, acne rosacea, superficial punctate keratitis, herpes zoster keratitis, iritis, cyclitis, and selected infective conjunctivitides. As a nasal spray, it can be used for the treatment and management of seasonal allergic rhinitis.\r\n\r\nMost prescription LE products, however, tend to be indicated for the treatment of post-operative inflammation and pain following ocular surgery . A number of such new formulations that have been approved include Kala Pharmaceutical's Inveltys - the first twice-daily (BID) ocular corticosteroid approved for this indication, designed specifically to enhance patient compliance and simplified dosing compared to all other similar ocular steroids that are dosed four times daily .\r\n\r\nMoreover, LE was purposefully engineered to be a 'soft drug', one that is designed to be active locally at the site of administration and then rapidly metabolized to inactive components after eliciting its actions at the desired location, thereby subsequently minimizing the chance for adverse effects .","82034-46-6","466.96","A number of prescription loteprednol etabonate ophthalmic products are specifically indicated for the treatment of post-operative inflammation and pain following ocular surgery .","Loteprednol etabonate (LE) belongs to a unique class of corticosteroids with potent anti-inflammatory effects designed to be active at the site of action . Animal studies have shown that LE has a binding affinity to steroid receptors that is 4.3 times greater than dexamethasone . This particular class of steroids consists of bioactive molecules whose in-vivo transformation to non-toxic substances can be predicted from their chemistry and knowledge of enzymatic pathways in the body . Cortienic acid is an inactive metabolite of hydrocortisone and analogs of cortienic acid are also devoid of corticosteroid activity . Specifically, LE is an ester derivative of one of these analogs, cortienic acid etabonate . In particular, LE possesses a metabolically labile 17 beta-chloromethyl ester function which was designed in order to be hydrolyzed to an inactive carboxylic acid moiety . This inactive metabolite is more hydrophilic and is thus readily eliminated from the body . LE also exhibits good ocular permeation properties and good skin permeation properties .","Corticosteroids like loteprednol etabonate inhibit the inflammatory response to a variety of inciting agents and likely delay or slow healing . They inhibit the edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation that are commonly associated with inflammation . While glucocorticoids are known to bind to and activate the glucocorticoid receptor, the molecular mechanisms involved in glucocorticoid/glucocorticoid receptor-dependent modulation of inflammation are not clearly established . Moreover, corticosteroids are thought to inhibit prostaglandin production through several independent mechanisms . In particular, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins . It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid . Arachidonic acid is released from membrane phospholipids by phospholipase A2 .  \r\n\r\nThe use of LE subsequently treats post-operative inflammation and pain following ocular surgery by managing the prostaglandin release, recruitment and travel of neutrophils and macrophages, and production of other inflammatory mediators that are intrinsically associated with the physical trauma of surgery .","Glucocorticoid receptor agonist","Therapeutic strategy associated"]
[319,"DB00875","approved; investigational; withdrawn","small molecule","Flupentixol","Flupenthixol; Flupenthixole; Flupentixolo","C23H25F3N2OS","[H]\\C(CCN1CCN(CCO)CC1)=C1/C2=CC=CC=C2SC2=C1C=C(C=C2)C(F)(F)F","Flupentixol is an antipsychotic drug of the thioxanthene group. It exists in two geometric isomers, the trans(E) and pharmacologically active cis(Z) forms. Flupentixol decanoate is one of the active ingredients found in injectable drug formulations: it is produced by esterification of cis(Z)‐flupentixol with decanoic acid. Flupentixol is an antagonist of both D1 and D2 dopamine receptors.\r\n\r\nAvailable as oral tablets or long-acting intramuscular injections, flupentixol is marketed under brand names such as Depixol and Fluanxol. It is approved for use in Canada and other countries around the world, but not in the US. It is used for the management of chronic schizophrenia in patients whose main manifestations do not include excitement, agitation or hyperactivity. It has been marketed to manage symptoms of depression in patients who may or may not exhibit signs of anxiety. In combination with , flupentixol is used to manage symptoms of anxiety, depression, and asthenia.","2709-56-0","434.52","Flupentixol is indicated for maintenance therapy of chronic schizophrenic patients whose main manifestations do not include excitement, agitation or hyperactivity.\r\n\r\nIt is indicated for the management of depression in adult patients who may, or may not, also be showing signs of anxiety.\r\n\r\nFlupentixol in combination with  is indicated to manage symptoms of anxiety, depression, and asthenia in adults.","Flupentixol is an antipsychotic agent with anxiolytic and mild sedative actions. It exerts weak anticholinergic and adrenergic effects. It possesses antiemetic actions. As flupentixol works by antagonizing dopamine actions, it can cause extrapyramidal effects, mostly at doses greater than 10 mg. In clinical trials, flupentixol-induced extrapyramidal effects have been managed with anti-Parkinsonian drugs. Drug esterification in the intramuscular formulation of the drug results in slow release of the drug from the injection site and a prolonged duration of action. Flupentixol has been investigated for use in mild to moderate depression: compared to other antidepressant agents, flupentixol has a rapid onset of action, where antidepressive effects were observed within the first two to three days after administration.\r\n\r\nAs with other antipsychotic agents, flupentixol can cause QTc prolongation and increase the risk of arrhythmias. In clinical trials, flupentixol was associated with the risk of cardiovascular disease, cerebrovascular adverse events, stroke, and venous thromboembolism. Flupentixol can elevate the levels of prolactin; however, the clinical significance of hyperprolactinemia caused by neuroleptic drugs is unclear. Long-term hyperprolactinemia, when associated with hypogonadism, may lead to decreased bone mineral density in both female and male subjects.\r\n\r\nInterestingly, recent studies show that flupentixol exhibits anti-tumour properties alone or synergistically with other anticancer drugs like gefitinib. One study demonstrated that _in vitro_, flupentixol docks to the ATP binding pocket of phosphatidylinositol 3-kinase (PI3K), a lipid kinase that activates signalling pathways that are often hyperactivated in some cancers. Flupentixol inhibited the PI3K/AKT pathway and survival of lung cancer cells _in vitro_ and _in vivo_.","The mechanism of action of flupentixol is not completely understood. The antipsychotic actions are mainly thought to arise from cis(Z)-flupentixol, the active stereoisomer, acting as an antagonist at both dopamine D<sub>1</sub> and D<sub>2</sub> receptors with equal affinities. Schizophrenia is a mental illness characterized by positive (such as hallucinations and delusions) and negative (such as affect flattening and apathy) symptoms. While several neurotransmitter systems are implicated in the pathophysiologic processes leading to the development of symptoms, the dopamine and glutamate systems have been extensively studied. It is generally understood that positive symptoms of schizophrenia arise from a dysregulated striatal dopamine pathway, leading to hyperstimulation of D<sub>2</sub> receptors. Many antipsychotic agents work by blocking D<sub>2</sub> receptors as antagonists; similarly, cis(Z)-flupentixol, the active stereoisomer, is an antagonist at D<sub>2</sub> receptors. However, there is now evidence that antipsychotic agents can work by blocking other dopamine receptor subtypes, such as D<sub>1</sub>, D<sub>3</sub>, or D<sub>4</sub> receptors. One study showed that cis(Z)-flupentixol is an antagonist at both dopamine D<sub>1</sub> and D<sub>2</sub> receptors with equal affinities, and binds to D3 and D4 receptors with lower affinities. It also binds to alpha-1 adrenoceptors. Antidepressant effects of flupentixol are understood to be mediated by antagonism at 5-HT<sub>2A</sub> receptors, which are commonly downregulated following repeated antidepressant treatment. Flupentixol also binds to 5-HT<sub>2C</sub> receptors.","Dopamine D2 receptor antagonist; Dopamine D1 receptor antagonist; 5-hydroxytryptamine receptor 2A antagonist; Alpha-1A adrenergic receptor antagonist; Dopamine D3 receptor antagonist; Dopamine D4 receptor antagonist; 5-hydroxytryptamine receptor 2C antagonist; Muscarinic acetylcholine receptor M1 antagonist","Indication associated"]
[320,"DB00876","approved","small molecule","Eprosartan","(E)-2-butyl-1-(p-carboxybenzyl)-α-2-thenylimidazole-5-acrylic acid; (E)-3-[2-n-butyl-1-{(4-carboxyphenyl)methyl}-1H-imidazol-5-yl]-2-(2-thienyl)methyl-2-propenoic acid; (E)-α{[2-butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazole-5-yl]methylene}-2-thiopheneproprionic acid","C23H24N2O4S","CCCCC1=NC=C(\\C=C(/CC2=CC=CS2)C(O)=O)N1CC1=CC=C(C=C1)C(O)=O","Eprosartan is an angiotensin II receptor antagonist used to treat hypertension. It performs 2 actions on the renin angiotensin system. By preventing the binding of angiotensin II to AT1, vascular smooth muscle relaxes and vasodilation occurs. By inhibiting norepinephrine production, blood pressure is further reduced.","133040-01-4","424.513","For the management of hypertension alone or in combination with other classes of antihypertensive agents. Also used as a first-line agent in the treatment of diabetic nephropathy, as well as a second-line agent in the treatment of congestive heart failure (only in those intolerant of ACE inhibitors).","Angiotensin II, the principal pressor agent of the renin-angiotensin system, is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme . It is responsible for effects such as vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Eprosartan selectively blocks the binding of angiotensin II to the AT<sub>1</sub> receptor, which in turn leads to multiple effects including vasodilation, a reduction in the secretion of vasopressin, and reduction in the production and secretion of aldosterone. The resulting effect is a decrease in blood pressure.","Eprosartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT<sub>1</sub> receptor found in many tissues (e.g., vascular smooth muscle, adrenal gland). There is also an AT<sub>2</sub> receptor found in many tissues but it is not known to be associated with cardiovascular homeostasis. Eprosartan does not exhibit any partial agonist activity at the AT<sub>1</sub> receptor. Its affinity for the AT<sub>1</sub> receptor is 1,000 times greater than for the AT<sub>2</sub> receptor. In vitro binding studies indicate that eprosartan is a reversible, competitive inhibitor of the AT<sub>1</sub> receptor. Eprosartan has also been shown to bind to AT<sub>1</sub> receptors both presynaptically and synaptically. Its action on presynaptic AT<sub>1</sub> receptors results in the inhibition of sympathetically stimulated noradrenaline release. Unlike ACE inhibitors, eprosartan and other ARBs do not interfere with response to bradykinins and substance P, which allows for the absence of adverse effects that are present in ACE inhibitors (eg. dry cough).","Type-1 angiotensin II receptor antagonist","Target associated"]
[321,"DB00880","approved; vet_approved","small molecule","Chlorothiazide","6-Chloro-1,1-dioxo-1,2-dihydro-1lambda*6*-benzo[1,2,4]thiadiazine-7-sulfonic acid amide; 6-chloro-7-sulfamoyl-2H-1,2,4-benzothiadiazine 1,1-dioxide; Chlorothiazid; Chlorothiazide; Chlorthiazide","C7H6ClN3O4S2","NS(=O)(=O)C1=C(Cl)C=C2NC=NS(=O)(=O)C2=C1","A thiazide diuretic with actions and uses similar to those of hydrochlorothiazide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p812)","58-94-6","295.723","Chlorothiazide is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. It is also indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe forms of hypertension.","Like other thiazides, chlorothiazide promotes water loss from the body (diuretics). It inhibits Na<sup>+</sup>/Cl<sup>-</sup> reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue. Chlorothiazide affects the distal renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosages, all thiazides are approximately equal in their diuretic efficacy. Chlorothiazide increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate. After oral doses, 10-15 percent of the dose is excreted unchanged in the urine. Chlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk.","As a diuretic, chlorothiazide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like chlorothiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of chlorothiazide is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle.","Solute carrier family 12 member 3 inhibitor; Carbonic anhydrase 1 inhibitor; Carbonic anhydrase 2 inhibitor","Therapeutic strategy associated"]
[322,"DB00881","approved; investigational","small molecule","Quinapril",null,"C25H30N2O5","CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@@H](C)C(=O)N1CC2=CC=CC=C2C[C@H]1C(O)=O","Quinapril is the ethyl ester prodrug of the non-sulfhydryl angiotensin converting enzyme inhibitor quinaprilat. It is used to treat hypertension and heart failure. ACE inhibitors are commonly used as a first line therapy in the treatment of hypertension, along with thiazide diuretics or beta blockers.\r\n\r\nQuinapril was granted FDA approval on 19 November 1991. A combination tablet with  was also approved on 28 December 1999.","85441-61-8","438.5161","Quinapril is indicated for the treatment of hypertension and as an adjunct therapy in the treatment of heart failure. Quinapril in combination with hydrochlorothiazide is indicated for the treatment of hypertension.","Quinapril is a prodrug of an angiotensin converting enzyme (ACE) inhibitor used in the treatment of hypertension or adjunct in the treatment of heart failure. Quinapril has a wide therapeutic window and a long duration of action as it is given in doses of 10-80mg once daily.","Angiotensin II constricts coronary blood vessels and is positively inotropic, which under normal circumstances, would increase vascular resistance and oxygen consumption. This action can eventually lead to myocyte hypertrophy and vascular smooth muscle cell proliferation. Angiotensin II also stimulates production of plasminogen activator inhibitor-1 (PAI-1), increasing the risk of thrombosis.\r\n\r\nQuinaprilat prevents the conversion of angiotensin I to angiotensin II by inhibition of angiotensin converting enzyme, and also reduces the breakdown of bradykinin. Reduced levels of angiotensin II lead to lower levels of PAI-1, reducing the risk of thrombosis, especially after a myocardial infarction.","Angiotensin-converting enzyme inhibitor","Indication associated"]
[323,"DB00883","approved; investigational","small molecule","Isosorbide dinitrate","1,4:3,6-Dianhydrosorbitol 2,5-dinitrate; D-Isosorbide dinitrate; Dianhydrosorbitol 2,5-dinitrate; Dinitroisosorbide; Dinitrosorbide; ISDN; Isosorbide 2,5-dinitrate; Isosorbide dinitrate; Sorbide nitrate; Sorbidnitrate","C6H8N2O8","[H][C@]12OC[C@H](O[N+]([O-])=O)[C@@]1([H])OC[C@H]2O[N+]([O-])=O","A vasodilator used in the treatment of angina pectoris. Its actions are similar to nitroglycerin but with a slower onset of action.","87-33-2","236.1363","For the prevention of angina pectoris due to coronary artery disease.","Isosorbide Dinitrate is a moderate to long acting oral organic nitrate used for the relief and prophylactic management of angina pectoris. It relaxes the vascular smooth muscle and consequent dilatation of peripheral arteries and veins, especially the latter. Dilatation of the veins promotes peripheral pooling of blood and decreases venous return to the heart, thereby reducing left ventricular end- diastolic pressure and pulmonary capillary wedge pressure (preload). Arteriolar relaxation reduces systemic vascular resistance, systolic arterial pressure, and mean arterial pressure.","Isosorbide dinitrate is converted to the active nitric oxide to activate guanylate cyclase. This activation increases levels of cyclic guanosine 3',5'-monophosphate (cGMP). cGMP activates protein kinases and causes a series of phosphorylation reactions which leads to dephosphorylation of myosin light chains of smooth muscle fibres. Finally there is a release of calcium ions which causes smooth muscle relaxation and vasodilation.","Atrial natriuretic peptide receptor 1 agonist","Indication associated"]
[324,"DB00884","approved; investigational","small molecule","Risedronic acid","Risedronate; Risedronic acid","C7H11NO7P2","OC(CC1=CN=CC=C1)(P(O)(O)=O)P(O)(O)=O","Risedronic acid is a third generation bisphosphonate that is used for the treatment of some forms of osteoperosis and Paget's disease. It functions by preventing resorption of bone.","105462-24-6","283.1123","Risedronic acid is indicated for the treatment of osteoperosis in men, treatment of Paget's disease, treatment and prevention of osteoperosis in postmenopausal women, and treatment and prevention of glucocorticoid-induced osteoperosis.","Risedronate is a pyridine-based bisphosphonate that inhibits bone resorption caused by osteoclasts.","Risedronatic acid binds to bone hydroxyapatite. Bone resorption causes local acidification, releasing risedronic acid which is that taken into osteoclasts by fluid-phase endocytosis. Endocytic vesicles are acidified, releasing risedronic acid to the cytosol of osteoclasts where they induce apoptosis through inhbition of farnesyl pyrophosphate synthase. Inhibition of osteoclasts results in decreased bone resorption.","Farnesyl pyrophosphate synthase inhibitor; Hydroxylapatite antagonist","Therapeutic strategy associated"]
[325,"DB00885","approved; investigational","small molecule","Pemirolast",null,"C10H8N6O","CC1=CC=CN2C(=O)C(=CN=C12)C1=NNN=N1","Pemirolast potassium is a slightly yellow powder that is soluble in water. It is a mast cell stabilizer that acts as an antiallergic agent. As an ophthalmic aqueous sterile solution, pemirolast is used for the prevention of itching of the eyes caused by allergies such as hay fever, and allergic conjunctivitis. Pemirolast is potentially useful for prophylaxis of pulmonary hypersensitivity reactions to drugs such as paclitaxel.","69372-19-6","228.2101","For the prevention of itching of the eyes caused by allergies such as hay fever, and allergic conjunctivitis","Pemirolast is used for the prophylactic treatment of itching of the eye associated with allergic conjunctivitis. Pemirolast potassium is a mast cell stabilizer that inhibits the <i>in vivo</i> Type I immediate hypersensitivity reaction. Pemirolast inhibits the antigen-induced release of inflammatory mediators (e.g., histamine, leukotriene C4, D4, E4) from human mast cells. Allergic reactions lead to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H<sub>1</sub>-receptors, produces pruritis and vasodilatation (allowing blood fluids to enter the area to cause swelling). Pemirolast is a histamine H1 antagonist. It competes with histamine for the normal H<sub>1</sub>-receptor sites on effector cells of blood vessels to provide effective, temporary relief of watery and itchy eyes.","Pemirolast binds to the histamine H<sub>1</sub> receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine. Pemirolast has also been observed to inhibit antigen-stimulated calcium ion influx into mast cells through the blockage of calcium channels. Pemirolast inhibits the chemotaxis of eosinophils into ocular tissue, and prevents inflammatory mediator release from human eosinophils.",null,"Therapeutic strategy associated"]
[326,"DB00886","investigational","small molecule","Omapatrilat","Omapatrilat; Omapatrilate","C19H24N2O4S2","[H][C@]12CCC[C@H](N1C(=O)[C@H](CCS2)NC(=O)[C@@H](S)CC1=CC=CC=C1)C(O)=O","Omapatrilat is an investigational drug that inhibits both neutral endopeptidase (NEP) and angiotensin converting enzyme (ACE). The inhibition of NEP elevates natriuretic peptide levels, increasing excretion of sodium in urine, dilating blood vessels, and reducing preload and ventricular remodeling. This drug from BMS was not approved by the FDA due to angioedema safety concerns.","167305-00-2","408.53","For the treatment of hypertension.","Omapatrilat is used to treat hypertension. Vasopeptidase inhibitor that simultaneously inhibits angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP). Omapatrilat lowers blood pressure by inhibiting the action of the angiotensin converting enzyme (ACE), which causes blood vessels to constrict. But unlike other drugs, omapatrilat also inhibits another enzyme known as neutral endopeptidase (NEP), which helps blood vessels relax. Omapatrilat demonstrated greater reduction in blood pressure than the ACE inhibitor lisinopril in individuals with salt-sensitive hypertension who typically do not respond well to ACE inhibitors.","Omapatrilat binds to both angiotensin converting enzyme and neutral endopeptidase. This results in a decrease renin-angiotensin-aldosterone production and increase natriuretic peptidase circulation.","Angiotensin-converting enzyme; Neprilysin","Indication associated"]
[327,"DB00896","approved","small molecule","Rimexolone","Rimexolon; Rimexolone","C24H34O3","[H][C@@]12C[C@@H](C)[C@](C)(C(=O)CC)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)C=C[C@]12C","Rimexolone is a 1% eye drop solution is a glucocorticoid steroid. It is used to treat inflammation in the eye. It is marketed as Vexol.","49697-38-3","370.533","For the treatment of postoperative inflammation following ocular surgery and in the treatment of anterior uveitis.","Rimexolone is a glucocorticoid corticosteroid for systemic use. Corticosteroids suppress the inflammatory response to a variety of inciting agents of a mechanical, chemical, or immunological nature. They inhibit edema, cellular infiltration, capillary dilatation, fibroblastic proliferation, deposition of collagen and scar formation associated with inflammation.","Rimexolone is a glucocorticoid receptor agonist. The antiinflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition of arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. By binding to the glucocorticoid receptor, this drug ultimately leads to changes in genetic transcription involving the lipocortins and prostaglandins.","Glucocorticoid receptor agonist","Therapeutic strategy associated"]
[328,"DB00903","approved; investigational","small molecule","Etacrynic acid","(2,3-Dichloro-4-(2-methylene-1-oxobutyl)phenoxy)acetic acid; Etacrinic acid; Etacrynic acid; Ethacrynate; Ethacrynic acid; Methylenebutyrylphenoxyacetic acid","C13H12Cl2O4","CCC(=C)C(=O)C1=C(Cl)C(Cl)=C(OCC(O)=O)C=C1","A compound that inhibits symport of sodium, potassium, and chloride primarily in the ascending limb of Henle, but also in the proximal and distal tubules. This pharmacological action results in excretion of these ions, increased urinary output, and reduction in extracellular fluid. This compound has been classified as a loop or high ceiling diuretic.","58-54-8","303.138","For the treatment of high blood pressure and edema caused by diseases like congestive heart failure, liver failure, and kidney failure.","Ethacrynic acid is a monosulfonamyl loop or high ceiling diuretic. Ethacrynic acid acts on the ascending limb of the loop of Henle and on the proximal and distal tubules. Urinary output is usually dose dependent and related to the magnitude of fluid accumulation. Water and electrolyte excretion may be increased several times over that observed with thiazide diuretics, since ethacrynic acid inhibits reabsorption of a much greater proportion of filtered sodium than most other diuretic agents. Therefore, ethacrynic acid is effective in many patients who have significant degrees of renal insufficiency. Ethacrynic acid has little or no effect on glomerular filtration or on renal blood flow, except following pronounced reductions in plasma volume when associated with rapid diuresis.","Ethacrynic acid inhibits symport of sodium, potassium, and chloride primarily in the ascending limb of Henle, but also in the proximal and distal tubules. This pharmacological action results in excretion of these ions, increased urinary output, and reduction in extracellular fluid. Diuretics also lower blood pressure initially by reducing plasma and extracellular fluid volume; cardiac output also decreases, explaining its antihypertensive action. Eventually, cardiac output returns to normal with an accompanying decrease in peripheral resistance. Its mode of action does not involve carbonic anhydrase inhibition.","Sodium/potassium-transporting ATPase subunit alpha-1 inhibitor; Solute carrier family 12 member 1 inhibitor; Lymphoid enhancer-binding factor 1; Glutathione S-transferase P inhibitor","Therapeutic strategy associated"]
[329,"DB00905","approved; investigational","small molecule","Bimatoprost","(Z)-7-((1R,2R,3R,5S)-3,5-Dihydroxy-2-((1E,3S)-3-hydroxy-5-phenyl-1-pentenyl)cyclopentyl)-N-ethyl-5-heptenamide","C25H37NO4","CCNC(=O)CCC\\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\\C=C\\[C@@H](O)CCC1=CC=CC=C1","Bimatoprost, also known as Latisse or Lumigan, belongs to a group of drugs called prostamides, which are synthetic structural analogs of prostaglandin. Bimatoprost, marketed by Allergan, is administered in both the ophthalmic solution and implant form. It has the ability to reduce ocular hypotension, proving effective in conditions such as ocular hypertension and glaucoma. Bimatoprost is also used to treat eyelash hypotrichosis, or sparse eyelash growth. It was initially approved by the FDA in 2001 for ocular hypertension and later approved for hypothrichosis in 2008, as eyelash growth became a desirable adverse effect for patients using this drug.","155206-00-1","415.5656","Bimatoprost is used for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension.\r\nThese patients must be intolerant to other intraocular pressure lowering medications or inadequately responsive to other treatments.\r\n\r\nBimatoprost is also indicated to treat eyelash hypotrichosis.","High intraocular pressure is a major risk factor for glaucoma-related visual field loss. A linear relationship exists between intraocular pressure and the risk of damaging the optic nerve, which can lead to considerable visual impairment. Therefore, conditions such as ocular hypertension and glaucoma can cause dangerous elevations of intraocular pressure. Bimatoprost rapidly decreases intraocular pressure and reduces the risk for visual field loss from ocular hypertension due to various causes.\r\n\r\nOther effects of this drug may include gradual changes in eyelid pigmentation, changes in iris pigmentation, changes in eyelash pigmentation, growth and thickness. Patients should be informed of these possible effects, especially if this drug is only administered to one eye, which may noticeably change in appearance with bimatoprost treatment.","Bimatoprost imitates the effects of prostamides, specifically prostaglandin F2α. Bimatoprost mildly stimulates aqueous humor outflow, relieving elevated intraocular pressure and decreasing the risk of optic nerve damage. It is thought that bimatoprost reduces intraocular pressure (IOP) in humans by causing an increase in outflow of the aqueous humor via the trabecular meshwork and uveoscleral pathways. It achieves the above effects by decreasing tonographic resistance to aqueous humor outflow.  Bimatoprost does not affect aqueous humor production.","Prostaglandin F2-alpha receptor agonist; Prostaglandin E2 receptor EP1 subtype agonist; Prostaglandin E2 receptor EP3 subtype agonist","Indication associated"]
[330,"DB00912","approved; investigational","small molecule","Repaglinide","Repaglinide","C27H36N2O4","CCOC1=C(C=CC(CC(=O)N[C@@H](CC(C)C)C2=CC=CC=C2N2CCCCC2)=C1)C(O)=O","Repaglinide is an oral antihyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus (NIDDM). It belongs to the meglitinide class of short-acting insulin secretagogues, which act by binding to β cells of the pancreas to stimulate insulin release. Repaglinide induces an early insulin response to meals decreasing postprandial blood glucose levels. It should only be taken with meals and meal-time doses should be skipped with any skipped meal. Approximately one month of therapy is required before a decrease in fasting blood glucose is seen. Meglitnides may have a neutral effect on weight or cause a slight increase in weight. The average weight gain caused by meglitinides appears to be lower than that caused by sulfonylureas and insulin and appears to occur only in those naïve to oral antidiabetic agents. Due to their mechanism of action, meglitinides may cause hypoglycemia although the risk is thought to be lower than that of sulfonylureas since their action is dependent on the presence of glucose. In addition to reducing postprandial and fasting blood glucose, meglitnides have been shown to decrease glycosylated hemoglobin (HbA1c) levels, which are reflective of the last 8-10 weeks of glucose control. Meglitinides appear to be more effective at lowering postprandial blood glucose than metformin, sulfonylureas and thiazolidinediones. Repaglinide is extensively metabolized in the liver and excreted in bile. Repaglinide metabolites do not possess appreciable hypoglycemic activity. Approximately 90% of a single orally administered dose is eliminated in feces and 8% in urine.","135062-02-1","452.5857","As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.","Insulin secretion by pancreatic &beta; cells is partly controlled by cellular membrane potential. Membrane potential is regulated through an inverse relationship between the activity of cell membrane ATP-sensitive potassium channels (ABCC8) and extracellular glucose concentrations. Extracellular glucose enters the cell via GLUT2 (SLC2A2) transporters. Once inside the cell, glucose is metabolized to produce ATP. High concentrations of ATP inhibit ATP-sensitive potassium channels causing membrane depolarization. When extracellular glucose concentrations are low, ATP-sensitive potassium channels open causing membrane repolarization. High glucose concentrations cause ATP-sensitive potassium channels to close resulting in membrane depolarization and opening of L-type calcium channels. The influx of calcium ions stimulates calcium-dependent exocytosis of insulin granules. Repaglinide increases insulin release by inhibiting ATP-sensitive potassium channels in a glucose-dependent manner.","Repaglinide activity is dependent on the presence functioning &beta; cells and glucose. In contrast to sulfonylurea insulin secretatogogues, repaglinide has no effect on insulin release in the absence of glucose. Rather, it potentiates the effect of extracellular glucose on ATP-sensitive potassium channel and has little effect on insulin levels between meals and overnight. As such, repaglinide is more effective at reducing postprandial blood glucose levels than fasting blood glucose levels and requires a longer duration of therapy (approximately one month) before decreases in fasting blood glucose are observed. The insulinotropic effects of repaglinide are highest at intermediate glucose levels (3 to 10 mmol/L) and it does not increase insulin release already stimulated by high glucose concentrations (greater than 15 mmol/L). Repaglinide appears to be selective for pancreatic &beta; cells and does not appear to affect skeletal or cardiac muscle or thyroid tissue.","ATP-binding cassette sub-family C member 8 inhibitor; Peroxisome proliferator-activated receptor gamma agonist","Target associated"]
[331,"DB00914","approved; investigational; withdrawn","small molecule","Phenformin","Fenformin; Phenformin; β-Phenethybiguanide","C10H15N5","NC(=N)NC(=N)NCCC1=CC=CC=C1","A biguanide hypoglycemic agent with actions and uses similar to those of metformin. Although it is generally considered to be associated with an unacceptably high incidence of lactic acidosis, often fatal, it is still available in some countries. (From Martindale, The Extra Pharmacopoeia, 30th ed, p290)","114-86-3","205.2596","For the reatment of type II diabetes mellitus.","Used to treat diabetes, phenformin is a biguanide (contains 2 guanidino groups) hypoglycemic agent with actions and uses similar to those of metformin (Glucophage). Both drugs work by (1) decreasing the absorption of glucose by the intestines, (2) decreasing the production of glucose in the liver, and by (3) increasing the body's ability to use insulin more effectively. More specifically, phenformin improves glycemic control by improving insulin sensitivity. Phenformin is generally considered to be associated with an unacceptably high incidence of actic acidosis. In general biguanides should be used only in stable type II diabetics who are free of liver, kidney and cardiovascular problems and who cannot be controlled with diet.","Phenformin binds to the AMP-activated protein kinase (AMPK). AMPK is an ultra-sensitive cellular energy sensor that monitors energy consumption and down-regulates ATP-consuming processes when activated. The biguanide phenformin has been shown to independently decrease ion transport processes, influence cellular metabolism and activate AMPK. Phenformin's hypoglycemic activity is related the effect it has in activating AMPK and fooling insulin sensitive cells into thinking that insulin levels are low and causing the body to use glucose as if in a state of low caloric consumption. This drug also seems to inhibit several varients of ATP-sensitive potassium channels (namely the receptor subtype Kir6.1).","5'-AMP-activated protein kinase catalytic subunit alpha-1 activator; ATP-sensitive inward rectifier potassium channel 8 inhibitor","Indication associated"]
[332,"DB00920","approved","small molecule","Ketotifen","Ketotifen","C19H19NOS","CN1CCC(CC1)=C1C2=C(SC=C2)C(=O)CC2=CC=CC=C12","Ketotifen is a benzocycloheptathiophene derivative with potent antihistaminic and mast cell stabilizing properties. It has a similar structure to some other first-generation antihistamines such as  and .\r\n\r\nKetotifen was first developed in Switzerland in 1970 by Sandoz Pharmaceuticals and was initially marketed for the treatment of anaphylaxis. In the US, it is now used in an over-the-counter ophthalmic formulation for the treatment of itchy eyes associated with allergies, and in Canada a prescription-only oral formulation is available and indicated as an add-on therapy for children with atopic asthma. In addition, oral ketotifen is used in Mexico and across Europe for the treatment of various allergic symptoms and disorders, including urticaria, mastocytosis, and food allergy.","34580-13-7","309.425","Administered orally, ketotifen is indicated as an add-on medication in the chronic treatment of mild atopic asthma in children. It is also available as an over-the-counter ophthalmic solution which is indicated for the temporary prevention of itching of the eye due to allergic conjunctivitis.","Ketotifen is a non-competitive histamine antagonist and mast cell stabilizer. Administered orally, it functions as a non-bronchodilator antiasthmatic drug by inhibiting the effects of endogenous substances known to be inflammatory mediators. While effects can take 6 to 12 weeks to become apparent, the use of ketotifen has been demonstrated to reduce the frequency, severity, and duration of asthma symptoms, and may allow for a reduction in the use of other asthma therapies.","The precise mechanism(s) through which ketotifen exerts its therapeutic effects are unclear. Ketotifen is a potent and non-competitive antagonist of H1 histamine receptors, which is likely to be a significant contributor to its anti-allergic activity. In addition, ketotifen stabilizes mast cells and has demonstrated _in vitro_ the ability to inhibit the release of allergic and inflammatory mediators such as histamine, leukotrienes C<sub>4</sub> and D<sub>4</sub> (i.e. SRS-A), and platelet-activating factor (PAF).\r\n\r\nOther _in vivo_ observations thought to contribute to ketotifen's efficacy in asthma include the inhibition of various PAF-mediated processes (e.g. airway hyperreactivity, eosinophil and platelet accumulation in the airways), prevention of leukotriene-induced bronchoconstriction, and suppression of eosinophil priming.","Histamine H1 receptor antagonist; 6-phosphogluconate dehydrogenase, decarboxylating inhibitor","Therapeutic strategy associated"]
[333,"DB00922","approved; investigational","small molecule","Levosimendan","Levosimendan","C14H12N6O","C[C@@H]1CC(=O)NN=C1C1=CC=C(NN=C(C#N)C#N)C=C1","Levosimendan increases calcium sensitivity to myocytes by binding to troponin C in a calcium dependent manner. This increases contractility without raising calcium levels. It also relaxes vascular smooth muscle by opening adenosine triphosphate sensitive potassium channels. Levosimendan is used to manage acutely decompensated congestive heart failure.","141505-33-1","280.2847","For short term treatment of acutely decompensated severe chronic heart failure (CHF). Also being investigated for use/treatment in heart disease.","Levosimendan is a new Ca<sup>2+</sup>-sensitizing inotropic agent. Ca<sup>2+</sup> sensitizers represent a new class of inotropic agents, which overcome the disadvantages associated with currently available inotropic agents in as they are not associated with an increased risk of arrhythmias, cell injury and death due to Ca<sup>2+</sup> overload in myocardial cells; they do not increase the activation energy; and they have the potential to reverse contractile dysfunction under pathophysiologic conditions, such as acidosis or myocardial stunning. Levosimendan has not been approved for use in the U.S. or Canada.","Levosimendan appears to increase myofilament calcium sensitivity by binding to cardiac troponin C in a calcium-dependent manner. This stabilizes the calcium-induced conformational change of troponin C, thereby (1) changing actin-myosin cross-bridge kinetics apparently without increasing the cycling rate of the cross-bridges or myocardial ATP consumption, (2) increasing the effects of calcium on cardiac myofilaments during systole and (3) improving contraction at low energy cost (inotropic effect). Calcium concentration and, therefore, sensitization decline during diastole, allowing normal or improved diastolic relaxation. Levosimendan also leads to vasodilation through the opening of ATP-sensitive potassium channels. By these inotropic and vasodilatory actions, levosimendan increases cardiac output without increasing myocardial oxygen demand. Levosimendan also has a selective phosphodiesterase (PDE)-III inhibitory action that may contribute to the inotropic effect of this compound under certain experimental conditions. It has been reported that levosimendan may act preferentially as a Ca<sup>2+</sup> sensitizer at lower concentrations, whereas at higher concentrations its action as a PDE-III inhibitor becomes more prominent in experimental animals and humans.","Troponin C, slow skeletal and cardiac muscles potentiator; ATP-sensitive inward rectifier potassium channel 11 inducer; ATP-sensitive inward rectifier potassium channel 8 inducer; cGMP-inhibited 3',5'-cyclic phosphodiesterase A inhibitor","Indication associated"]
[334,"DB00924","approved","small molecule","Cyclobenzaprine","(3-Dibenzo[a,d]cyclohepten-5-ylidene-propyl)-dimethyl-amine; Cyclobenzaprine; N,N-dimethyl-5H-dibenzo(a,d)cycloheptene-Δ5,γ-propylamine","C20H21N","CN(C)CCC=C1C2=CC=CC=C2C=CC2=CC=CC=C12","Cyclobenzaprine, a centrally-acting muscle relaxant, was first synthesized in 1961 and has been available for human use since 1977. It was initially studied for use as antidepressant given its structural similarity to tricyclic antidepressants - it differs from  by only a single double bond. Since its approval, it has remained relatively popular as an adjunctive, short-term treatment for acute skeletal muscle spasms secondary to musculoskeletal injury.","303-53-7","275.3874","Cyclobenzaprine is indicated as a short-term (2-3 weeks) adjunct therapy, along with rest and physical therapy, for relief of muscle spasm associated with acute, painful musculoskeletal conditions. It has not been found effective in the treatment of spasticity originating from cerebral or spinal cord disease, or spasticity in children with cerebral palsy. Cyclobenzaprine is also occasionally used off-label for reducing pain and sleep disturbances in patients with fibromyalgia.","Cyclobenzaprine is a skeletal muscle relaxant that works on areas of the brainstem to reduce skeletal muscle spasm, though its exact pharmacodynamic behaviour is currently unclear. Despite its long half-life, it is relatively short-acting with a typical duration of action of 4-6 hours. Cyclobenzaprine has been reported to contribute to the development of serotonin syndrome when used in combination with other serotonergic medications. Symptoms of serotonin syndrome may include autonomic instability, changes to mental status, neuromuscular abnormalities, or gastrointestinal symptoms - treatment with cyclobenzaprine should be discontinued immediately if any of these reactions occur during therapy.","The exact mechanism of action of cyclobenzaprine has not been fully elucidated in humans, and much of the information available regarding its mechanism has been ascertained from early animal studies. There is some evidence that cyclobenzaprine exerts its effects at the supraspinal level, specifically within the locus coeruleus of the brainstem, with little-to-no action at neuromuscular junctions or directly on skeletal musculature. Action on the brainstem is thought to result in diminished activity of efferent alpha and gamma motor neurons, likely mediated by inhibition of coeruleus-spinal or reticulospinal pathways, and ultimately depressed spinal cord interneuron activity.\r\n\r\nMore recently it has been suggested that inhibition of descending serotonergic pathways in the spinal cord via action on 5-HT2 receptors may contribute to cyclobenzaprine’s observed effects.","5-hydroxytryptamine receptor 2A antagonist; 5-hydroxytryptamine receptor 2B antagonist; 5-hydroxytryptamine receptor 2C antagonist; 5-hydroxytryptamine receptor 6 antagonist; Sodium-dependent serotonin transporter inhibitor; Sodium-dependent noradrenaline transporter inhibitor; 5-hydroxytryptamine receptor 7 antagonist; Toll-like receptor 4 inhibitor; Aldehyde oxidase inhibitor","Target associated"]
[335,"DB00925","approved","small molecule","Phenoxybenzamine","Fenossibenzamina; Phenoxybenzamine; POB","C18H22ClNO","CC(COC1=CC=CC=C1)N(CCCl)CC1=CC=CC=C1","An alpha-adrenergic antagonist with long duration of action. It has been used to treat hypertension and as a peripheral vasodilator.","59-96-1","303.826","For the treatment of phaeochromocytoma (malignant), benign prostatic hypertrophy and malignant essential hypertension.","Phenoxybenzamine is indicated for the control of episodes of hypertension and sweating that occur with a disease called pheochromocytoma. If tachycardia is excessive, it may be necessary to use a beta-blocking agent concomitantly. Phenoxybenzamine is a long-acting, adrenergic, alpha-receptor blocking agent which can produce and maintain \"chemical sympathectomy\" by oral administration. It increases blood flow to the skin, mucosa and abdominal viscera, and lowers both supine and erect blood pressures. It has no effect on the parasympathetic system. Phenoxybenzamine works by blocking alpha receptors in certain parts of the body. Alpha receptors are present in the muscle that lines the walls of blood vessels. When the receptors are blocked by Phenoxybenzamine, the muscle relaxes and the blood vessels widen. This widening of the blood vessels results in a lowering of blood pressure.","Phenoxybenzamine produces its therapeutic actions by blocking alpha receptors, leading to a muscle relaxation and a widening of the blood vessels. This widening of the blood vessels results in a lowering of blood pressure.","Alpha-1A adrenergic receptor antagonist; Alpha-2A adrenergic receptor antagonist; Alpha-2C adrenergic receptor antagonist; Alpha-2B adrenergic receptor antagonist; Calmodulin inhibitor; Beta-2 adrenergic receptor; Alpha-1B adrenergic receptor antagonist; Alpha-1D adrenergic receptor antagonist","Indication associated"]
[336,"DB00929","approved","small molecule","Misoprostol","Misoprostol","C22H38O5","CCCCC(C)(O)C\\C=C\\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(=O)OC","Misoprostol is a prostaglandin analog used to reduce the risk of NSAID related ulcers, manage miscarriages, prevent post partum hemorrhage, and also for first trimester abortions. The stimulation of prostaglandin receptors in the stomach reduces gastric acid secretion, while stimulating these receptors in the uterus and cervix can increase the strength and frequency of contractions and decrease cervical tone.\r\n\r\nMisoprostol was granted FDA approval on 27 December 1988.","59122-46-2","382.5341","Misoprostol is indicated as a tablet to reduce the risk of NSAID induced gastric ulcers but not duodenal ulcers in high risk patients. Misoprostol is also formulated in combination with diclofenac to treat symptoms of osteoarthritis or rheumatoid arthritis in patients with a high risk of developing gastric ulcers. Misoprostol is used off label for the management of miscarriages, prevention of post partum hemorrhage, and is also used alone or in combination with mifepristone in other countries for first trimester abortions.","Misoprostol is a prostaglandin E1 analog used to reduce the risk of NSAID induced gastric ulcers by reducing secretion of gastric acid from parietal cells. Misoprostol is also used to manage miscarriages and used alone or in combination with mifepristone for first trimester abortions. An oral dose of misoprostol has an 8 minute onset of action and a duration of action of approximately 2 hours, a sublingual dose has an 11 minute onset of action and a duration of action of approximately 3 hours, a vaginal dose has a 20 minute onset of action and a duration of action of approximately 4 hours, and a rectal dose has a 100 minute onset of action and a duration of action of approximately 4 hours.","Misoprostol is a synthetic prostaglandin E1 analog that stimulates prostaglandin E1 receptors on parietal cells in the stomach to reduce gastric acid secretion. Mucus and bicarbonate secretion are also increased along with thickening of the mucosal bilayer so the mucosa can generate new cells. \r\n\r\nMisoprostol binds to smooth muscle cells in the uterine lining to increase the strength and frequency of contractions as well as degrade collagen and reduce cervical tone.","Prostaglandin E2 receptor EP3 subtype agonist; Prostaglandin E2 receptor EP2 subtype agonist; Prostaglandin E2 receptor EP4 subtype agonist; Prostaglandin E2 receptor EP1 subtype agonist","Indication associated"]
[337,"DB00934","approved; investigational","small molecule","Maprotiline","Maprotiline","C20H23N","CNCCCC12CCC(C3=CC=CC=C13)C1=CC=CC=C21","Maprotiline is a tetracyclic antidepressant with similar pharmacological properties to tricyclic antidepressants (TCAs). Similar to TCAs, maprotiline inhibits neuronal norepinephrine reuptake, possesses some anticholinergic activity, and does not affect monoamine oxidase activity. It differs from TCAs in that it does not appear to block serotonin reuptake. Maprotiline may be used to treat depressive affective disorders, including dysthymic disorder (depressive neurosis) and major depressive disorder. Maprotiline is effective at reducing symptoms of anxiety associated with depression.","10262-69-8","277.4033","For treatment of depression, including the depressed phase of bipolar depression, psychotic depression, and involutional melancholia, and may also be helpful in treating certain patients suffering severe depressive neurosis.","Maprotiline is a tetracyclic antidepressant. Although its main therapeutic use is in the treatment of depression, it has also been shown to exert a sedative effect on the anxiety component that often accompanies depression. In one sleep study, it was shown that maprotiline increases the duration of the REM sleep phase in depressed patients, compared to imipramine which reduced the REM sleep phase. Maprotiline is a strong inhibitor of noradrenaline reuptake in the brain and peripheral tissues, however it is worthy to note that it is a weak inhibitor of serotonergic uptake. In addition, it displays strong antihistaminic action (which may explain its sedative effects) as well as weak anticholinergic action. Maprotiline also has lower alpha adrenergic blocking activity than amitriptyline.","Maprotiline exerts its antidepressant action by inhibition of presynaptic uptake of catecholamines, thereby increasing their concentration at the synaptic clefts of the brain. In single doses, the effect of maprotiline on the EEG revealed a rise in the alpha-wave density, a reduction of the alpha-wave frequency and an increase in the alpha-wave amplitude. However, as with other tricyclic antidepressants, maprotiline lowers the convulsive threshold. Maprotiline acts as an antagonist at central presynaptic &alpha;<sub>2</sub>-adrenergic inhibitory autoreceptors and hetero-receptors, an action that is postulated to result in an increase in central noradrenergic and serotonergic activity. Maprotiline is also a moderate peripheral &alpha;<sub>1</sub> adrenergic antagonist, which may explain the occasional orthostatic hypotension reported in association with its use. Maprotiline also inhibits the amine transporter, delaying the reuptake of noradrenaline and norepinephrine. Lastly, maprotiline is a strong inhibitor of the histamine H<sub>1</sub> receptor, which explains its sedative actions.","Sodium-dependent noradrenaline transporter inhibitor; Histamine H1 receptor antagonist; Muscarinic acetylcholine receptor M1 antagonist; Muscarinic acetylcholine receptor M2 antagonist; Muscarinic acetylcholine receptor M3 antagonist; Muscarinic acetylcholine receptor M4 antagonist; Muscarinic acetylcholine receptor M5 antagonist; Alpha-1 adrenergic receptors antagonist; 5-hydroxytryptamine receptor 2A binder; 5-hydroxytryptamine receptor 2C binder; 5-hydroxytryptamine receptor 7 antagonist; Dopamine D2 receptor binder; Alpha-2 adrenergic receptors antagonist","Indication associated"]
[338,"DB00936","approved; investigational; vet_approved","small molecule","Salicylic acid","2-Carboxyphenol; 2-Hydroxybenzoic acid; O-carboxyphenol; O-hydroxybenzoic acid; Salicylic acid","C7H6O3","OC(=O)C1=CC=CC=C1O","A compound obtained from the bark of the white willow and wintergreen leaves, and also prepared synthetically. It has bacteriostatic, fungicidal, and keratolytic actions. Its salts, the salicylates, are used as analgesics.","69-72-7","138.1207","Key additive in many skin-care products for the treatment of acne, psoriasis, callouses, corns, keratosis pilaris and warts.","Salicylic acid treats acne by causing skin cells to slough off more readily, preventing pores from clogging up. This effect on skin cells also makes salicylic acid an active ingredient in several shampoos meant to treat dandruff. Use of straight salicylic solution may cause hyperpigmentation on unpretreated skin for those with darker skin types (Fitzpatrick phototypes IV, V, VI), as well as with the lack of use of a broad spectrum sunblock. Subsalicylate in combination with bismuth form the popular stomach relief aid known commonly as Pepto-Bismol. When combined the two key ingredients help control diarrhea, nausea, heartburn, and even gas. It is also very mildly anti-biotic.","Salicylic acid directly irreversibly inhibits COX-1 and COX-2 to decrease conversion of arachidonic acid to precursors of prostaglandins and thromboxanes. Salicylate's use in rheumatic diseases is due to it's analgesic and anti-inflammatory activity. Salicylic acid is a key ingredient in many skin-care products for the treatment of acne, psoriasis, calluses, corns, keratosis pilaris, and warts. Salicylic acid allows cells of the epidermis to more readily slough off. Because of its effect on skin cells, salicylic acid is used in several shampoos used to treat dandruff. Salicylic acid is also used as an active ingredient in gels which remove verrucas (plantar warts). Salicylic acid competitively inhibits oxidation of uridine-5-diphosphoglucose (UDPG) with nicotinamide adenosine dinucleotide (NAD) and noncompetitively with UDPG. It also competitively inhibits the transferring of the glucuronyl group of uridine-5-phosphoglucuronic acid (UDPGA) to a phenolic acceptor. Inhibition of mucopoly saccharide synthesis is likely responsible for the slowing of wound healing with salicylates.","Prostaglandin G/H synthase 1 inhibitor; Prostaglandin G/H synthase 2 inhibitor; Aldo-keto reductase family 1 member C1 inhibitor","Therapeutic strategy associated"]
[339,"DB00937","approved; illicit","small molecule","Diethylpropion","(±)-diethylpropion; 1-phenyl-2-diethylamino-1-propanone; 2-(diethylamino)-1-phenyl-1-propanone; 2-(diethylamino)propiophenone; alpha-Benzoyltriethylamine; alpha-Diethylaminopropiophenone; Amfepramone; Diethylcathinone","C13H19NO","CCN(CC)C(C)C(=O)C1=CC=CC=C1","A appetite depressant considered to produce less central nervous system disturbance than most drugs in this therapeutic category. It is also considered to be among the safest for patients with hypertension. (From AMA Drug Evaluations Annual, 1994, p2290)","90-84-6","205.2961","Used in the management of exogenous obesity as a short-term adjunct (a few weeks) in a regimen of weight reduction based on caloric restriction.","Diethylpropion is a sympathomimetic stimulant drug marketed as an appetite suppressant. Chemically, it is the N,N-diethyl analog of cathinone. Its mechanism of action is similar to other appetite suppressants such as sibutramine, phentermine and dextroamphetamine.","Diethylpropion is an amphetamine that stimulates neurons to release or maintain high levels of a particular group of neurotransmitters known as catecholamines; these include dopamine and norepinephrine. High levels of these catecholamines tend to suppress hunger signals and appetite. Diethylpropion (through catecholamine elevation) may also indirectly affect leptin levels in the brain. It is theorized that diethylpropion can raise levels of leptin which signal satiety. It is also theorized that increased levels of the catecholamines are partially responsible for halting another chemical messenger known as neuropeptide Y. This peptide initiates eating, decreases energy expenditure, and increases fat storage.","Sodium-dependent noradrenaline transporter inhibitor; Sodium-dependent dopamine transporter inhibitor","Indication associated"]
[340,"DB00939","approved; vet_approved","small molecule","Meclofenamic acid","Meclofenamate; Meclofenamic acid; N-(2,6-dichloro-3-methylphenyl)anthranilic acid; N-(2,6-dichloro-m-tolyl)anthranilic acid; N-(3-methyl-2,6-dichlorophenyl)anthranilic acid","C14H11Cl2NO2","CC1=C(Cl)C(NC2=CC=CC=C2C(O)=O)=C(Cl)C=C1","A non-steroidal anti-inflammatory agent with antipyretic and antigranulation activities. It also inhibits prostaglandin biosynthesis.","644-62-2","296.149","For the relief of mild to moderate pain, for the treatment of primary dysmenorrhea and for the treatment of idiopathic heavy menstrual blood loss. Also for relief of the signs and symptoms of acute and chronic rheumatoid arthritis and osteoarthritis.","Meclofenamic acid is a nonsteroidal agent which has demonstrated anti-inflammatory, analgesic, and antipyretic activity in laboratory animals.","The mode of action, like that of other nonsteroidal anti-inflammatory agents, is not known. Therapeutic action does not result from pituitary-adrenal stimulation. In animal studies, meclofenamic acid was found to inhibit prostaglandin synthesis and to compete for binding at the prostaglandin receptor site. In vitro meclofenamic acid was found to be an inhibitor of human leukocyte 5-lipoxygenase activity. These properties may be responsible for the anti-inflammatory action of meclofenamic acid. There is no evidence that meclofenamic acid alters the course of the underlying disease.","Prostaglandin G/H synthase 1 inhibitor; Prostaglandin G/H synthase 2 inhibitor; Arachidonate 5-lipoxygenase inhibitor; Potassium voltage-gated channel subfamily KQT member 2 other; Potassium voltage-gated channel subfamily KQT member 3 other","Therapeutic strategy associated"]
[341,"DB00940","approved; investigational","small molecule","Methantheline","Methantheline; Methantheline cation; Methantheline ion; Methanthelinium; Methanthelinum","C21H26NO3","CC[N+](C)(CC)CCOC(=O)C1C2=CC=CC=C2OC2=CC=CC=C12","Methantheline is a synthetic antispasmodic. Antispasmodics are used to relieve cramps or spasms of the stomach, intestines, and bladder. Methantheline is used to treat intestine or stomach ulcers (peptic ulcer disease), intestine problems (irritable bowel syndrome), pancreatitis, gastritis, biliary dyskinesia, pylorosplasm, or urinary problems (reflex neurogenic bladder in children).","5818-17-7","340.436","For the treatment of peptic ulcer disease, irritable bowel syndrome, pancreatitis, gastritis, biliary dyskinesia, pylorosplasm, and reflex neurogenic bladder in children.","Methantheline is a synthetic quarternary ammonium antimuscarinic used to relieve cramps or spasms of the stomach, intestines, and bladder. It can be used together with antacids or other medicines, such as H2-receptor antagonists, in the treatment of peptic ulcer. Methantheline inhibits muscarinic actions at postganglionic parasympathetic neuroeffector sites.","Methantheline inhibits the muscarinic actions of acetylcholine on structures innervated by postganglionic cholinergic nerves as well as on smooth muscles that respond to acetylcholine but lack cholinergic innervation. These postganglionic receptor sites are present in the autonomic effector cells of the smooth muscle, cardiac muscle, sinoatrial and atrioventricular nodes, and exocrine glands. Depending on the dose, anticholinergics may reduce the motility and secretory activity of the gastrointestinal system, and the tone of the ureter and urinary bladder and may have a slight relaxant action on the bile ducts and gallbladder.","Muscarinic acetylcholine receptor M1 antagonist; Histamine H2 receptor antagonist; Muscarinic acetylcholine receptor M2; Muscarinic acetylcholine receptor M3; Muscarinic acetylcholine receptor M4; Muscarinic acetylcholine receptor M5","Indication associated"]
[342,"DB00946","approved; investigational","small molecule","Phenprocoumon","3-(1-Phenylpropyl)-4-hydroxycoumarin; 3-(1'-Phenyl-propyl)-4-oxycoumarin; 3-(alpha-Ethylbenzyl)-4-hydroxycoumarin; 3-(alpha-Phenylpropyl)-4-hydroxycoumarin; 4-Hydroxy-3-(1-phenylpropyl)-2H-1-benzopyran-2-one; 4-hydroxy-3-(1-phenylpropyl)-2H-chromen-2-one; Fenprocumone; Phenprocoumarol; Phenprocoumarole; Phenprocoumon; Phenprocumone","C18H16O3","CCC(C1=CC=CC=C1)C1=C(O)C2=C(OC1=O)C=CC=C2","Coumarin derivative that acts as a long-acting oral anticoagulant.","435-97-2","280.3178","Used for the prevention and treatment of thromboembolic disease including venous thrombosis, thromboembolism, and pulmonary embolism as well as for the prevention of ischemic stroke in patients with atrial fibrillation (AF).","Phenprocoumon, a coumarin anticoagulant, thins the blood by antagonizing vitamin K which is required for the production of clotting factors in the liver. Anticoagulants such as phenprocoumon have no direct effect on an established thrombus, nor do they reverse ischemic tissue damage (damage caused by an inadequate blood supply to an organ or part of the body). However, once a thrombus has occurred, the goal of anticoagulant treatment is to prevent further extension of the formed clot and prevent secondary thromboembolic complications which may result in serious and possibly fatal sequelae.","Phenprocoumon inhibits vitamin K reductase, resulting in depletion of the reduced form of vitamin K (vitamin KH2). As vitamin K is a cofactor for the carboxylation of glutamate residues on the N-terminal regions of vitamin K-dependent proteins, this limits the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulant proteins. The synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S is inhibited. Depression of three of the four vitamin K-dependent coagulation factors (factors II, VII, and X) results in decreased prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.","Vitamin K epoxide reductase complex subunit 1 inhibitor","Indication associated"]
[343,"DB00950","approved; investigational","small molecule","Fexofenadine","4-(1-Hydroxy-4-(4-(hydroxydiphenylmethyl)-1-piperidinyl)butyl)-alpha,alpha-dimethylbenzeneacetic acid; Carboxyterfenadine; Fexofenadine; Terfenadine acid metabolite; Terfenadine carboxylate; Terfenadine-COOH","C32H39NO4","CC(C)(C(O)=O)C1=CC=C(C=C1)C(O)CCCN1CCC(CC1)C(O)(C1=CC=CC=C1)C1=CC=CC=C1","Fexofenadine is an over-the-counter second-generation antihistamine used in the treatment of various allergic symptoms. It is selective for the H<sub>1</sub> receptor, carries little-to-no activity at off-targets, and does not cross the blood-brain barrier - this is in contrast to previous first-generation antihistamines, such as , which readily bind to off-targets that contribute to side effects such as sedation. Fexofenadine is the major active metabolite of  and is administered as a racemic mixture in which both enantiomers display approximately equivalent antihistamine activity.","83799-24-0","501.6564","In the United States, fexofenadine is indicated for the symptomatic treatment of allergic rhinitis in patients ≥2 years old and chronic idiopathic urticaria in patients ≥6 months old. In Canada, fexofenadine carries the same indications but is approved only for patients ≥12 years old. Fexofenadine is also available in combination with  for the symptomatic treatment of season allergic rhinitis in patients ≥12 years old.","Fexofenadine relieves allergy symptoms by antagonizing the actions of histamine, an endogenous compound predominantly responsible for allergic symptomatology. The relatively long duration of action of fexofenadine (approximately 24 hours) allows for once or twice daily dosing, and its rapid absorption allows for an onset of action within 1-3 hours. Fexofenadine should not be taken with fruit juice, as this may impair its absorption.","The H<sub>1</sub> histamine receptor is responsible for mediating hypersensitivity and allergic reactions. Exposure to an allergen results in degranulation of mast cells and basophils, which then release histamine and other inflammatory mediators. Histamine binds to, and activates, H<sub>1</sub> receptors, which results in the further release of pro-inflammatory cytokines, such as interleukins, from basophils and mast cells. These downstream effects of histamine binding are responsible for a wide variety of allergic symptoms, such as pruritus, rhinorrhea, and watery eyes.\r\n\r\nFexofenadine is considered an “inverse agonist” of the H<sub>1</sub> receptor because it binds to and stabilizes the inactive form of the receptor, preventing its activation and subsequent downstream effects. It has a potent and selective affinity for H<sub>1</sub> receptors, and there is no evidence that it carries antidopaminergic, antiserotonergic, anticholinergic, sedative, or adrenergic blocking activity. Fexofenadine does not cross the blood-brain barrier and thus is unlikely to cause significant CNS effects.","Histamine H1 receptor antagonist","Therapeutic strategy associated"]
[344,"DB00954","experimental","small molecule","Dirithromycin","(9S)-9-deoxo-11-deoxy-9,11-(imino((1R)-2-(2-methoxyethoxy)ethylidene)oxy)erythromycin; Dirithromycin","C42H78N2O14","CC[C@H]1OC(=O)[C@H](C)[C@@H](O[C@H]2C[C@@](C)(OC)[C@@H](O)[C@H](C)O2)[C@H](C)[C@@H](O[C@@H]2O[C@H](C)C[C@@H]([C@H]2O)N(C)C)[C@](C)(O)C[C@@H](C)[C@@H]2N[C@@H](COCCOC)O[C@H]([C@H]2C)[C@]1(C)O","Dirithromycin is a macrolide glycopeptide antibiotic used to treat many different types of bacterial infections, such as bronchitis, pneumonia, tonsillitis, and even skin infections.","62013-04-1","835.086","For the treatment of the following mild-to-moderate infections caused by susceptible strains of microorganisms: acute bacterial exacerbations of chronic bronchitis, secondary bacterial infection of acute bronchitis, community-acquired pneumonia, pharyngitis/tonsilitis, and uncomplicated skin and skin structure infections.","Dirithromycin is a pro-drug which is converted non-enzymatically during intestinal absorption into the microbiologically active moiety erythromycylamine. Erythromycylamine exerts its activity by binding to the 50S ribosomal subunits of susceptible mircoorganisms resulting in inhibition of protein synthesis. Dirithromycin/erythromycylamine has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections: <i>Staphylococcus aureus</i> (methicillin-susceptible strains only), <i>Streptococcus pneumoniae</i>, <i>Streptococcus pyogenes</i>, <i>Haemophilus influenzae</i>, <i>Legionella pneumophila</i>, <i>Moraxella catarrhalis</i>, and <i>Mycoplasma pneumoniae</i>.","Dirithromycin prevents bacteria from growing, by interfering with their protein synthesis. Dirithromycin binds to the 50S subunit of the 70S bacterial ribosome, and thus inhibits the translocation of peptides. Dirithromycin has over 10 times higher affinity to the subunit 50S than erythromycin. In addition, dirithromycin binds simultaneously in to two domains of 23S RNA of the ribosomal subunit 50S, where older macrolides bind only in one. Dirithromycin can also inhibit the formation of ribosomal subunits 50S and 30S.","23S ribosomal RNA inhibitor","Indication associated"]
[345,"DB00959","approved; vet_approved","small molecule","Methylprednisolone","(6α,11β)-11,17,21-trihydroxy-6-methylpregna-1,4-diene-3,20-dione; 1-dehydro-6α-methylhydrocortisone; 6α-methyl-11β,17α,21-triol-1,4-pregnadiene-3,20-dione; delta(1)-6alpha-Methylhydrocortisone; Methylprednisolone","C22H30O5","[H][C@@]12CC[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])C[C@H](C)C2=CC(=O)C=C[C@]12C","Methylprednisolone is a  derivative glucocorticoid with higher potency than . It was first described in the literature in the late 1950s.\r\n\r\nMethylprednisolone was granted FDA approval on 24 October 1957. In the outbreak of COVID-19, low dose methylprednisolone-based therapy was successful in treating COVID-19-associated pneumonia in one patient with long-term immunosuppression. The efficacy of methylprednisolone in novel coronavirus pneumonia is being investigated further in clinical trials.","83-43-2","374.4706","Oral and intramuscular methylprednisolone are indicated for a number of endocrine,  rheumatic, collagen, dermatologic, allergic, ophthalmic, respiratory, hematologic, neoplastic, edematous, gastrointestinal, nervous system, and other disorders. Intra-articular and soft tissue injections are indicated for short term treatment of acute gouty arthritis, acute and subactute bursitis, acute nonspecific tenosynovitis, epicondylitis, rheumatoid arthritis, and synovitis of osteoarthritis. Intralesional injections are indicated for alopecia areata, discoid lupus erythematosus, keloids, lichen planus, lichen simplex chronicus and psoriatic plaques, necrobiosis lipoidica diabeticorum, and localized hypertrophic infiltrated inflammatory lesions of granuloma annulare.","Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals. Corticosteroids have a wide therapeutic window as patients may require doses that are multiples of what the body naturally produces. Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.","The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.\r\n\r\nGlucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10.\r\n\r\nLower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.","Glucocorticoid receptor agonist; Annexin A1 agonist","Therapeutic strategy associated"]
[346,"DB00960","approved; investigational","small molecule","Pindolol","1-(1H-indol-4-yloxy)-3-(isopropylamino)propan-2-ol; 1-(1H-indol-4-yloxy)-3-(propan-2-ylamino)-propan-2-ol; 1-(1H-indol-4-yloxy)-3-[(1-methylethyl)amino]propan-2-ol; 4-(2-hydroxy-3-isopropylaminopropoxy)-indole; Pindolol","C14H20N2O2","CC(C)NCC(O)COC1=CC=CC2=C1C=CN2","Pindolol is a first generation non-selective beta blocker used in the treatment of hypertension. Early research into the use of pindolol found it had chronotropic effects, and so further investigation focused on the treatment of arrhythmia. Research into pindolol's use in the treatment of hypertension began in the early 1970s.\r\n\r\nPindolol was granted FDA approval on 3 September 1982.","13523-86-9","248.3208","Pindolol is indicated in the management of hypertension. In Canada, it is also indicated in the prophylaxis of angina.","Pindolol is a nonselective beta blocker indicated in the management of hypertension and prophylaxis of angina. It has a short duration of action as it is given twice daily, and a wide therapeutic window as doses can range from 10-60 mg/day. Patients should be counselled regarding the risk of cardiac failure, exacerbating ischemic heart disease with sudden withdrawal, nonallergic bronchospasm, masking hypoglycemia in diabetics, and masking hyperthyroidism.","The beta-1 adrenoceptor is a G-protein-coupled receptor. Agonism of the beta-1 adrenoceptor allows the Gs subunit to upregulate adenylyl cyclase, converting ATP to cyclic AMP (cAMP). Increased concentrations of cAMP activate cAMP-dependant kinase A, phosphorylating calcium channels, raising intracellular calcium, increasing calcium exchange through the sarcoplasmic reticulum, and increasing cardiac inotropy. cAMP-dependant kinase A also phosphorylates myosin light chains, increasing smooth muscle contractility. Increased smooth muscle contractility in the kidney releases renin.\r\n\r\nPindolol is a non-selective beta blocker. Blocking beta-1 adrenergic receptors in the heart results in decreased heart rate and blood pressure. By blocking beta-1 receptors in the juxtaglomerular apparatus, pindolol inhibits the release of renin, which inhibits angiotensin II and aldosterone release. Reduced angiotensin II inhibits vasoconstriction and reduced aldosterone inhibits water retention.\r\n\r\nBeta-2 adrenoceptors located in the kidneys and peripheral blood vessels use a similar mechanism to activate cAMP-dependant kinase A to increase smooth muscle contractility. Blocking of the beta-2 adrenoceptor relaxes smooth muscle, leading to vasodilation.","Beta-1 adrenergic receptor partial agonist; Beta-2 adrenergic receptor partial agonist; 5-hydroxytryptamine receptor 1A antagonist&inhibitor&ligand; 5-hydroxytryptamine receptor 1B other/unknown&ligand; Beta-3 adrenergic receptor agonist; Beta adrenergic receptor inhibitor","Indication associated"]
[347,"DB00963","approved","small molecule","Bromfenac","[2-Amino-3-(4-bromo-benzoyl)-phenyl]-acetic acid; 2-amino-3-(4-bromobenzoyl)benzeneacetic acid; Bromfenac","C15H12BrNO3","NC1=C(CC(O)=O)C=CC=C1C(=O)C1=CC=C(Br)C=C1","Bromfenac is a nonsteroidal anti-inflammatory drug (NSAID) for ophthalmic use. Ophthalmic NSAIDs are becoming a cornerstone for the management of ocular pain and inflammation. Their well-characterized anti-inflammatory activity, analgesic property, and established safety record have also made NSAIDs an important tool to optimize surgical outcomes.","91714-94-2","334.165","For the treatment of postoperative inflammation in patients who have undergone cataract extraction.","Bromfenac ophthalmic solution is a sterile, topical, nonsteroidal anti-inflammatory drug (NSAID) for ophthalmic use.","The mechanism of its action is thought to be due to its ability to block prostaglandin synthesis by inhibiting cyclooxygenase 1 and 2. Prostaglandins have been shown in many animal models to be mediators of certain kinds of intraocular inflammation. In studies performed in animal eyes, prostaglandins have been shown to produce disruption of the blood-aqueous humor barrier, vasodilation, increased vascular permeability, leukocytosis, and increased intraocular pressure.","Prostaglandin G/H synthase 2 inhibitor; Prostaglandin G/H synthase 1 inhibitor","Therapeutic strategy associated"]
[348,"DB00968","approved","small molecule","Methyldopa","(S)-(-)-alpha-Methyldopa; 3-Hydroxy-alpha-methyl-L-tyrosine; Alpha medopa; alpha-Methyl dopa; alpha-methyl-L-dopa; Alphamethyldopa; AMD; Anhydrous methyldopa; L-alpha-Methyldopa; L-Methyl Dopa; Methyl dopa; Methyldopa; Methyldopa anhydrous; α-Methyl dopa; α-methyl-L-dopa","C10H13NO4","C[C@](N)(CC1=CC=C(O)C(O)=C1)C(O)=O","Methyldopa, or α-methyldopa, is a centrally acting sympatholytic agent and an antihypertensive agent. It is an analog of DOPA (3,4‐hydroxyphenylanine), and it is a prodrug, meaning that the drug requires biotransformation to an active metabolite for therapeutic effects. Methyldopa works by binding to alpha(α)-2 adrenergic receptors as an agonist, leading to the inhibition of adrenergic neuronal outflow and reduction of vasoconstrictor adrenergic signals. Methyldopa exists in two isomers D-α-methyldopa and L-α-methyldopa, which is the active form.\r\n\r\nFirst introduced in 1960 as an antihypertensive agent, methyldopa was considered to be useful in certain patient populations, such as pregnant women and patients with renal insufficiency. Since then, methyldopa was largely replaced by newer, better-tolerated antihypertensive agents; however, it is still used as monotherapy  or in combination with . Methyldopa is also available as intravenous injection, which is used to manage hypertension when oral therapy is unfeasible and to treat hypertensive crisis.","555-30-6","211.2145","Methyldopa is indicated for the management of hypertension as monotherapy  or in combination with hydrochlorothiazide. Methyldopa injection is used to manage hypertensive crises.","Antihypertensive effects of methyldopa are mostly mediated by its pharmacologically active metabolite, alpha-methylnorepinephrine, which works as an agonist at central inhibitory alpha-adrenergic receptors. Stimulation of alpha-adrenergic receptors leads to decreased peripheral sympathetic tone and reduced arterial pressure. Methyldopa causes a net reduction in the tissue concentration of serotonin, dopamine, norepinephrine, and epinephrine. Overall, methyldopa lowers both standing blood pressure and especially supine blood pressure, with infrequent symptomatic postural hypotension. Methyldopa also reduces plasma renin activity but has negligible effects on glomerular filtration rate, renal blood flow, or filtration fraction. It also has no direct effect on cardiac function but in some patients, a slowed heart rate may occur.\r\n\r\nFollowing oral administration, blood-pressure-lowering effects are observed within 12 to 24 hours in most patients, and a maximum reduction in blood pressure occurs in 4 to 6 hours. Blood pressure returns to pre-treatment levels within 24 to 48 hours following drug discontinuation. Following intravenous administration, the blood-pressure-lowering effects of methyldopa last for about 10 to 16 hours.","The exact mechanism of methyldopa is not fully elucidated; however, the main mechanisms of methyldopa involve its actions on alpha-adrenergic receptor and the aromatic L-amino acid decarboxylase enzyme, to a lesser extent. The sympathetic outflow is regulated by alpha (α)-2 adrenergic receptors and imidazoline receptors expressed on adrenergic neurons within the rostral ventrolateral medulla. Methyldopa is metabolized to α‐methylnorepinephrine via dopamine beta-hydroxylase activity and, consequently, alpha-methylepinephrine via phenylethanolamine-N-methyltransferase activity. Mediating the therapeutic effects of methyldopa, α‐methylnorepinephrine and α-methylepinephrine active metabolites are agonists at presynaptic alpha-2 adrenergic receptors in the brainstem. Stimulating alpha-2 adrenergic receptors results in the inhibition of adrenergic neuronal outflow and attenuation of norepinephrine release in the brainstem. Consequently, the output of vasoconstrictor adrenergic signals to the peripheral sympathetic nervous system is reduced, leading to a reduction in blood pressure.\r\n\r\nThe L-isomer of alpha-methyldopa also reduces blood pressure by inhibiting aromatic L-amino acid decarboxylase, also known as DOPA decarboxylase, which is an enzyme responsible for the syntheses of dopamine and serotonin. Inhibiting this enzyme leads to depletion of biogenic amines such as norepinephrine. However, inhibition of aromatic L-amino acid decarboxylase plays a minimal role in the blood-pressure‐lowering effect of methyldopa.","Alpha-2A adrenergic receptor agonist; Aromatic-L-amino-acid decarboxylase inhibitor","Therapeutic strategy associated"]
[349,"DB00969","approved; withdrawn","small molecule","Alosetron","2,3,4,5-Tetrahydro-5-methyl-2-((5-methyl-1H-imidazol-4-yl)methyl)-1H-pyrido(4,3-b)indol-1-one; Alosetron","C17H18N4O","CN1C2=C(C3=CC=CC=C13)C(=O)N(CC1=C(C)NC=N1)CC2","Alosetron is a 5-HT3 antagonist used only for the management of severe diarrhoea-predominant irritable bowel syndrome (IBS) in women. Alosetron has an antagonist action on the 5-HT3 receptors and thus may modulate serotonin-sensitive gastrointestinal (GI) processes. Alosetron was voluntarily withdrawn from the US market in November 2000 by the manufacturer due to numerous reports of severe adverse effects including ischemic colitis, severely obstructed or ruptured bowel, and death. In June 2002, the FDA approved a supplemental new drug application allowing the remarketing of the drug under restricted conditions of use.","122852-42-0","294.351","Only for the treatment of symptoms of severe diarrhea-predominant irritable bowel syndrome (IBS) in women with chronic symptoms (generally lasting greater than 6 months) who does not present with anatomic or biochemical GI abnormalities and have not responded to conventional therapy.","Alosetron is a potent and selective antagonist of the serotonin 5-HT<sub>3</sub> receptor type. Activation of these receptors and the resulting neuronal depolarization affects the regulation of visceral pain, colonic transit, and GI secretions processes that are related to IBS. By blocking these receptors, alosetron is able to effectively control IBS.","Alosetron is a potent and selective 5-HT<sub>3</sub> receptor antagonist. 5-HT<sub>3</sub> receptors are nonselective cation channels that are extensively distributed on enteric neurons in the human gastrointestinal tract, as well as other peripheral and central locations. Activation of these channels and the resulting neuronal depolarization affect the regulation of visceral pain, colonic transit and gastrointestinal secretions, processes that relate to the pathophysiology of irritable bowel syndrome (IBS). 5-HT<sub>3</sub> receptor antagonists such as alosetron inhibit activation of non-selective cation channels which results in the modulation of serotonin-sensitive GI motor and sensory processes.","5-hydroxytryptamine receptor 3A antagonist","Indication associated"]
[350,"DB00975","approved","small molecule","Dipyridamole","Dipyridamine; Dipyridamole; Dipyudamine; Dypyridamol","C24H40N8O4","OCCN(CCO)C1=NC2=C(N=C(N=C2N2CCCCC2)N(CCO)CCO)C(=N1)N1CCCCC1","A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. (From AMA Drug Evaluations Annual, 1994, p752)","58-32-2","504.6256","For as an adjunct to coumarin anticoagulants in the prevention of postoperative thromboembolic complications of cardiac valve replacement and also used in prevention of angina.","Dipyridamole, a non-nitrate coronary vasodilator that also inhibits platelet aggregation, is combined with other anticoagulant drugs, such as warfarin, to prevent thrombosis in patients with valvular or vascular disorders. Dipyridamole is also used in myocardial perfusion imaging, as an antiplatelet agent, and in combination with aspirin for stroke prophylaxis.","Dipyridamole likely inhibits both adenosine deaminase and phosphodiesterase, preventing the degradation of cAMP, an inhibitor of platelet function. This elevation in cAMP blocks the release of arachidonic acid from membrane phospholipids and reduces thromboxane A2 activity. Dipyridamole also directly stimulates the release of prostacyclin, which induces adenylate cyclase activity, thereby raising the intraplatelet concentration of cAMP and further inhibiting platelet aggregation.","cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A inhibitor; Adenosine deaminase inhibitor; cGMP-specific 3',5'-cyclic phosphodiesterase inhibitor; cAMP-specific 3',5'-cyclic phosphodiesterase 4A inhibitor; Calcipressin-1; Alpha-1-acid glycoprotein 1","Therapeutic strategy associated"]
[351,"DB00976","approved","small molecule","Telithromycin","Telithromycin","C43H65N5O10","[H][C@@]12[C@@H](C)C(=O)[C@H](C)C[C@@](C)(OC)[C@H](O[C@@H]3O[C@H](C)C[C@@H]([C@H]3O)N(C)C)[C@@H](C)C(=O)[C@@H](C)C(=O)O[C@H](CC)[C@@]1(C)OC(=O)N2CCCCN1C=NC(=C1)C1=CC=CN=C1","Telithromycin, a semi-synthetic erythromycin derivative, belongs to a new chemical class of antibiotics called ketolides. Ketolides have been recently added to the macrolide-lincosamide-streptogramin class of antibiotics. Similar to the macrolide antibiotics, telithromycin prevents bacterial growth by interfering with bacterial protein synthesis. Telithromycin binds to the 50S subunit of the 70S bacterial ribosome and blocks further peptide elongation. Binding occurs simultaneously at to two domains of 23S RNA of the 50S ribosomal subunit, domain II and V, where older macrolides bind only to one. It is used to treat mild to moderate respiratory infections.","191114-48-4","812.018","For the treatment of <i>Pneumococcal</i> infection, acute sinusitis, acute bacterial tonsillitis, acute bronchitis and bronchiolitis, lower respiratory tract infection and lobar (pneumococcal) pneumonia.","Telithromycin is a ketolide antibiotic which has an antimicrobial spectrum similar or slightly broader than that of penicillin. It is often used as an alternative in patients who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma. Telithromycin prevents bacterial growth by binding to bacterial 50S ribosomal subunits and interfering with bacterial peptide translocation and elongation.","Telithromycin acts by binding to domains II and V of 23S rRNA of the 50S ribosomal subunit. By binding at domain II, telithromycin retains activity against gram-positive cocci (e.g. Streptococcus pneumoniae) in the presence of resistance mediated by methylases (erm genes) that alter the binding site at domain V. Telithromycin may also inhibit the assembly of nascent ribosomal units. Compared to erythromycin A, telithromycin binds to the 23S rRNA with 10 times greater affinity in erythromycin-susceptible organisms and 25 times greater affinity in macrolide-resistant strains. This increased binding affinity may be conferred by the C11-12 carbamate side chain of telithromycin. The  side chain appears to maintain binding at domain II in the presence of resistance mediated by alterations in domain V.","23S ribosomal RNA inhibitor","Indication associated"]
[352,"DB00977","approved","small molecule","Ethinylestradiol","17-ethinyl-3,17-estradiol; 17-ethinyl-3,17-oestradiol; 17-ethinylestradiol; 17alpha-Ethinyl estradiol; 17α-ethynylestradiol; Ethinyl estradiol; Ethinylestradiol; Ethinyloestradiol; Ethynyl estradiol","C20H24O2","[H][C@@]12CC[C@@](O)(C#C)[C@@]1(C)CC[C@]1([H])C3=C(CC[C@@]21[H])C=C(O)C=C3","Ethinylestradiol was first synthesized in 1938 by Hans Herloff Inhoffen and Walter Hohlweg at Schering. It was developed in an effort to create an estrogen with greater oral bioavailability. These properties were achieved by the substitution of an ethinyl group at carbon 17 of . Ethinylestradiol soon replaced  in contraceptive pills.\r\n\r\nEthinylestradiol was granted FDA approval on 25 June 1943.","57-63-6","296.4034","Ethinylestradiol is combined with other drugs for use as a contraceptive, premenstrual dysphoric disorder, moderate acne, moderate to severe vasomotor symptoms of menopause, prevention of postmenopausal osteoporosis.","Ethinylestradiol is a synthetic estrogen that decreases luteinizing hormone to decrease endometrial vascularization, and decreases gonadotrophic hormone to prevent ovulation. It has a long duration of action as it is taken once daily, and a wide therapeutic index as overdoses are generally not associated with serious adverse effects. Patients should be counselled regarding the risks of thrombotic events.","Ethinylestradiol is a synthetic estrogenic compound. Use of estrogens have a number of effects on the body including reduced bone density. Combined oral contraceptives suppress ovulation by suppressing gonadotrophic hormone, thickening cervical mucus to prevent the travel of sperm, and preventing changes in the endometrium required for implantation of a fertilized egg. Ethinylestradiol decreases luteinizing hormone, decreasing vascularity in the endometrium. It also increases sex hormone binding globulin.","Estrogen receptor alpha agonist; Nuclear receptor subfamily 1 group I member 2 agonist","Indication associated"]
[353,"DB00978","approved; investigational","small molecule","Lomefloxacin","(±)-1-ethyl-6,8-difluoro-1,4-dihydro-7-(3-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid; 1,4-Dihydro-6,8-difluoro-1-ethyl-7-(3-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid; LFLX; Lomefloxacin","C17H19F2N3O3","CCN1C=C(C(O)=O)C(=O)C2=CC(F)=C(N3CCNC(C)C3)C(F)=C12","Lomefloxacin is a fluoroquinolone antibiotic, used to treat bacterial infections including bronchitis and urinary tract infections (UTIs). Additionally, it has been employed for the prophylaxis of UTIs prior to surgery as well.","98079-51-7","351.3479","For the treatment of bacterial infections of the respiratory tract (chronic bronchitis) and urinary tract, and as a pre-operative prophylactic to prevent urinary tract infection caused by: <i>S.pneumoniae</i>, <i>H.influenzae</i>, <i>S.aureus</i>, <i>P.aeruginosa</i>, <i>E. cloacae</i>, <i>P. mirabilis</i>, <i>C. civersus</i>, <i>S. asprphyticus</i>, <i>E.coli</i>, and <i>K.pneumoniae</i>.","Lomefloxacin is a fluoroquinolone antibiotic used to treat chronic bronchitis, as well as complicated and uncomplicated urinary tract infections. It is also used as a prophylactic or preventative treatment to prevent urinary tract infections in patients undergoing transrectal or transurethral surgical procedures. Flouroquinolones such as lomefloxacin possess excellent activity against gram-negative aerobic bacteria such as <i>E.coli</i> and <i>Neisseria gonorrhoea</i> as well as gram-positive bacteria including <i>S. pneumoniae</i> and <i>Staphylococcus aureus</i>. They also posses effective activity against shigella, salmonella, campylobacter, gonococcal organisms, and multi drug resistant pseudomonas and enterobacter.","Lomefloxacin is a bactericidal fluoroquinolone agent with activity against a wide range of gram-negative and gram-positive organisms. The bactericidal action of lomefloxacin results from interference with the activity of the bacterial enzymes DNA gyrase and topoisomerase IV, which are needed for the transcription and replication of bacterial DNA. DNA gyrase appears to be the primary quinolone target for gram-negative bacteria. Topoisomerase IV appears to be the preferential target in gram-positive organisms. Interference with these two topoisomerases results in strand breakage of the bacterial chromosome, supercoiling, and resealing. As a result DNA replication and transcription is inhibited.","DNA topoisomerase 4 subunit A inhibitor; DNA gyrase subunit A inhibitor; DNA topoisomerase 2-alpha inhibitor","Indication associated"]
[354,"DB00982","approved","small molecule","Isotretinoin","(7E,9E,11E,13Z)-retinoic acid; 13-cis-retinoic acid; 13-cis-Vitamin A acid; 13-RA; cis-RA; Isotretinoin; Neovitamin A acid","C20H28O2","C\\C(\\C=C\\C1=C(C)CCCC1(C)C)=C/C=C/C(/C)=C\\C(O)=O","Isotretinoin is a retinoid derivative of vitamin A used in the treatment of severe recalcitrant acne. It was most widely marketed under the brand name Accutane, which has since been discontinued. Isotretinoin is associated with major risks in pregnancy and is therefore only available under the iPLEDGE program in the United States. The first isotretinoin-containing product was FDA approved on 7 May 1982.","4759-48-2","300.4351","Isotretinoin is indicated to treat severe recalcitrant nodular acne and patients ≥12 years enrolled in the iPLEDGE program.","The pharmacodynamics of isotretinoin are poorly understood.","Isotretinoin produces its effects through altering progress through the cell cycle, cell differentiation, survival, and apoptosis. These actions reduce sebum production, preventing the blockage of pores, and growth of acne causing bacteria. Isotretinoin and 4-oxo-isotretinoin both significantly reduce the production of sebum. Isotretinoin has little to no affinity for retinol binding proteins (RBPs) and retinoic acid nuclear receptors (RARs). Tretinoin and 4-oxo-tretinion bind to the RAR-γ receptor, which is suspected to be part of the action of acne treatment by isotretinoin. Isotretinoin induces apoptosis in sebocytes, leading to a decrease in sebum production. Isotretinoin also reduces the formation of comedones by reducing hyperkeratinization through an unknown mechanism. Isotretinoin does not directly kill bacteria but it does reduce the size of sebum ducts and makes the microenvironment less hospitable to acne causing bacteria. It may also increase immune mechanisms and alter chemotaxis of monocytes to reduce inflammation.\r\n\r\nThere is preliminary evidence suggesting isotretinoin may interact with FoxO1, which may explain a substantial number of isotretinoin's unexplained actions.","Retinoic acid receptor alpha other/unknown; Retinoic acid receptor gamma","Therapeutic strategy associated"]
[355,"DB00988","approved","small molecule","Dopamine","2-(3,4-dihydroxyphenyl)ethylamine; 3-Hydroxytyramine; 3,4-Dihydroxyphenethylamine; 4-(2-aminoethyl)-1,2-benzenediol; 4-(2-Aminoethyl)benzene-1,2-diol; 4-(2-aminoethyl)catechol; 4-(2-aminoethyl)pyrocatechol; Oxytyramine","C8H11NO2","NCCC1=CC(O)=C(O)C=C1","One of the catecholamine neurotransmitters in the brain.  It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (receptors, dopamine) mediate its action.","51-61-6","153.1784","For the correction of hemodynamic imbalances present in the shock syndrome due to myocardial infarction, trauma, endotoxic septicemia, open-heart surgery, renal failure, and chronic cardiac decompensation as in congestive failure","Dopamine is a natural catecholamine formed by the decarboxylation of 3,4-dihydroxyphenylalanine (DOPA). It is a precursor to norepinephrine in noradrenergic nerves and is also a neurotransmitter in certain areas of the central nervous system, especially in the nigrostriatal tract, and in a few peripheral sympathetic nerves. Dopamine produces positive chronotropic and inotropic effects on the myocardium, resulting in increased heart rate and cardiac contractility. This is accomplished directly by exerting an agonist action on beta-adrenoceptors and indirectly by causing release of norepinephrine from storage sites in sympathetic nerve endings.","Dopamine is a precursor to norepinephrine in noradrenergic nerves and is also a neurotransmitter in certain areas of the central nervous system. Dopamine produces positive chronotropic and inotropic effects on the myocardium, resulting in increased heart rate and cardiac contractility. This is accomplished directly by exerting an agonist action on beta-adrenoceptors and indirectly by causing release of norepinephrine from storage sites in sympathetic nerve endings. In the brain, dopamine actas as an agonist to the five dopamine receptor subtypes (D!, D2, D3, D4, D5).","Dopamine D2 receptor agonist; Dopamine D1 receptor agonist; Dopamine D5 receptor agonist; Dopamine D3 receptor agonist; Dopamine D4 receptor agonist; Sodium-dependent dopamine transporter inducer; Dopamine beta-hydroxylase ligand; 5-hydroxytryptamine receptor 1A binder; 5-hydroxytryptamine receptor 7 binder; D(1) dopamine receptor agonist; Sodium-dependent noradrenaline transporter inhibitor; Sodium-dependent serotonin transporter inhibitor; 5-hydroxytryptamine receptor 3A; 5-hydroxytryptamine receptor 3B; Superoxide dismutase [Cu-Zn]; Synaptic vesicular amine transporter","Indication associated"]
[356,"DB00991","approved","small molecule","Oxaprozin","Oxaprozin","C18H15NO3","OC(=O)CCC1=NC(=C(O1)C1=CC=CC=C1)C1=CC=CC=C1","Oxaprozin is a non-narcotic, non-steroidal anti-inflammatory drug (NSAID), used to relieve the inflammation, swelling, stiffness, and joint pain associated with osteoarthritis and rheumatoid arthritis.","21256-18-8","293.3166","Used to relieve the inflammation, swelling, stiffness, and joint pain associated with rheumatoid arthritis and osteoarthritis.","Oxaprozin is a nonsteroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. Oxaprozin is used to treat rheumatoid arthritis, osteoarthritis, dysmenorrhea, and to alleviate moderate pain.","Anti-inflammatory effects of Oxaprozin are believed to be due to inhibition of cylooxygenase in platelets which leads to the blockage of prostaglandin synthesis. Antipyretic effects may be due to action on the hypothalamus, resulting in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation. Oxaprozin is a non-selective NSAID, with a cell assay system showing lower COX-2 selectivity implying higher COX-1 selectivity.","Prostaglandin G/H synthase 1 inhibitor; Prostaglandin G/H synthase 2 inhibitor","Therapeutic strategy associated"]
[357,"DB00993","approved","small molecule","Azathioprine","6-((1-Methyl-4-nitro-1H-imidazol-5-yl)thio)-1H-purine; 6-(1'-Methyl-4'-nitro-5'-imidazolyl)-mercaptopurine; Azathioprine","C9H7N7O2S","CN1C=NC(=C1SC1=NC=NC2=C1NC=N2)[N+]([O-])=O","Azathioprine is a prodrug of 6-mercaptopurine, first synthesized in 1956 by Gertrude Elion, William Lange, and George Hitchings in an attempt to produce a derivative of 6-mercaptopurine with a better therapeutic index. Azathioprine is used to treat inflammatory conditions like rheumatoid arthritis and as an immunosuppressant in the prevention of renal transplant rejection.\r\n\r\nAzathiprine was granted FDA approval on 20 March 1968.","446-86-6","277.263","Azathioprine is indicated to treat rheumatoid arthritis and prevent renal transplant rejection.","Azathioprine is an immunosuppressive agent which functions through modulation of rac1 to induce T cell apoptosis, as well as other unknown immunosuppressive functions. It has a long duration of action as it is given daily, and has a narrow therapeutic index. Patients should be counselled regarding the risk of malignancies of the skin and lymphomas.","Azathioprine's mechanism of action is not entirely understood but it may be related to inhibition of purine synthesis, along with inhibition of B and T cells.\r\n\r\n6-thioguanine triphosphate, a metabolite of azathioprine, modulates activation of rac1 when costimulated with CD28, inducing T cell apoptosis. This may be mediated through rac1's action on mitogen-activated protein kinase, NF-kappaB.","Ras-related C3 botulinum toxin substrate 1 modulator","Therapeutic strategy associated"]
[358,"DB00994","approved; vet_approved","small molecule","Neomycin","Fradiomycin; Kaomycine; Neomycin; Vonamycin",null,null,"Neomycin is a broad-spectrum aminoglycoside antibiotic drug that is derived from the metabolic products of _Streptomyces fradiae_. Neomycin is a complex comprised of three components, neomycin A, B, and C. Neomycin B, also known as , is the most active component of the complex and neomycin C is the isomer of neomycin B, making these two stereoisomers the active components of neomycin. Neomycin A, or , is a moiety that conjoins two molecules of neomycin B and C together. Neomycin is active against both gram-positive and gram-negative organisms and mediates its pharmacological action by binding to bacterial ribosomes and inhibiting protein synthesis, which is crucial for the survival of bacteria. \r\n\r\nNeomycin sulfate is the most common form for pharmaceutical preparations; because the compound is a complex, the amount of neomycin in products is measured in units. Neomycin sulfate as monotherapy is available in an oral solution for adjunct use in the treatment of hepatic coma. It is also used in combination with  sulfates and  in otic suspensions for use in the treatment of bacterial infections in the external auditory canal, including infections caused by medical procedures in the ear. Neomycin is also used in combination with  sulfates and  in ophthalmic preparations for use in the treatment of inflammatory conditions and infections in the eye. Neomycin is also available in over-the-counter topical products to prevent minor skin infections.","1404-04-2",null,"Oral neomycin sulfate is indicated as an adjunctive therapy in hepatic coma (portal-system encephalopathy) by reducing ammonia-forming bacteria in the intestinal tract. It is strongly recommended that oral neomycin is only used in infections that are proven or strongly suspected to be caused by susceptible bacteria to reduce the risk of the development of drug-resistant bacteria.\r\n\r\nNeomycin, in combination with polymyxin B sulfates and hydrocortisone in otic suspensions, is used in the treatment of superficial bacterial infections of the external auditory canal caused by organisms susceptible to the antibiotics. This otic formulation is also used in the treatment of infections of mastoidectomy and fenestration cavities caused by organisms susceptible to the antibiotics.\r\n\r\nThe ophthalmic solution containing neomycin in combination with polymyxin B sulfates and dexamethasone is used to treat steroid-responsive inflammatory ocular conditions for which a corticosteroid is indicated and where bacterial infection or a risk of bacterial infection exists.","Neomycin mediates its bactericidal action by inhibiting bacterial protein synthesis, thereby suppressing the growth and survival of susceptible bacteria. Following oral administration, the duration of bactericidal activity of neomycin ranged from 48 to 72 hours. By decreasing colonic bacteria that produce ammonia, neomycin was shown to be effective as an adjunctive therapy in hepatic coma to improve neurologic symptoms. \r\n\r\nNeomycin is active against both gram positive and gram negative organisms, including the major _E. coli_ species resident in the colon as well as the enteropathogenic forms of _E. coli_. It is also active against _Klebsiella_-_Enterobacter_ group. Resistant strains of _E. coli_, _Klebsiella_ and _Proteus spp_. may emerge from neomycin therapy. Neomycin has no antifungal activity and has some activity against some protozoa.","Like other aminoglycoside antibiotic drugs, neomycin inhibits bacterial ribosomes by binding to the 30S ribosomal subunit of susceptible bacteria and disrupting the translational machinery of bacterial protein synthesis. Bacterial translation is normally initiated by the mRNA binding to the 30S ribosomal subunit and subsequent binding with 50S subunit for elongation.","30S ribosomal protein S12 inhibitor; 16S ribosomal RNA inhibitor; Extracellular calcium-sensing receptor","Indication associated"]
[359,"DB00995","approved; investigational","small molecule","Auranofin","(1-Thio-beta-D-glucopyranosato)(triethylphosphine)gold 2,3,4,6-tetraacetate; 2,3,4,6-Tetra-O-acetyl-1-thio-beta-D-glucopyranosato-S (triethylphosphine)gold; Auranofin; Triethylphosphine gold","C20H34AuO9PS","CCP(CC)(CC)=[Au]S[C@@H]1O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O","Auranofin is a gold salt that is capable of eliciting pharmacologic actions that suppress inflammation and stimulate cell-mediated immunity. It has subsequently been listed by the World Health Organization as a member of the antirheumatic agent category. Auranofin appears to induce heme oxygenase 1 (HO-1) mRNA. Heme oxygenase 1 is an inducible heme-degrading enzyme with anti-inflammatory properties.","34031-32-8","678.484","Used in the treatment of active, progressive or destructive forms of inflammatory arthritis, such as adult rheumatoid arthritis.","Auranofin is a gold salt used in treating inflammatory arthritis. Gold salts are called second-line drugs because they are often considered when the arthritis progresses in spite of antiinflammatory drugs (NSAIDs and corticosteroids).","Inflammatory arthritis can cause joint swelling, warmth, pain, and tenderness; one cause of this condition is rheumatoid arthritis. In patients with rheumatoid arthritis, gold salts such as auranofin can be administered to decrease joint inflammation and prevent the destruction of bones and cartilage. Though the mechanism of action of auranofin is not fully established in rheumatoid arthritis, this drug has been shown to inhibit phagocytosis and the release of antibodies and enzymes that play a role in cytotoxic reactions, suppressing the inflammatory response. \r\n\r\nAside from its probable immune effects in inflammatory arthritis, studies have shown that auranofin inhibits thioredoxin reductase. This enzyme has various roles in cell homeostasis, including the regulation of free radicals. Thioredoxin reductase can be over expressed in various types of tumours, rendering it an attractive target for anticancer drug development. Studies have shown that inhibiting thioredoxin reductase can cause oxidative stress and apoptosis of tumour cells by increasing the formation of free radicals. Aurofin's thiol ligand binds with high affinity to thiol and selenol groups, forming irreversible reaction products. One study showed that treatment with auranofin increased the production or reactive oxygen species and caused elevation of intracellular calcium concentration in platelets, leading to cell death. Another study showed that auranofin enhanced the production of free radicals, governing T-cell activation.","Peroxiredoxin-5, mitochondrial inhibitor; Inhibitor of nuclear factor kappa-B kinase subunit beta inhibitor","Therapeutic strategy associated"]
[360,"DB00996","approved; investigational","small molecule","Gabapentin","1-(Aminomethyl)cyclohexaneacetic acid; Gabapentin","C9H17NO2","NCC1(CC(O)=O)CCCCC1","Gabapentin is a structural analogue of the inhibitory neurotransmitter gamma-aminobutyric acid () that was first approved for use in the United States in 1993. It was originally developed as a novel anti-epileptic for the treatment of certain types of seizures - today it is also widely used to treat neuropathic pain. Gabapentin has some stark advantages as compared with other anti-epileptics, such as a relatively benign adverse effect profile, wide therapeutic index, and lack of appreciable metabolism making it unlikely to participate in pharmacokinetic drug interactions.. It is structurally and functionally related to another GABA derivative, .","60142-96-3","171.2368","In the United States, gabapentin is officially indicated for the treatment of postherpetic neuralgia in adults and for the adjunctive treatment of partial-onset seizures, with or without secondary generalization, in patients 3 years of age and older. In Europe, gabapentin is indicated for adjunctive therapy in the treatment of partial-onset seizures, with or without secondary generalization, in patients 6 years of age and older and as monotherapy in patients 12 years of age and older. It is also used in adults for the treatment of various types of peripheral neuropathic pain, such as painful diabetic neuropathy.","Gabapentin is an anti-convulsant medication that inhibits the release of excitatory neurotransmitters, allowing for its use against pathologic neurotransmission such as that seen in neuropathic pain and seizure disorders. It has a wide therapeutic index, with doses in excess of 8000 mg/kg failing to cause a fatal reaction in rats.\r\n\r\nGabapentin is ineffective in absence seizures and should be used in caution in patients with mixed seizure disorders involving absence seizures. Gabapentin has been associated with drug reaction with eosinophilia and systemic symptoms (DRESS), otherwise known as multi-organ hypersensitivity. This reaction can prove fatal and early symptoms such as fever, lymphadenopathy, and rash should be promptly investigated.","The precise mechanism through which gabapentin exerts its therapeutic effects is unclear. The primary mode of action appears to be at the auxillary α2δ-1 subunit of voltage-gated calcium channels (though a low affinity for the α2δ-2 subunit has also been reported). The major function of these subunits is to facilitate the movement of pore-forming α1 subunits of calcium channels from the endoplasmic reticulum to the cell membrane of pre-synaptic neurons. There is evidence that chronic pain states can cause an increase in the expression of α2δ subunits and that these changes correlate with hyperalgesia. Gabapentin appears to inhibit the action of α2δ-1 subunits, thus decreasing the density of pre-synaptic voltage-gated calcium channels and subsequent release of excitatory neurotransmitters. It is likely that this inhibition is also responsible for the anti-epileptic action of gabapentin.\r\n\r\nThere is some evidence that gabapentin also acts on adenosine receptors and voltage-gated potassium channels, though the clinical relevance of its action at these sites is unclear.","Voltage-dependent calcium channel subunit alpha-2/delta-1 inhibitor; Voltage-dependent calcium channel subunit alpha-2/delta-2 inhibitor; Voltage-dependent N-type calcium channel inhibitor; Adenosine receptor A1 agonist; Potassium voltage-gated channel subfamily KQT member 3 activator; Potassium voltage-gated channel subfamily KQT member 5 activator","Indication associated"]
[361,"DB00999","approved; vet_approved","small molecule","Hydrochlorothiazide","HCTZ; Hydrochlorothiazide","C7H8ClN3O4S2","NS(=O)(=O)C1=C(Cl)C=C2NCNS(=O)(=O)C2=C1","Hydrochlorothiazide is the most commonly prescribed thiazide diuretic. It is indicated to treat edema and hypertension. Hydrochlorothiazide use is common but declining in favour of angiotensin converting enzyme inhibitors. Many combination products are available containing hydrochlorothiazide and angiotensin converting enzyme inhibitors or angiotensin II receptor blockers.\r\n\r\nHydrochlorothiazide was granted FDA approval on 12 February 1959.","58-93-5","297.739","Hydrochlorothiazide is indicated alone or in combination for the management of edema associated with congestive heart failure, hepatic cirrhosis, nephrotic syndrome, acute glomerulonephritis, chronic renal failure, and corticosteroid and estrogen therapy. Hydrochlorothiazide is also indicated alone or in combination for the management of hypertension.","Hydrochlorothiazide prevents the reabsorption of sodium and water from the distal convoluted tubule, allowing for the increased elimination of water in the urine. Hydrochlorothiazide has a wide therapeutic window as dosing is individualized and can range from 25-100mg. Hydrochlorothiazide should be used with caution in patients with reduced kidney or liver function.","Hydrochlorothiazide is transported from the circulation into epithelial cells of the distal convoluted tubule by the organic anion transporters OAT1, OAT3, and OAT4. From these cells, hydrochlorothiazide is transported to the lumen of the tubule by multidrug resistance associated protein 4 (MRP4).\r\n\r\nNormally, sodium is reabsorbed into epithelial cells of the distal convoluted tubule and pumped into the basolateral interstitium by a sodium-potassium ATPase, creating a concentration gradient between the epithelial cell and the distal convoluted tubule that promotes the reabsorption of water.\r\n\r\nHydrochlorothiazide acts on the proximal region of the distal convoluted tubule, inhibiting reabsorption by the sodium-chloride symporter, also known as Solute Carrier Family 12 Member 3 (SLC12A3). Inhibition of SLC12A3 reduces the magnitude of the concentration gradient between the epithelial cell and distal convoluted tubule, reducing the reabsorption of water.","Solute carrier family 12 member 3 inhibitor; Calcium-activated potassium channel subunit alpha-1 inhibitor","Indication associated"]
[362,"DB01000","approved","small molecule","Cyclacillin","(1-aminocyclohexyl)penicillin; (2S,5R,6R)-6-{[(1-aminocyclohexyl)carbonyl]amino}-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; 6-(1-aminocyclohexanecarboxamido)penicillanic acid; 6-(1-aminocyclohexylcarboxamido)penicillanic acid; Ciclacillin; Cyclacillin","C15H23N3O4S","[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)C1(N)CCCCC1)C(O)=O","A cyclohexylamido analog of penicillanic acid.","3485-14-1","341.426","For the treatment of bacterial infections caused by susceptible organisms.","Cyclacillin, a penicillin, is a cyclohexylamido analog of penicillanic acid. Cyclacillin is more resistant to beta-lactamase hydrolysis than ampicillin, is much better absorbed when given by mouth and, as a result, the levels reached in the blood and in the urine are considerably higher than those obtained with the same dose of ampicillin. Cyclacillin has been replaced by newer penicillin treatments.","The bactericidal activity of cyclacillin results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins (PBPs). Cyclacillin is stable in the presence of a variety of b-lactamases, including penicillinases and some cephalosporinases.","Penicillin-binding protein 1A inhibitor; Penicillin-binding protein 3 inhibitor; Penicillin binding protein 2a inhibitor; Penicillin-binding protein inhibitor","Indication associated"]
[363,"DB01003","approved","small molecule","Cromoglicic acid","5-[3-(2-carboxy-4-oxo-4H-5-chromenyloxy)-2-hydroxypropoxy]-4-oxo-4H-2-chromenecarboxylic acid; Cromoglicate; Cromoglicic acid; Cromoglycate; Cromoglycic acid; Cromolyn","C23H16O11","OC(COC1=CC=CC2=C1C(=O)C=C(O2)C(O)=O)COC1=CC=CC2=C1C(=O)C=C(O2)C(O)=O","A chromone complex that acts by inhibiting the release of chemical mediators from sensitized mast cells. It is used in the prophylactic treatment of both allergic and exercise-induced asthma, but does not affect an established asthmatic attack.","16110-51-3","468.3665","For the management of patients with bronchial asthma. Also used in the treatment of vernal keratoconjunctivitis, vernal conjunctivitis, and vernal keratitis.","Cromoglicate or cromolyn (USAN), a synthetic compound, inhibits antigen-induced bronchospasms and, hence, is used to treat asthma and allergic rhinitis. Cromoglicate is used as an ophthalmic solution to treat conjunctivitis and is taken orally to treat systemic mastocytosis and ulcerative colitis.","Cromoglicate inhibits degranulation of mast cells, subsequently preventing the release of histamine and slow-reacting substance of anaphylaxis (SRS-A), mediators of type I allergic reactions. Cromoglicate also may reduce the release of inflammatory leukotrienes. Cromoglicate may act by inhibiting calcium influx.","Protein S100-P antagonist","Therapeutic strategy associated"]
[364,"DB01004","approved; investigational","small molecule","Ganciclovir","2-(6-Amino-purin-9-ylmethoxy)-propane-1,3-diol; 2-amino-9-((1,3-dihydroxypropan-2-yloxy)methyl)-1H-purin-6(9H)-one; 2-amino-9-((1,3-dihydroxypropan-2-yloxy)methyl)-3H-purin-6(9H)-one; 2-amino-9-((1,3-dihydroxypropan-2-yloxy)methyl)-9H-purin-6-ol; 2-Amino-9-(2-hydroxy-1-hydroxymethyl-ethoxymethyl)-1,9-dihydro-purin-6-one; 2-amino-9-(2-hydroxy-1-hydroxymethylethoxymethyl)-6,9-dihydro-1H-6-purinone; 9-((2-Hydroxy-1-(hydroxymethyl)ethoxy)methyl)guanine; 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine; GA2; Ganciclovir; Gancyclovir","C9H13N5O4","NC1=NC2=C(N=CN2COC(CO)CO)C(=O)N1","An acyclovir analog that is a potent inhibitor of the Herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from AIDS-associated cytomegalovirus infections.","82410-32-0","255.2306","For induction and maintenance in the treatment of cytomegalovirus (CMV) retinitis in immunocompromised patients, including patients with acquired immunodeficiency syndrome (AIDS). Also used in the treatment of severe cytomegalovirus (CMV) disease, including CMV pneumonia, CMV gastrointestinal disease, and disseminated CMV infections, in immunocompromised patients.","Ganciclovir is a synthetic nucleoside analogue of 2'-deoxyguanosine that inhibits replication of herpes viruses both <i>in vitro</i> and <i>in vivo</i>. Sensitive human viruses include cytomegalovirus (CMV), herpes simplex virus -1 and -2 (HSV-1, HSV-2), Epstein-Barr virus (EBV) and varicella zoster virus (VZV), however clinical studies have been limited to assessment of efficacy in patients with CMV infection. Ganciclovir is a prodrug that is structurally similar to acyclovir. It inhibits virus replication by its encorporation into viral DNA. This encorporation inhibits dATP and leads to defective DNA, ceasing or retarding the viral machinery required to spread the virus to other cells.","Ganciclovir's antiviral activity inhibits virus replication. This inhibitory action is highly selective as the drug must be converted to the active form by a virus-encoded cellular enzyme, thymidine kinase (TK). TK catalyzes phosphorylation of ganciclovir to the monophosphate, which is then subsequently converted into the diphosphate by cellular guanylate kinase and into the triphosphate by a number of cellular enzymes. <i>In vitro</i>, ganciclovir triphosphate stops replication of herpes viral DNA. When used as a substrate for viral DNA polymerase, ganciclovir triphosphate competitively inhibits dATP leading to the formation of 'faulty' DNA. This is where ganciclovir triphosphate is incorporated into the DNA strand replacing many of the adenosine bases. This results in the prevention of DNA synthesis, as phosphodiester bridges can longer to be built, destabilizing the strand. Ganciclovir inhibits viral DNA polymerases more effectively than it does cellular polymerase, and chain elongation resumes when ganciclovir is removed.","DNA polymerase catalytic subunit inhibitor; DNA incorporation into and destabilization; Thymidine kinase inducer","Indication associated"]
[365,"DB01008","approved; investigational","small molecule","Busulfan","1,4-Bis(methanesulfonoxy)butane; 1,4-Butanediol dimethanesulfonate; 1,4-Dimesyloxybutane; 1,4-Dimethanesulfonoxybutane; Busulphan; Tetramethylene bis(methanesulfonate)","C6H14O6S2","CS(=O)(=O)OCCCCOS(C)(=O)=O","Busulfan is a bifunctional alkylating agent, having a selective immunosuppressive effect on bone marrow. It is not a structural analog of the nitrogen mustards. It has been used in the palliative treatment of chronic myeloid leukemia (myeloid leukemia, chronic), but although symptomatic relief is provided, no permanent remission is brought about. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), busulfan is listed as a known carcinogen.","55-98-1","246.302","For use in combination with cyclophosphamide as a conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation for chronic myelogenous  (myeloid, myelocytic, granulocytic) leukemia (FDA has designated busulfan as an orphan drug for this use). It is also used as a component of pretransplant conditioning regimens in patients undergoing bone marrow transplantation for acute myeloid leukemia and nonmalignant diseases.","Busulfan is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn leads to a miscoding of DNA. Alkylating agents are cell cycle-nonspecific and work by three different mechanisms, all of which achieve the same end result - disruption of DNA function and cell death. Overexpression of MGST2, a glutathione s-transferase, is thought to confer resistance to busulfan. The role of MGST2 in the metabolism of busulfan is unknown however.","Busulfan is an alkylating agent that contains 2 labile methanesulfonate groups attached to opposite ends of a 4-carbon alkyl chain. Once busulfan is hydrolyzed, the methanesulfonate groups are released and carbonium ions are produced. These carbonium ions alkylate DNA, which results in the interference of DNA replication and RNA transcription, ultimately leading to the disruption of nucleic acid function. Specifically, its mechanism of action through alkylation produces guanine-adenine intrastrand crosslinks. These crosslinks occur through a SN2 reaction guanine N7 nucleophilically attacks the carbon adjacent to the mesylate leaving group. This kind of damage cannot be repaired by cellular machinery and thus the cell undergoes apoptosis.","DNA cross-linking/alkylation","Therapeutic strategy associated"]
[366,"DB01009","approved; vet_approved","small molecule","Ketoprofen","2-(3-Benzoylphenyl)propionic acid; 3-Benzoyl-alpha-methylbenzeneacetic acid; 3-Benzoyl-α-methylbenzeneacetic acid; 3-Benzoylhydratropic acid; Ketoprofen; m-Benzoylhydratropic acid","C16H14O3","CC(C(O)=O)C1=CC(=CC=C1)C(=O)C1=CC=CC=C1","Ketoprofen, a propionic acid derivative, is a nonsteroidal anti-inflammatory agent (NSAIA) with analgesic and antipyretic properties.","22071-15-4","254.2806","For symptomatic treatment of acute and chronic rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, primary dysmenorrhea and mild to moderate pain associated with musculotendinous trauma (sprains and strains), postoperative (including dental surgery) or postpartum pain.","Ketoprofen is a nonsteroidal anti-inflammatory agent (NSAIA) with analgesic and antipyretic properties. Ketoprofen has pharmacologic actions similar to those of other prototypical NSAIDs, which inhibit prostaglandin synthesis. Ketoprofen is used to treat rheumatoid arthritis, osteoarthritis, dysmenorrhea, and alleviate moderate pain.","The anti-inflammatory effects of ketoprofen are believed to be due to inhibition cylooxygenase-2 (COX-2), an enzyme involved in prostaglandin synthesis via the arachidonic acid pathway. This results in decreased levels of prostaglandins that mediate pain, fever and inflammation. Ketoprofen is a non-specific cyclooxygenase inhibitor and inhibition of COX-1 is thought to confer some of its side effects, such as GI upset and ulceration. Ketoprofen is thought to have anti-bradykinin activity, as well as lysosomal membrane-stabilizing action. Antipyretic effects may be due to action on the hypothalamus, resulting in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation.","Prostaglandin G/H synthase 1 inhibitor; Prostaglandin G/H synthase 2 inhibitor; C-X-C chemokine receptor type 1 other","Therapeutic strategy associated"]
[367,"DB01012","approved","small molecule","Cinacalcet","(R)-α-methyl-N-[3-[3-(trifluoromethyl)phenyl]propyl]-1-naphthalenemethane amine; Cinacalcet; CNC; N-((1R)-1-(Naphthalen-1-yl)ethyl)-3-(3-(trifluoromethyl)phenyl)propan-1-amine","C22H22F3N","C[C@@H](NCCCC1=CC(=CC=C1)C(F)(F)F)C1=CC=CC2=CC=CC=C12","Cinacalcet is a calcimimetic sold by Amgen under the trade name Sensipar® in North America and Australia and as Mimpara® in Europe. It is used to treat hyperparathyroidism due to parathyroid tumours or renal failure.","226256-56-0","357.412","For the treatment of secondary hyperparathyroidism in patients with Chronic Kidney Disease who are on hemodialysis or peritoneal dialysis. Also for the treatment of hypercalcemia in patients with parathyroid carcinoma.","Cinacalcet is a drug that acts as a calcimimetic (i.e. it mimics the action of calcium on tissues). Secondary hyperparathyroidism (HPT) in patients with chronic kidney disease (CKD) is a progressive disease, associated with increases in parathyroid hormone (PTH) levels and derangements in calcium and phosphorus metabolism. Increased PTH stimulates osteoclastic activity resulting in cortical bone resorption and marrow fibrosis. The goals of treatment of secondary hyperparathyroidism are to lower levels of PTH, calcium, and phosphorus in the blood, in order to prevent progressive bone disease and the systemic consequences of disordered mineral metabolism. In CKD patients on dialysis with uncontrolled secondary HPT, reductions in PTH are associated with a favorable impact on bone-specific alkaline phosphatase (BALP), bone turnover and bone fibrosis. Cinacalcet reduces calcium levels by increasing the sensitivity of the calcium sensing receptor to extracellular calcium.","Cinacalcet directly lowers parathyroid hormone levels by increasing the sensitivity of the calcium sensing receptors to activation by extracellular calcium, resulting in the inhibition of PTH secretion. The reduction in PTH is associated with a concomitant decrease in serum calcium levels.","Extracellular calcium-sensing receptor agonist","Therapeutic strategy associated"]
[368,"DB01013","approved","small molecule","Clobetasol propionate","21-chloro-9-fluoro-11β,17-dihydroxy-16β-methylpregna-1,4-diene-3,20-dione 17-propionate; clobetasol 17-propanoate; clobetasol 17-propionate; Clobetasol propionate; Clobetasol propionate E","C25H32ClFO5","[H][C@@]12C[C@H](C)[C@](OC(=O)CC)(C(=O)CCl)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])CCC2=CC(=O)C=C[C@]12C","Clobetasol propionate is a prednisolone derivative with higher specificity for glucocorticoid receptors than mineralocorticoid receptors. It has demonstrated superior activity compared to  and was first described in the literature in 1974.\r\n\r\nClobetasol Propionate was granted FDA approval on 27 December 1985.","25122-46-7","466.97","Clobetasol propionate is indicated to treat moderate to severe plaque psoriasis as well as inflammatory and pruritic manifestations of corticosteroid responsive dermatoses.","Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals. Clobetasol propionate is generally applied twice daily so the duration of action is long. Corticosteroids have a wide therapeutic window as patients may require doses that are multiples of what the body naturally produces. Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.","The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.\r\n\r\nGlucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10.\r\n\r\nLower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.","Glucocorticoid receptor agonist; Annexin A1 inducer; Mineralocorticoid receptor agonist","Therapeutic strategy associated"]
[369,"DB01014","approved; investigational","small molecule","Balsalazide","(E)-5-((4-(((2-carboxyethyl)amino)carbonyl)phenyl)azo)-2-hydroxybenzoic acid; (E)-5-({p-[(2-carboxyethyl)carbamoyl]phenyl}azo)-2-salicylic acid; 3-(2-{4-[(2-carboxyethyl)carbamoyl]phenyl}hydrazinylidene)-6-oxocyclohexa-1,4-diene-1-carboxylic acid; 5-[4-(2-carboxy-ethylcarbamoyl)-phenylazo]-2-hydroxy-benzoic acid; Balsalazide","C17H15N3O6","OC(=O)CCNC(=O)C1=CC=C(C=C1)\\N=N\\C1=CC=C(O)C(=C1)C(O)=O","Balsalazide is an anti-inflammatory drug used in the treatment of Inflammatory Bowel Disease. It is sold under the name \"Colazal\" in the US and \"Colazide\" in the UK.\r\n\r\nThe chemical name is (E)-5- phenyl]azo] -2-hydroxybenzoic acid. It is usually administered as the disodium salt.\r\n\r\nBalsalazide works by deliverying mesalazine to the large intestine to act directly on ulcerative colitis. Mesalazine is also known as 5-aminosalicylic acid, or 5-ASA.","80573-04-2","357.3175","For the treatment of mildly to moderately active ulcerative colitis.","Balsalazide is a prodrug that has little or no pharmacologic activity until it is enzymatically cleaved in the colon to produce mesalamine (5-aminosalicylic acid), an anti inflammatory drug indicated for the treatment of mildly to moderately active ulcerative colitis. Balsalazide disodium is delivered intact to the colon where it is cleaved by bacterial azoreduction to release equimolar quantities of mesalamine, which is the therapeutically active portion of the molecule, and the intert 4-aminobenzoyl-(beta)-alanine. As a result, the spectrum of pharmacologic activity of balsalazide is similar to that of mesalamine.","The mechanism of action of 5-aminosalicylic acid is unknown, but appears exert its anti-inflammatory effects locally (in the GI tract) rather than systemically. Mucosal production of arachidonic acid metabolites, both through the cyclooxygenase pathways (catalyzes the formation of prostaglandin precursors from arachidonic acid), and through the lipoxygenase pathways (catalyzes the formation of leukotrienes and hydroxyeicosatetraenoic acids from arachidonic acid and its metabolites), is increased in patients with chronic inflammatory bowel disease. Therefore, it is possible that 5-aminosalicylic acid diminishes inflammation by blocking production of arachidonic acid metabolites in the colon through both the inhibition of cyclooxygenase and lipoxygenase.","Peroxisome proliferator-activated receptor gamma agonist; Prostaglandin G/H synthase 2 inhibitor; Prostaglandin G/H synthase 1 inhibitor; Arachidonate 5-lipoxygenase inhibitor","Therapeutic strategy associated"]
[370,"DB01015","approved","small molecule","Sulfamethoxazole","3-(p-Aminophenylsulfonamido)-5-methylisoxazole; 3-Sulfanilamido-5-methylisoxazole; 4-Amino-N-(5-methyl-3-isoxazolyl)benzenesulfonamide; SMX; Sulfamethoxazole; Sulphamethoxazole","C10H11N3O3S","CC1=CC(NS(=O)(=O)C2=CC=C(N)C=C2)=NO1","Sulfamethoxazole is a bacteriostatic sulfonamide antibiotic that interferes with folic acid synthesis in susceptible bacteria. It is generally given in combination with , which inhibits a sequential step in bacterial folic acid synthesis - these agents work synergistically to block two consecutive steps in the biosynthesis of nucleic acids and proteins which are necessary for bacterial growth and division, and using them in conjunction helps to slow the development of bacterial resistance. In this combination, sulfamethoxazole is useful for the treatment of a variety of bacterial infections, including those of the urinary, respiratory, and gastrointestinal tracts.","723-46-6","253.278","Sulfamethoxazole is indicated in combination with trimethoprim, in various formulations, for the following infections caused by bacteria with documented susceptibility: urinary tract infections, acute otitis media in pediatric patients (when clinically indicated), acute exacerbations of chronic bronchitis in adults, enteritis caused by susceptible _Shigella_, prophylaxis and treatment of _Pneumocystis jiroveci_ pneumonia, and travelers' diarrhea caused by enterotoxigenic _E. coli_.\r\n\r\nIn Canada, additional indications include the adjunctive treatment of cholera, treatment of bacillary dysentery, nocardiosis, and second-line treatment of brucellosis in combination with  or .","Sulfamethoxazole is a bacteriostatic sulfonamide antibiotic that inhibits a critical step in bacterial folate synthesis. It is generally given in combination with , a dihydrofolate reductase inhibitor, which inhibits the reduction of dihydrofolic acid to tetrahydrofolic acid. Studies have shown that bacterial resistance develops more slowly with the combination of the two drugs than with either trimethoprim or sulfamethoxazole alone, as together they inhibit sequential steps in the bacterial folate synthesis pathway.\r\n\r\nSulfonamides, including sulfamethoxazole, have been implicated in hypersensitivity reactions - these agents should be discontinued at the first sign of a developing rash, as this may signal the start of a more severe reaction such as Stevens-Johnson syndrome or toxic epidermal necrolysis. Sulfamethoxazole treatment may contribute to folate deficiency and should therefore be used with caution in patients at a higher risk of developing a deficiency. Hemolysis has been observed in patients with glucose-6-phosphate dehydrogenase deficiency who are using sulfamethoxazole/trimethoprim.","Sulfamethoxazole is a sulfonamide that inhibits bacterial dihydrofolic acid synthesis due to its structural similarity to an endogenous substrate, para-aminobenzoic acid (PABA). Most bacteria meet their need for folic acid by synthesizing it from PABA, as opposed to Animalia that require exogenous folic acid sources. Sulfamethoxazole competitively inhibits dihydropteroate synthase, the enzyme responsible for bacterial conversion of PABA to dihydrofolic acid. Inhibition of this pathway prevents the synthesis of tetrahydrofolate and, ultimately, the synthesis of bacterial purines and DNA, resulting in a bacteriostatic effect.","Dihydropteroate synthase antagonist","Indication associated"]
[371,"DB01016","approved","small molecule","Glyburide","1-((p-(2-(5-chloro-o-anisamido)ethyl)phenyl)sulfonyl)-3-cyclohexylurea; 1-(p-(2-(5-chloro-2-methoxybenzamido)ethyl)benzenesulfonyl)-3-cyclohexylurea; 5-chloro-N-(2-(4-((((cyclohexylamino)carbonyl)amino)sulfonyl)phenyl)ethyl)-2-methoxybenzamide; Glyburide","C23H28ClN3O5S","COC1=C(C=C(Cl)C=C1)C(=O)NCCC1=CC=C(C=C1)S(=O)(=O)NC(=O)NC1CCCCC1","Glyburide is a second generation sulfonylurea used to treat patients with diabetes mellitus type II. It is typically given to patients who cannot be managed with the standard first line therapy, . Glyburide stimulates insulin secretion through the closure of ATP-sensitive potassium channels on beta cells, raising intracellular potassium and calcium ion concentrations.\r\n\r\nGlyburide was granted FDA approval on 1 May 1984. A formulation with metformin was granted FDA approval on on 31 July 2000.","10238-21-8","494.004","Glyburide is indicated alone or as part of combination product with metformin, as an adjunct to diet and exercise, to improve glycemic control in adults with type 2 diabetes mellitus.","Glyburide is a second generation sulfonylurea that stimulates insulin secretion through the closure of ATP-sensitive potassium channels on beta cells, raising intracellular potassium and calcium ion concentrations. Glibenclamide has a long duration of action as it is given once daily, and a wide therapeutic index as patients are started at doses as low as 0.75mg but that can increase as high as 10mg or more. Patients taking glyburide should be cautioned regarding an increased risk of cardiovascular mortality as seen with tolbutamide, another sulfonylurea.","Glyburide belongs to a class of drugs known as sulfonylureas.  These drugs act by closing ATP-sensitive potassium channels on pancreatic beta cells. The ATP-sensitive potassium channels on beta cells are known as sulfonylurea receptor 1 (SUR1).\r\n\r\nUnder low glucose concentrations, SUR1 remains open, allowing for potassium ion efflux to create a -70mV membrane potential.\r\n\r\nNormally SUR1 closes in response to high glucose concentrations, the membrane potential of the cells becomes less negative, the cell depolarizes, voltage gated calcium channels open, calcium ions enter the cell, and the increased intracellular calcium concentration stimulates the release of insulin containing granules.\r\n\r\nGlyburide bypasses this process by forcing SUR1 closed and stimulating increased insulin secretion.","Sulfonylurea receptor 1, Kir6.2 blocker; ATP-binding cassette sub-family C member 9 modulator; Bile salt export pump inhibitor; ATP-binding cassette sub-family A member 1 inhibitor; Mitochondrial ATP-sensitive potassium channel inhibitor; Carnitine O-palmitoyltransferase 1, liver isoform inhibitor; Cystic fibrosis transmembrane conductance regulator antagonist; Transient receptor potential cation channel subfamily M member 4 inhibitor","Indication associated"]
[372,"DB01017","approved; investigational","small molecule","Minocycline","(4S,4aS,5aR,12aS)-4,7-bis(dimethylamino)-3,10,12,12a-tetrahydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide; 7-Dimethylamino-6-demethyl-6-deoxytetracycline; Minocyclin; Minocycline; Minomycin","C23H27N3O7","[H][C@@]12CC3=C(C(O)=CC=C3N(C)C)C(=O)C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@]1([H])C2","Minocycline was first described in the literacture in 1966. It is a second generation tetracycline antibiotic that is active against gram-negative and gram-positive bacteria. Like other semisynthetic tetracyclines, minocycline has modifications to carbons 7-9 on the D ring to generate higher efficacy than previous tetracyclines.\r\n\r\nMinocycline was granted FDA approval on 30 June 1971.","10118-90-8","457.4764","Oral and topical minocycline are indicated to treat inflammatory lesions of acne vulgaris. Subgingival microspheres are indicated as an adjunct treatment in the reduction of pocket depth in adults with periodontitis. Oral and intravenous formulations are indicated to treat infections of susceptible microorganisms. These include rickettsiae, _Mycoplasma pneumoniae_, _Chlamydia trachomatis_, _Chlamydophila psittaci_, _Chlamydia trachomatis_, _Ureaplasma urealyticum_, _Borrelia recurrentis_, _Haemophilus ducreyi_, _Yersinia pestis_, _Francisella tularensis_, _Vibrio cholerae_, _Campylobacter fetus_, _Brucella_ species, _Bartonella bacilliformis_, _Klebsiella granulomatis_, _Escherichia coli_, _Enterobacter aerogenes_, _Shigella_ species, _Acinetobacter_ species, _Haemophilus influenzae_, and _Kelbsiella_ species.","Minocycline is a tetracycline antibiotic that binds to the bacterial 30S ribosomal subunit and interferes with protein synthesis. It is generally given 2-4 times daily, so the duration of action is short. Intravenous minocycline should not exceed 400mg in 24 hours. Patients should be counselled regarding the risks related to tooth and bone development, pseudomembranous colitis, central nervous system side effects, and pseudotumor cerebri.","Tetracyclines enter bacterial cells through OmpF and OmpC porins by coordinating with cations like magnesium. This allows tetracyclines into the periplasm where they dissociate, allowing the lipophilic tetracycline to diffuse into the bacterial cytoplasm. Tetracyclines prevent aminoacyl-tRNA from binding to the 30S ribosome, inhibiting protein synthesis.","30S ribosomal protein S9 inhibitor; 30S ribosomal protein S4 inhibitor; 16S ribosomal RNA inhibitor; Interleukin-1 beta modulator; Arachidonate 5-lipoxygenase inhibitor; Matrix metalloproteinase-9 inhibitor; Vascular endothelial growth factor A inhibitor; Caspase-1 negative modulator; Caspase-3 negative modulator; Cytochrome c negative modulator; Mitogen-activated Protein Kinases inhibitor; Nitric oxide synthase, inducible inhibitor","Target associated"]
[373,"DB01020","approved","small molecule","Isosorbide mononitrate","IS 5-MN; IS-5-MN; IS-5MN; ISMN; Iso-5-mononitrate; Isosorbide 5-mononitrate; Isosorbide 5-nitrate; Isosorbide mononitrate; Isosorbide-5-mononitrate; Monosorbitrate","C6H9NO6","[H][C@]12OC[C@@H](O[N+]([O-])=O)[C@@]1([H])OC[C@@H]2O","Isosorbide mononitrate is an organic nitrate with vasodilating properties. It is an anti-anginal agent that works by relaxing the smooth muscles of both arteries and veins, but but predominantly veins to reduce cardiac preload. Isosorbide mononitrate is an active metabolite of . Like other organic nitrates, isosorbide mononitrate acts as a prodrug for its active metabolite, , which mediates the therapeutic action of isosorbide mononitrate. Isosorbide mononitrate has a longer duration of action than  due to its slow onset of absorption and metabolism.\r\n\r\nFirst approved by the FDA in 1991, isosorbide mononitrate is used for the prevention and management of angina pectoris caused by coronary artery disease; however, the onset of action of orally-administered isosorbide mononitrate is not rapid enough to offset an acute anginal episode. It is available in oral tablets generically and under the brand name ISMO and Monoket. The extended-release forms of the drug are also available generically and under the brand name Imdur.","16051-77-7","191.1388","Isosorbide mononitrate is indicated for the prevention and management of angina pectoris due to coronary artery disease. The onset of action of oral isosorbide mononitrate is not sufficiently rapid to be useful in aborting an acute anginal episode.","Isosorbide mononitrate is an anti-anginal agent and vasodilator that relaxes vascular smooth muscle to prevent and manage angina pectoris. The pharmacological action is mediated by the active metabolite, , which is released when isosorbide mononitrate is metabolized. Nitric oxide works on both arteries and veins, but predominantly veins: by relaxing veins and reducing the central venous pressure, nitric oxide causes venous pooling and a decrease in the venous return to the heart, thus decreasing cardiac preload. In healthy subjects, the stroke volume is decreased and venous pooling can occur in the standing posture, leading to postural hypotension and dizziness. \r\n\r\nAt therapeutic doses of isosorbide mononitrate, nitric oxide has a bigger effect on larger muscular arteries over small resistance arteries. Arterial relaxation leads to reduced systemic vascular resistance and systolic blood (aortic) pressure, decreasing to decreased cardiac afterload. The direct dilator effect on coronary arteries opposes the coronary artery spasm in variant angina or angina pectoris. At larger doses, nitric oxide causes the resistance arteries and arterioles to dilate, reducing arterial pressure via coronary vasodilatation. This leads to increased coronary blood flow. Reduced cardiac preload and afterload caused by nitric oxide causes a reduction in myocardial oxygen consumption; decreased myocardial oxygen demand, along with increased coronary blood flow, leads to an increased in the oxygen content of coronary sinus blood  and the relief from ischemia. \r\n\r\nThe end effect of isosorbide mononitrate include decreased cardiac oxygen consumption, redistribution coronary flow toward ischemic areas via collaterals, and the relief of coronary spasms. Nitric oxide can also increase the rate of relaxation of cardiac muscles, which is an effect outside of vascular smooth muscles. Organic nitrates can also relax other types of smooth muscles, including esophageal and biliary smooth muscle. The anti-anginal activity of isosorbide mononitrate was observed about 1 hour after dosing, and the peak effect was achieved from 1-4 hours after dosing. The duration of anti-anginal action of at least 12 hours was observed with an asymmetrical dosing regimen.","Isosorbide mononitrate acts as a prodrug for nitric oxide (NO), which is a potent vasodilator gas that is released when the drug is metabolized. NO activates soluble guanylyl cyclase in vascular endothelial cells, which increases the intracellular concentrations of cyclic GMP (cGMP). cGMP activates cGMP-dependent protein kinases, such as protein kinase G and I, which activates the downstream intracellular cascades. The downstream cascade results in reduced intracellular concentrations of calcium, caused by processes including inhibition of IP<sub>3</sub>-mediated pathway, phosphorylation of big calcium-activated potassium channel leading to cell hyperpolarization and reduced calcium influx, and increased calcium efflux via the Ca2+-ATPase-pump. Reduced intracellular calcium concentrations lead to the dephosphorylation of myosin light chains and the relaxation of smooth muscle cells.","Guanylate cyclase soluble subunit alpha-2 activator","Indication associated"]
[374,"DB01021","approved; vet_approved","small molecule","Trichlormethiazide","Trichlormethiazide","C8H8Cl3N3O4S2","NS(=O)(=O)C1=C(Cl)C=C2NC(NS(=O)(=O)C2=C1)C(Cl)Cl","A thiazide diuretic with properties similar to those of hydrochlorothiazide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p830)","133-67-5","380.656","Used in the treatment of oedema (including that associated with heart failure) and hypertension.","Trichloromethiazide is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. Trichloromethiazide has also been found useful in edema due to various forms of renal dysfunction such as nephrotic syndrome, acute glomer-ulonephritis, and chronic renal failure. Trichloromethiazide is also indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe forms of hypertension. Like other thiazides, Trichloromethiazide promotes water loss from the body (diuretics). They inhibit Na<sup>+</sup>/Cl<sup>-</sup> reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue.","Trichlormethiazide seemingly appears to inhibit the active reabsorption of chloride in the ascending loop of Henle. Additionally, it may also do the same for sodium. These actions subsequently alter electrolyte transfer in the proximal tubule. This results in excretion of sodium, chloride, and water and, hence, diuresis. As a diuretic, Trichloromethiazide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like Trichloromethiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of Trichloromethiazide is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle.","Solute carrier family 12 member 3 inhibitor; Sodium/potassium-transporting ATPase subunit alpha-1 inhibitor; Carbonic anhydrase 1 inhibitor; Carbonic anhydrase 2 inhibitor; Carbonic anhydrase 4 inhibitor","Therapeutic strategy associated"]
[375,"DB01023","approved; investigational","small molecule","Felodipine","(±)-ethyl methyl 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate; 3-ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate; 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid ethyl methyl ester; Felodipine","C18H19Cl2NO4","CCOC(=O)C1=C(C)NC(C)=C(C1C1=C(Cl)C(Cl)=CC=C1)C(=O)OC","Felodipine is a long-acting 1,4-dihydropyridine calcium channel blocker (CCB)b. It acts primarily on vascular smooth muscle cells by stabilizing voltage-gated L-type calcium channels in their inactive conformation. By inhibiting the influx of calcium in smooth muscle cells, felodipine prevents calcium-dependent myocyte contraction and vasoconstriction. Felodipine is the most potent CCB in use and is unique in that it exhibits fluorescent activity. In addition to binding to L-type calcium channels, felodipine binds to a number of calcium-binding proteins, exhibits competitive antagonism of the mineralcorticoid receptor, inhibits the activity of calmodulin-dependent cyclic nucleotide phosphodiesterase, and blocks calcium influx through voltage-gated T-type calcium channels. Felodipine is used to treat mild to moderate essential hypertension.","72509-76-3","384.254","For the treatment of mild to moderate essential hypertension.","Felodipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. There are at least five different types of calcium channels in Homo sapiens: L-, N-, P/Q-, R- and T-type. It was widely accepted that CCBs target L-type calcium channels, the major channel in muscle cells that mediates contraction; however, some studies have shown that felodipine also binds to and inhibits T-type calcium channels. T-type calcium channels are most commonly found on neurons, cells with pacemaker activity and on osteocytes. The pharmacologic significance of T-type calcium channel blockade is unknown. Felodipine also binds to calmodulin and inhibits calmodulin-dependent calcium release from the sarcoplasmic reticulum. The effect of this interaction appears to be minor.  Another study demonstrated that felodipine attenuates the activity of calmodulin-dependent cyclic nucleotide phosphodiesterase (CaMPDE) by binding to the PDE-1B1 and PDE-1A2 enzyme subunits. CaMPDE is one of the key enzymes involved in cyclic nucleotides and calcium second messenger systems. Felodipine also acts as an antagonist to the mineralcorticoid receptor by competing with aldosterone for binding and blocking aldosterone-induced coactivator recruitment of the mineralcorticoid receptor. Felodipine is able to bind to skeletal and cardiac muscle isoforms of troponin C, one of the key regulatory proteins in muscle contraction. Though felodipine exhibits binding to many endogenous molecules, its vasodilatory effects are still thought to be brought about primarily through inhibition of voltage-gated L-type calcium channels. Similar to other DHP CCBs, felodipine binds directly to inactive calcium channels stabilizing their inactive conformation. Since arterial smooth muscle depolarizations are longer in duration than cardiac muscle depolarizations, inactive channels are more prevalent in smooth muscle cells. Alternative splicing of the alpha-1 subunit of the channel gives felodipine additional arterial selectivity. At therapeutic sub-toxic concentrations, felodipine has little effect on cardiac myocytes and conduction cells.","Felodipine decreases arterial smooth muscle contractility and subsequent vasoconstriction by inhibiting the influx of calcium ions through voltage-gated L-type calcium channels. It reversibly competes against nitrendipine and other DHP CCBs for DHP binding sites in vascular smooth muscle and cultured rabbit atrial cells. Calcium ions entering the cell through these channels bind to calmodulin. Calcium-bound calmodulin then binds to and activates myosin light chain kinase (MLCK). Activated MLCK catalyzes the phosphorylation of the regulatory light chain subunit of myosin, a key step in muscle contraction. Signal amplification is achieved by calcium-induced calcium release from the sarcoplasmic reticulum through ryanodine receptors. Inhibition of the initial influx of calcium decreases the contractile activity of arterial smooth muscle cells and results in vasodilation. The vasodilatory effects of felodipine result in an overall decrease in blood pressure. Felodipine may be used to treat mild to moderate essential hypertension.","Voltage-dependent L-type calcium channel subunit alpha-1C inhibitor; Voltage-dependent calcium channel subunit alpha-2/delta-1 inhibitor; Voltage-dependent L-type calcium channel subunit beta-2 inhibitor; Voltage-dependent L-type calcium channel subunit alpha-1D inhibitor; Voltage-dependent L-type calcium channel subunit alpha-1S inhibitor; Voltage-dependent T-type calcium channel subunit alpha-1H inhibitor; Voltage-dependent calcium channel subunit alpha-2/delta-2 inhibitor; Calmodulin other; Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B inhibitor; Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A inhibitor; Mineralocorticoid receptor antagonist; Troponin C, skeletal muscle other; Troponin C, slow skeletal and cardiac muscles other","Indication associated"]
[376,"DB01024","approved","small molecule","Mycophenolic acid","(e)-6-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-5-phthalanyl)-4-methyl-4-hexenoic acid; Mycophenolate; Mycophenolic acid","C17H20O6","COC1=C(C\\C=C(/C)CCC(O)=O)C(O)=C2C(=O)OCC2=C1C","Mycophenolic acid is an an immunosuppresant drug and potent anti-proliferative, and can be used in place of the older anti-proliferative azathioprine. It is usually used as part of triple therapy including a calcineurin inhibitor (ciclosporin or tacrolimus) and prednisolone. It is also useful in research for the selection of animal cells that express the E. coli gene coding for XGPRT (xanthine guanine phosphoribosyltransferase).","24280-93-1","320.3371","For the prophylaxis of organ rejection in patients receiving allogeneic renal transplants, administered in combination with cyclosporine and corticosteroids.","Mycophenolic acid is an antibiotic substance derived from <i>Penicillium stoloniferum</i>. It blocks de novo biosynthesis of purine nucleotides by inhibition of the enzyme inosine monophosphate dehydrogenase. Mycophenolic acid is important because of its selective effects on the immune system. It prevents the proliferation of T-cells, lymphocytes, and the formation of antibodies from B-cells. It also may inhibit recruitment of leukocytes to inflammatory sites.","Mycophenolic acid is a potent, selective, uncompetitive, and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), and therefore inhibits the de novo pathway of guanosine nucleotide synthesis without incorporation into DNA. Because T- and B-lymphocytes are critically dependent for their proliferation on de novo synthesis of purines, whereas other cell types can utilize salvage pathways, mycophenolic acid has potent cytostatic effects on lymphocytes. Mycophenolic acid inhibits proliferative responses of T- and B-lymphocytes to both mitogenic and allospecific stimulation. Addition of guanosine or deoxyguanosine reverses the cytostatic effects of mycophenolic acid on lymphocytes. Mycophenolic acid also suppresses antibody formation by B-lymphocytes. Mycophenolic acid prevents the glycosylation of lymphocyte and monocyte glycoproteins that are involved in intercellular adhesion to endothelial cells and may inhibit recruitment of leukocytes into sites of inflammation and graft rejection.","Inosine-5'-monophosphate dehydrogenase 1 inhibitor; Inosine-5'-monophosphate dehydrogenase 2 inhibitor","Therapeutic strategy associated"]
[377,"DB01029","approved; investigational","small molecule","Irbesartan","2-butyl-3-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1,3-diazaspiro[4.4]non-1-en-4-one; Irbesartan","C25H28N6O","CCCCC1=NC2(CCCC2)C(=O)N1CC1=CC=C(C=C1)C1=CC=CC=C1C1=NNN=N1","Irbesartan is an angiotensin receptor blocker (ARB) indicated to treat hypertension or diabetic nephropathy. It can also be used as part of a combination product with  for patients not well controlled or not expected to be well controlled on monotherapy. Unlike angiotensin converting enzyme inhibitors, ARBs are not associated with a dry cough.\r\n\r\nIrbesartan was granted FDA approval on 30 September 1997.","138402-11-6","428.5294","Irbesartan is indicated to treat hypertension and diabetic nephropathy in hypertensive patients with type 2 diabetes, elevated serum creatinine, and proteinuria. A combination product with hydrochlorothiazide is indicated for hypertension in patients with uncontrolled hypertension with monotherapy or first line in patients not expected to be well controlled with monotherapy.","Irbesartan is an angiotensin receptor blocker used to treat hypertension and diabetic nephropathy. It has a long duration of action as it is usually taken once daily and a wide therapeutic index as doses may be as low as 150mg daily but doses of 900mg/day were well tolerated in healthy human subjects.","Irbesartan prevents angiotensin II binding to the AT<sub>1</sub> receptor in tissues like vascular smooth muscle and the adrenal gland. Irbesartan and its active metabolite bind the AT<sub>1</sub> receptor with 8500 times more affinity than they bind to the AT<sub>2</sub> receptor. Irbesartan's prevention of angiotensin II binding causes vascular smooth muscle relaxation and prevents the secretion of aldosterone, lowering blood pressure.\r\n\r\nAngiotensin II would otherwise bind to the AT<sub>1</sub> receptor, inducing vasoconstriction and aldosterone secretion, raising blood pressure.","Type-1 angiotensin II receptor antagonist; Transcription factor AP-1 other/unknown","Target associated"]
[378,"DB01030","approved; investigational","small molecule","Topotecan","9-[(dimethylamino)methyl]-10-hydroxy-(4S)-camptothecin; Topotecan","C23H23N3O5","CC[C@@]1(O)C(=O)OCC2=C1C=C1N(CC3=CC4=C(C=CC(O)=C4CN(C)C)N=C13)C2=O","An antineoplastic agent used to treat ovarian cancer. It works by inhibiting DNA topoisomerases, type I.","123948-87-8","421.4458","For the treatment of advanced ovarian cancer in patients with disease that has recurred or progressed following therapy with platinum-based regimens. Also used as a second-line therapy for treatment-sensitive small cell lung cancer, as well as in combination with cisplatin for the treatment of stage IV-B, recurrent, or persistent cervical cancer not amenable to curative treatment with surgery and/or radiation therapy.","Topotecan, a semi-synthetic derivative of camptothecin (a plant alkaloid obtained from the <i>Camptotheca acuminata</i> tree), is an anti-tumor drug with topoisomerase I-inhibitory activity similar to irinotecan. DNA topoisomerases are enzymes in the cell nucleus that regulate DNA topology (3-dimensional conformation) and facilitate nuclear processes such as DNA replication, recombination, and repair. During these processes, DNA topoisomerase I creates reversible single-stranded breaks in double-stranded DNA, allowing intact single DNA strands to pass through the break and relieve the topologic constraints inherent in supercoiled DNA. The 3'-DNA terminus of the broken DNA strand binds covalently with the topoisomerase enzyme to form a catalytic intermediate called a cleavable complex. After DNA is sufficiently relaxed and the strand passage reaction is complete, DNA topoisomerase reattaches the broken DNA strands to form the unaltered topoisomers that allow transcription to proceed. Topotecan interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal cells can be affected by the medicine, other effects may also occur. Unlike irinotecan, topotecan is found predominantly in the inactive carboxylate form at neutral pH and it is not a prodrug.","Topotecan has the same mechanism of action as irinotecan and is believed to exert its cytotoxic effects during the S-phase of DNA synthesis. Topoisomerase I relieves torsional strain in DNA by inducing reversible single strand breaks. Topotecan binds to the topoisomerase I-DNA complex and prevents religation of these single strand breaks. This ternary complex interferes with the moving replication fork, which leads to the induction of replication arrest and lethal double-stranded breaks in DNA. As mammalian cells cannot efficiently repair these double strand breaks, the formation of this ternary complex eventually leads to apoptosis (programmed cell death).\r\n\r\nTopotecan mimics a DNA base pair and binds at the site of DNA cleavage by intercalating between the upstream (−1) and downstream (+1) base pairs. Intercalation displaces the downstream DNA, thus preventing religation of the cleaved strand. By specifically binding to the enzyme–substrate complex, Topotecan acts as an uncompetitive inhibitor.","DNA topoisomerase 1 inhibitor; DNA topoisomerase I, mitochondrial inhibitor; DNA intercalation","Therapeutic strategy associated"]
[379,"DB01032","approved; investigational","small molecule","Probenecid","4-((Dipropylamino)sulfonyl)benzoic acid; p-(Dipropylsulfamoyl)benzoic acid; Probenecid; Probenecid acid","C13H19NO4S","CCCN(CCC)S(=O)(=O)C1=CC=C(C=C1)C(O)=O","The prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy.","57-66-9","285.359","For the reduction of serum uric acid concentrations in chronic gouty arthritis and tophaceous gout in patients with frequent disabling gout attacks. Has also been effectively used to promote uric acid excretion in hyperuricemia secondary to the administration of thiazide and related diuretics.","Probenecid is a uricosuric and renal tubular blocking agent and is used in combination with colchicine to treat chronic gouty arthritis when complicated by frequent, recurrent acute attacks of gout. It inhibits the reabsorption of urate at the proximal convoluted tubule, thus increasing the urinary excretion of uric acid and decreasing serum urate levels. Effective uricosuria reduces the miscible urate pool, retards urate deposition, and promotes resorption of urate deposits. At the proximal and distal tubles, probenecid competitively inhibits the secretion of many weak organic acids including penicillins, most cephalosporins, and some other β-lactam antibiotics. This results in an increase in the plasma concentrations of acidic drugs eliminated principally by renal secretion, but only a slight increase if the drug is eliminated mainly by filtration. Thus, the drug can be used for therapeutic advantages to increase concentrations of certain β-lactam antibiotics in the treatment of gonorrhea, neurosyphilis, or pelvic inflammatory disease (PID).","Probenecid inhibits the tubular reabsorption of urate, thus increasing the urinary excretion of uric acid and decreasing serum urate levels. Probenecid may also reduce plasma binding of urate and inhibit renal secretion of uric acid at subtherapeutic concentrations. The mechanism by which probenecid inhibits renal tubular transport is not known, but the drug may inhibit transport enzymes that require a source of high energy phosphate bonds and/or nonspecifically interfere with substrate access to protein receptor sites on the kidney tubules.","Solute carrier family 22 member 6 inhibitor; Solute carrier family 22 member 11 inhibitor; Solute carrier family 22 member 8 inhibitor; Pannexin-1 antagonist; Taste receptor type 2 member 16","Therapeutic strategy associated"]
[380,"DB01034","experimental","small molecule","Cerulenin","(2R,3S)-3-((4E,7E)-Nona-4,7-dienoyl)-oxirane-2-carboxylic acid amide; (2R,3S)-3-((4E,7E)-nona-4,7-dienoyl)oxirane-2-carboxamide; Cerulenin","C12H17NO3","[H][C@]1(O[C@]1([H])C(=O)CC\\C=C\\C\\C=C\\C)C(N)=O","Cerulenin is an antifungal agent whose activity interferes with or otherwise acts to prevent the formation of fatty acids and sterols. In fatty acid synthesis, reported to bind in equimolar ratio to b-keto-acyl-ACP synthase. In sterol synthesis, inhibits HMG-CoA synthetase activity. It is also shown to inhibit feeding and induce dramatic weight loss in mice. It is found naturally in the Cephalosporium caerulensfungus.","17397-89-6","223.272","For use as a biochemical tool, Cerulenin is shown to cause dramatic weight loss in animals","Cerulenin is an antifungal antibiotic isolated from <i>Cephalosporium caerulens</i>. It interrupts fungal growth by inhibiting the biosynthesis of sterols and fatty acids (inhibits bacterial fatty acid synthesis). It also inhibits HMG-CoA synthetase activity. Cerulenin produces metabolic effects similar to effects of leptin, but through mechanisms that are independent of, or down-stream from, both leptin and melanocortin receptors.","Irreversibly binds to fatty acid synthase, specifically b-ketoacyl-acyl carrier protein synthase (FabH, FabB and FabF condensation enzymes). A number of tumor cells and cell lines have been observed to have highly upregulated expression and activity of fatty acid synthase (FAS). Inhibition of FAS by cerulenin leads to cytotoxicity and apoptosis in human cancer cell lines, an effect believed to be mediated by the accumulation of malonyl-coenzyme A in cells with an upregulated FAS pathway.","3-oxoacyl-[acyl-carrier-protein] synthase 1 inhibitor; 3-oxoacyl-[acyl-carrier-protein] synthase 2 inhibitor; 3-oxoacyl-[acyl-carrier-protein] synthase 3 inhibitor; Fatty acid synthase inhibitor","Therapeutic strategy associated"]
[381,"DB01037","approved; investigational; vet_approved","small molecule","Selegiline","(−)-selegiline; L-Deprenalin; Selegiline","C13H17N","C[C@H](CC1=CC=CC=C1)N(C)CC#C","A selective, irreversible inhibitor of Type B monoamine oxidase. It is used in newly diagnosed patients with Parkinson's disease. It may slow progression of the clinical disease and delay the requirement for levodopa therapy. It also may be given with levodopa upon onset of disability. (From AMA Drug Evaluations Annual, 1994, p385) The compound without isomeric designation is Deprenyl.","14611-51-9","187.286","Monotherapy for initial treatment of Parkinson's disease, as well as an adjunct therapy in patients with a decreased response to levodopa/carbadopa. Also used for the palliative treatment of mild to moderate Alzheimer's disease and at higher doses, for the treatment of depression.","Dopamine is an essential chemical that occurs in many parts of the body. It is the premature degradation of dopamine that results in the symptoms of Parkinson's disease. Monoamine oxidase (MAO) is an enzyme which accelerates the breakdown of dopamine. Selegiline can prolong the effects of dopamine in the brain by preventing its breakdown through seletively blocking MAO-B. It also may prevent the removal of dopamine between nerve endings and enhance release of dopamine from nerve cells.","Although the mechanisms for selegiline's beneficial action in the treatment of Parkinson's disease are not fully understood, the selective, irreversible inhibition of monoamine oxidase type B (MAO-B) is thought to be of primary importance. MAO-B is involved in the oxidative deamination of dopamine in the brain. Selegiline binds to MAO-B within the nigrostriatal pathways in the central nervous system, thus blocking microsomal metabolism of dopamine and enhancing the dopaminergic activity in the substantial nigra. Selegiline may also increase dopaminergic activity through mechanisms other than inhibition of MAO-B. At higher doses, selegiline can also inhibit monozmine oxidase type A (MAO-A), allowing it to be used for the treatment of depression.","Amine oxidase [flavin-containing] B inhibitor; Amine oxidase [flavin-containing] A inhibitor","Indication associated"]
[382,"DB01041","approved; investigational; withdrawn","small molecule","Thalidomide","(+-)-N-(2,6-dioxo-3-Piperidyl)phthalimide; (+-)-Thalidomide; (±)-N-(2,6-dioxo-3-piperidyl)phthalimide; (±)-thalidomide; 1,3-dioxo-2-(2,6-dioxopiperidin-3-yl)isoindoline; 2,6-dioxo-3-phthalimidopiperidine; 3-Phthalimidoglutarimide; alpha-(N-Phthalimido)glutarimide; alpha-N-Phthalylglutaramide; N-(2,6-dioxo-3-piperidyl)phthalimide; N-Phthaloylglutamimide; N-Phthalylglutamic acid imide; Thalidomide; α-(N-phthalimido)glutarimide; α-N-phthalylglutaramide; α-phthalimidoglutarimide","C13H10N2O4","O=C1N(C2CCC(=O)NC2=O)C(=O)C2=CC=CC=C12","A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor-alpha from monocytes, and modulates other cytokine action.","50-35-1","258.2295","For the acute treatment of the cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL). Also for use as maintenance therapy for prevention and suppression of the cutaneous manifestations of ENL recurrence.","Thalidomide is an immunomodulatory agent with a spectrum of activity that is not fully characterized. Thalidomide is racemic &mdash; it contains both left and right handed isomers in equal amounts: one enantiomer is effective against morning sickness, and the other is teratogenic. The enantiomers are converted to each other in vivo. That is, if a human is given D-thalidomide or L-thalidomide, both isomers can be found in the serum. Hence, administering only one enantiomer will not prevent the teratogenic effect in humans.","In patients with erythema nodosum leprosum (ENL) the mechanism of action is not fully understood. Available data from in vitro studies and preliminary clinical trials suggest that the immunologic effects of this compound can vary substantially under different conditions, but may be related to suppression of excessive tumor necrosis factor-alpha (TNF-a) production and down-modulation of selected cell surface adhesion molecules involved in leukocyte migration. For example, administration of thalidomide has been reported to decrease circulating levels of TNF-a in patients with ENL, however, it has also been shown to increase plasma TNF-a levels in HIV-seropositive patients. As a cancer treatment, the drug may act as a VEGF inhibitor.","Protein cereblon inhibitor; Tumor necrosis factor inhibitor; Nuclear factor NF-kappa-B p105 subunit antagonist; DNA intercalation; Fibroblast growth factor receptor 2 antagonist; Prostaglandin G/H synthase 2 antagonist; alpha1-acid glycoprotein binder","Target associated"]
[383,"DB01044","approved; investigational","small molecule","Gatifloxacin","1-Cyclopropyl-1,4-dihydro-6-fluoro-8-methoxy-7-(3-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid; 1-cyclopropyl-6-fluoro- 8-methoxy-7-(3-methylpiperazin-1-yl)- 4-oxo-quinoline-3-carboxylic acid; Gatifloxacin; Gatifloxacin anhydrous","C19H22FN3O4","COC1=C2N(C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNC(C)C1)C1CC1","Gatifloxacin is an antibiotic agent and a member of the fourth-generation fluoroquinolone family. It works by inhibiting the bacterial enzymes DNA gyrase and topoisomerase IV. It was first introduced by Bristol-Myers Squibb in 1999 under the brand name Tequin® for the treatment of respiratory tract infections. Gatifloxacin is available as tablets and in various aqueous solutions for intravenous therapy. It is also available as eye drops under the brand name Zymar® marketed by Allergan.","112811-59-3","375.3941","For the treatment of bronchitis, sinusitis, community-acquired pneumonia, and skin infections (abscesses, wounds) caused by S. pneumoniae, H. influenzae, S. aureus, M. pneumoniae, C. pneumoniae, L. pneumophila, S. pyogenes","Gatifloxacin is a synthetic broad-spectrum 8-methoxyfluoroquinolone antibacterial agent for oral or intravenous administration. is bactericidal and its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase, which allows the untwisting required to replicate one DNA double helix into two. Notably the drug has 100 times higher affinity for bacterial DNA gyrase than for mammalian. Gatifloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria. It should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.","The bactericidal action of Gatifloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, and recombination.","DNA gyrase subunit A inhibitor; DNA gyrase subunit B inhibitor; DNA topoisomerase 4 subunit A inhibitor; DNA topoisomerase 4 subunit B inhibitor","Indication associated"]
[384,"DB01047","approved; investigational","small molecule","Fluocinonide","Fluocinonide","C26H32F2O7","[H][C@@]12C[C@@]3([H])[C@]4([H])C[C@H](F)C5=CC(=O)C=C[C@]5(C)[C@@]4(F)[C@@H](O)C[C@]3(C)[C@@]1(OC(C)(C)O2)C(=O)COC(C)=O","A topical glucocorticoid used in the treatment of eczema.","356-12-7","494.5249","A topical anti-inflammatory product for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses.","Fluocinonide is a potent glucocorticoid steroid used topically as anti-inflammatory agent for the treatment of skin disorders such as eczema. It mediates its effects to relieve itching, redness, dryness, crusting, scaling, inflammation, and discomfort associated with inflammatory skin conditions.","Fluocinonide is a potent glucocorticoid steroid used topically as anti-inflammatory agent for the treatment of skin disorders such as eczema. Fluocinonide binds to the cytosolic glucocorticoid receptor. After binding the receptor the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes. The anti-inflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. Specifically glucocorticoids induce lipocortin-1 (annexin-1) synthesis, which then binds to cell membranes preventing the phospholipase A2 from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. Cyclooxygenase (both COX-1 and COX-2) expression is also suppressed, potentiating the effect. In another words, the two main products in inflammation Prostaglandins and Leukotrienes are inhibited by the action of Glucocorticoids. Glucocorticoids also stimulate the lipocortin-1 escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines etc.) from neutrophils, macrophages and mastocytes. Additionally the immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding.  Like other glucocorticoid agents Fluocinolone acetonide acts as a physiological antagonist to insulin by decreasing glycogenesis (formation of glycogen). It also promotes the breakdown of lipids (lipolysis), and proteins, leading to the mobilization of extrahepatic amino acids and ketone bodies. This leads to increased circulating glucose concentrations (in the blood). There is also decreased glycogen formation in the liver.","Glucocorticoid receptor agonist; Smoothened homolog agonist","Therapeutic strategy associated"]
[385,"DB01050","approved","small molecule","Ibuprofen","(±)-2-(p-isobutylphenyl)propionic acid; (±)-ibuprofen; (±)-p-isobutylhydratropic acid; (±)-α-methyl-4-(2-methylpropyl)benzeneacetic acid; (4-isobutylphenyl)-α-methylacetic acid; (RS)-ibuprofen; 2-(4-isobutylphenyl)propanoic acid; 4-isobutylhydratropic acid; Ibuprofen; Ibuprophen; α-(4-isobutylphenyl)propionic acid; α-(p-isobutylphenyl)propionic acid","C13H18O2","CC(C)CC1=CC=C(C=C1)C(C)C(O)=O","Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) derived from propionic acid and it is considered the first of the propionics. The formula of ibuprofen is 2-(4-isobutylphenyl) propionic acid and its initial development was in 1960 while researching for a safer alternative for aspirin. Ibuprofen was finally patented in 1961 and this drug was first launched against rheumatoid arthritis in the UK in 1969 and USA in 1974. It was the first available over-the-counter NSAID.\r\n\r\nOn the available products, ibuprofen is administered as a racemic mixture. Once administered, the R-enantiomer undergoes extensive interconversion to the S-enantiomer _in vivo_ by the activity of the alpha-methylacyl-CoA racemase. In particular, it is generally proposed that the S-enantiomer is capable of eliciting stronger pharmacological activity than the R-enantiomer.","15687-27-1","206.2808","Ibuprofen is the most commonly used and prescribed NSAID. It is very common over the counter medication widely used as an analgesic, anti-inflammatory and antipyretic.\r\n\r\nThe use of ibuprofen and its enantiomer  in a racemic mix is common for the management of mild to moderate pain related to dysmenorrhea, headache, migraine, postoperative dental pain, spondylitis, osteoarthritis, rheumatoid arthritis, and soft tissue disorder.\r\n\r\nDue to its activity against prostaglandin and thromboxane synthesis, ibuprofen has been attributed to alteration of platelet function and prolongation of gestation and labor.\r\n\r\nAs ibuprofen is a widely used medication, the main therapeutic indications are:\r\n\r\n* Patent Ductus Arteriosus - it is a neonatal condition wherein the ductus arteriosus (blood vessel that connects the main pulmonary artery to the proximal descending aorta) fails to close after birth causing severe risk of heart failure. The prostaglandin inhibition of ibuprofen has been studied for the treatment of this condition as it is known that prostaglandin E2 is responsible for keeping the ductus arteriosus open.\r\n\r\n* Rheumatoid- and osteo-arthritis - ibuprofen is very commonly used in the symptomatic treatment of inflammatory, musculoskeletal and rheumatic disorders.\r\n\r\n* Cystic fibrosis - the use of high dosages of ibuprofen has been proven to decrease inflammation and decreasing polymorphonuclear cell influx in the lungs.\r\n\r\n* Orthostatic hypotension - ibuprofen can induce sodium retention and antagonize the effect of diuretics which has been reported to be beneficial for patients with severe orthostatic hypotension.\r\n\r\n* Dental pain - ibuprofen is used to manage acute and chronic orofacial pain.\r\n\r\n* Minor pain - ibuprofen is widely used to reduce minor aches and pains as well as to reduce fever and manage dysmenorrhea. It is very commonly used for the relief of acute indications such as fever and tension headaches.\r\n\r\n* Investigational uses - efforts have been put into developing ibuprofen for the prophylaxis of Alzheimer's disease, Parkinson disease, and breast cancer.","Ibuprofen has multiple actions in different inflammatory pathways involved in acute and chronic inflammation. The main effects reported in ibuprofen are related to the control of pain, fever and acute inflammation by the inhibition of the synthesis of prostanoids by COX-1 and COX-2. Pain relief is attributed to peripheral affected regions and central nervous system effects in the pain transmission mediated by the dorsal horn and higher spinothalamic tract. Some reports have tried to link the pain regulation with a possible enhancement on the synthesis of endogenous cannabinoids and action on the NMDA receptors. The effect on pain has been shown to be related to the cortically evoked potentials.\r\n\r\nThe antipyretic effect is reported to be linked to the effect on the prostanoid synthesis due to the fact that the prostanoids are the main signaling mediator of pyresis in the hypothalamic-preoptic region.\r\n\r\nThe use of ibuprofen in dental procedures is attributed to the local inhibition of prostanoid production as well as to anti-oedemic activity and an increase of plasma beta-endorphins. Some reports have suggested a rapid local reduction of the expression of COX-2 in dental pulp derived by the administration of ibuprofen.\r\n\r\nThe administration of ibuprofen in patients with rheumatic diseases has shown to control joint symptoms. \r\n\r\nIbuprofen is largely used in OTC products such as an agent for the management of dysmenorrhea which has been proven to reduce the amount of menstrual prostanoids and to produce a reduction in the uterine hypercontractility. As well, it has been reported to reduce significantly the fever and the pain caused by migraines. This effect is thought to be related to the effect on platelet activation and thromboxane A2 production which produces local vascular effects in the affected regions. This effect is viable as ibuprofen can enter in the central nervous system.\r\n\r\nIn the investigational uses of ibuprofen, it has been reported to reduce neurodegeneration when given in low doses over a long time. On the other hand, its use in Parkinson disease is related to the importance of inflammation and oxidative stress in the pathology of this condition. The use of ibuprofen for breast cancer is related to a study that shows a decrease of 50% in the rate of breast cancer.","The exact mechanism of action of ibuprofen is unknown. However, ibuprofen is considered an NSAID and thus it is a non-selective inhibitor of cyclooxygenase, which is an enzyme involved in prostaglandin (mediators of pain and fever) and thromboxane (stimulators of blood clotting) synthesis via the arachidonic acid pathway.\r\n\r\nIbuprofen is a non-selective COX inhibitor and hence, it inhibits the activity of both COX-1 and COX-2. The inhibition of COX-2 activity decreases the synthesis of prostaglandins involved in mediating inflammation, pain, fever, and swelling while the inhibition of COX-1 is thought to cause some of the side effects of ibuprofen including GI ulceration.","Prostaglandin G/H synthase 2 inhibitor; Prostaglandin G/H synthase 1 inhibitor; Apoptosis regulator Bcl-2 modulator; Thrombomodulin inducer; Fatty acid-binding protein, intestinal binder; Peroxisome proliferator-activated receptor gamma activator; Cystic fibrosis transmembrane conductance regulator inhibitor; Peroxisome proliferator-activated receptor alpha activator; Platelet glycoprotein Ib alpha chain inducer; Protein S100-A7 inducer","Target associated"]
[386,"DB01053","approved; vet_approved","small molecule","Benzylpenicillin","(2S,5R,6R)-3,3-dimethyl-7-oxo-6-(phenylacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; 6-(2-phenylacetamido)penicillanic acid; Bensylpenicillin; Benzyl benicillin; Benzylpenicillin; Benzylpenicillinic acid; Free penicillin II; PCG; Penicillin G; PG","C16H18N2O4S","[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)CC1=CC=CC=C1)C(O)=O","Benzylpenicillin (Penicillin G) is narrow spectrum antibiotic used to treat infections caused by susceptible bacteria. It is a natural penicillin antibiotic that is administered intravenously or intramuscularly due to poor oral absorption. Penicillin G may also be used in some cases as prophylaxis against susceptible organisms.\r\n \r\nNatural penicillins are considered the drugs of choice for several infections caused by susceptible gram positive aerobic organisms, such as *Streptococcus pneumoniae*, groups A, B, C and G streptococci, nonenterococcal group D streptococci, viridans group streptococci, and non-penicillinase producing staphylococcus. Aminoglycosides may be added for synergy against group B streptococcus (*S. agalactiae*), *S. viridans*, and *Enterococcus faecalis*. The natural penicillins may also be used as first or second line agents against susceptible gram positive aerobic bacilli such as *Bacillus anthracis*, *Corynebacterium diphtheriae*, and *Erysipelothrix rhusiopathiae*. Natural penicillins have limited activity against gram negative organisms; however, they may be used in some cases to treat infections caused by *Neisseria meningitidis* and *Pasteurella*. They are not generally used to treat anaerobic infections. Resistance patterns, susceptibility and treatment guidelines vary across regions.","61-33-6","334.39","For use in the treatment of severe infections caused by penicillin G-susceptible microorganisms when rapid and high penicillin levels are required such as in the treatment of septicemia, meningitis, pericarditis, endocarditis and severe pneumonia.","Penicillin G is a penicillin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. The name \"penicillin\" can either refer to several variants of penicillin available, or to the group of antibiotics derived from the penicillins. Penicillin G has <i>in vitro</i> activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of penicillin G results from the inhibition of cell wall synthesis and is mediated through penicillin G binding to penicillin binding proteins (PBPs). Penicillin G is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases.","By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, penicillin G inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that penicillin G interferes with an autolysin inhibitor.","Penicillin-binding protein 3 inhibitor; Solute carrier family 22 member 8 substrate&inhibitor; Solute carrier family 15 member 1 substrate&inhibitor; Solute carrier family 15 member 2 inhibitor","Indication associated"]
[387,"DB01054","approved; investigational","small molecule","Nitrendipine","1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid ethyl methyl ester; Nitrendipine","C18H20N2O6","CCOC(=O)C1=C(C)NC(C)=C(C1C1=CC(=CC=C1)[N+]([O-])=O)C(=O)OC","Nitrendipine is a calcium channel blocker with marked vasodilator action. It is an effective antihypertensive agent and differs from other calcium channel blockers in that it does not reduce glomerular filtration rate and is mildly natriuretic, rather than sodium retentive.","39562-70-4","360.3612","For the treatment of mild to moderate hypertension","Nitrendipine, a dihydropyridine calcium-channel blocker, is used alone or with an angiotensin-converting enzyme inhibitor, to treat hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina. Nitrendipine is similar to other peripheral vasodilators. Nitrendipine inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.","By deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, Nitrendipine inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.","Voltage-dependent L-type calcium channel subunit alpha-1C inhibitor; Voltage-dependent calcium channel subunit alpha-2/delta-1 inhibitor; Voltage-dependent L-type calcium channel subunit beta-2 inhibitor; Voltage-dependent L-type calcium channel subunit alpha-1D inhibitor; Voltage-dependent L-type calcium channel subunit alpha-1S inhibitor; Voltage-dependent calcium channel subunit alpha-2/delta-2 inhibitor; Voltage-dependent T-type calcium channel subunit alpha-1H inhibitor","Indication associated"]
[388,"DB01055","experimental","small molecule","Mimosine","(L)-Mimosine; (S)-2-amino-3-(3-hydroxy-4-oxo-4H-pyridin-1-yl)propanoate; L-Mimosine; Leucaenine; Leucaenol; Leucenine; Leucenol; Mimosin","C8H10N2O4","N[C@@H](CN1C=CC(=O)C(O)=C1)C(O)=O","Mimosine is an antineoplastic alanine-substituted pyridine derivative isolated from _Leucena glauca_.","500-44-7","198.176",null,"Mimosine inhibits DNA synthesis at the level of elongation of nascent chains by altering deoxyribonucleotide metabolism. It arrests the cell cycle in the late G(1) phase.","Mimosine causes inhibition of DNA replication, changes in the progression of the cells in the cell cycle, and apoptosis. Mimosine appears to introduce breaks into DNA. Mimosine is an iron/zinc chelator. Iron depletion induces DNA double-strand breaks in treated cells, and activates a DNA damage response that results in focal phosphorylation of histones. This leads to inhibition of DNA replication and/or DNA elongation. Some studies indicate that mimosine prevents the initiation of DNA replication, whereas other studies indicate that mimosine disrupts elongation of the replication fork by impairing deoxyribonucleotide synthesis by inhibiting the activity of the iron-dependent enzyme ribonucleotide reductase and the transcription of the cytoplasmic serine hydroxymethyltransferase gene (SHMT). Inhibition of serine hydroxymethyltransferase is moderated by a zinc responsive unit located in front of the SHMT gene.","Serine hydroxymethyltransferase, cytosolic inhibitor; C-C motif chemokine 2 inhibitor; Tyrosinase inhibitor","Therapeutic strategy associated"]
[389,"DB01064","approved; investigational","small molecule","Isoprenaline","(±)-isoprenaline; (±)-isoproterenol; 1-(3,4-dihydroxyphenyl)-2-(isopropylamino)ethanol; 1-(3,4-dihydroxyphenyl)-2-isopropylaminoethanol; 3,4-dihydroxy-α-[(isopropylamino)methyl]benzyl alcohol; Isoprenaline; Isopropyl noradrenaline; Isoproterenol; N-isopropyl-β-dihydroxyphenyl-β-hydroxyethylamine; N-Isopropylnoradrenaline; N-Isopropylnorepinephrine; α-(isopropylaminomethyl)protocatechuyl alcohol","C11H17NO3","CC(C)NCC(O)C1=CC(O)=C(O)C=C1","Isoprenaline is a non-selective beta adrenergic receptor agonist indicated to treat heart block, Adams-Stokes attacks, bronchospasm in anesthesia, cadiac arrest, hypovolemic shocks, septic shock, hypoperfusion, congestive hear failure, and cardiogenic shock.\r\n\r\nIsoprenaline research in the 1940s found that this isopropyl analog of epinephrine dilated the bronchi, as well as raising the heart rate and cardiac output, without vasoconstriction. The US patent from 1943 states that this compound had a wider therapeutic index and a stronger action than .\r\n\r\nIsoprenaline was granted FDA approval on 19 February 1948.","7683-59-2","211.2576","Isoprenaline is indicated to treat mild or transient episodes of heart block not requiring electric shock or pacemakers, serious episodes of heart block and Adams-Stokes attacks not caused by ventricular tachycardia or fibrillation, and bronchospasm during anesthesia. Isoprenaline is also indicated for cases of cardiac arrest until preferable treatments like electric shock and pacemakers are available. Isoprenaline is also indicated as an adjunct therapy to fluid and electrolyte replacement therapy in hypovolemic shock, septic shock, hypoperfusion, congestive heart failure, and cardiogenic shock.","Isoprenaline is a non-selective beta adrenergic receptor agonist used in a number of indications for the heart, as well as bronchospasm in anesthesia. Isoprenaline has a short duration of action as it is rapidly cleared, and a wide therapeutic index. Patients should be counselled regarding the risks of isoprenaline in the treatment of cardiogenic shock following myocardial infarction, paradoxical worsening of heart block, or precipitation of Adams-Stokes attacks.","Isoprenaline is a non-selective beta adrenergic receptor agonist. Agonism of beta-1 and beta-2 adrenergic receptors causes the alpha subunit of G-protein coupled receptors to exchange GMP for GTP, activating them, and allowing the alpha subunit to dissociate from the beta and gamma subunits. Dissociation of the alpha subunit activates adenylate cyclase, converting ATP to cyclic AMP. Cyclic AMP activates protein kinase A (PKA), which phosphorylates cardiac L-type calcium channels such as Ca<sub>v</sub>1.2. These channels depolarize cells by inward active transport of calcium ions.\r\n\r\nAgonism of beta-1 adrenergic receptors lead to increased strength of contractility, conduction of nerve impulses, speed of relaxation, and rate in the heart. \r\n\r\nAgonism of beta-2 adrenergic receptors leads to glycogenolysis in the liver, glucagon release from the pancreas, and activation of the renin-angiotensin-aldosterone system.\r\n\r\nIn the alveoli, agonism of beta-2 adrenergic receptors, activates similar pathways to the heart, however the end result is regulation of sodium channels, the cystic fibrosis transmembrane conductance regulator (CFTR), and sodium potassium ATPase. PKA phosphorylates scaffolding proteins and sodium channels, increasing the number of sodium channels on the apical side of alveolar cells and increasing active transport of sodium ions into cells. Agonism of beta-2 adrenergic receptors can also increase chloride ion transport across CFTR. Together, these actions lead to passive transport of water out of the alveoli, and the clearance of alveolar fluid.","Beta-1 adrenergic receptor agonist; Beta-2 adrenergic receptor agonist&binder; Beta-3 adrenergic receptor agonist; Superoxide dismutase [Cu-Zn] stabilization","Therapeutic strategy associated"]
[390,"DB01066","approved; investigational","small molecule","Cefditoren","Cefditoren","C19H18N6O5S3","[H][C@]12SCC(\\C=C/C3=C(C)N=CS3)=C(N1C(=O)[C@H]2NC(=O)C(=N/OC)\\C1=CSC(N)=N1)C(O)=O","Cefditoren is an oral third-generation cephalosporin. It is commonly marketed under the trade name Spectracef by Cornerstone BioPharma.","104145-95-1","506.578","For the treatment of mild to moderate infections in adults and adolescents (12 years of age or older) which are caused by susceptible strains of microorganisms in acute bacterial exacerbation of chronic bronchitis, community-acquired pneumonia, pharyngitis/tonsillitis, and uncomplicated skin and skin-structure infections.","Cefditoren pivoxil is a prodrug which is hydrolyzed by esterases during absorption, and the drug is distributed in the circulating blood as active cefditoren. Cefditoren is a cephalosporin with antibacterial activity against gram-positive and gram-negative pathogens. Cefditoren is effective against <i>Staphylococcus aureus</i> (methicillin-susceptible strains, including b-lactamase-producing strains), penicillin-susceptible strains of <i>Staphylococcus aureus</i> and <i>Streptococcus pneumoniae</i>, <i>Streptococcus pyogenes</i>, <i>Haemophilus influenzae</i> (including b-lactamase-producing strains), <i>Haemophilus parainfluenzae</i> (including b-lactamase-producing strains), <i>Moraxella catarrhalis</i> (including b-lactamase-producing strains), <i>Streptococcus agalactiae</i>, <i>Streptococcus</i> Groups C and G, and <i>Streptococcus</i>, viridans group (penicillin-susceptible and -intermediate strains).","The bactericidal activity of cefditoren results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins (PBPs). Cefditoren is stable in the presence of a variety of b-lactamases, including penicillinases and some cephalosporinases.","Penicillin-binding protein 2B inhibitor; Penicillin-binding protein 1A inhibitor","Indication associated"]
[391,"DB01067","approved; investigational","small molecule","Glipizide","1-cyclohexyl-3-({p-[2-(5-methylpyrazinecarboxamido)ethyl]phenyl}sulfonyl)urea; N-{4-[β-(5-methylpyrazine-2-carboxamido)ethyl]benzenesulphonyl}-N'-cyclohexylurea","C21H27N5O4S","CC1=NC=C(N=C1)C(=O)NCCC1=CC=C(C=C1)S(=O)(=O)NC(=O)NC1CCCCC1","Glipizide is an oral hypoglycemic agent in the second-generation sulfonylurea drug class that is used to control blood sugar levels in patients with type 2 diabetes mellitus. It was first introduced in 1984  and is available in various countries including Canada and the U.S. According to the 2018 Clinical Practice Guidelines by Diabetes Canada, sulfonylurea drugs are considered a second-line glucose-lowering therapy following metformin. Because sulfonylureas require functional pancreatic beta cells for their therapeutic effectiveness, sulfonylureas are more commonly used for early-stage type 2 diabetes when there is no progressed pancreatic failure. Compared to the first-generation sulfonylureas, such as  and , second-generation sulfonylureas contain a more non-polar side chain in their chemical structure, which enhances their hypoglycemic potency. Compared to other members of the sulfonylurea drug group, glipizide displays rapid absorption and onset of action with the shortest half-life and duration of action, reducing the risk for long-lasting hypoglycemia that is often observed with blood glucose-lowering agents. Glipizide was first approved by the FDA in 1994 and is available in extended-release tablets under the brand name Glucotrol®, as well as in combination with metformin under the brand name Metaglip®.","29094-61-9","445.535","Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.","Glipizide is a blood glucose-lowering agent. The initial onset of blood glucose-lowering effect occurs around 30 minutes post-administration with the duration of action lasting for about 12 to 24 hours. While the chronic use of glipizide does not result in elevations in the fasting insulin levels over time, the postprandial insulin response, or insulin response to a meal, is observed to be enhanced, even after 6 months of treatment. The main therapeutic actions of glipizide primarily occur at the pancreas where the insulin release is stimulated, but glipizide also mediates some extrapancreatic effects, such as the promotion of insulin signaling effects on the muscles, fat, or liver cells. Due to its action on the endogenous cells, sulfonylureas including glipizide is associated with a risk for developing hypoglycemia and weight gain in patients receiving the drug. Chronic administration of glipizide may result in down-regulation of the sulfonylurea receptors on pancreatic beta cells, which are molecular targets of the drug, leading to a reduced effect on insulin secretion. \r\n\r\nLike other sulfonylureas, glipizide may work on pancreatic delta (δ) cells and alpha (α) cells to stimulate the secretion of somatostatin and suppress the secretion of glucagon, which are peptide hormones that regulate neuroendocrine and metabolic pathways. Other than its primary action on the pancreas, glipizide also exerts other biological actions outside of the pancreas, or \"extrapancreatic effects\", which is similar to other members of the sulfonylurea drug class. Glipizide may enhance the glucose uptake into the skeletal muscles and potentiate the action of insulin in the liver. Other effects include inhibited lipolysis in the liver and adipose tissue, inhibited hepatic glucose output, and increased uptake and oxidation of glucose. It has also been demonstrated by several studies that the chronic therapeutic use of sulfonylureas may result in an increase in insulin receptors expressed on monocytes, adipocytes, and erythrocytes.","Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder with increasing prevalence worldwide. Characterized by higher-than-normal levels of blood glucose, T2DM is a complex disorder that arises from the interaction between genetic, environmental and behavioral risk factors. Insulin is a peptide hormone that plays a critical role in regulating blood glucose levels. In response to high blood glucose levels, insulin promotes the uptake of glucose into the liver, muscle cells, and fat cells for storage. Although there are multiple events occurring that lead to the pathophysiology of T2DM, the disorder mainly involves insulin insensitivity as a result of insulin resistance, declining insulin production, and eventual failure of beta cells of pancreatic islets that normally produce insulin. Early management with lifestyle intervention, such as controlled diet and exercise, is critical in reducing the risk of long-term secondary complications, such as cardiovascular mortality.\r\n\r\nGlipizide, like other sulfonylurea drugs, is an insulin secretagogue, which works by stimulating the insulin release from the pancreatic beta cells thereby increasing the plasma concentrations of insulin. Thus, the main therapeutic action of the drug depends on the functional beta cells in the pancreatic islets. Sulfonylureas bind to the sulfonylurea receptor expressed on the pancreatic beta-cell plasma membrane, leading to the closure of the ATP-sensitive potassium channel and reduced potassium conductance. This results in depolarization of the pancreatic beta cell and opening of the voltage-sensitive calcium channels, promoting calcium ion influx. Increased intracellular concentrations of calcium ions in beta cells stimulates the secretion, or exocytosis, of insulin granules from the cells. Apart from this main mechanism of action, the blood-glucose-lowering effect of glipizide involves increased peripheral glucose utilization via stimulating hepatic gluconeogenesis and by increasing the number and sensitivity of insulin receptors.","ATP-binding cassette sub-family C member 8 inhibitor; Peroxisome proliferator-activated receptor gamma agonist","Therapeutic strategy associated"]
[392,"DB01070","approved","small molecule","Dihydrotachysterol","Anti-tetany substance 10; Dihydrotachysterol","C28H46O","CC(C)[C@@H](C)\\C=C\\[C@@H](C)[C@@]1([H])CC[C@@]2([H])\\C(CCC[C@]12C)=C\\C=C1/C[C@@H](O)CC[C@@H]1C","A vitamin D that can be regarded as a reduction product of vitamin D2.","67-96-9","398.6642","Used for the prevention and treatment of rickets or osteomalacia, and to manage hypocalcemia associated with hypoparathyroidism or pseudohypoparathyroidism. Also used for the treatment of vitamin D dependent rickets, rickets or osteomalacia secondary to long-term high dose anticonvulsant therapy, early renal osteodystrophy, osteoporosis (in conjunction with calcium), and hypophosphatemia associated with Fanconi syndrome (with treatment of acidosis).","Dihydrotachysterol is hydroxylated in the liver to 25-hydroxydihydrotachysterol, which is the major circulating active form of the drug. It does not undergo further hydroxylation by the kidney and therefore is the analogue of 1, 25-dihydroxyvitamin D. Dihydrotachysterol is effective in the elevation of serum calcium by stimulating intestinal calcium absorption and mobilizing bone calcium in the absence of parathyroid hormone and of functioning renal tissue. Dihydrotachysterol also increases renal phosphate excretion.","Once hydroxylated to 25-hydroxydihydrotachysterol, the modified drug binds to the vitamin D receptor. The bound form of the vitamin D receptor serves as a transcriptional regulator of bone matrix proteins, inducing the expression of osteocalcin and suppressing synthesis of type I collagen. Vitamin D (when bound to the vitamin D receptor)stimulates the expression of a number of proteins involved in transporting calcium from the lumen of the intestine, across the epithelial cells and into blood. This stimulates intestinal calcium absorption and increases renal phosphate excretion. These are functions that are normally carried out by the parathyroid hormone.","Vitamin D3 receptor agonist","Indication associated"]
[393,"DB01074","approved; investigational","small molecule","Perhexiline","Perhexilene; Perhexiline","C19H35N","C(C(C1CCCCC1)C1CCCCC1)C1CCCCN1","Perhexiline is a coronary vasodilator used especially for angina of effort. It may cause neuropathy and hepatitis.","6621-47-2","277.4879","For the management of severe angina pectoris.","Used in the treatment of unresponsive or refractory angina. Perhexiline increases glucose metabolism at the expense of free-fatty-acid metabolism, enhancing oxygen efficiency during myocardial ischaemia. Perhexiline also potentiates platelet responsiveness to nitric oxide both in patients with angina and patients with acute coronary syndrome. The predominant mechanism of this particular perhexiline effect is an increase in platelet cGMP responsiveness. Perhexiline also may reduce the potential for nitric oxide clearance by neutrophil-derived oxygen. Perhexiline relieves symptoms of angina, improves exercise tolerance, and increases the workload needed to induce ischaemia when used as monotherapy. The primary therapeutic roles for perhexiline are as short-term therapy (less than 3 months duration) in patients with severe ischaemia awaiting coronary revascularisation or long-term therapy in patients with ischaemic symptoms refractory to other therapeutic measures.","Perhexiline binds to the mitochondrial enzyme carnitine palmitoyltransferase (CPT)-1 and CPT-2. It acts by shifting myocardial substrate utilisation from long chain fatty acids to carbohydrates through inhibition of CPT-1 and, to a lesser extent, CPT-2, resulting in increased glucose and lactate utilization. This results in increased ATP production for the same O2 consumption as before and consequently increases myocardial efficiency.","Carnitine O-palmitoyltransferase 1, liver isoform inhibitor; Carnitine O-palmitoyltransferase 2, mitochondrial inhibitor; Potassium voltage-gated channel subfamily H member 2","Indication associated"]
[394,"DB01079","approved; investigational; withdrawn","small molecule","Tegaserod","1-(((5-Methoxyindol-3-yl)methylene)amino)-3-pentylguanidine","C16H23N5O","CCCCCNC(=N)N\\N=C\\C1=CNC2=C1C=C(OC)C=C2","Novartis' brand name Zelnorm (tegaserod) had originally received approval from the US FDA in 2002 for the treatment of irritable bowel syndrome with constipation (IBS-C). It was, however, voluntarily withdrawn from widespread use in the US market in 2007 after concerns arose over the possibility that tegaserod could potentially cause dangerous cardiovascular events in patients. Since then, closer evaluations of the original data suggesting such cardiovascular risk have resulted in the limited reintroduction or 're-approval' of tegaserod for treatment of IBS-C specifically in female patients less than 65 years of age and whom are considered to be at a lower risk of a cardiovascular event than the broader population. Zelnorm (tegaserod) by Sloan Pharma subsequently gained re-approval in April of 2019. Nevertheless, tegaserod remains un-approved in certain regions.\r\n\r\nDespite the relative complications involved in its history of regulatory approval, ever since its first introduction in 2002 tegaserod remains the only therapy for IBS-C that possesses the unique mechanism of action of acting on serotonin-4 (5-HT(4)) receptors in smooth muscle cells and in the gastrointestinal wall to facilitate actions like esophageal relaxation, peristaltic gut movement, and natural secretions in the gut, among others.","145158-71-0","301.394","Tegaserod is a serotonin-4 (5-HT4) receptor agonist indicated for the treatment of adult women less than 65 years of age with irritable bowel syndrome with constipation (IBS-C) . The safety and effectiveness of tegaserod in men with IBS-C have not been established .","In general, it has been determined that tegaserod is an agonist of serotonin type-4 (5-HT(4)) receptors, an antagonist at 5-HT(2B) receptors, but is expected to possess minimal binding to 5-HT(1) receptors, and virtually no affinity for 5-HT(3) or dopamine receptors .\r\n\r\nIn clinical trials with tegaserod, centrally analyzed ECGs were recorded in 4,605 male and female patients receiving tegaserod 6 mg twice daily or placebo for IBS-C and other related motility disorders . No subject receiving the agent had an absolute QTcF above 480 ms . An increase in QTcF of 30 to 60 ms was observed in 7% of patients receiving tegaserod and 8% receiving placebo . An increase in QTcF of greater than 60 ms was observed in 0.3% and 0.2% of subjects, respectively . The effects of tegaserod on the QTcF interval were ultimately not considered to be clinically meaningful .\r\n\r\nFurthermore, it was determined that there is a potential for tegaserod and its main metabolite (the M29 metabolite) to increase platelet aggregation in vitro . In one in vitro study, at concentrations up to 10-times the maximum plasma concentration (Cmax) at the recommended dose, tegaserod significantly increased platelet aggregation in a concentration-dependent manner up to 74% (range 11% to 74%) compared to a control vehicle (with potentiation by various agonists) . In another in vitro study, the M29 metabolite, at concentrations up to 0.6-times the Cmax of M29 also showed a 5% to 16% increase in platelet aggregation compared to the control vehicle . The clinical implications of these in vitro platelet aggregation results remain unclear .","Irritable bowel syndrome (IBS) is a complex functional disorder comprised of various abnormal and discomforting effects on the gastrointestinal tract and bowel function . Although the cause of IBS has yet to be formally elucidated, patient experience has demonstrated that the disorder is typically associated with abdominal pain, abdominal distension, cramping or bloating, variations in urgency for bowel movements, feelings of incomplete evacuation, gastroesophageal reflux, and various other effects . In particular, IBS that features constipation as a predominant effect is categorized as constipation-predominant IBS, or IBS-C .\r\n\r\nConcurrently, 5-Hydroxytryptamine (5-HT, or serotonin) has demonstrated the ability to elicit significant regulatory actions on gastrointestinal motility . Specifically, it has been shown that the activation of 5-HT(4) receptors located on motor neurons and interneurons in the gastrointestinal wall can cause the release of acetylcholine, substance P, and calcitonin gene-related peptide that can all facilitate the propulsion of material through the gut . Moreover, when 5-HT(4) receptors located in smooth muscle cells are also activated, activities that may alleviate symptoms of IBS-C like esophageal relaxation and the inhibition of human colonic circular muscle contraction can also occur . Additionally, activating 5-HT(4) on enteric neurons and enterocytes also cause natural fluid secretion in the gut - an action which also strongly assists in promoting the movement of content along the gastrointestinal tract .\r\n\r\nAlternatively, it has also been observed that 5-HT may participate in generating visceral hyperalgesia in IBS, an observation supported in part by the finding of increased amounts of 5-HT and its metabolites in the plasma of patients experiencing IBS  It has therefore also been proposed that antagonism of 5-HT(2B) receptors can lead to inhibition of both 5-HT mediated gastrointestinal motility and visceral hypersensitivity .\r\n\r\nSubsequently, because tegaserod is considered to be an agonist of the 5-HT(4) receptor and an antagonist of the 5-HT(2B) receptor at clinically relevant levels, it is believed that tegaserod may elicit its mechanism of action by facilitating activities associated with the activation and antagonism of the 5-HT(4) and 5-HT(2B) receptors, like stimulating peristaltic gastrointestinal reflexes and intestinal secretion, inhibiting visceral sensitivity, enhancing basal motor activity, and normalizing impaired motility throughout the gastrointestinal tract, among other actions .","5-hydroxytryptamine receptor 4 antagonist&partial agonist; 5-hydroxytryptamine receptor 2B antagonist; 5-hydroxytryptamine receptor 2C antagonist; 5-hydroxytryptamine receptor 2A antagonist","Therapeutic strategy associated"]
[395,"DB01082","approved; vet_approved","small molecule","Streptomycin","2,4-diguanidino-3,5,6-trihydroxycyclohexyl 5-deoxy-2-O-(2-deoxy-2-methylamino-alpha-L-glucopyranosyl)-3-C-formyl-beta-L-lyxopentanofuranoside; Streptomycin","C21H39N7O12","CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@H]1[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](NC(N)=N)[C@@H](O)[C@@H]2NC(N)=N)O[C@@H](C)[C@]1(O)C=O","Streptomycin, an antibiotic derived from _Streptomyces griseus_, was the first aminoglycoside to be discovered and used in practice in the 1940s. Selman Waksman and eventually Albert Schatz were recognized with the Nobel Prize in Medicine for their discovery of streptomycin and its antibacterial activity. Although streptomycin was the first antibiotic determined to be effective against mycobacterium tuberculosis, it has fallen out of favor due to resistance and is now primarily used as adjunctive treatment in cases of multi-drug resistant tuberculosis.","57-92-1","581.5741","Although streptomycin was the first antibiotic available for the treatment of mycobacterium tuberculosis, it is now largely a second line option due to resistance and toxicity. Streptomycin may also be used to treat a variety of other infections caused by susceptible strains of aerobic bacteria where other less toxic agents are ineffective. Examples include: _Yersinia pestis_, _Francisella tularensis_, _Brucella_, _Calymmatobacterium granulomatis_ (donovanosis, granuloma inguinale), _H. ducreyi_ (chancroid), _H. influenzae_ (in respiratory, endocardial, and meningeal infections - concomitantly with another antibacterial agents). _K. pneumoniae_ pneumonia (concomitantly with another antibacterial agent), _E.coli_, _Proteus_, _A.aerogenes_, _K. pneumoniae_, and \r\n_Enterococcus faecalis_ in urinary tract infections, _Streptococcus viridans_, _Enterococcus faecalis_ (in endocardial infections - concomitantly with penicillin), and Gram-negative bacillary bacteremia (concomitantly with another antibacterial agent).","Although streptomycin originally had broad gram-negative and gram-positive coverage, its spectrum of activity has been significantly narrowed due to antibiotic resistance. Streptomycins current spectrum of activity includes susceptible strains of Yersinia pestis, Francisella tularensis, Brucella, Calymmatobacterium granulomatis, H. ducreyi, H. influenza, K. pneumoniae pneumonia, E.coli, Proteus, A. aerogenes, K. pneumoniae, Enterococcus faecalis, Streptococcus viridans, Enterococcus faecalis, and Gram-negative bacillary bacteremia. Streptomycin is not reliably active against pseudomonas aeruginosa. \r\n\r\nSimilar to other aminoglycosides, streptomycin is considered to have a narrow therapeutic index. Characteristic toxicities of streptomycin include nephrotoxicity and ototoxicity. Patients should be carefully monitored for early signs of hearing loss and vestibular dysfunction in order to prevent permanent damage to sensorineural cells. Neuromuscular blockade has also been rarely reported.","There are 3 key phases of aminoglycoside entry into cells. The first “ionic binding phase” occurs when polycationic aminoglycosides bind electrostatically to negatively charged components of bacterial cell membranes including with lipopolysaccharides and phospholipids within the outer membrane of Gram-negative bacteria and to teichoic acids and phospholipids within the cell membrane of Gram-positive bacteria. This binding results in displacement of divalent cations and increased membrane permeability, allowing for aminoglycoside entry.\r\n\r\nThe second “energy-dependent phase I” of aminoglycoside entry into the cytoplasm relies on the proton-motive force and allows a limited amount of aminoglycoside access to its primary intracellular target - the bacterial 30S ribosome. This ultimately results in the mistranslation of proteins and disruption of the cytoplasmic membrane. Finally, in the “energy-dependent phase II” stage, concentration-dependent bacterial killing is observed. Aminoglycoside rapidly accumulates in the cell due to the damaged cytoplasmic membrane, and protein mistranslation and synthesis inhibition is amplified.\r\n\r\nHence, aminoglycosides have both immediate bactericidal effects through membrane disruption and delayed bactericidal effects through impaired protein synthesis; observed experimental data and mathematical modeling support this two-mechanism model.\r\n\r\nInhibition of protein synthesis is a key component of aminoglycoside efficacy. Structural and cell biological studies suggest that aminoglycosides bind to the 16S rRNA in helix 44 (h44), near the A site of the 30S ribosomal subunit, altering interactions between h44 and h45. This binding also displaces two important residues, A1492 and A1493, from h44, mimicking normal conformational changes that occur with successful codon-anticodon pairing in the A site. Overall, aminoglycoside binding has several negative effects including inhibition of translation, initiation, elongation, and ribosome recycling. Recent evidence suggests that the latter effect is due to a cryptic second binding site situated in h69 of the 23S rRNA of the 50S ribosomal subunit. Also, by stabilizing a conformation that mimics correct codon-anticodon pairing, aminoglycosides promote error-prone translation. Mistranslated proteins can incorporate into the cell membrane, inducing the damage discussed above.","16S ribosomal RNA inhibitor; 23S ribosomal RNA inhibitor; 30S ribosomal protein S12 inhibitor; Cytoplasmic membrane incorporation into and destabilization; Bacterial outer membrane incorporation into and destabilization; Protein-arginine deiminase type-4 inhibitor","Indication associated"]
[396,"DB01088","approved; investigational","small molecule","Iloprost","Iloprost","C22H32O4","[H][C@]12C[C@@H](O)[C@H](\\C=C\\[C@@H](O)C(C)CC#CC)[C@@]1([H])C\\C(C2)=C\\CCCC(O)=O","Iloprost is a synthetic analogue of prostacyclin PGI2 that dilates systemic and pulmonary arterial vascular beds. It is used to treat pulmonary arterial hypertension (PAH).","78919-13-8","360.494","Used for the treatment of pulmonary arterial hypertension.","Iloprost is a synthetic analogue of prostacyclin PGI2 that dilates systemic and pulmonary arterial vascular beds. It was shown to affect platelet aggregation, but whether this effect contributes to its vasodilatory action has not been elucidated. There are two diastereoisomers of iloprost and the 4S isomer is reported to exhibit a higher potency in dilating blood vessels compared to the 4R isomer.","Iloprost is a second generation structural analog of prostacyclin (PGI) with about ten-fold greater potency than the first generation stable analogs, such as carbaprostacyclin. Iloprost binds with equal affinity to human prostacyclin (Prostanoid IP) and prostaglandin EP1 receptors. Iloprost constricts the ilium and fundus circular smooth muscle as strongly as prostaglandin E2 (PGE2) itself. Iloprost inhibits the ADP, thrombin, and collagen-induced aggregation of human platelets. In whole animals, iloprost acts as a vasodilator, hypotensive, antidiuretic, and prolongs bleeding time. All of these properties help to antagonize the pathological changes that take place in the small pulmonary arteries of patients with pulmonary hypertension.","Prostacyclin receptor agonist; Prostaglandin E2 receptor EP1 subtype agonist; cAMP-specific 3',5'-cyclic phosphodiesterase 4A inducer; cAMP-specific 3',5'-cyclic phosphodiesterase 4B inducer; cAMP-specific 3',5'-cyclic phosphodiesterase 4C inducer; cAMP-specific 3',5'-cyclic phosphodiesterase 4D inducer; Tissue-type plasminogen activator other/unknown; Prostaglandin D2 receptor 2 agonist","Therapeutic strategy associated"]
[397,"DB01089","approved","small molecule","Deserpidine","(3β,16β,17α,18β,20α)-17-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]yohimban-16-carboxylic acid methyl ester; 11-demethoxyreserpine; 11-desmethoxyreserpine; Canescine; Deserpidine; Raunormine; Recanescine","C32H38N2O8","[H][C@]12C[C@@H](OC(=O)C3=CC(OC)=C(OC)C(OC)=C3)[C@H](OC)[C@@H](C(=O)OC)[C@@]1([H])C[C@@]1([H])N(CCC3=C1NC1=CC=CC=C31)C2","Deserpidine is an ester alkaloid drug isolated from Rauwolfia canescens (family Apocynaceae) with antipsychotic and antihypertensive properties that has been used for the control of high blood pressure and for the relief of psychotic behavior.","131-01-1","578.6527","For the treatment of hypertension.","Deserpidine, an alkaloid of <i>Rauwolfia canescens</i>, is used as an antihypertensive. Rauwolfia alkaloids work by controlling nerve impulses along certain nerve pathways. As a result, they act on the heart and blood vessels to lower blood pressure.","Deserpidine's mechanism of action is through inhibition of the ATP/Mg<sup>2+</sup> pump responsible for the sequestering of neurotransmitters into storage vesicles located in the presynaptic neuron. The neurotransmitters that are not sequestered in the storage vesicle are readily metabolized by monoamine oxidase (MAO) causing a reduction in catecholamines.","Synaptic vesicular amine transporter inhibitor","Therapeutic strategy associated"]
[398,"DB01090","approved","small molecule","Pentolinium","Pentolineum; Pentolonium; Pentolonum","C15H32N2","C[N+]1(CCCCC[N+]2(C)CCCC2)CCCC1","Pentolinium is a nicotinic antagonist that has been used as a ganglionic blocking agent in hypertension.","144-44-5","240.428","Used to produce controlled hypotension during surgical procedures and in hypertensive crises.","Pentolinium acts as a ganglionic blocking agent. Pentolinium inhibits release of adrenaline and noradrenaline from adrenergic nerves. It is used as an antihypertensive, and can be administered orally, intramuscularly, and subcutaneously.","Pentolinium binds to the nicotinic (ganglion) acetylcholine receptor. This receptor/channel is permeable to a range of divalent cations including calcium, the influx of which may activate a potassium current which hyperpolarizes the cell membrane. Blockage of the receptor leads to smooth muscle relaxation and vasodilaton.","Neuronal acetylcholine receptor subunit alpha-10 antagonist; Neuronal acetylcholine receptor subunit alpha-3 antagonist; Neuronal acetylcholine receptor subunit beta-4 antagonist","Therapeutic strategy associated"]
[399,"DB01092","approved","small molecule","Ouabain","3-(α-L-rhamnopyranosyloxy)-1β,5β,11α,14,19-pentahydroxy-5β-card-20(22)-enolide; G-Strophanthin; Ouabagenin L-Rhamnoside; Ouabain anhydrous; Ouabaine; Oubain","C29H44O12","[H][C@@]12CC[C@]3(O)C[C@H](C[C@@H](O)[C@]3(CO)[C@@]1([H])[C@H](O)C[C@]1(C)[C@H](CC[C@]21O)C1=CC(=O)OC1)O[C@@H]1O[C@@H](C)[C@H](O)[C@@H](O)[C@H]1O","A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like digitalis. It is commonly used in cell biological studies as an inhibitor of the NA(+)-K(+)-exchanging ATPase.","630-60-4","584.6525","For the treatment of atrial fibrillation and flutter and heart failure","Ouabain, a cardiac glycoside similar to digitoxin, is used to treat congestive heart failure and supraventricular arrhythmias due to reentry mechanisms, and to control ventricular rate in the treatment of chronic atrial fibrillation.","Ouabain inhibits the Na-K-ATPase membrane pump, resulting in an increase in intracellular sodium and calcium concentrations. Increased intracellular concentrations of calcium may promote activation of contractile proteins (e.g., actin, myosin). Ouabain also acts on the electrical activity of the heart, increasing the slope of phase 4 depolarization, shortening the action potential duration, and decreasing the maximal diastolic potential.","Sodium/potassium-transporting ATPase subunit alpha-1 inhibitor; Sodium/potassium-transporting ATPase subunit alpha-2 inhibitor; Sodium/potassium-transporting ATPase subunit alpha-3 inhibitor","Indication associated"]
[400,"DB01093","approved; vet_approved","small molecule","Dimethyl sulfoxide","Dimethyl sulfoxide; Dimethyl sulfur oxide; Dimethyl sulphoxide; DMSO; Methylsulfinylmethane; S(O)Me2; Sulfinylbis(methane)","C2H6OS","CS(C)=O","A highly polar organic liquid, that is used widely as a chemical solvent. Because of its ability to penetrate biological membranes, it is used as a vehicle for topical application of pharmaceuticals. It is also used to protect tissue during cryopreservation. Dimethyl sulfoxide shows a range of pharmacological activity including analgesia and anti-inflammation.","67-68-5","78.133","For the symptomatic relief of patients with interstitial cystitis.","Dimethyl Sulfoxide may have anti-inflammatory, antioxidant and analgesic activities. Dimethyl Sulfoxide also readily penetrates cellular membranes. The membrane-penetrating ability of dimethyl sulfoxide may enhance diffusion of other substances through the skin. For this reason, mixtures of idoxuridine and dimethyl sulfoxide have been used for topical treatment of herpes zoster in the United Kingdom.","The mechanism of dimethyl sulfoxide's actions is not well understood. Dimethyl sulfoxide has demonstrated antioxidant activity in certain biological settings. For example, the cardiovascular protective effect of dimethyl sulfoxide in copper-deficient rats is thought to occur by an antioxidant mechanism. It is also thought that dimethyl sulfoxide's possible anti-inflammatory activity is due to antioxidant action.",null,"Therapeutic strategy associated"]
[401,"DB01094","experimental","small molecule","Hesperetin","(−)-(S)-hesperetin; (−)-hesperetin; (S)-2,3-dihydro-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-4H-1-benzopyran-4-one; 3',5,7-Trihydroxy-4'-methoxyflavanone; Hesperitin","C16H14O6","COC1=C(O)C=C(C=C1)[C@@H]1CC(=O)C2=C(O)C=C(O)C=C2O1","Hesperetin belongs to the flavanone class of flavonoids. Hesperetin, in the form of its glycoside , is the predominant flavonoid in lemons and oranges.","520-33-2","302.2788","For lowering cholesterol and, possibly, otherwise favorably affecting lipids. <i>In vitro</i> research also suggests the possibility that hesperetin might have some anticancer effects and that it might have some anti-aromatase activity, as well as activity again.","Hesperetin is a cholesterol lowering flavanoid found in a number of citrus juices. It appears to reduce cholesteryl ester mass and inhibit apoB secretion by up to 80%. Hesperetin may have antioxidant, anti-inflammatory, anti-allergic, hypolipidemic, vasoprotective and anticarcinogenic actions.","Hesperetin reduces or inhibits the activity of acyl-coenzyme A:cholesterol acyltransferase genes (ACAT<sub>1</sub> and ACAT<sub>2</sub>) and it reduces microsomal triglyceride transfer protein (MTP) activity. Hesperetin also seems to upregulate the LDL receptor. This leads to the reduced assembly and secretion of apoB-containing lipoproteins and enhanced reuptake of those lipoproteins, thereby lowering cholesterol levels.","Sterol O-acyltransferase 1 inhibitor; Sterol O-acyltransferase 2 inhibitor; Microsomal triglyceride transfer protein large subunit antagonist; Sex hormone-binding globulin","Therapeutic strategy associated"]
[402,"DB01095","approved","small molecule","Fluvastatin","Fluvastatin","C24H26FNO4","CC(C)N1C(\\C=C\\C(O)CC(O)CC(O)=O)=C(C2=CC=CC=C12)C1=CC=C(F)C=C1","Fluvastatin is an antilipemic agent that competitively inhibits hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase. HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonic acid, the rate-limiting step in cholesterol biosynthesis. Fluvastatin belongs to a class of medications called statins and is used to reduce plasma cholesterol levels and prevent cardiovascular disease. It is also the first entirely synthetic HMG-CoA reductase inhibitor and is structurally distinct from the fungal derivatives of this therapeutic class. Fluvastatin is a racemate comprising equimolar amounts of (3R,5S)- and (3S,5R)-fluvastatin.","93957-54-1","411.473","To be used as an adjunct to dietary therapy to prevent cardiovascular events. May be used as secondary prevention in patients with coronary heart disease (CHD) to reduce the risk of requiring coronary revascularization procedures, for reducing progression of coronary atherosclerosis in hypercholesterolemic patients with CHD, and for the treatment of primary hypercholesterolemia and mixed dyslidipidemia.","Fluvastatin, the first synthetically-derived HMG-CoA reductase inhibitor, is a hydrophilic, acidic, antilipemic agent used to lower cholesterol and triglyceride levels associated with primary hypercholesterolemia and mixed dyslipidemia (Fredrickson types IIa and IIb), to slow the progression of coronary atherosclerosis in patients with CHD and as secondary prevention therapy in patients with CHD to reduce the risk of requiring coronary revascularization procedures. Although similar to lovastatin, simvastatin, and pravastatin, fluvastatin has a shorter half-life, no active metabolites, extensive protein binding, and minimal CSF penetration. Fluvastatin acts primarily in the liver. It is prepared as a racemate of two erythro enantiomers of which the 3R,5S enantiomer exerts the pharmacologic effect.","Fluvastatin selectively and competitively inhibits the hepatic enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase. HMG-CoA reductase is responsible for converting HMG-CoA to mevalonate, the rate-limiting step in cholesterol biosynthesis. Inhibition results in a decrease in hepatic cholesterol levels which stimulates the synthesis of LDL receptors and increases hepatic uptake of LDL cholesterol. The end result is decreased levels of plasma total and LDL cholesterol.","3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor; Histone deacetylase 2 inhibitor","Target associated"]
[403,"DB01097","approved; investigational","small molecule","Leflunomide","5-Methyl-N-(4-(trifluoromethyl)phenyl)-4-isoxazolecarboxamide; 5-Methylisoxazole-4-carboxylic acid (4-trifluoromethyl)anilide; alpha,alpha,alpha-Trifluoro-5-methyl-4-isoxazolecarboxy-p-toluidide; Leflunomide","C12H9F3N2O2","CC1=C(C=NO1)C(=O)NC1=CC=C(C=C1)C(F)(F)F","Leflunomide is a pyrimidine synthesis inhibitor belonging to the DMARD (disease-modifying antirheumatic drug) class of drugs, which are chemically and pharmacologically very heterogeneous. Leflunomide was approved by FDA and in many other countries (e.g., Canada, Europe) in 1999.","75706-12-6","270.2073","For the management of the signs and symptoms of active rheumatoid arthritis (RA) to improve physical function and to slow the progression of structural damage associated with the disease. Has also been used for the prevention of acute and chronic rejection in recipients of solid organ trasnplants and is designated by the FDA as an orphan drug for this use.","Leflunomide is a pyrimidine synthesis inhibitor indicated in adults for the treatment of active rheumatoid arthritis (RA). RA is an auto-immune disease characterized by high T-cell activity. T cells have two pathways to synthesize pyrimidines: the salvage pathways and the de novo synthesis. At rest, T lymphocytes meet their metabolic requirements by the salvage pathway. Activated lymphocytes need to expand their pyrimidine pool 7- to 8-fold, while the purine pool is expanded only 2- to 3-fold. To meet the need for more pyrimidines, activated T cells use the de novo pathway for pyrimidine synthesis. Therefore, activated T cells, which are dependent on de novo pyrimidine synthesis, will be more affected by leflunomide's inhibition of dihydroorotate dehydrogenase than other cell types that use the salvage pathway of pyrimidine synthesis.","Leflunomide is a prodrug that is rapidly and almost completely metabolized following oral administration to its pharmacologically active metabolite, A77 1726. This metabolite is responsible for essentially all of the drug's activity in-vivo. The mechanism of action of leflunomide has not been fully determined, but appears to primarily involve regulation of autoimmune lymphocytes. It has been suggested that leflunomide exerts its immunomodulating effects by preventing the expansion of activated autoimmune lymphocytes via interferences with cell cycle progression. In-vitro data indicates that leflunomide interferes with cell cycle progression by inhibiting dihydroorotate dehydrogenase (a mitochondrial enzyme involved in de novo pyrimidine ribonucleotide uridine monophosphate (rUMP)synthesis) and has antiproliferative activity. Human dihydroorotate dehydrogenase consists of 2 domains: an α/β-barrel domain containing the active site and an α-helical domain that forms a tunnel leading to the active site. A77 1726 binds to the hydrophobic tunnel at a site near the flavin mononucleotide. Inhibition of dihydroorotate dehydrogenase by A77 1726 prevents production of rUMP by the de novo pathway; such inhibition leads to decreased rUMP levels, decreased DNA and RNA synthesis, inhibition of cell proliferation, and G1 cell cycle arrest. It is through this action that leflunomide inhibits autoimmune T-cell proliferation and production of autoantibodies by B cells. Since salvage pathways are expected to sustain cells arrested in the G1 phase, the activity of leflunomide is cytostatic rather than cytotoxic. Other effects that result from reduced rUMP levels include interference with adhesion of activated lymphocytes to the synovial vascular endothelial cells, and increased synthesis of immunosuppressive cytokines such as transforming growth factor-β (TGF-β). Leflunomide is also a tyrosine kinase inhibitor. Tyrosine kinases activate signalling pathways leading to DNA repair, apoptosis and cell proliferation. Inhibition of tyrosine kinases can help to treating cancer by preventing repair of tumor cells.","Dihydroorotate dehydrogenase (quinone), mitochondrial inhibitor; Aryl hydrocarbon receptor agonist; Protein-tyrosine kinase 2-beta antagonist","Therapeutic strategy associated"]
[404,"DB01103","investigational","small molecule","Quinacrine","2-methoxy-6-chloro-9-diethylaminopentylaminoacridine; 3-chloro-7-methoxy-9-(1-methyl-4-diethylaminobutylamino)acridine; 6-chloro-9-((4-(diethylamino)-1-methylbutyl)amino)-2-methoxyacridine; Mepacrine; N4-(6-chloro-2-methoxy-9-acridinyl)-N1,N1-diethyl-1,4-pentanediamine","C23H30ClN3O","CCN(CC)CCCC(C)NC1=C2C=C(OC)C=CC2=NC2=C1C=CC(Cl)=C2","An acridine derivative formerly widely used as an antimalarial but superseded by chloroquine in recent years. It has also been used as an anthelmintic and in the treatment of giardiasis and malignant effusions. It is used in cell biological experiments as an inhibitor of phospholipase A2.","83-89-6","399.957","For the treatment of giardiasis and cutaneous leishmaniasis and the management of malignant effusions.","Quinacrine has been used as an antimalarial drug and as an antibiotic. It is used to treat giardiasis, a protozoal infection of the intestinal tract, and certain types of lupus erythematosus, an inflammatory disease that affects the joints, tendons, and other connective tissues and organs. Quinacrine may be injected into the space surrounding the lungs to prevent reoccurrence of pneumothorax. The exact way in which quinacrine works is unknown. It appears to interfere with the parasite's metabolism.","The exact mechanism of antiparasitic action is unknown; however, quinacrine binds to deoxyribonucleic acid (DNA) in vitro by intercalation between adjacent base pairs, inhibiting transcription and translation to ribonucleic acid (RNA). Quinacrine does not appear to localize to the nucleus of Giaridia trophozoites, suggesting that DNA binding may not be the primary mechanism of its antimicrobial action. Fluorescence studies using Giardia suggest that the outer membranes may be involved. Quinacrine inhibits succinate oxidation and interferes with electron transport. In addition, by binding to nucleoproteins, quinacrine suppress the lupus erythematous cell factor and acts as a strong inhibitor of cholinesterase.","DNA intercalation; 85/88 kDa calcium-independent phospholipase A2 inhibitor; Cytosolic phospholipase A2 inhibitor; Inactive phospholipase C-like protein 1 inhibitor","Therapeutic strategy associated"]
[405,"DB01104","approved","small molecule","Sertraline","(+)-Sertraline; (1S-cis)-1,2,3,4-tetrahydro-4-(3,4-dichlorophenyl)-N-methyl-1-naphthalenamine; (1S,4S)-sertraline; cis-(+)-sertraline; Sertraline","C17H17Cl2N","CN[C@H]1CC[C@@H](C2=CC(Cl)=C(Cl)C=C2)C2=CC=CC=C12","Sertraline is a popular antidepressant medication commonly known as a selective serotonin reuptake inhibitor (SSRI), and is similar to drugs such as  and . Despite marked structural differences between compounds in this drug class, SSRIs exert similar pharmacological effects.\r\n\r\nSeveral weeks of therapy with sertraline may be required before beneficial effects are noticed. Sertraline displays enhanced safety or tolerability than other classes of antidepressants, which frequently cause high levels of drowsiness, dizziness, blurred vision, and other undesirable effects.","79617-96-2","306.23","Sertraline is indicated for the management of major depressive disorder (MDD), post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), panic disorder (PD), premenstrual dysphoric disorder (PMDD), and social anxiety disorder (SAD). Common off-label uses for sertraline include the prevention of post stroke depression, generalized anxiety disorder (GAD), fibromyalgia, premature ejaculation, migraine prophylaxis, diabetic neuropathy, and neurocardiogenic syncope.\r","Sertraline improves or relieves the symptoms of depression, OCD, post-traumatic stress disorder, obsessive-compulsive disorder, panic disorder, and premenstrual dysphoric disorder via the inhibition of serotonin reuptake. Clinical studies have shown that it improves cognition in depressed patients. It has less sedative, anticholinergic, and cardiovascular effects than the tricyclic antidepressant drugs because it does not exert significant anticholinergic, antihistamine, or adrenergic (alpha1, alpha2, beta) blocking activity. The onset of action and beneficial effects are usually noticed after 4-6 weeks, for reasons that are not fully understood and currently under investigation.","Sertraline selectively inhibits the reuptake of serotonin (5-HT) at the presynaptic neuronal membrane, thereby increasing serotonergic activity. This results in an increased synaptic concentration of serotonin in the CNS, which leads to numerous functional changes associated with enhanced serotonergic neurotransmission. These changes are believed to be responsible for the antidepressant action and beneficial effects in obsessive-compulsive (and other anxiety related disorders). It has been hypothesized that obsessive-compulsive disorder, like depression, is also caused by the disregulation of serotonin.\r\n\r\nIn animal studies, chronic administration of sertraline results in down-regulation of brain norepinephrine receptors. Sertraline displays affinity for sigma-1 and 2 receptor binding sites, but binds with stronger affinity to sigma-1 binding sites. In vitro, sertraline shows little to no affinity for GABA, dopaminergic, serotonergic (5HT1A, 5HT1B, 5HT2), or benzodiazepine receptors. It exerts weak inhibitory actions on the neuronal uptake of norepinephrine and dopamine and exhibits no inhibitory effects on the monoamine oxidase enzyme.","Sodium-dependent serotonin transporter inhibitor&binder&downregulator; Sodium-dependent dopamine transporter inhibitor&binder; Sigma receptor inhibitor&binder; Sodium-dependent noradrenaline transporter inhibitor&downregulator; Equilibrative nucleoside transporter 4","Indication associated"]
[406,"DB01109","approved; investigational","small molecule","Heparin","Heparinic acid; Unfractionated heparin",null,null,"Unfractionated heparin (UH) is a heterogenous preparation of anionic, sulfated glycosaminoglycan polymers with weights ranging from 3000 to 30,000 Da. It is a naturally occurring anticoagulant released from mast cells. It binds reversibly to antithrombin III (ATIII) and greatly accelerates the rate at which ATIII inactivates coagulation enzymes thrombin (factor IIa) and factor Xa. UH is different from low molecular weight heparin (LMWH) in the following ways: the average molecular weight of LMWH is about 4.5 kDa whereas it is 15 kDa for UH; UH requires continuous infusions; activated partial prothrombin time (aPTT) monitoring is required when using UH; and UH has a higher risk of bleeding and higher risk of osteoporosis in long term use. Unfractionated heparin is more specific than LMWH for thrombin. Furthermore, the effects of UH can typically be reversed by using protamine sulfate.","9005-49-6",null,"Unfractionated heparin is indicated for prophylaxis and treatment of venous thrombosis and its extension, prevention of post-operative deep venous thrombosis and pulmonary embolism and prevention of clotting in arterial and cardiac surgery. In cardiology, it is used to prevent embolisms in patients with atrial fibrillation and as an adjunct antithrombin therapy in patients with unstable angina and/or non-Q wave myocardial infarctions (i.e. non-ST elevated acute coronary artery syndrome) who are on platelet glycoprotein (IIb/IIIa) receptor inhibitors. Additionally, it is used to prevent clotting during dialysis and surgical procedures, maintain the patency of intravenous injection devices and prevent in vitro coagulation of blood transfusions and in blood samples drawn for laboratory values.","Unfractionated heparin is a highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from 3000 to 30,000 daltons. Heparin is obtained from liver, lung, mast cells, and other cells of vertebrates. Heparin is a well-known and commonly used anticoagulant which has antithrombotic properties. Heparin inhibits reactions that lead to the clotting of blood and the formation of fibrin clots both in vitro and in vivo. Small amounts of heparin in combination with antithrombin III, a heparin cofactor,) can inhibit thrombosis by inactivating Factor Xa and thrombin. Once active thrombosis has developed, larger amounts of heparin can inhibit further coagulation by inactivating thrombin and preventing the conversion of fibrinogen to fibrin. Heparin also prevents the formation of a stable fibrin clot by inhibiting the activation of the fibrin stabilizing factor. Heparin prolongs several coagulation tests. Of all the coagulation tests, activated partial prothrombin time (aPTT) is the most clinically important value.","Under normal circumstances, antithrombin III (ATIII) inactivates thrombin (factor IIa) and factor Xa. This process occurs at a slow rate. Administered heparin binds reversibly to ATIII and leads to almost instantaneous inactivation of factors IIa and Xa The heparin-ATIII complex can also inactivate factors IX, XI, XII and plasmin. The mechanism of action of heparin is ATIII-dependent. It acts mainly by accelerating the rate of the neutralization of certain activated coagulation factors by antithrombin, but other mechanisms may also be involved. The antithrombotic effect of heparin is well correlated to the inhibition of factor Xa. Heparin is not a thrombolytic or fibrinolytic. It prevents progression of existing clots by inhibiting further clotting. The lysis of existing clots relies on endogenous thrombolytics.","Antithrombin-III potentiator; Coagulation factor X inhibitor; P-selectin inhibitor; Fibroblast growth factor receptor 4; Fibroblast growth factor 4; Fibroblast growth factor 19; Fibroblast growth factor receptor 1; Fibroblast growth factor 1; Fibroblast growth factor receptor 2; Fibroblast growth factor 2; Platelet factor 4; Hepatocyte growth factor","Target associated"]
[407,"DB01110","approved; investigational; vet_approved","small molecule","Miconazole","1-(2,4-Dichloro-beta-((2,4-dichlorobenzyl)oxy)phenethyl)imidazole; 1-[2-(2,4-Dichloro-benzyloxy)-2-(2,4-dichloro-phenyl)-ethyl]-1H-imidazole; Miconazole","C18H14Cl4N2O","ClC1=CC(Cl)=C(COC(CN2C=CN=C2)C2=C(Cl)C=C(Cl)C=C2)C=C1","Miconazole is a broad-spectrum azole antifungal with some activity against Gram-positive bacteria as well. It is widely used to treat mucosal yeast infections, including both oral and vaginal infections; although intravenous miconazole is no longer available, a wide variety of suppositories, creams, gels, and tablet-based products are available. Miconazole is thought to act primarily through the inhibition of fungal CYP450 14α-lanosterol demethylase activity.\r\n\r\nMiconazole was first synthesized in 1969 and first granted FDA approval on January 8, 1974, for sale by INSIGHT Pharmaceuticals as a topical cream. It is currently available as a variety of prescription and over the counter products. Despite having been in clinical use for an extended period, resistance to miconazole among susceptible organisms is relatively low.","22916-47-8","416.129","Miconazole is indicated for the local treatment of oropharyngeal candidiasis in adult patients and for the adjunctive treatment of diaper dermatitis complicated by candidiasis in immunocompetent patients aged four weeks and older. Miconazole is available as both a suppository and cream for the treatment of vaginal yeast infections and the relief of associated vulvar itching and irritation. Lastly, miconazole cream is effective in treating athlete's foot (tinea pedis), jock itch (tinea cruris), ringworm infections (tinea corporis), pityriasis (formerly tinea) versicolor, and cutaneous candidiasis.","Miconazole is an azole antifungal that functions primarily through inhibition of a specific demethylase within the CYP450 complex. As miconazole is typically applied topically and is minimally absorbed into the systemic circulation following application, the majority of patient reactions are limited to hypersensitivity and cases of anaphylaxis. Patients using intravaginal miconazole products are advised not to rely on contraceptives to prevent pregnancy and sexually transmitted infections, as well as not to use tampons concurrently.","Miconazole is an azole antifungal used to treat a variety of conditions, including those caused by _Candida_ overgrowth. Unique among the azoles, miconazole is thought to act through three main mechanisms. The primary mechanism of action is through inhibition of the CYP450 14α-lanosterol demethylase enzyme, which results in altered ergosterol production and impaired cell membrane composition and permeability, which in turn leads to cation, phosphate, and low molecular weight protein leakage.\r\n\r\nIn addition, miconazole inhibits fungal peroxidase and catalase while not affecting NADH oxidase activity, leading to increased production of reactive oxygen species (ROS). Increased intracellular ROS leads to downstream pleiotropic effects and eventual apoptosis.\r\n\r\nLastly, likely as a result of lanosterol demethylation inhibition, miconazole causes a rise in intracellular levels of farnesol. This molecule participates in quorum sensing in _Candida_, preventing the transition from yeast to mycelial forms and thereby the formation of biofilms, which are more resistant to antibiotics. In addition, farnesol is an inhibitor of drug efflux ABC transporters, namely _Candida_ CaCdr1p and CaCdr2p, which may additionally contribute to increased effectiveness of azole drugs.","Cytochrome P450 51 inhibitor; Nitric oxide synthase, endothelial inhibitor; Nitric oxide synthase, inducible inhibitor; Nuclear receptor subfamily 1 group I member 2 partial agonist; Calcium-activated potassium channel inhibitor; Voltage-gated Potassium Channels inhibitor; Inward rectifier potassium channel inhibitor; Voltage gated L-type calcium channel inhibitor","Therapeutic strategy associated"]
[408,"DB01111","approved; vet_approved","small molecule","Colistimethate","Colistin methanesulfonic acid; Colistin sulfomethate; Colistinmethanesulfonic acid","C58H105N16O28S5","CCC(C)CCCCC(=O)NC(CCNCS([O-])(=O)=O)C(=O)NC(C(C)O)C(=O)NC(CCNCS([O-])(=O)=O)C(=O)NC1CCNC(=O)C(NC(=O)C(CCNCS([O-])(=O)=O)NC(=O)C(CCNCS([O-])(=O)=O)NC(=O)C(CC(C)C)NC(=O)C(CC(C)C)NC(=O)C(CCNCS([O-])(=O)=O)NC1=O)C(C)O","Colistimethate is an antibiotic that has been shown to have bactericidal activity against aerobic gram-negative microorganisms. Colistimethate is particularly indicated when the infection is caused by sensitive strains of Pseudomonas aeruginosa.","12705-41-8","1634.87","For the treatment of acute or chronic infections due to sensitive strains of certain gram-negative bacilli, particularly _Pseudomonas aeruginosa_.","Colistimethate is a polymyxin antibiotic agent. Originally, colistimethate sodium was thought to be less toxic than polymyxin B; however, if the drugs are administered at comparable doses, their toxicities may be similar. Polymyxins are cationic polypeptides that disrupt the bacterial cell membrane through a detergentlike mechanism. With the development of less toxic agents, such as extended-spectrum penicillins and cephalosporins, parenteral polymyxin use was largely abandoned, except for the treatment of multidrug-resistant pulmonary infections in patients with cystic fibrosis. More recently, however, the emergence of multidrug-resistant gram-negative bacteria, such as _Pseudomonas aeruginosa_ and _Acinetobacter baumannii_, and the lack of new antimicrobial agents have led to the revived use of the polymyxins.","Colistimethate is a surface active agent which penetrates into and disrupts the bacterial cell membrane. Colistimethate is polycationic and has both hydrophobic and lipophilic moieties. It interacts with the bacterial cytoplasmic membrane, changing its permeability. This effect is bactericidal. There is also evidence that polymyxins enter the cell and precipitate cytoplasmic components, primarily ribosomes.","Bacterial outer membrane incorporation into and destabilization","Therapeutic strategy associated"]
[409,"DB01112","approved","small molecule","Cefuroxime","(6R,7R)-3-[(carbamoyloxy)methyl]-7-{[(2Z)-2-furan-2-yl-2-(methoxyimino)acetyl]amino}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; Cefuroxim; Cefuroxime; Cephuroxime","C16H16N4O8S","[H][C@]12SCC(COC(N)=O)=C(N1C(=O)[C@H]2NC(=O)C(=N/OC)\\C1=CC=CO1)C(O)=O","Broad-spectrum cephalosporin antibiotic resistant to beta-lactamase. It has been proposed for infections with gram-negative and gram-positive organisms, gonorrhea, and haemophilus.","55268-75-2","424.385","For the treatment of many different types of bacterial infections such as bronchitis, sinusitis, tonsillitis, ear infections, skin infections, gonorrhea, and urinary tract infections.","Cefuroxime is a &beta;-lactam type antibiotic. More specifically, it is a second-generation cephalosporin. Cephalosporins work the same way as penicillins: they interfere with the peptidoglycan synthesis of the bacterial wall by inhibiting the final transpeptidation needed for the cross-links. This effect is bactericidal. Cefuroxime is effective against the following organisms: Aerobic Gram-positive Microorganisms: <i>Staphylococcus aureus</i>, <i>Streptococcus pneumoniae</i>, <i>Streptococcus pyogenes</i>. Aerobic Gram-negative Microorganisms: <i>Escherichia coli</i>, <i>Haemophilus influenzae</i> (including beta-lactamase-producing strains), <i>Haemophilus parainfluenzae</i>, <i>Klebsiella pneumoniae</i>, <i>Moraxella catarrhalis</i> (including beta-lactamase-producing strains), <i>Neisseria gonorrhoeae</i> (including beta-lactamase-producing strains). Spirochetes: <i>Borrelia burgdorferi</i>. Cefuroxime axetil is the prodrug","Cefuroxime, like the penicillins, is a beta-lactam antibiotic. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that cefuroxime interferes with an autolysin inhibitor.","Penicillin-binding protein 1A inhibitor","Indication associated"]
[410,"DB01115","approved","small molecule","Nifedipine","Nifedipine","C17H18N2O6","COC(=O)C1=C(C)NC(C)=C(C1C1=CC=CC=C1[N+]([O-])=O)C(=O)OC","Nifedipine, or BAY a 1040, is a first generation dihydropyridine L-type calcium channel blocker, similar to . Nifedipine was developed by Bayer and first described in the literature, along with other dihydropyridines, in 1972. Since nifedipine's development, second and third generation dihydropyridines have been developed with slower onsets and longer durations of action. The most popular of the third generation dihydropyridines is .\r\n\r\nNifedipine was granted FDA approval on 31 December 1981.","21829-25-4","346.3346","Nifedipine capsules are indicated to treat vasospastic angina and chronic stable angina. Extended release tablets are indicated to treat vasospastic angina, chronic stable angina, and hypertension.","Nifedipine is an inhibitor of L-type voltage gated calcium channels that reduces blood pressure and increases oxygen supply to the heart. Immediate release nifedipine's duration of action requires dosing 3 times daily. Nifedipine dosing is generally 10-120mg daily. Patients should be counselled regarding the risk of excessive hypotension, angina, and myocardial infarction.","Nifedipine blocks voltage gated L-type calcium channels in vascular smooth muscle and myocardial cells. This blockage prevents the entry of calcium ions into cells during depolarization, reducing peripheral arterial vascular resistance and dilating coronary arteries. These actions reduce blood pressure and increase the supply of oxygen to the heart, alleviating angina.","Voltage-dependent L-type calcium channel subunit alpha-1C inhibitor; Nuclear receptor subfamily 1 group I member 2 agonist; Calmodulin inhibitor; Voltage-dependent L-type calcium channel subunit alpha-1D inhibitor; Voltage-dependent L-type calcium channel subunit alpha-1S inhibitor; Voltage-dependent L-type calcium channel subunit beta-2 inhibitor; Potassium voltage-gated channel subfamily D member 3 inhibitor; Voltage-dependent T-type calcium channel inhibitor","Indication associated"]
[411,"DB01116","approved; investigational","small molecule","Trimethaphan","Thimethaphan; Trimetaphan; Trimetaphanum","C22H25N2OS","O=C1N(CC2=CC=CC=C2)C2C[S+]3CCCC3C2N1CC1=CC=CC=C1","A nicotinic antagonist that has been used as a ganglionic blocker in hypertension, as an adjunct to anesthesia, and to induce hypotension during surgery.","7187-66-8","365.512","For the controlled reduction of blood pressure during surgery and in the treatment of hypertensive emergencies.","Trimethaphan is indicated for production of controlled hypotension during surgery to reduce bleeding into the surgical field and also for rapid reduction of blood pressure in the treatment of hypertensive emergencies, especially in patients with acute dissecting aneurysm, and in the emergency treatment of pulmonary edema in patients with pulmonary hypertension associated with systemic hypertension.","Trimethaphan is a ganglionic blocking agent prevents stimulation of postsynaptic receptors by competing with acetylcholine for these receptor sites. Additional effects may include direct peripheral vasodilation and release of histamine. Trimethaphan's hypotensive effect is due to reduction in sympathetic tone and vasodilation, and is primarily postural.","Neuronal acetylcholine receptor subunit alpha-10 antagonist","Therapeutic strategy associated"]
[412,"DB01117","approved","small molecule","Atovaquone","2-(trans-4-(p-Chlorophenyl)cyclohexyl)-3-hydroxy-1,4-naphthoquinone; Atovaquone","C22H19ClO3","OC1=C([C@H]2CC[C@@H](CC2)C2=CC=C(Cl)C=C2)C(=O)C2=CC=CC=C2C1=O","Atovaquone is a hydroxynaphthoquinone, or an analog of ubiquinone, that has antimicrobial and antipneumocystis activity. It is being used in antimalarial protocols.","95233-18-4","366.837","For the treatment or prevention of <i>Pneumocystis carinii</i> pneumonia in patients who are intolerant to trimethoprim-sulfamethoxazole (TMP-SMX). Also indicated for the acute oral treatment of mild to moderate PCP in patients who are intolerant to TMP-SMX.","Atovaquone is a highly lipophilic drug that closely resembles the structure . Its inhibitory effect being comparable to ubiquinone, atovaquone can act by selectively affecting mitochondrial electron transport and parallel processes such as ATP and pyrimidine biosynthesis in atovaquone-responsive parasites. Cytochrome bc1 complex (complex III) seems to serve as a highly discriminating molecular target for atovaquone in Plasmodia. There is no significant risk for myelosuppression associated with atovaquone, making this drug a beneficial therapeutic agent for recipients of bone marrow transplantation.","The mechanism of action against <i>Pneumocystis carinii</i> has not been fully elucidated. In Plasmodium species, the site of action appears to be the cytochrome bc1 complex (Complex III). Several metabolic enzymes are linked to the mitochondrial electron transport chain via ubiquinone. Inhibition of electron transport by atovaquone will result in indirect inhibition of these enzymes. The ultimate metabolic effects of such blockade may include inhibition of nucleic acid and ATP synthesis. Atovaquone also has been shown to have good <i>in vitro</i> activity against <i>Toxoplasma gondii</i>.","Cytochrome b inhibitor; Dihydroorotate dehydrogenase (quinone), mitochondrial inhibitor; Dihydroorotate dehydrogenase (quinone), mitochondrial inhibitor","Indication associated"]
[413,"DB01118","approved; investigational","small molecule","Amiodarone","2-Butyl-3-(3,5-diiodo-4-(2-diethylaminoethoxy)benzoyl)benzofuran; 2-Butyl-3-benzofuranyl 4-(2-(diethylamino)ethoxy)-3,5-diiodophenyl ketone; 2-n-Butyl-3',5'-diiodo-4'-N-diethylaminoethoxy-3-benzoylbenzofuran; Amiodarone","C25H29I2NO3","CCCCC1=C(C(=O)C2=CC(I)=C(OCCN(CC)CC)C(I)=C2)C2=C(O1)C=CC=C2","Amiodarone is a benzofuran derivative, anti-arrhythmic drug used commonly in a variety of settings. Most known for its approved indication in life-threatening ventricular arrhythmias, it is also used off-label in the outpatient and inpatient setting for atrial fibrillation. Because of its ability to cause serious toxicity and possibly death, amiodarone use should be reserved for its approved indications, according to prescribing information.","1951-25-3","645.3116","The FDA approved indications for amiodarone are recurrent ventricular fibrillation (VF)\r\nand recurrent hemodynamically unstable ventricular tachycardia (VT). The FDA emphasizes that this drug should only be given in these conditions when they are clinically documented and have not responded to normal therapeutic doses of other antiarrhythmic agents, or when other drugs are not tolerated by the patient.\r\n\r\nOff-label indications include atrial fibrillation and supraventricular tachycardia.","After intravenous administration, amiodarone acts to relax smooth muscles that line vascular walls, decreases peripheral vascular resistance (afterload), and increases the cardiac index by a small amount. Administration by this route also decreases cardiac conduction, preventing and treating arrhythmias. When it is given orally, however, amiodarone does not lead to significant changes in the left ventricular ejection fraction. Similar to other anti-arrhythmic agents, controlled clinical trials do not confirm that oral amiodarone increases survival. \r\n\r\nAmiodarone prolongs the QRS duration and QT interval.  In addition, a decreased SA (sinoatrial) node automaticity occurs with a decrease in AV node conduction velocity. Ectopic pacemaker automaticity is also inhibited. Thyrotoxicosis or hypothyroidism may also result from the administration of amiodarone, which contains high levels of iodine, and interferes with normal thyroid function.","Amiodarone is considered a class III anti-arrhythmic drug. It blocks potassium currents that cause repolarization of the heart muscle during the third phase of the cardiac action potential. As a result amiodarone increases the duration of the action potential as well as the effective refractory period for cardiac cells (myocytes). Therefore, cardiac muscle cell excitability is reduced, preventing and treating abnormal heart rhythms.\r\n\r\nUnique from other members of the class III anti-arrhythmic drug class, amiodarone also interferes with the functioning of beta-adrenergic receptors, sodium channels, and calcium channels channels. These actions, at times, can lead to undesirable effects, such as hypotension, bradycardia, and Torsades de pointes (TdP). In addition to the above, amiodarone may increase activity of peroxisome proliferator-activated receptors, leading to steatogenic changes in the liver or other organs. Finally, amiodarone has been found to bind to the thyroid receptor due to its iodine content, potentially leading to amiodarone induced hypothyroidism or thyrotoxicosis.","HERG human cardiac K+ channel inhibitor; Beta adrenergic receptor inhibitor&downregulator; Voltage-dependent T-type calcium channel subunit alpha-1I inhibitor; Voltage gated L-type calcium channel inhibitor; Thyroid hormone receptor antagonist&binder; Peroxisome proliferator-activated receptor gamma agonist; Peroxisome proliferator-activated receptor alpha agonist; Peroxisome proliferator-activated receptor gamma coactivator 1-beta agonist","Target associated"]
[414,"DB01119","approved","small molecule","Diazoxide","Diazoxide","C8H7ClN2O2S","CC1=NS(=O)(=O)C2=C(N1)C=CC(Cl)=C2","A benzothiadiazine derivative that is a peripheral vasodilator used for hypertensive emergencies. It lacks diuretic effect, apparently because it lacks a sulfonamide group.","364-98-7","230.671","Used parentally to treat hypertensive emergencies. Also used to treat hypoglycemia secondary to insulinoma.","Diazoxide is a potassium channel activator. Its mechanism of action revolves around enhancing cell membrane permeability to potassium ions. This action consequently elicits the relaxation of local smooth muscles. This switches off voltage-gated calcium ion channels which inhibits the generation of an action potential.","Diazoxide inhibits insulin release from the pancreas, by opening potassium channels in the beta cell membrane. Diazoxide is chemically related to thiazide diuretics but does not inhibit carbonic anhydrase and does not have chloriuretic or natriuretic activity. It also exhibits hypotensive activity by reducing arteriolar smooth muscle and vascular resistance.","ATP-sensitive inward rectifier potassium channel 11 inducer; Carbonic anhydrase 1 inhibitor; Carbonic anhydrase 2 inhibitor; Sodium/potassium-transporting ATPase subunit alpha-1 other; Calcium-activated potassium channel subunit alpha-1 other","Indication associated"]
[415,"DB01124","approved; investigational","small molecule","Tolbutamide","1-Butyl-3-(p-methylphenylsulfonyl)urea; 1-Butyl-3-(p-tolylsulfonyl)urea; 1-Butyl-3-tosylurea; 1-p-Toluenesulfonyl-3-butylurea; 3-(p-Tolyl-4-sulfonyl)-1-butylurea; N-(4-Methylbenzenesulfonyl)-N'-butylurea; N-(4-Methylphenylsulfonyl)-N'-butylurea; N-(p-Methylbenzenesulfonyl)-N'-butylurea; N-(Sulfonyl-p-methylbenzene)-N'-N-butylurea; N-Butyl-N'-(4-methylphenylsulfonyl)urea; N-Butyl-N'-(p-tolylsulfonyl)urea; N-Butyl-N'-p-toluenesulfonylurea; N-n-Butyl-N'-tosylurea; Tolbutamide; Tolylsulfonylbutylurea","C12H18N2O3S","CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1","Tolbutamide is an oral antihyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus (NIDDM). It is structurally similar to acetohexamide, chlorpropamide and tolazamide and belongs to the sulfonylurea class of insulin secretagogues, which act by stimulating β cells of the pancreas to release insulin. Sulfonylureas increase both basal insulin secretion and meal-stimulated insulin release. Medications in this class differ in their dose, rate of absorption, duration of action, route of elimination and binding site on their target pancreatic β cell receptor. Sulfonylureas also increase peripheral glucose utilization, decrease hepatic gluconeogenesis and may increase the number and sensitivity of insulin receptors. Sulfonylureas are associated with weight gain, though less so than insulin. Due to their mechanism of action, sulfonylureas may cause hypoglycemia and require consistent food intake to decrease this risk. The risk of hypoglycemia is increased in elderly, debilitated and malnourished individuals. Tolbutamide appears to be metabolized in the liver. Tolbutamide and its metabolites are excreted in urine (75-85%) and feces.","64-77-7","270.348","For treatment of NIDDM (non-insulin-dependent diabetes mellitus) in conjunction with diet and exercise.","Tolbutamide, a first-generation sulfonylurea antidiabetic agent, is used with diet to lower blood glucose levels in patients with diabetes mellitus type II. Tolbutamide is twice as potent as the related second-generation agent glipizide. Tolbutamide lowers blood sugar by stimulating the pancreas to secrete insulin and helping the body use insulin efficiently. The pancreas must be able to produce insulin for this drug to work.","Sulfonylureas lower blood glucose in patients with NIDDM by directly stimulating the acute release of insulin from functioning beta cells of pancreatic islet tissue by an unknown process that involves a sulfonylurea receptor (receptor 1) on the beta cell. Sulfonylureas inhibit the ATP-potassium channels on the beta cell membrane and potassium efflux, which results in depolarization and calcium influx, calcium-calmodulin binding, kinase activation, and release of insulin-containing granules by exocytosis, an effect similar to that of glucose.","ATP-binding cassette sub-family C member 8 inhibitor; ATP-sensitive inward rectifier potassium channel 1 inhibitor","Indication associated"]
[416,"DB01125","approved","small molecule","Anisindione","2-(4-Methoxyphenyl)-1H-indene-1,3(2H)-dione; 2-(4-Methoxyphenyl)indan-1,3-dione; 2-(p-Methoxyphenyl)-1,3-indandione; 2-(p-Methoxyphenyl)indane-1,3-dione; 2-p-Anisyl-1,3-indandione; 2-para-Anisyl-1,3-indandione; Anisin indandione; Anisindione","C16H12O3","COC1=CC=C(C=C1)C1C(=O)C2=CC=CC=C2C1=O","Anisindione is a synthetic anticoagulant and an indanedione derivative. Its anticoagulant action is mediated through the inhibition of the vitamin K-mediated gamma-carboxylation of precursor proteins that are critical in forming the formation of active procoagulation factors II, VII, IX, and X, as well as the anticoagulant proteins C and S, in the liver.","117-37-3","252.2647","For the prophylaxis and treatment of venous thrombosis and its extension, the treatment of atrial fibrillation with embolization, the prophylaxis and treatment of pulmonary embolism, and as an adjunct in the treatment of coronary occlusion.","Anisindione is a synthetic anticoagulant and an indanedione derivative. It is prescribed only if you cannot take coumarin-type anticoagulants such as coumadin as anisindione is a powerful drug with serious potential side effects. Anticoagulants decrease the clotting ability of the blood and therefore help to prevent harmful clots from forming in the blood vessels. These medicines are sometimes called blood thinners, although they do not actually thin the blood. They also will not dissolve clots that already have formed, but they may prevent the clots from becoming larger and causing more serious problems.","Like phenindione, to which it is related chemically, anisindione exercises its therapeutic action by reducing the prothrombin activity of the blood. By inhibiting the vitamin K&ndash;mediated gamma-carboxylation of precursor proteins, the formation of active procoagulation factors II, VII, IX, and X, as well as the anticoagulant proteins C and S is prevented. Anisindione has no direct thrombolytic effect and does not reverse ischemic tissue damage, although it may limit extension of existing thrombi and prevent secondary thromboembolic complications.","Vitamin K-dependent gamma-carboxylase inhibitor","Indication associated"]
[417,"DB01126","approved; investigational","small molecule","Dutasteride","(5α,17β)-N-(2,5-bis(trifluoromethyl)phenyl)-3-oxo-4-azaandrost-1-ene-17-carboxamide; Dutasteride; α,α,α,α',α',α'-hexafluoro-3-oxo-4-aza-5α-androst-1-ene-17β-carboxy-2',5'-xylidide","C27H30F6N2O2","[H][C@@]1(CC[C@@]2([H])[C@]3([H])CC[C@@]4([H])NC(=O)C=C[C@]4(C)[C@@]3([H])CC[C@]12C)C(=O)NC1=CC(=CC=C1C(F)(F)F)C(F)(F)F","Dutasteride is an oral synthetic 4-azasteroid commonly marketed under the trade name Avodart. It is a novel dual 5α-reductase inhibitor that works by blocking both isoforms of 5α-reductase enzymes in a potent, selective, and irreversible manner. Type I and II 5α-reductase enzymes convert testosterone into dihydrotestosterone (DHT), a primary hormonal mediator that plays a role in the development and enlargement of the prostate gland. Dutasteride was approved by the FDA in 2001 for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men as monotherapy or in combination with the α-adrenergic antagonist  to enhance the therapeutic response. Its clinical efficacy against benign prostate hyperplasia in male patients is comparable to that of , a specific type II 5α-reductase inhibitor. However, unlike finasteride, dutasteride is not yet indicated for the treatment of androgenic alopecia although it was demonstrated to be effective in several randomized, double-blind, placebo-controlled trials in androgenetic alopecia.","164656-23-9","528.5297","Indicated for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate gland to improve symptoms, and reduce the risk of acute urinary retention and the need for BPH-related surgery alone or in combination with .","Dutasteride is a synthetic 4-azasteroid compound that selectively inhibits both the type I and type II isoforms of steroid 5α-reductase, an intracellular enzyme that converts testosterone to 5α-dihydrotestosterone (DHT). Dutasteride works by reducing the levels of circulating DHT. It was also shown to reduce the size of the prostate gland, improve urinary flow, and symptoms of benign prostatic hyperplasia alone or in combination with tamsulosin. The effect of the reduction of DHT by dutasteride is dose-dependent, with the maximum effect observed within 1-2 weeks following initial administration. \r\n\r\nAfter 1 and 2 weeks of daily dosing with dutasteride 0.5 mg, median serum DHT concentrations were reduced by 85% and 90%, respectively. The serum concentrations of DHT were maintained to be decreased by more than 90% in 85% of patients following 1 years' administration of oral dutasteride 0.5 mg/day. As evident from the clinical studies, dutasteride may also cause decreases in serum PSA in the presence of prostate cancer.","The 5α-reductase is a nuclear-bound steroid intracellular enzyme primarily located in the prostatic stromal cell that converts the androgen testosterone into the more active metabolite, 5α-dihydrotestosterone (DHT). DHT is considered to be the primary androgen playing a role in the initial development and subsequent enlargement of the prostate gland. It serves as the hormonal mediator for the hyperplasia upon accumulation within the prostate gland. DHT displays a higher affinity towards androgen receptors in the prostate gland compared to testosterone and by acting on the androgen receptors, DHT modulates genes that are responsible for cell proliferation. Responsible for the synthesis of approximately one-third of circulating DHT, type I 5α-reductase is predominant in the sebaceous glands of most regions of skin, including the scalp, and liver. The type II 5a-reductase isozyme is primarily found in the prostate, seminal vesicles, epididymides, and hair follicles as well as liver, and is responsible for two-thirds of circulating DHT. Due to its dual inhibition of both isoenzymes of 5α-reductase, dutasteride causes a near-complete suppression of DHT. Compared to a 70% reduction of serum DHT levels caused by , a near-complete suppression of serum DHT-more than 90% is seen with dutasteride.\r\n\r\nBy forming a stable complex with both type II and type II 5α-reductase, dutasteride inhibits its enzymatic action of converting testosterone to 5α-dihydrotestosterone (DHT), which is the androgen primarily responsible for the initial development and subsequent enlargement of the prostate gland. It is proposed that DHT is the principal androgen responsible for prostatic growth in later life-normal masculinization of the external genitalia and maturation of the prostate gland during development-thus reducing the serum DHT levels results in reduced prostatic volume and increased epithelial apoptosis. Dutasteride is a competitive and specific inhibitor of both Type I and Type II 5α-reductase isoenzymes and when evaluated under _in vitro_ and _in vivo_ conditions, the dissociation of the drug from the drug-enzyme complex is reported to be extremely slow. Dutasteride does not bind to the human androgen receptor.","3-oxo-5-alpha-steroid 4-dehydrogenase 2 inhibitor; 3-oxo-5-alpha-steroid 4-dehydrogenase 1 inhibitor","Therapeutic strategy associated"]
[418,"DB01130","approved; investigational","small molecule","Prednicarbate","Prednicarbate","C27H36O8","[H][C@@]12CC[C@](OC(=O)OCC)(C(=O)COC(=O)CC)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)C=C[C@]12C","Prednicarbate is a relatively new topical corticosteroid drug that displays a similar potency as . It is used in the treatment of inflammatory skin diseases, such as atopic dermatitis. It has a favorable benefit-risk ratio, with an inflammatory action similar to that of a medium potency corticosteroid, but with a low potential to cause skin atrophy. The anti-inflammation action of corticosteroids is associated with the inhibition of the interleukin 1-alpha cytokine within keratinocytes. IL-1a is also found in fibroblasts, where it is responsible for proliferation, collagenase induction and IL-6 synthesis, which are related to skin thickness.","73771-04-7","488.577","For the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses.","Corticosteroids diffuse across cell membranes and complex with specific cytoplasmic receptors. These complexes then enter the cell nucleus, bind to DNA (chromatin), and stimulate transcription of messenger RNA (mRNA) and subsequent protein synthesis of various inhibitory enzymes responsible for the anti-inflammatory effects of topical corticosteroids. These anti-inflammatory effects include inhibition of early processes such as edema, fibrin deposition, capillary dilatation, movement of phagocytes into the area, and phagocytic activities. Later processes, such as capillary production, collagen deposition, and keloid formation also are inhibited by corticosteroids.","In common with other topical corticosteroids, prednicarbate has anti-inflammatory, antipruritic, and vasoconstrictive properties. In general, the mechanism of the anti-inflammatory activity of topical steroids is unclear. However, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2.","Glucocorticoid receptor agonist","Therapeutic strategy associated"]
[419,"DB01134","experimental; vet_approved","small molecule","Desoxycorticosterone pivalate","11-deoxycorticosterone pivalate; Deoxycorticosterone pivalate; Deoxycorticosterone trimethylacetate; Deoxycortone pivalate; Deoxycortone trimethylacetate; Desoxycorticosterone pivalate; Desoxycorticosterone trimethylacetate; Desoxycortone pivalate; DOCP; DTMA","C26H38O4","[H][C@@]1(CC[C@@]2([H])[C@]3([H])CCC4=CC(=O)CC[C@]4(C)[C@@]3([H])CC[C@]12C)C(=O)COC(=O)C(C)(C)C","Desoxycorticosterone pivalate is a mineralocorticoid hormone and an analog of desoxycorticosterone. It is white, odorless, and stable in air. It is practically insoluble in water, sparingly soluble in acetone, slightly soluble in methanol, ether and vegetable oils. Federal (U.S.A.) law restricts this drug to use by or on the order of a licensed veterinarian.","808-48-0","414.586","Examined for treatment of adrenocortical insufficiency especially in multiple sclerosis, congenital cerebral palsy, polyarteritis nodosa, and rheumatoid arthritis. Currently only approved in treating cats and dogs for the treatment of Addison's disease.","Used to treat adrenocortical insufficiency, desoxycorticosterone pivalate is a mineralocorticoid hormone and an analogue of desoxycorticosterone. It primarily acts on the metabolism of sodium, potassium and water. When the drug is given, there is decreased excretion of sodium accompanied by increased excretion of potassium; the concentration of sodium in the blood is thereby increased whereas that of potassium is decreased. There is a concomitant increase in the volume of blood and extracellular fluids, with a fall in hematocrit. It increases the rate of renal tubular absorption of sodium.","Desoxycorticosterone Pivalate binds to the mineralocorticoid receptor. Mineralocorticoids are a family of steroids, secreted by the adrenal cortex, necessary for the regulation of a number of metabolic processes including electrolyte regulation. Desoxycorticosterone pivalate exerts its effect through its interaction with the mineralocorticoid receptor (MR), whereby it reacts with the receptor proteins to form a steroid-receptor complex. This complex moves into the nucleus, where it binds to chromatin which results in genetic transcription of cellular DNA to messenger RNA. The steroid hormones appear to induce transcription and synthesis of specific proteins, which produce the physiological effects seen after administration.","Mineralocorticoid receptor agonist","Indication associated"]
[420,"DB01136","approved; investigational","small molecule","Carvedilol","(+-)-1-(Carbazol-4-yloxy)-3-((2-(o-methoxyphenoxy)ethyl)amino)-2-propanol","C24H26N2O4","COC1=CC=CC=C1OCCNCC(O)COC1=CC=CC2=C1C1=CC=CC=C1N2","Carvedilol is a racemic mixture where the S(-) enantiomer is a beta adrenoceptor blocker and the R(+) enantiomer is both a beta and alpha-1 adrenoceptor blocker. It is currently used to treat heart failure, left ventricular dysfunction, and hypertension. The dual action of carvedilol is advantageous in combination therapies as moderate doses of 2 drugs have a decreased incidence of adverse effects compared to high dose monotherapy in the treatment of moderate hypertension.\r\n\r\nCarvedilol was granted FDA approval on 14 September 1995.","72956-09-3","406.4742","Carvedilol is indicated to treat mild to severe heart failure, left ventricular dysfunction after myocardial infarction with ventricular ejection fraction ≤40%, or hypertension.","Carvedilol reduces tachycardia through beta adrenergic antagonism and lowers blood pressure through alpha-1 adrenergic antagonism. It has a long duration of action as it is generally taken once daily and has a broad therapeutic index as patients generally take 10-80mg daily. Patients taking carvedilol should not abruptly stop taking this medication as this may exacerbate coronary artery disease.","Carvedilol inhibits exercise induce tachycardia through its inhibition of beta adrenoceptors. Carvedilol's action on alpha-1 adrenergic receptors relaxes smooth muscle in vasculature, leading to reduced peripheral vascular resistance and an overall reduction in blood pressure. At higher doses, calcium channel blocking and antioxidant activity can also be seen. The antioxidant activity of carvedilol prevents oxidation of low density lipoprotein and its uptake into coronary circulation.","Beta-1 adrenergic receptor antagonist; Alpha-1A adrenergic receptor antagonist&potentiator; NADH dehydrogenase [ubiquinone] 1 subunit C2 inhibitor; Beta-2 adrenergic receptor antagonist; Vascular endothelial growth factor A other; Natriuretic peptides B other; Gap junction alpha-1 protein other; Potassium voltage-gated channel subfamily H member 2 inhibitor; Vascular cell adhesion protein 1 inhibitor; Alpha-1D adrenergic receptor antagonist; Alpha-1B adrenergic receptor antagonist; Alpha-2C adrenergic receptor antagonist; Alpha-2B adrenergic receptor antagonist; Alpha-2A adrenergic receptor antagonist; E-selectin inhibitor; Hypoxia-inducible factor 1-alpha modulator; Inward rectifier potassium channel 4 inhibitor; Inward rectifier potassium channel 2 inhibitor; Alpha-1 adrenergic receptors inhibitor","Indication associated"]
[421,"DB01138","approved","small molecule","Sulfinpyrazone","1,2-Diphenyl-3,5-dioxo-4-(2-phenylsulfinylethyl)pyrazolidine; 1,2-Diphenyl-4-(2'-phenylsulfinethyl)-3,5-pyrazolidinedione; 4-(2-Benzenesulfinylethyl)-1,2-diphenylpyrazolidine-3,5-dione; Sulfinpyrazone; Sulfoxyphenylpyrazolidine; Sulphinpyrazone","C23H20N2O3S","O=C1C(CCS(=O)C2=CC=CC=C2)C(=O)N(N1C1=CC=CC=C1)C1=CC=CC=C1","A uricosuric drug that is used to reduce the serum urate levels in gout therapy. It lacks anti-inflammatory, analgesic, and diuretic properties.","57-96-5","404.482","For the treatment of gout and gouty arthritis.","Sulfinpyrazone's pharmacologic activity is the potentiation of the urinary excretion of uric acid. It is useful for reducing the blood urate levels in patients with chronic tophaceous gout and acute intermittent gout, and for promoting the resorption of tophi.","Sulfinpyrazone is an oral uricosuric agent (pyrazolone derivative) used to treat chronic or intermittent gouty arthritis. Sulfinpyrazone competitively inhibits the reabsorption of uric acid at the proximal convoluted tubule, thereby facilitating urinary excretion of uric acid and decreasing plasma urate concentrations.  This is likely done through inhibition of the urate anion transporter (hURAT1) as well as the human organic anion transporter 4 (hOAT4). Sulfinpyrazone is not intended for the treatment of acute attacks because it lacks therapeutically useful analgesic and anti-inflammatory effects. Sulfinpyrazone and its sulfide metabolite possess COX inhibitory effects. Sulfinpyrazone has also been shown to be a UDP-glucuronsyltransferase inhibitor and a very potent CYP2C9 inhibitor.  Sulfinpyrazone is also known to be a cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor as well as an inhibitor of several multridrug resistance proteins (MRPs).","Canalicular multispecific organic anion transporter 1 inhibitor; Multidrug resistance-associated protein 1 inhibitor; Solute carrier family 22 member 12 inhibitor; Nuclear receptor subfamily 1 group I member 2 activator","Therapeutic strategy associated"]
[422,"DB01140","approved; vet_approved; withdrawn","small molecule","Cefadroxil","CDX; Cefadroxil; Cefadroxil anhydrous; Cephadroxil; D-Cefadroxil","C16H17N3O5S","[H][C@]12SCC(C)=C(N1C(=O)[C@H]2NC(=O)[C@H](N)C1=CC=C(O)C=C1)C(O)=O","Long-acting, broad-spectrum, water-soluble, cephalexin derivative.","50370-12-2","363.388","For the treatment of the following infections (skin, UTI, ENT) caused by; <i>S. pneumoniae, H. influenzae, staphylococci, S. pyogenes</i> (group A beta-hemolytic streptococci), <i>E. coli, P. mirabilis, Klebsiella</i> sp, coagulase-negative staphylococci and <i>Streptococcus pyogenes</i>","Cefadroxil, a first-generation cephalosporin antibiotic, is used to treat urinary tract infections, skin and skin structure infections, pharyngitis, and tonsillitis.","Like all beta-lactam antibiotics, cefadroxil binds to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, causing the inhibition of the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that cefadroxil interferes with an autolysin inhibitor.","Penicillin-binding protein 3 inhibitor; Penicillin-binding protein 1A inhibitor; Penicillin-binding protein 1b inhibitor; Penicillin-binding protein 2B inhibitor","Indication associated"]
[423,"DB01142","approved; investigational","small molecule","Doxepin","Doxepin","C19H21NO","[H]C(CCN(C)C)=C1C2=CC=CC=C2COC2=CC=CC=C12","Doxepin is a psychotropic agent with antidepressant and anxiolytic properties. It is a tertiary amine that can be presented as (E) and (Z) stereoisomers with the (Z) stereoisomer corresponding to . Doxepin commonly produces a 5:1 (E):(Z) racemic mixture. \r\n\r\nIn a strict sense, doxepin is not a tricyclic antidepressant but it is commonly associated with the class since it shares a lot of properties with members of the drug family including , , , , ,  and . \r\n\r\nDoxepin was developed by Pfizer and FDA approved in 1969 as an antidepressant. However, in 2010 it was approved for the treatment of insomnia. The latter indication was presented by Pernix Therapeutics.","1668-19-5","279.3761","Oral doxepin is approved for the following indications:\r\n\r\n- Treatment of depression and/or anxiety.\r\n- Treatment of depression and/or anxiety associated with different conditions, including alcoholism, organic disease and manic-depressive disorders.\r\n- Treatment of psychotic depressive disorders with associated anxiety.\r\n- Treatment of involutional depression. \r\n- Treatment of manic-depressive disorder.\r\n- Treatment of insomnia characterized by difficulties with sleep maintenance.\r\n\r\nTopical doxepin is also approved for short-term (up to 8 days) management of moderate pruritus in adult patients with atopic dermatitis, pruritus or lichen simplex chronicus.\r\n\r\nOff-label, doxepin is used topically for the management of neuropathic pain.\r\n\r\nDepression is a common medical illness that causes feelings of sadness and or loss of interest in prior enjoyable activities. This condition can lead to emotional and physical disturbances that can decrease the ability of a person to function in a regular environment.\r\n\r\nAnxiety is a normal reaction of the body towards a normal danger. When the anxious state is exacerbated or appears on situations without danger, it is defined as an anxiety disorder. This disorders can appear in different forms such as phobias, panic, obsessive-compulsive disorder and post-traumatic stress disorder.\r\n\r\nInsomnia is a sleep disorder that directly affects the quality of life of the individual. It is characterized by the complication either to fall asleep or to stay asleep. This condition can be occasional or chronic.\r\n\r\nPruritus is defined as an unpleasant skin reaction that provokes the urge to scratch. It can be localized or generalized and it can appear in an acute or chronic manner.\r\n\r\nNeuropathic pain occurs due to the damage or dysfunction of the peripheral or central nervous system rather than stimulation of the pain receptors.","Similar to other tricyclic antidepressants, doxepin was shown, in preclinical trials, to decrease the electrical activity of the brain, prolong the hexobarbital-induced sleep and block avoidance behavior without affecting the conditioned emotional response. At high doses, it also produces symptoms of central nervous system depression.\r\n\r\nDoxepin is known to cause antidepressant, sedative, and anticholinergic effects. At high doses, its anticholinergic and antiadrenergic properties are the most prevalent which limit its efficacy. These effects are observed at high doses where its affinity for H1 histamine receptor is lost and its binding to other receptors is observed.\r\n\r\nThe maximal antidepressive effects of doxepin are present around two weeks following initiation of therapy. However, the sedative effects of doxepin, usually used for the treatment of insomnia or anxiety, are observed immediately after administration.","Doxepin exact mechanism of action is not very clear. However, doxepin is known to be a selective histamine H1 receptor blocker. This effect on histamine receptors indicates effectiveness in skin conditions.\r\n\r\nBreaking its function according to the different effect, doxepin's antidepressive action is primarily associated with the inhibition of the central nervous system biogenic amine reuptake; more specifically, norepinephrine and serotonin at synaptic nerve terminals. This effect increases the level of monoamines in the synaptic site which in order increases the activity at the post-synaptic neuron receptor sites. It has been suggested that doxepin also desensitizes both serotonin 1A receptors and beta-adrenergic receptors.\r\n\r\nIt is known that the lack of dopamine transporters in the frontal cortex and the transmission of dopamine in this region is largely inactivated by the effect of norepinephrine reuptake. Hence, doxepin action on the frontal cortex is suggested to increase dopamine neurotransmission in this area.","Histamine H1 receptor antagonist; Histamine H2 receptor antagonist; Sodium-dependent noradrenaline transporter inhibitor; Sodium-dependent serotonin transporter inhibitor; 5-hydroxytryptamine receptor 2A antagonist; 5-hydroxytryptamine receptor 2B antagonist; 5-hydroxytryptamine receptor 2C antagonist; Muscarinic acetylcholine receptor M1 antagonist; Muscarinic acetylcholine receptor M2 antagonist; Muscarinic acetylcholine receptor M3 antagonist; Muscarinic acetylcholine receptor M4 antagonist; Muscarinic acetylcholine receptor M5 antagonist; Alpha-1A adrenergic receptor antagonist; Alpha-1B adrenergic receptor antagonist; Alpha-1D adrenergic receptor antagonist; 5-hydroxytryptamine receptor 1A antagonist; 5-hydroxytryptamine receptor 6 binder; Histamine H4 receptor binder; Potassium voltage-gated channel subfamily H member 2 inhibitor","Indication associated"]
[424,"DB01143","approved; investigational","small molecule","Amifostine","Amifostine; Amifostine anhydrous; Aminopropylaminoethyl thiophosphate","C5H15N2O3PS","NCCCNCCSP(O)(O)=O","A phosphorothioate proposed as a radiation-protective agent. It causes splenic vasodilation and may block autonomic ganglia.","20537-88-6","214.223","For reduction in the cumulative renal toxicity in patients with ovarian cancer (using cisplatin) and moderate to severe xerostomia in patients undergoing post-operative radiation treatment for head and neck cancer.","Amifostine is an organic thiophosphate cytoprotective agent indicated to reduce the cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer or non-small cell lung cancer and also to reduce the incidence of moderate to severe xerostomia in patients undergoing post-operative radiation treatment for head and neck cancer. Amifostine is a prodrug that is dephosphorylated by alkaline phosphatase in tissues to a pharmacologically active free thiol metabolite, believed to be responsible for the reduction of the cumulative renal toxicity of cisplatin and for the reduction of the toxic effects of radiation on normal oral tissues. Healthy cells are preferentially protected because amifostine and metabolites are present in healthy cells at 100-fold greater concentrations than in tumour cells.","The thiol metabolite is responsible for most of the cytoprotective and radioprotective properties of amifostine. It is readily taken up by cells where it binds to and detoxifies reactive metabolites of platinum and alkylating agents as well as scavenges free radicals. Other possible effects include inhibition of apoptosis, alteration of gene expression and modification of enzyme activity.","Alkaline phosphatase, placental-like inducer","Therapeutic strategy associated"]
[425,"DB01149","approved; withdrawn","small molecule","Nefazodone","1-(3-(4-(m-Chlorophenyl)-1-piperazinyl)propyl)-3-ethyl-4-(2-phenoxyethyl)-delta2-1,2,4-triazolin-5-one; Nefazodone","C25H32ClN5O2","CCC1=NN(CCCN2CCN(CC2)C2=CC(Cl)=CC=C2)C(=O)N1CCOC1=CC=CC=C1","Nefazodone hydrochloride (trade name Serzone) is an antidepressant drug marketed by Bristol-Myers Squibb. Its sale was discontinued in 2003 in some countries, due to the small possibility of hepatic (liver) injury. Drug-induced hepatic injuries were associated with an risk of elevated need for a liver transplant, or even death, with the incidence of severe liver damage was shown to be approximately 1 in 250,000 to 300,000 patient-years. On May 20, 2004, Bristol-Myers Squibb discontinued the sale of Serzone in the United States.","83366-66-9","470.007","For the treatment of depression.","Nefazodone, an antidepressant synthetically derived phenylpiperazine, is used to treat major depression. Although it is structurally similar to trazodone, nefazodone has a mechanism of action different from other antidepressants and, hence, lacks the risk for major cardiovascular toxicity seen with tricyclics and insomnia and inhibition of REM sleep seen with the selective serotonin reuptake inhibitors.","Within the serotonergic system, nefazodone acts as an antagonist at type 2 serotonin (5-HT<sub>2</sub>) post-synaptic receptors and, like fluoxetine-type antidepressants, inhibits pre-synaptic serotonin (5-HT) reuptake. These mechanisms increase the amount of serotonin available to interact with 5-HT receptors. Within the noradrenergic system, nefazodone inhibits norepinephrine uptake minimally. Nefazodone also antagonizes alpha(1)-adrenergic receptors, producing sedation, muscle relaxation, and a variety of cardiovascular effects. Nefazodone's affinity for benzodiazepine, cholinergic, dopaminergic, histaminic, and beta or alpha(2)-adrenergic receptors is not significant.","5-hydroxytryptamine receptor 2A antagonist; 5-hydroxytryptamine receptor 2C antagonist; Sodium-dependent serotonin transporter inhibitor; 5-hydroxytryptamine receptor 1A antagonist; Sodium-dependent noradrenaline transporter inhibitor; Sodium-dependent dopamine transporter inhibitor; Alpha-1B adrenergic receptor other/unknown; Alpha-2A adrenergic receptor antagonist; Alpha-1A adrenergic receptor antagonist; Potassium voltage-gated channel subfamily H member 2 antagonist","Indication associated"]
[426,"DB01150","approved","small molecule","Cefprozil","Cefprozil; Cefprozil anhydrous","C18H19N3O5S","[H][C@]12SCC(C=CC)=C(N1C(=O)[C@@]2([H])NC(=O)[C@H](N)C1=CC=C(O)C=C1)C(O)=O","Cefprozil is a cephalosporin antibiotic that is commonly employed to treat a variety of bacterial infections, including those of the ear and skin, bronchitis, and others.","92665-29-7","389.426","For the treatment of the following infections (respiratory, skin, soft tissue, UTI, ENT) caused by; S. pneumoniae, H. influenzae, staphylococci, S. pyogenes (group A beta-hemolytic streptococci), E. coli, P. mirabilis, Klebsiella sp, coagulase-negative staph","Cefprozil, a semisynthetic, second-generation cephalosporin, is used to treat otitis media, soft-tissue infections, and respiratory tract infections.","Cefprozil, like the penicillins, is a beta-lactam antibiotic. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that cefprozil interferes with an autolysin inhibitor.","Penicillin-binding protein 1A inhibitor; Penicillin-binding protein 2x inhibitor; Penicillin-binding protein 2B inhibitor","Indication associated"]
[427,"DB01151","approved; investigational","small molecule","Desipramine","5-(gamma-methylaminopropyl)iminodibenzyl; 5-(γ-methylaminopropyl)iminodibenzyl; Desipramine; Desmethylimipramine; DMI; Monodemethylimipramine; N-(3-methylaminopropyl)iminobibenzyl; Norimipramine","C18H22N2","CNCCCN1C2=CC=CC=C2CCC2=CC=CC=C12","Desipramine hydrochloride is a dibenzazepine-derivative tricyclic antidepressant (TCA). TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, desipramine does not affect mood or arousal, but may cause sedation. In depressed individuals, desipramine exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Secondary amine TCAs, such as desipramine and nortriptyline, are more potent inhibitors of norepinephrine reuptake than tertiary amine TCAs, such as amitriptyline and doxepine. TCAs also down-regulate cerebral cortical &beta;-adrenergic receptors and sensitize post-synaptic serotonergic receptors with chronic use. The antidepressant effects of TCAs are thought to be due to an overall increase in serotonergic neurotransmission. TCAs also block histamine-H<sub>1</sub> receptors, &alpha;<sub>1</sub>-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively. See toxicity section below for a complete listing of side effects. Desipramine exerts less anticholinergic and sedative side effects compared to tertiary amine TCAs, such as amitriptyline and clomipramine. Desipramine may be used to treat depression, neuropathic pain (unlabeled use), agitation and insomnia (unlabeled use) and attention-deficit hyperactivity disorder (unlabeled use).","50-47-5","266.3807","For relief of symptoms in various depressive syndromes, especially endogenous depression. It has also been used to manage chronic peripheral neuropathic pain, as a second line agent for the management of anxiety disorders (e.g. panic disorder, generalized anxiety disorder), and as a second or third line agent in the ADHD management.","Desipramine, a secondary amine tricyclic antidepressant, is structurally related to both the skeletal muscle relaxant cyclobenzaprine and the thioxanthene antipsychotics such as thiothixene. It is the active metabolite of imipramine, a tertiary amine TCA. The acute effects of desipramine include inhibition of noradrenaline re-uptake at noradrenergic nerve endings and inhibition of serotonin (5-hydroxy tryptamine, 5HT) re-uptake at the serotoninergic nerve endings in the central nervous system. Desipramine exhibits greater noradrenergic re-uptake inhibition compared to the tertiary amine TCA imipramine. In addition to inhibiting neurotransmitter re-uptake, desipramine down-regulates beta-adrenergic receptors in the cerebral cortex and sensitizes serotonergic receptors with chronic use. The overall effect is increased serotonergic transmission. Antidepressant effects are typically observed 2 - 4 weeks following the onset of therapy though some patients may require up to 8 weeks of therapy prior to symptom improvement. Patients experiencing more severe depressive episodes may respond quicker than those with mild depressive symptoms.","Desipramine is a tricyclic antidepressant (TCA) that selectively blocks reuptake of norepinephrine (noradrenaline) from the neuronal synapse. It also inhibits serotonin reuptake, but to a lesser extent compared to tertiary amine TCAs such as imipramine. Inhibition of neurotransmitter reuptake increases stimulation of the post-synaptic neuron.  Chronic use of desipramine also leads to down-regulation of beta-adrenergic receptors in the cerebral cortex and sensitization of serotonergic receptors. An overall increase in serotonergic transmission likely confers desipramine its antidepressant effects. Desipramine also possesses minor anticholinergic activity, through its affinity for muscarinic receptors. TCAs are believed to act by restoring normal levels of neurotransmitters via synaptic reuptake inhibition and by increasing serotonergic neurotransmission via serotonergic receptor sensitization in the central nervous system.","Sodium-dependent noradrenaline transporter inhibitor; Beta-2 adrenergic receptor antagonist; Sodium-dependent serotonin transporter inhibitor; 5-hydroxytryptamine receptor 2A antagonist; Beta-1 adrenergic receptor other; Sphingomyelin phosphodiesterase inhibitor; Histamine H1 receptor antagonist; Alpha-1 adrenergic receptors antagonist; Muscarinic acetylcholine receptor M1 antagonist; Muscarinic acetylcholine receptor M2 antagonist; Muscarinic acetylcholine receptor M3 antagonist; Muscarinic acetylcholine receptor M4 antagonist; Muscarinic acetylcholine receptor M5 antagonist; 5-hydroxytryptamine receptor 1A binder; 5-hydroxytryptamine receptor 2C binder; Dopamine D2 receptor binder; Alpha-2 adrenergic receptors binder","Indication associated"]
[428,"DB01155","approved; investigational","small molecule","Gemifloxacin","Gemifloxacin","C18H20FN5O4","CO\\N=C1/CN(CC1CN)C1=NC2=C(C=C1F)C(=O)C(=CN2C1CC1)C(O)=O","Gemifloxacin is a quinolone antibacterial agent with a broad-spectrum activity that is used in the treatment of acute bacterial exacerbation of chronic bronchitis and mild-to-moderate pneumonia. It is available in oral formulations. Gemifloxacin acts by inhibiting DNA synthesis through the inhibition of both DNA gyrase and topoisomerase IV, which are essential for bacterial growth.","175463-14-6","389.3809","For the treatment of bacterial infection caused by susceptible strains such as <i>S. pneumoniae</i>, <i>H. influenzae</i>, <i>H. parainfluenzae</i>, or <i>M. catarrhalis</i>, <i>S. pneumoniae</i> (including multi-drug resistant strains ), <i>M. pneumoniae</i>, <i>C. pneumoniae</i>, or <i>K. pneumoniae</i>.","Gemifloxacin is a quinolone/fluoroquinolone antibiotic. Gemifloxacin is bactericidal and its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase, which allows the untwisting required to replicate one DNA double helix into two. Notably the drug has 100 times higher affinity for bacterial DNA gyrase than for mammalian. Gemifloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria.","The bactericidal action of gemifloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, and recombination.","DNA topoisomerase 4 subunit A inhibitor; DNA gyrase subunit A inhibitor","Indication associated"]
[429,"DB01156","approved","small molecule","Bupropion","Amfebutamone; Bupropion","C13H18ClNO","CC(NC(C)(C)C)C(=O)C1=CC(Cl)=CC=C1","Bupropion (also known as the brand name product Wellbutrin®) is a norepinephrine/dopamine-reuptake inhibitor (NDRI) used most commonly for the management of Major Depressive Disorder (MDD), Seasonal Affective Disorder (SAD), and as an aid for smoking cessation. Bupropion exerts its pharmacological effects by weakly inhibiting the enzymes involved in the uptake of the neurotransmitters norepinephrine and dopamine from the synaptic cleft, therefore prolonging their duration of action within the neuronal synapse and the downstream effects of these neurotransmitters. More specifically, bupropion binds to the norepinephrine transporter (NET) and the dopamine transporter (DAT).\r\n\r\nBupropion was originally classified as an \"atypical\" antidepressant because it does not exert the same effects as the classical antidepressants such as Monoamine Oxidase Inhibitors (MAOIs), Tricyclic Antidepressants (TCAs), or Selective Serotonin Reuptake Inhibitors (SSRIs). While it has comparable effectiveness to typical first-line options for the treatment of depression such as SSRIs, bupropion is a unique option for the treatment of MDD as it lacks any clinically relevant serotonergic effects, typical of other mood medications, or any effects on histamine or adrenaline receptors. Lack of activity at these receptors results in a more tolerable side effect profile; bupropion is less likely to cause sexual side effects, sedation, or weight gain as compared to SSRIs or TCAs, for example.\r\n\r\nWhen used as an aid to smoking cessation, bupropion is thought to confer its anti-craving and anti-withdrawal effects by inhibiting dopamine reuptake, which is thought to be involved in the reward pathways associated with nicotine, and through the antagonism of the nicotinic acetylcholinergic receptor. A Cochrane Review of meta-analyses of available treatment modalities for smoking cessation found that abstinence rates approximately doubled when bupropion was used as compared to placebo, and was found to have similar rates of smoking cessation as  replacement therapy (NRT).\r\n\r\nBupropion is sometimes used as an add-on agent to first-line treatments of depression such as selective serotonin reuptake inhibitor (SSRI) medications when there is a treatment-failure or only partial response. Bupropion is also used off-label for the management of Attention/Deficit-Hyperactivity Disorder (ADHD) in adults with comorbid bipolar depression to avoid mood destabilization caused by typical stimulant medications used for the treatment of ADHD.\r\n\r\nWhen used in combination with  in the marketed product ContraveⓇ for chronic weight management, the two components are thought to have effects on areas of the brain involved in the regulation of food intake. This includes the hypothalamus, which is involved in appetite regulation, and the mesolimbic dopamine circuit, which is involved in reward pathways. Studies have shown that the combined activity of bupropion and  increase the firing rate of hypothalamic pro-opiomelanocortin (POMC) neurons and blockade of opioid receptor-mediated POMC auto-inhibition, which are associated with a reduction in food intake and increased energy expenditure. The combination of naltrexone and bupropion was shown to result in a statistically significant weight loss, with a mean change in body weight of -6.3% compared to -1.3% for placebo.","34911-55-2","239.741","Bupropion is indicated for the treatment of major depressive disorder (MDD), seasonal affective disorder (SAD), and as an aid to smoking cessation. \r\n\r\nWhen used in combination with  as the marketed product ContraveⓇ, bupropion is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of: 30 kg/m^2 or greater (obese) or 27 kg/m^2 or greater (overweight) in the presence of at least one weight-related comorbid condition (e.g., hypertension, type 2 diabetes mellitus, or dyslipidemia).\r\n\r\nBupropion is also used off-label as a first-line treatment in patients with ADHD and comorbid bipolar disorder when used as an adjunct to mood stabilizers.","Bupropion is chemically unrelated to tricyclic, tetracyclic, selective serotonin re-uptake inhibitors, or other known antidepressant agents. Compared to classical tricyclic antidepressants, Bupropion is a relatively weak inhibitor of the neuronal uptake of norepinephrine and dopamine. In addition, Bupropion does not inhibit monoamine oxidase. Bupropion has been found to be essentially inactive at the serotonin transporter (SERT)(IC50 >10 000 nM), however both bupropion and its primary metabolite hydroxybupropion have been found to block the function of cation-selective serotonin type 3A receptors (5-HT3ARs). \r\n\r\nBupropion produces dose-related central nervous system (CNS) stimulant effects in animals, as evidenced by increased locomotor activity, increased rates of responding in various schedule-controlled operant behaviour tasks, and, at high doses, induction of mild stereotyped behaviour . Due to these stimulant effects and selective activity at dopamine and norepinephrine receptors, bupropion has been identified as having an abuse potential. Bupropion has a similar structure to the controlled substance , and has been identified as having mild amphetamine-like activity, particularly when inhaled or injected.\r\n\r\nBupropion is also known to lower the seizure threshold, making any pre-existing seizure conditions a contraindication to its use. This risk is exacerbated when bupropion is combined with other drugs or substances that lower the seizure threshold, such as , or in clinical situations that would increase the risk of a seizure such as abrupt alcohol or benzodiazepine withdrawal. As norepinephrine has been shown to have anticonvulsant properties, bupropion's inhibitory effects on NET are thought to contribute to its pro-convulsant activity.\r\n\r\nBupropion has been shown to increase blood pressure and pose a risk for exacerbation of unmanaged or pre-existing hypertension, however, clinical trials of bupropion in smokers with CVD have not identified an increased incidence of CV events including stroke or heart attack. In clinical trials, the mean increase in systolic blood pressure associated with the use of bupropion was found to be 1.3 mmHg.","Bupropion is a norepinephrine/dopamine-reuptake inhibitor (NDRI) that exerts its pharmacological effects by weakly inhibiting the enzymes involved in the uptake of the neurotransmitters norepinephrine and dopamine from the synaptic cleft, therefore prolonging their duration of action within the neuronal synapse and the downstream effects of these neurotransmitters. More specifically, bupropion binds to the norepinephrine transporter (NET) and the dopamine transporter (DAT). \r\n\r\nBupropion was originally classified as an \"atypical\" antidepressant because it does not exert the same effects as the classical antidepressants such as Monoamine Oxidase Inhibitors (MAOIs), Tricyclic Antidepressants (TCAs), or Selective Serotonin Reuptake Inhibitors (SSRIs). While it has comparable effectiveness to typical first-line options for the treatment of depression such as SSRIs, bupropion is a unique option for the treatment of MDD as it lacks any clinically relevant serotonergic effects, typical of other mood medications, or any effects on histamine or adrenaline receptors. Lack of activity at these receptors results in a more tolerable side effect profile; bupropion is less likely to cause sexual side effects, sedation, or weight gain as compared to SSRIs or TCAs, for example.\r\n\r\nWhen used as an aid to smoking cessation, bupropion is thought to confer its anti-craving and anti-withdrawal effects by inhibiting dopamine reuptake, which is thought to be involved in the reward pathways associated with nicotine, and through the antagonism of the nicotinic acetylcholinergic receptor (AChR), thereby blunting the effects of nicotine. Furthermore, the stimulatory effects produced by bupropion in the central nervous system are similar to nicotine's effects, making low doses of bupropion a suitable option as a nicotine substitute.  \r\n\r\nWhen used in combination with  in the marketed product ContraveⓇ for chronic weight management, the two components are thought to have effects on areas of the brain involved in the regulation of food intake. This includes the hypothalamus, which is involved in appetite regulation, and the mesolimbic dopamine circuit, which is involved in reward pathways. Studies have shown that the combined activity of bupropion and  increase the firing rate of hypothalamic pro-opiomelanocortin (POMC) neurons and blockade of opioid receptor-mediated POMC auto-inhibition, which are associated with a reduction in food intake and increased energy expenditure. This combination was also found to reduce food intake when injected directly into the ventral tegmental area of the mesolimbic circuit in mice, which is an area associated with the regulation of reward pathways.","Sodium-dependent dopamine transporter inhibitor; Sodium-dependent noradrenaline transporter inhibitor; Neuronal acetylcholine receptor subunit alpha-3 antagonist; 5-hydroxytryptamine receptor 3A negative modulator","Indication associated"]
[430,"DB01157","approved; investigational","small molecule","Trimetrexate","Trimetrexate","C19H23N5O3","COC1=CC(NCC2=C(C)C3=C(C=C2)N=C(N)N=C3N)=CC(OC)=C1OC","A nonclassical folic acid inhibitor through its inhibition of the enzyme dihydrofolate reductase. It is being tested for efficacy as an antineoplastic agent and as an antiparasitic agent against pneumocystis pneumonia in AIDS patients. Myelosuppression is its dose-limiting toxic effect.","52128-35-5","369.4176","For use, with concurrent leucovorin administration (leucovorin protection), as an alternative therapy for the treatment of moderate-to-severe <i>Pneumocystis carinii</i> pneumonia (PCP) in immunocompromised patients, including patients with the acquired immunodeficiency syndrome (AIDS). Also used to treat several types of cancer including colon cancer.","Trimetrexate, a non-classical folate antagonist, is a synthetic inhibitor of the enzyme dihydrofolate reductase (DHFR). During DNA synthesis and cellular reproduction, folic acid is reduced to tetrahydrofolic acid by the enzyme folic acid reductase. By interfering with the reduction of folic acid, trimetrexate interferes with tissue cell reproduction. Generally, the most sensitive cells to the antimetabolite effect of trimetrexate are those cells which are most actively proliferating such as malignant cells, dermal epithelium, buccal and intestinal mucosa, bone marrow, fetal cells, and cells of the urinary bladder. Because the proliferation of cells in malignant tissues is greater than in most normal tissues, trimetrexate may impair the growth of the malignant tissues without causing irreversible damage to normal tissues. Due to very serious and potentially life-threatening side-effects of this drug, leucovorin must be co-administered for at least 72 hours after the last dose.","In vitro studies have shown that trimetrexate is a competitive inhibitor of dihydrofolate reductase (DHFR) from bacterial, protozoan, and mammalian sources. DHFR catalyzes the reduction of intracellular dihydrofolate to the active coenzyme tetrahydrofolate. Inhibition of DHFR results in the depletion of this coenzyme, leading directly to interference with thymidylate biosynthesis, as well as inhibition of folate-dependent formyltransferases, and indirectly to inhibition of p.r.n. biosynthesis. The end result is disruption of DNA, RNA, and protein synthesis, with consequent cell death.","Dihydrofolate reductase inhibitor","Indication associated"]
[431,"DB01162","approved","small molecule","Terazosin","1-(4-Amino-6,7-dimethoxy-2-quinazolinyl)-4-((tetrahydro-2-furanyl)carbonyl)piperazine; Terazosin; Terazosine","C19H25N5O4","COC1=C(OC)C=C2C(N)=NC(=NC2=C1)N1CCN(CC1)C(=O)C1CCCO1","Terazosin is a quinazoline derivative alpha-1-selective adrenergic blocking agent indicated for benign prostatic hyperplasia and hypertension. Terazosin blocks adrenaline's action on alpha-1 adrenergic receptors, causing relaxation of smooth muscle in blood vessels and the prostate.","63590-64-7","387.4329","Terazosin is indicated for use in treating symptomatic benign prostatic hyperplasia and hypertension.","Terazosin is a quinazoline derivative alpha-1-selective adrenergic blocker.","Terazosin is selective for alpha-1-adrenoceptors but not their individual subtypes. Inhibition of these alpha-1-adrenoceptors results in relaxation of smooth muscle in blood vessels and the prostate, lowering blood pressure and improving urinary flow. Smooth muscle cells accounts for roughly 40% of the volume of the prostate and so their relaxation reduces pressure on the urethra.\r\n\r\nIt has also been shown that catecholamines induce factors responsible for mitogenesis and alpha-1-adrenergic receptor blockers inhibit this effect.\r\n\r\nA final long term mechanism of terazosin and other alpha-1-adrenergic receptor blockers is the induction of apoptosis of prostate cells. Treatment with terazosin enhances the expression of transforming growth factor beta-1 (TGF-beta1), which upregulates p27kip1, and the caspase cascade.","Alpha-1A adrenergic receptor antagonist; Alpha-1B adrenergic receptor antagonist; Alpha-1D adrenergic receptor antagonist; Potassium voltage-gated channel subfamily H member 2 inhibitor; Potassium voltage-gated channel subfamily H member 6 inhibitor; Potassium voltage-gated channel subfamily H member 7 inhibitor; Transforming growth factor beta-1 inducer","Therapeutic strategy associated"]
[432,"DB01169","approved; investigational","small molecule","Arsenic trioxide","Arsenic oxide; Arsenic trioxide; Arsenic(III) oxide; Arsenolite; Arsenous oxide; Arsenous oxide anhydride; Diarsenic oxide; Diarsenic trioxide; White arsenic","As2O3","O=[As]O[As]=O","Arsenic trioxide is a chemotherapeutic agent of idiopathic function used to treat leukemia that is unresponsive to first line agents. It is suspected that arsenic trisulfide induces cancer cells to undergo apoptosis. In general, arsenic is known to be a naturally toxic substance capable of eliciting a variety of dangerous adverse effects. The enzyme thioredoxin reductase has recently been identified as a target for arsenic trioxide.","1327-53-3","197.84","For induction of remission and consolidation in patients with acute promyelocytic leukemia (APL), and whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression","Arsenic Trioxide is indicated for induction of remission and consolidation in patients with acute promyelocytic leukemia (APL) who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy.","The mechanism of action of Arsenic Trioxide is not completely understood. Arsenic trioxide causes morphological changes and DNA fragmentation characteristic of apoptosis in NB4 human promyelocytic leukemia cells <i>in vitro</i>. Arsenic trioxide also causes damage or degradation of the fusion protein PML/RAR-alpha. It is suspected that arsenic trioxide induces cancer cells to undergo apoptosis.","Inhibitor of nuclear factor kappa-B kinase subunit beta inducer; Thioredoxin reductase 1, cytoplasmic inhibitor; Transcription factor AP-1 inducer; G1/S-specific cyclin-D1 antagonist; Mitogen-activated protein kinase 3 inducer; Mitogen-activated protein kinase 1 inducer; RAC-alpha serine/threonine-protein kinase inducer; Cyclin-dependent kinase inhibitor 1; Histone deacetylase 1; Protein PML","Therapeutic strategy associated"]
[433,"DB01170","approved","small molecule","Guanethidine","(2-(hexahydro-1(2h)-azocinyl)ethyl)guanidine; (2-(Octahydro-1-azocinyl)ethyl)guanidine; 2-(1-N,N-Heptamethyleneimino)ethylguanidine; 2-(1'-Azacyclooctyl)ethylguanidine; Azocine, 1-(2-guanidinoethyl)octahydro-; Guanethidine; Guanidine, (2-(hexahydro-1(2H)-azocinyl)ethyl)-; Heptamethylenimine, 1-(2-guanidinoethyl)-; N-(2-Perhydroazocin-1-ylethyl)guanidine","C10H22N4","NC(N)=NCCN1CCCCCCC1","An antihypertensive agent that acts by inhibiting selectively transmission in post-ganglionic adrenergic nerves. It is believed to act mainly by preventing the release of norepinephrine at nerve endings and causes depletion of norepinephrine in peripheral sympathetic nerve terminals as well as in tissues.","55-65-2","198.3085","For the treatment of moderate and severe hypertension, either alone or as an adjunct, and for the treatment of renal hypertension.","High blood pressure can cause the heart and arteries to not function properly. This can damage the blood vessels of the brain, heart, and kidneys, resulting in a stroke, heart failure, or kidney failure. High blood pressure may also increase the risk of heart attacks. These problems may be less likely to occur if blood pressure is controlled. Guanethidine works by decreasing the heart rate and relaxing the blood vessels so that blood can flow more easily through the body, thereby reducing these risks. It is a postganglionic sympathetic nerve terminal blocker that prevents the release of norepinephrine from nerve terminals.","Guanethidine acts at the sympathetic neuroeffector junction by inhibiting or interfering with the release and/or distribution of norepinephrine (NE), rather than acting at the effector cell by inhibiting the association of norepinephrine with its receptors. It is taken up by norepinephrine transporters to be concentrated within the transmitter vesicles in place of NE, leading to gradual depletion of NE stores in the nerve endings. Guanethidine at the nerve terminal blocks the release of noradrenaline in response to an action potential. In contrast to ganglionic blocking agents, Guanethidine suppresses equally the responses mediated by alpha-and beta-adrenergic receptors but does not produce parasympathetic blockade. Since sympathetic blockade results in modest decreases in peripheral resistance and cardiac output, Guanethidine lowers blood pressure in the supine position. It further reduces blood pressure by decreasing the degree of vasoconstriction that normally results from reflex sympathetic nervous activity upon assumption of the upright posture, thus reducing venous return and cardiac output more.","Sodium-dependent noradrenaline transporter inducer","Indication associated"]
[434,"DB01172","approved; investigational; vet_approved","small molecule","Kanamycin","4,6-diamino-2-hydroxy-1,3-cyclohexane 3,6'diamino-3,6'-dideoxydi-α-D-glucoside; 4,6-diamino-2-hydroxy-1,3-cyclohexylene 3,6'-diamino-3,6'-dideoxydi-D-glucopyranoside; Kanamycin A","C18H36N4O11","NC[C@H]1O[C@H](O[C@@H]2[C@@H](N)C[C@@H](N)[C@H](O[C@H]3O[C@H](CO)[C@@H](O)[C@H](N)[C@H]3O)[C@H]2O)[C@H](O)[C@@H](O)[C@@H]1O","Kanamycin (also known as kanamycin A) is an aminoglycoside bacteriocidal antibiotic, available in oral, intravenous, and intramuscular forms, and used to treat a wide variety of infections. Kanamycin is isolated from the bacterium Streptomyces kanamyceticus and its most commonly used form is kanamycin sulfate.","59-01-8","484.4986","For treatment of infections where one or more of the following are the known or suspected pathogens: <i>E. coli</i>, <i>Proteus</i> species (both indole-positive and indole-negative), <i>E. aerogenes, K. pneumoniae, S. marcescens,</i> and <i>Acinetobacter</i> species.","Kanamycin is an aminoglycoside antibiotic. Aminoglycosides work by binding to the bacterial 30S ribosomal subunit, causing misreading of t-RNA, leaving the bacterium unable to synthesize proteins vital to its growth. Aminoglycosides are useful primarily in infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some mycobacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. Infections caused by Gram-positive bacteria can also be treated with aminoglycosides, but other types of antibiotics are more potent and less damaging to the host. In the past the aminoglycosides have been used in conjunction with penicillin-related antibiotics in streptococcal infections for their synergistic effects, particularly in endocarditis. Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi and viruses.","Aminoglycosides like kanamycin \"irreversibly\" bind to specific 30S-subunit proteins and 16S rRNA. Specifically Kanamycin binds to four nucleotides of 16S rRNA and a single amino acid of protein S12. This interferes with decoding site in the vicinity of nucleotide 1400 in 16S rRNA of 30S subunit. This region interacts with the wobble base in the anticodon of tRNA. This leads to interference with the initiation complex, misreading of mRNA so incorrect amino acids are inserted into the polypeptide leading to nonfunctional or toxic peptides and the breakup of polysomes into nonfunctional monosomes.","30S ribosomal protein S12 inhibitor; 16S ribosomal RNA inhibitor","Indication associated"]
[435,"DB01180","approved","small molecule","Rescinnamine","3,4,5-Trimethoxycinnamoyl methyl reserpate; Rescinnamine","C35H42N2O9","[H][C@]12C[C@@H](OC(=O)C=CC3=CC(OC)=C(OC)C(OC)=C3)[C@H](OC)[C@@H](C(=O)OC)[C@@]1([H])C[C@@]1([H])N(CCC3=C1NC1=C3C=CC(OC)=C1)C2","Rescinnamine is an angiotensin-converting enzyme inhibitor used as an antihypertensive drug. It is an alkaloid obtained from _Rauwolfia serpentina_ and other species of _Rauwolfia_.","24815-24-5","634.716","For the treatment of hypertension.","Used to treat hypertension. Rescinnamine inhibits angiotensin-converting enzyme. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex and general vasoconstriction, both of which lead to increases vascular resistance. By inhibiting angiotensin II, aldosterone reabsorption is decreased as well as vasoconstriction. This combined effect serves to decrease blood pressure.","Rescinnamine Binds to and inhibits the angiotensin converting enzyme. Rescinnamine competes with angiotensin I for binding at the angiotensin-converting enzyme, blocking the conversion of angiotensin I to angiotensin II. Inhibition of ACE results in decreased plasma angiotensin II. As angiotensin II is a vasoconstrictor and a negative-feedback mediator for renin activity, lower concentrations result in a decrease in blood pressure and stimulation of baroreceptor reflex mechanisms, which leads to decreased vasopressor activity and to decreased aldosterone secretion.","Angiotensin-converting enzyme inhibitor","Indication associated"]
[436,"DB01182","approved","small molecule","Propafenone","1-(2-(2-hydroxy-3-(propylamino)propoxy)phenyl)-3-phenyl-1-propanone; 2-(2'-hydroxy-3'-propylaminopropoxy)-ω-phenylpropiophenone; Propafenone","C21H27NO3","CCCNCC(O)COC1=C(C=CC=C1)C(=O)CCC1=CC=CC=C1","An antiarrhythmia agent that is particularly effective in ventricular arrhythmias. It also has weak beta-blocking activity. The drug is generally well tolerated.","54063-53-5","341.444","Used to prolong the time to recurrence of paroxysmal atrial fibrillation/flutter (PAF) associated with disabling symptoms in patients without structural heart disease. Also used for the treatment of life-threatening documented ventricular arrhythmias, such as sustained ventricular tachycardia.","Propafenone is a Class 1C antiarrhythmic drug with local anesthetic effects, and a direct stabilizing action on myocardial membranes. It is used in the treatment of atrial and ventricular arrhythmias. It acts by inhibiting sodium channels to restrict the entry of sodium into cardiac cells resulting in reduced excitation. Propafenone has local anesthetic activity approximately equal to procaine.","The electrophysiological effect of propafenone manifests itself in a reduction of upstroke velocity (Phase 0) of the monophasic action potential. In Purkinje fibers, and to a lesser extent myocardial fibers, propafenone reduces the fast inward current carried by sodium ions, which is responsible for the drugs antiarrhythmic actions. Diastolic excitability threshold is increased and effective refractory period prolonged. Propafenone reduces spontaneous automaticity and depresses triggered activity. At very high concentrations in vitro, propafenone can inhibit the slow inward current carried by calcium but this calcium antagonist effect probably does not contribute to antiarrhythmic efficacy.","Sodium channel protein type 5 subunit alpha inhibitor; Potassium voltage-gated channel subfamily H member 2 inhibitor; Beta-1 adrenergic receptor antagonist; Beta-2 adrenergic receptor antagonist","Indication associated"]
[437,"DB01183","approved; vet_approved","small molecule","Naloxone","(−)-naloxone; 1-N-Allyl-14-hydroxynordihydromorphinone; 17-allyl-3,14-dihydroxy-4,5α-epoxymorphinan-6-one","C19H21NO4","OC1=CC=C2C[C@H]3N(CC=C)CC[C@@]45[C@@H](OC1=C24)C(=O)CC[C@@]35O","Naloxone is an opioid antagonist medication used to block or reverse the effects of opioid drugs, particularly within the setting of drug overdoses which are rapidly becoming a leading cause of death worldwide. More specifically, naloxone has a high affinity for μ-opioid receptors, where it acts as an inverse agonist, causing the rapid removal of any other drugs bound to these receptors. When taken in large quantities, opioid medications such as , , , , or  are capable of causing life-threatening symptoms such as respiratory depression, reduced heart rate, slurred speech, drowsiness, and constricted pupils. If untreated, this can progress to vomiting, absent pulse and breathing, loss of consciousness, and even death. Naloxone is indicated for the rapid reversal of these symptoms of central nervous system depression in opioid overdose. It's important to note that naloxone only works on opioid receptors within the body, and is therefore not capable of reversing the effects of non-opioid medications such as stimulants like  or , or benzodiazepines like  or . \r\n\r\nAlso known as the brand name product Narcan, naloxone is currently available by intramuscular (IM) or subcutaneous (SubQ) injection, nasal spray, or intravenous (IV) infusion. Naloxone IM injections are commonly available in the form of \"kits\", which is ideal for making overdose treatment accessible and readily available for administration by minimally trained individuals within the community. Kits commonly include the supplies necessary to treat an overdose in a non-medical setting such as alcohol swabs, syringes, a rescue breathing mask, and instructions for use. Frequently also carried by medical and emergency personnel and at events known to be associated with heavy drug use like music festivals, naloxone kits are considered a key component of harm reduction strategies.\r\n\r\nWhen injected intramuscularly (IM), naloxone acts within 3-5 minutes. Administration of naloxone is associated with very few side effects. Notably, if injected into a person not currently using opioid medications, there would be no noticeable effects at all. However, for individuals using opioid medications or experiencing an overdose, IM injection of naloxone rapidly reverses opioid effects and can cause the injected individual to immediately experience withdrawal symptoms. Common symptoms of opioid withdrawal include nausea, vomiting, sweating, runny nose, aches, and diarrhea. Although certainly physically uncomfortable, opioid withdrawal symptoms are not life-threatening; administration of naloxone is therefore appropriate for any person appearing to have any symptoms of an opioid overdose. Due to its short duration of action, persons injected with naloxone should be monitored for responsiveness and potentially injected a second time or taken to the hospital.\r\n\r\nNaloxone is also available within the combination product Suboxone with the opioid medication . Suboxone is used for the maintenance treatment of opioid dependence and addiction. When taken orally, naloxone has no pharmacological effect and does not reduce the effectiveness of the opioid effect of buprenorphine. The primary purpose of including naloxone within Suboxone is to act as a deterrent to injection, as injected naloxone would rapidly reverse the effects of buprenorphine.\r\n\r\nNaloxone was granted FDA approval on 13 April 1971.","465-65-6","327.3743","Naloxone nasal sprays are indicated for the emergency treatment of an opioid overdose or suspected opioid overdose. Intramuscular, intravenous, and subcutaneous injections are indicated for complete or partial reversal of opioid depression, diagnosis of known or suspected opioid overdose, and as an adjunct therapy in the treatment of septic shock.\r\n\r\nSublingual tablets and films are formulated with  for the treatment of opioid dependence. Naloxone is also formulated with  as an oral tablet for severe pain.\r\n\r\nNaloxone has been used off-label for the treatment of neuraxial opioid-induced pruritus.","Naloxone is an opioid receptor antagonist indicated in the reversal of opioid overdoses. Naloxone has a shorter duration of action than opioids and multiple doses may be required. The therapeutic window of naloxone is wide, as it has no effect if a patient has not taken opioids. Patients treated with naloxone may experience opioid withdrawal and a person administering naloxone should be aware that reversal of opioid overdoses may not resolve all the symptoms a patient is experiencing if other drugs are involved.","Naloxone is a competitive inhibitor of the µ-opioid receptor. Naloxone antagonizes the action of opioids, reversing their effects. If a patient has not taken opioids, naloxone does not have a significant effect on patients.","Mu-type opioid receptor antagonist; Delta-type opioid receptor antagonist; Kappa-type opioid receptor antagonist; Cyclic AMP-responsive element-binding protein 1 other/unknown; Estrogen receptor alpha antagonist&other/unknown; Toll-like receptor 4 inhibitor; Liver carboxylesterase 1 binder","Target associated"]
[438,"DB01188","approved; investigational","small molecule","Ciclopirox","6-cyclohexyl-1-hydroxy-4-methyl-2(1H)-pyridinone","C12H17NO2","CC1=CC(=O)N(O)C(=C1)C1CCCCC1","Ciclopirox olamine (used in preparations called Batrafen, Loprox, Mycoster, Penlac and Stieprox) is a synthetic antifungal agent for topical dermatologic treatment of superficial mycoses. In particular, the agent is especially effective in treating Tinea versicolor.","29342-05-0","207.2689","Used as a topical treatment in immunocompetent patients with mild to moderate onychomycosis of fingernails and toenails without lunula involvement, due to <i>Trichophyton rubrum</i>.","Ciclopirox is a broad-spectrum antifungal medication that also has antibacterial and anti-inflammatory properties. Its main mode of action is thought to be its high affinity for trivalent cations, which inhibit essential co-factors in enzymes. Ciclopirox exhibits either fungistatic or fungicidal activity in vitro against a broad spectrum of fungal organisms, such as dermatophytes, yeasts, dimorphic fungi, eumycetes, and actinomycetes. In addition to its broad spectrum of action, ciclopirox also exerts antibacterial activity against many Gram-positive and Gram-negative bacteria. Furthermore, the anti-inflammatory effects of ciclopirox have been demonstrated in human polymorphonuclear cells, where ciclopirox has inhibited the synthesis of prostaglandin and leukotriene. Ciclopirox can also exhibit its anti-inflammatory effects by inhibiting the formation of 5-lipoxygenase and cyclooxygenase.","Unlike antifungals such as itraconazole and terbinafine, which affect sterol synthesis, ciclopirox is thought to act through the chelation of polyvalent metal cations, such as Fe<sup>3+</sup> and Al<sup>3+</sup>. These cations inhibit many enzymes, including cytochromes, thus disrupting cellular activities such as mitochondrial electron transport processes and energy production. Ciclopirox also appears to modify the plasma membrane of fungi, resulting in the disorganization of internal structures. The anti-inflammatory action of ciclopirox is most likely due to inhibition of 5-lipoxygenase and cyclooxygenase.\r\nciclopirox may exert its effect by disrupting DNA repair, cell division signals and structures (mitotic spindles) as well as some elements of intracellular transport.","Sodium/potassium-transporting ATPase subunit alpha-1 binder","Therapeutic strategy associated"]
[439,"DB01191","approved; illicit; investigational; withdrawn","small molecule","Dexfenfluramine","(+)-fenfluramine; (S)-fenfluramine; (S)-N-ethyl-1-[3-(trifluoromethyl)phenyl]propan-2-amine; d-N-ethyl-α-methyl-m-trifluoromethylphenethylamine; Dexfenfluramine; Dextrofenfluramine","C12H16F3N","CCN[C@@H](C)CC1=CC=CC(=C1)C(F)(F)F","Dexfenfluramine, also marketed under the name Redux, is a serotoninergic anorectic drug. For a fairly limited time during the middle of the nineties, the US FDA had approved it for use in managing weight loss. However, following multiple concerns about the cardiovascular side-effects of the drug, such approval was withdrawn.","3239-44-9","231.2573","For the management of obesity including weight loss and maintenance of weight loss in patients on a reduced calorie diet","Used to treat diabetes and obesity, Dexfenfluramine decreases caloric intake by increasing serotonin levels in the brain&rsquo;s synapses. Dexfenfluramine acts as a serotonin reuptake inhibitor. It also causes release of serotonin from the synaptosomes.","Dexfenfluramine binds to the serotonin reuptake pump. This causes inhbition of serotonin reuptake. The increased levels of serotonin lead to greater serotonin receptor activation which in turn lead to enhancement of serotoninergic transmission in the centres of feeding behavior located in the hypothalamus. This suppresses the appetite for carbohydrates.","Sodium-dependent serotonin transporter inhibitor; 5-hydroxytryptamine receptor 2C agonist","Therapeutic strategy associated"]
[440,"DB01193","approved; investigational","small molecule","Acebutolol","(±)-acebutolol; 3'-acetyl-4'-(2-hydroxy-3-(isopropylamino)propoxy)butyranilide; 5'-butyramido-2'-(2-hydroxy-3-isopropylaminopropoxy)acetophenone; Acebutolol; N-(3-acetyl-4-[2-hydroxy-3-(isopropylamino)propoxy]phenyl)butanamide; N-[3-acetyl-4-[2-hydroxy-3-[(1-methylethyl)amino]propoxy]phenyl]butanamide","C18H28N2O4","CCCC(=O)NC1=CC=C(OCC(O)CNC(C)C)C(=C1)C(C)=O","A cardioselective beta-adrenergic antagonist with little effect on the bronchial receptors. The drug has stabilizing and quinidine-like effects on cardiac rhythm as well as weak inherent sympathomimetic action.","37517-30-9","336.4259","For the management of hypertension and ventricular premature beats in adults.","Acebutolol is a cardioselective, beta-adrenoreceptor blocking agent, which possesses mild intrinsic sympathomimetic activity (ISA) in its therapeutically effective dose range. In general, beta-blockers reduce the work the heart has to do and allow it to beat more regularly. Acebutolol has less antagonistic effects on peripheral vascular &szlig;2-receptors at rest and after epinephrine stimulation than nonselective beta-antagonists. Low doses of acebutolol produce less evidence of bronchoconstriction than nonselective agents like propranolol but more than atenolol.","Acebutolol is a selective &beta;1-receptor antagonist. Activation of &beta;1-receptors by epinephrine increases the heart rate and the blood pressure, and the heart consumes more oxygen. Acebutolol blocks these receptors, lowering the heart rate and blood pressure. This drug then has the reverse effect of epinephrine. In addition, beta blockers prevent the release of renin, which is a hormone produced by the kidneys which leads to constriction of blood vessels.","Beta-1 adrenergic receptor partial agonist; Beta-2 adrenergic receptor partial agonist","Indication associated"]
[441,"DB01194","approved","small molecule","Brinzolamide","Brinzolamide","C12H21N3O5S3","CCN[C@H]1CN(CCCOC)S(=O)(=O)C2=C1C=C(S2)S(N)(=O)=O","Brinzolamide is a highly specific, non-competitive, reversible carbonic anhydrase inhibitor. Carbonic anhydrase (CA) is an enzyme found in many tissues of the body including the eye. It catalyzes the reversible reaction involving the hydration of carbon dioxide and the dehydration of carbonic acid. In humans, carbonic anhydrase exists as a number of isoenzymes, the most active being carbonic anhydrase II (CA-II). Inhibition of carbonic anhydrase in the ciliary processes of the eye decreases aqueous humor secretion, presumably by slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport. The result is a reduction in intraocular pressure. Brinzolamide is indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma.","138890-62-7","383.507","For the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma.","Used in the treatment of glaucoma, brinzolamide inhibits aqueous humor formation and reduces elevated intraocular pressure. Elevated intraocular pressure is a major risk factor in the pathogenesis of optic nerve damage and glaucomatous visual field loss. Brinzolamide can decrease intraocular pressure by approximately 16-19% in patients with elevated intraocular pressure.","Brinzolamide is a highly specific inhibitor of CA-II, which is the main CA isoenzyme involved in the secretion of aqueous humor. Inhibition of CA in the ciliary process of the eye slows the formation of bicarbonate, and reduces sodium and fluid transport. This results in a reduction in the rate of aqueous humor secretion and the intraocular pressure. Brinzolamide is absorbed systemically following topical ocular administration. Since it has a high affinity for CA-II, brinzolamide binds extensively to red blood cells, where CA-II is primarily found. As sufficient CA-II activity remains, adverse effects resulting from the systemic inhibition of CA by brinzolamide are not observed. The metabolite N-desethyl brinzolamide is also formed. This metabolite binds to CA and accumulates in red blood cells as well. In the presence of brinzolamide, the metabolite binds mainly to carbonic anhydrase I (CA-I).","Carbonic anhydrase 2 inhibitor; Carbonic anhydrase 1 inhibitor; Carbonic anhydrase 4 inhibitor; Carbonic anhydrase 5A, mitochondrial inhibitor; Carbonic anhydrase 3 inhibitor","Indication associated"]
[442,"DB01195","approved; withdrawn","small molecule","Flecainide","(±)-flecainide; Flecaine; Flecainide; N-(2-Piperidinylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide","C17H20F6N2O3","FC(F)(F)COC1=CC(C(=O)NCC2CCCCN2)=C(OCC(F)(F)F)C=C1","Flecainide is a Class I anti-arrhythmic agent like  and . Flecainide’s development began in 1966 and was first synthesized in 1972 as an attempt to generate new anesthetics. It is used to prevent supraventricular and ventricular arrhythmias, as well as paroxysmal atrial fibrillation and flutter.\r\n\r\nFlecainide was granted FDA approval on 31 October 1985.","54143-55-4","414.3427","In New Zealand and America, flecainide is indicated to prevent supraventricular arrhythmias and ventricular arrhythmias. In the United States, it is also indicated to prevent paroxysmal atrial fibrillation and flutter.","Flecainide inhibits the action of sodium and potassium ion channels in the heart, raising the threshold for depolarization and correcting arrhythmias. Flecainide has a long duration of action, allowing for once daily dosing. The therapeutic index is narrow. Patients should not take this medication if there is already structural heart disease or left ventricular systolic dysfunction.","Flecainide blocks fast inward sodium channels and slowly unbinds during diastole, prolonging the refractory period of the heart. This blockade also shortens the duration of action potentials through the Purkinjie fibers. Flecainide also prevents delayed rectifier potassium channels from opening, lengthening the action potential through ventricular and atrial muscle fibers. Finally, flecainide also blocks ryanodine receptor opening, reducing calcium release from sarcoplasmic reticulum, which reduces depolarization of cells.","Sodium channel protein type 5 subunit alpha inhibitor; Sodium channel protein type 4 subunit alpha inhibitor; Potassium voltage-gated channel subfamily H member 2 inhibitor; Ryanodine receptor 2 inhibitor","Indication associated"]
[443,"DB01196","approved; investigational","small molecule","Estramustine","17β-Estradiol 3-(bis(2-chloroethyl)carbamate); Estradiol 3-(N,N-bis(2-chloroethyl)carbamate)","C23H31Cl2NO3","[H][C@@]12CC[C@H](O)[C@@]1(C)CC[C@]1([H])C3=CC=C(OC(=O)N(CCCl)CCCl)C=C3CC[C@@]21[H]","A nitrogen mustard linked to estradiol, usually as phosphate; used to treat prostatic neoplasms; also has radiation protective properties.","2998-57-4","440.403","For the palliative treatment of patients with metastatic and/or progressive carcinoma of the prostate","Estramustine is an antineoplastic agent indicated in the palliative treatment of patients with metastatic and/or progressive carcinoma of the prostate. Estramustine is a combination of estradiol with nitrogen mustard. In vivo, the nitrogen-mustard moiety becomes active and participates in alkylation of DNA or other cellular components.. This causes DNA damage in rapidly dividing cancerous cells leading to cell death and ideally, tumor shrinkage.","Estramustine is a derivative of estradiol with a nitrogen mustard moiety. This gives it alkylating properties. In vivo, the nitrogen mustard component is active and can alklyate DNA and other cellular components (such as tubulin components) of rapidly dividing cells. This causes DNA strandbreaks or misscoding events. This leads to apoptosis and cell death. Also, due to the drugs estrogen component, it can bind more selectively to active estrogen receptors.","Microtubule-associated protein 2 antagonist; Microtubule-associated protein 1A antagonist; Estrogen receptor alpha agonist; Estrogen receptor beta other/unknown","Therapeutic strategy associated"]
[444,"DB01197","approved","small molecule","Captopril","(2S)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]pyrrolidine-2-carboxylic acid; Captopril; Captopryl; CP; D-2-methyl-3-mercaptopropanoyl-L-proline; D-3-mercapto-2-methylpropanoyl-L-proline; L-Captopril","C9H15NO3S","C[C@H](CS)C(=O)N1CCC[C@H]1C(O)=O","Captopril is a potent, competitive inhibitor of angiotensin-converting enzyme (ACE), the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). Captopril may be used in the treatment of hypertension.","62571-86-2","217.285","For the treatment of essential or renovascular hypertension (usually administered with other drugs, particularly thiazide diuretics). May be used to treat congestive heart failure in combination with other drugs (e.g. cardiac glycosides, diuretics, &beta;-adrenergic blockers). May improve survival in patients with left ventricular dysfunction following myocardial infarction. May be used to treat nephropathy, including diabetic nephropathy.","Captopril, an ACE inhibitor, antagonizes the effect of the RAAS. The RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from the granular cells of the juxtaglomerular apparatus in the kidneys. In the blood stream, renin cleaves circulating angiotensinogen to ATI, which is subsequently cleaved to ATII by ACE. ATII increases blood pressure using a number of mechanisms. First, it stimulates the secretion of aldosterone from the adrenal cortex. Aldosterone travels to the distal convoluted tubule (DCT) and collecting tubule of nephrons where it increases sodium and water reabsorption by increasing the number of sodium channels and sodium-potassium ATPases on cell membranes. Second, ATII stimulates the secretion of vasopressin (also known as antidiuretic hormone or ADH) from the posterior pituitary gland. ADH stimulates further water reabsorption from the kidneys via insertion of aquaporin-2 channels on the apical surface of cells of the DCT and collecting tubules. Third, ATII increases blood pressure through direct arterial vasoconstriction. Stimulation of the Type 1 ATII receptor on vascular smooth muscle cells leads to a cascade of events resulting in myocyte contraction and vasoconstriction. In addition to these major effects, ATII induces the thirst response via stimulation of hypothalamic neurons. ACE inhibitors inhibit the rapid conversion of ATI to ATII and antagonize RAAS-induced increases in blood pressure. ACE (also known as kininase II) is also involved in the enzymatic deactivation of bradykinin, a vasodilator. Inhibiting the deactivation of bradykinin increases bradykinin levels and may sustain its effects by causing increased vasodilation and decreased blood pressure.","There are two isoforms of ACE: the somatic isoform, which exists as a glycoprotein comprised of a single polypeptide chain of 1277; and the testicular isoform, which has a lower molecular mass and is thought to play a role in sperm maturation and binding of sperm to the oviduct epithelium. Somatic ACE has two functionally active domains, N and C, which arise from tandem gene duplication. Although the two domains have high sequence similarity, they play distinct physiological roles. The C-domain is predominantly involved in blood pressure regulation while the N-domain plays a role in hematopoietic stem cell differentiation and proliferation. ACE inhibitors bind to and inhibit the activity of both domains, but have much greater affinity for and inhibitory activity against the C-domain. Captopril, one of the few ACE inhibitors that is not a prodrug, competes with ATI for binding to ACE and inhibits and enzymatic proteolysis of ATI to ATII. Decreasing ATII levels in the body decreases blood pressure by inhibiting the pressor effects of ATII as described in the Pharmacology section above. Captopril also causes an increase in plasma renin activity likely due to a loss of feedback inhibition mediated by ATII on the release of renin and/or stimulation of reflex mechanisms via baroreceptors. Captopril’s affinity for ACE is approximately 30,000 times greater than that of ATI.","Angiotensin-converting enzyme inhibitor; 72 kDa type IV collagenase inhibitor; Matrix metalloproteinase-9 inhibitor; Leukotriene A-4 hydrolase inhibitor; B1 bradykinin receptor","Indication associated"]
[445,"DB01200","approved; investigational","small molecule","Bromocriptine","2-Bromo-alpha-ergocryptine; 2-Bromo-alpha-ergokryptin; 2-Bromo-alpha-ergokryptine; 2-bromo-α-ergocryptine; 2-bromo-α-ergokryptin; 2-bromo-α-ergokryptine; Bromocriptine; Bromocryptine; Bromoergocriptine; Bromoergocryptine","C32H40BrN5O5","[H][C@@]12CCCN1C(=O)[C@H](CC(C)C)N1C(=O)[C@](NC(=O)[C@H]3CN(C)[C@]4([H])CC5=C(Br)NC6=CC=CC(=C56)C4=C3)(O[C@@]21O)C(C)C","Bromocriptine mesylate is a semisynthetic ergot alkaloid derivative with potent dopaminergic activity. It is indicated for the management of signs and symptoms of Parkinsonian Syndrome. Bromocriptine also inhibits prolactin secretion and may be used to treat dysfunctions associated with hyperprolactinemia. It also causes sustained suppression of somatotropin (growth hormone) secretion in some patients with acromegaly. Bromocriptine has been associated with pulmonary fibrosis.","25614-03-3","654.595","For the treatment of galactorrhea due to hyperprolactinemia, prolactin-dependent menstrual disorders and infertility, prolactin-secreting adenomas, prolactin-dependent male hypogonadism, as adjunct therapy to surgery or radiotherapy for acromegaly or as monotherapy is special cases, as monotherapy in early Parksinsonian Syndrome or as an adjunct with levodopa in advanced cases with motor complications. Bromocriptine has also been used off-label to treat restless legs syndrome and neuroleptic malignant syndrome.","Bromocriptine stimulates centrally-located dopaminergic receptors resulting in a number of pharmacologic effects. Five dopamine receptor types from two dopaminergic subfamilies have been identified. The dopaminergic D1 receptor subfamily consists of D<sub>1</sub> and D<sub>5</sub> subreceptors, which are associated with dyskinesias. The dopaminergic D2 receptor subfamily consists of D<sub>2</sub>, D<sub>3</sub> and D<sub>4</sub> subreceptors, which are associated with improvement of symptoms of movement disorders. Thus, agonist activity specific for D2 subfamily receptors, primarily D<sub>2</sub> and D<sub>3</sub> receptor subtypes, are the primary targets of dopaminergic antiparkinsonian agents. It is thought that postsynaptic D<sub>2</sub> stimulation is primarily responsible for the antiparkinsonian effect of dopamine agonists, while presynaptic D<sub>2</sub> stimulation confers neuroprotective effects. This semisynthetic ergot derivative exhibits potent agonist activity on dopamine D<sub>2</sub>-receptors. It also exhibits agonist activity (in order of decreasing binding affinity) on 5-hydroxytryptamine (5-HT)<sub>1D</sub>, dopamine D<sub>3</sub>, 5-HT<sub>1A</sub>, 5-HT<sub>2A</sub>, 5-HT<sub>1B</sub>, and 5-HT<sub>2C</sub> receptors, antagonist activity on &alpha;<sub>2A</sub>-adrenergic, &alpha;<sub>2C</sub>, &alpha;<sub>2B</sub>, and dopamine D<sub>1</sub> receptors, partial agonist activity at receptor 5-HT<sub>2B</sub>, and inactivates dopamine D<sub>4</sub> and 5-HT<sub>7</sub> receptors. Parkinsonian Syndrome manifests when approximately 80% of dopaminergic activity in the nigrostriatal pathway of the brain is lost. As this striatum is involved in modulating the intensity of coordinated muscle activity (e.g. movement, balance, walking), loss of activity may result in dystonia (acute muscle contraction), Parkinsonism (including symptoms of bradykinesia, tremor, rigidity, and flattened affect), akathesia (inner restlessness), tardive dyskinesia (involuntary muscle movements usually associated with long-term loss of dopaminergic activity), and neuroleptic malignant syndrome, which manifests when complete blockage of nigrostriatal dopamine occurs. High dopaminergic activity in the mesolimbic pathway of the brain causes hallucinations and delusions; these side effects of dopamine agonists are manifestations seen in patients with schizophrenia who have overractivity in this area of the brain. The hallucinogenic side effects of dopamine agonists may also be due to 5-HT<sub>2A</sub> agonism. The tuberoinfundibular pathway of the brain originates in the hypothalamus and terminates in the pituitary gland. In this pathway, dopamine inhibits lactotrophs in anterior pituitary from secreting prolactin. Increased dopaminergic activity in the tuberoinfundibular pathway inhibits prolactin secretion making bromocriptine an effective agent for treating disorders associated with hypersecretion of prolactin. Pulmonary fibrosis may be associated bromocriptine’s agonist activity at 5-HT<sub>1B</sub> and 5-HT<sub>2B</sub> receptors.","The dopamine D<sub>2</sub> receptor is a 7-transmembrane G-protein coupled receptor associated with G<sub>i</sub> proteins. In lactotrophs, stimulation of dopamine D<sub>2</sub> receptor causes inhibition of adenylyl cyclase, which decreases intracellular cAMP concentrations and blocks IP3-dependent release of Ca<sup>2+</sup> from intracellular stores. Decreases in intracellular calcium levels may also be brought about via inhibition of calcium influx through voltage-gated calcium channels, rather than via inhibition of adenylyl cyclase. Additionally, receptor activation blocks phosphorylation of p42/p44 MAPK and decreases MAPK/ERK kinase phosphorylation. Inhibition of MAPK appears to be mediated by c-Raf and B-Raf-dependent inhibition of MAPK/ERK kinase. Dopamine-stimulated growth hormone release from the pituitary gland is mediated by a decrease in intracellular calcium influx through voltage-gated calcium channels rather than via adenylyl cyclase inhibition. Stimulation of dopamine D<sub>2</sub> receptors in the nigrostriatal pathway leads to improvements in coordinated muscle activity in those with movement disorders.","Dopamine D2 receptor agonist; Dopamine D3 receptor agonist; 5-hydroxytryptamine receptor 1D agonist; Alpha-2A adrenergic receptor agonist; 5-hydroxytryptamine receptor 1A agonist; Alpha-2C adrenergic receptor agonist; Alpha-2B adrenergic receptor agonist; 5-hydroxytryptamine receptor 2B agonist; Dopamine D4 receptor antagonist; 5-hydroxytryptamine receptor 2A agonist; 5-hydroxytryptamine receptor 1B agonist; 5-hydroxytryptamine receptor 2C agonist; Dopamine D5 receptor agonist; Dopamine D1 receptor agonist; Alpha-1A adrenergic receptor antagonist&agonist; Alpha-1B adrenergic receptor antagonist&agonist; Alpha-1D adrenergic receptor agonist; 5-hydroxytryptamine receptor 7 antagonist","Therapeutic strategy associated"]
[446,"DB01203","approved","small molecule","Nadolol","Nadolol","C17H27NO4","CC(C)(C)NCC(O)COC1=CC=CC2=C1C[C@H](O)[C@H](O)C2","Nadolol is a nonselective beta adrenal receptor blocker that is used to lower blood pressure. Nonselective beta adrenal receptor blockers may no longer be first line in the treatment of hypertension as newer generations of beta adrenal receptor blockers have higher selectivity and offer better rates of adverse effects.\r\n\r\nNadolol was granted FDA approval on 10 December 1979.","42200-33-9","309.4006","Nadolol is indicated to treat angina pectoris and hypertension. Another product formulated with  is indicated to treat hypertension.","Nadolol is a nonselective beta adrenal receptor blocker that is used to lower blood pressure. It has a long duration of action as it is usually taken once daily and a wide therapeutic index as patients start at doses of 40mg daily but may be increased to doses as high as 240mg daily. Patients taking nadolol should not aburptly stop taking it as this may lead to exacerbation of ischemic heart disease.","Although nadolol is described as a non selective beta blocker, it does not interact with beta 3 adrenal receptors. Antagonism of beta-1 and beta-2 adrenoceptors in the heart inhibits cyclic AMP and its signalling pathway, decreasing the strength and speed of contractions as well as the speed of relaxation and conduction. Antagonism of beta-2 adrenoceptors in the smooth muscle cells of the vasculature inhibits their relaxation, leading to an increase in peripheral vascular resistance and reducing the risk of severe hypotension. The increase in peripheral vascular resistance may contribute to the decrease in insulin sensitivity associated with nadolol use. Antagonism of beta-1 adrenoceptors in the juxtaglomerular apparatus of the kidney inhibits the release of renin, and therefore angiotensin II mediated vasoconstriction, aldosterone mediated water retention, and the release of epinephrine. Antagonism of beta-2 adrenoceptors in the liver and skeletal muscle inhibits glycogenolysis, in the lungs prevents bronchodilation, and in the pancrease inhibits insulin release.","Beta-1 adrenergic receptor antagonist; Beta-2 adrenergic receptor antagonist","Indication associated"]
[447,"DB01207","experimental","small molecule","Ridogrel","Ridogrel","C18H17F3N2O3","OC(=O)CCCCO\\N=C(\\C1=CN=CC=C1)C1=CC(=CC=C1)C(F)(F)F","Ridogrel is a dual action drug useful for the prevention of systemic thrombo-embolism and as an adjunctive agent to thrombolytic therapy in acute myocardial infarction. However, there currently are no clinical indications for preferential use of ridogrel over aspirin.","110140-89-1","366.3344","Used as an adjunctive therapy to induce thrombolysis in patients suffering acute myocardial infarction.","Ridogrel, a combined thromboxane synthase inhibitor and receptor antagonist, is used with streptokinase as an adjunctive therapy to reduce the formation and size of blood clots. Blood clots can cause ischemic cardiac events (heart attacks). Ridogrel has the dual property of inhibiting the synthesis of thromboxane and blocking the receptors of thromboxane/prostaglandin/endoperoxides. It has been shown to accelerate the speed of recanalization and to delay or prevent reocclusion during systemic thrombolysis with tissue plasminogen activator (streptokinase). Ridogrel is a more potent antiplatelet agent than aspirin and might offer an advantage over aspirin as an adjunct to thrombolysis in patients suffering from acute myocardial infarction. While aspirin inhibits cyclooxygenase, the enzyme responsible for producing thromboxane, ridogrel inhibits thromboxane synthesis directly. A recent comparison between aspirin and ridogrel in as adjunct to thrombolysis in patients with acute myocardial infarction demonstrated that ridogrel is not superior to aspirin in enhancing the fibrinolytic efficacy of streptokinase but might be more effective in preventing new ischemic events. Clinical experience with this drug is still relatively limited.","Ridogrel inhibits thromboxane A2 synthase and also blocks the thromboxane A2/prostaglandin endoperoxide receptors.\r\nThromboxane synthetase produces thromboxane in platelets. Thromboxane is a vasoconstrictor and facilitates the clumping of platelets. Therefore by inhibiting the production and promotion of thromboxane, thrombolysis is enhanced.","Thromboxane A2 receptor antagonist; Thromboxane-A synthase inhibitor","Indication associated"]
[448,"DB01208","approved; investigational; withdrawn","small molecule","Sparfloxacin","cis-5-Amino-1-cyclopropyl-7-(3,5-dimethyl-1-piperazinyl)-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid; Sparfloxacin","C19H22F2N4O3","C[C@H]1CN(C[C@@H](C)N1)C1=C(F)C(N)=C2C(=O)C(=CN(C3CC3)C2=C1F)C(O)=O","Sparfloxacin is a fluoroquinolone antibiotic indicated for bacterial infections. Sparfloxacin exerts its antibacterial activity by inhibiting DNA gyrase, a bacterial topoisomerase. DNA gyrase is an essential enzyme which controls DNA topology and assists in DNA replication, repair, deactivation, and transcription.","110871-86-8","392.3998","For the treatment of adults with the following infections caused by susceptible strains microorganisms: community-acquired pneumonia (caused by <i>Chlamydia pneumoniae</i>, <i>Haemophilus influenzae</i>, <i>Haemophilus parainfluenzae</i>, <i>Moraxella catarrhalis</i>, <i>Mycoplasma pneumoniae</i>, or <i>Streptococcus pneumoniae</i>) and acute bacterial exacerbations of chronic bronchitis (caused by <i>Chlamydia pneumoniae</i>, <i>Enterobacter cloacae</i>, <i>Haemophilus influenzae</i>, <i>Haemophilus parainfluenzae</i>, <i>Klebsiella pneumoniae</i>, <i>Moraxella catarrhalis</i>, <i>Staphylococcus aureus</i>, or <i>Streptococcus pneumoniae</i>).","Sparfloxacin is a synthetic fluoroquinolone broad-spectrum antimicrobial agent in the same class as ofloxacin and norfloxacin. Sparfloxacin has in vitro activity against a wide range of gram-negative and gram-positive microorganisms. Sparfloxacin exerts its antibacterial activity by inhibiting DNA gyrase, a bacterial topoisomerase. DNA gyrase is an essential enzyme which controls DNA topology and assists in DNA replication, repair, deactivation, and transcription. Quinolones differ in chemical structure and mode of action from (beta)-lactam antibiotics. Quinolones may, therefore, be active against bacteria resistant to (beta)-lactam antibiotics. Although cross-resistance has been observed between sparfloxacin and other fluoroquinolones, some microorganisms resistant to other fluoroquinolones may be susceptible to sparfloxacin. In vitro tests show that the combination of sparfloxacin and rifampin is antagonistic against Staphylococcus aureus.","The bactericidal action of sparfloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, and recombination.","DNA topoisomerase 4 subunit A inhibitor; DNA gyrase subunit A inhibitor; DNA topoisomerase 2-alpha inhibitor","Indication associated"]
[449,"DB01210","approved","small molecule","Levobunolol","(-)-Bunolol; (S)-5-(3-((1,1-dimethylethyl)amino)-2-hydroxypropoxy)-3,4-dihydro-1(2H)-naphthalenone; Levobunolol","C17H25NO3","CC(C)(C)NC[C@H](O)COC1=CC=CC2=C1CCCC2=O","A nonselective beta-adrenoceptor antagonist used in the treatment of glaucoma.","47141-42-4","291.3853","For lowering intraocular pressure (IOP) and may be used in patients with chronic open-angle glaucoma or ocular hypertension.","Levobunolol is an ophthalmic beta-blocker, equally effective at &beta;(1)- and &beta;(2)-receptor sites. Levobunolol reduces both elevated and normal IOP in patients with or without glaucoma. In patients with elevated IOP, levobunolol reduces mean IOP by approximately 25-40% from baseline. As the drug is a nonselective &beta-adrenergic blocking agent, it can produce both systemic pulmonary and cardiovascular effects following topical application to the eye. These effects include adverse pulmonary effects (eg. bronchoconstriction, increased airway resistance), and a decrease in blood pressure and heart rate.","Levobunolol's mechanism of action in reducing IOP is not clearly defined, but is believed to be due to a reduction of the production of aqueous humor via blockage of endogenous catecholamine-stimulated increases in cyclic adenosine monophosphate (AMP) concentrations within the ciliary processes.","Beta-2 adrenergic receptor antagonist; Beta-1 adrenergic receptor antagonist","Indication associated"]
[450,"DB01212","approved","small molecule","Ceftriaxone","Ceftriaxone; Rocephin","C18H18N8O7S3","[H][C@]12SCC(CSC3=NC(=O)C(=O)NN3C)=C(N1C(=O)[C@H]2NC(=O)C(=N/OC)\\C1=CSC(N)=N1)C(O)=O","Ceftriaxone is a broad-spectrum third-generation cephalosporin antibiotic. It has a very long half-life compared to other cephalosporins and is high penetrable into the meninges, eyes, and inner ear. Ceftriaxone has broader and stronger gram-negative coverage then first or second-generation cephalosporins, but worse activity against methicillin-susceptible S.aureus. Ceftriaxone is a commonly used antimicrobial due to its good activity against multi-drug resistant Enterobacteriaceae, its relatively safe adverse effect profile, and its long half-life which allows for the convenience of daily or twice-daily dosing.","73384-59-5","554.58","Ceftriaxone is used for the treatment of the infections (respiratory, skin, soft tissue, UTI, ENT) caused by susceptible organisms. Organisms that are generally susceptible to ceftriaxone include S. pneumoniae, S. pyogenes (group A beta-hemolytic streptococci), coagulase-negative staphylococci, Some Enterobacter spp, H. influenzae, N. gonorrhoeae, P. mirabilis, E. coli, Klebsiella spp, M. catarrhalis, B. burgdorferi, and some oral anaerobes.","Ceftriaxone is a cephalosporin/cephamycin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. Ceftriaxone has <i>in vitro</i> activity against gram-positive aerobic, gram-negative aerobic, and anaerobic bacteria. The bactericidal activity of ceftriaxone results from the inhibition of cell wall synthesis and is mediated through ceftriaxone binding to penicillin-binding proteins (PBPs). Ceftriaxone is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended-spectrum beta-lactamases. However, resistance to ceftriaxone usually occurs through beta-lactamase hydrolysis, altered PBPs, or reduced bacterial cell permeability. Ceftriaxone should not be mixed with or giving in the same IV line as diluents/products containing calcium as they may cause ceftriaxone to precipitate. Ceftriaxone use may also cause biliary sludge or gallbladder pseudolithiasis.","Ceftriaxone works by inhibiting the mucopeptide synthesis in the bacterial cell wall. The beta-lactam moiety of ceftriaxone binds to carboxypeptidases, endopeptidases, and transpeptidases in the bacterial cytoplasmic membrane. These enzymes are involved in cell-wall synthesis and cell division. Binding of ceftriaxone to these enzymes causes the enzyme to lose activity; therefore, the bacteria produce defective cell walls, causing cell death.","Penicillin-binding protein 2B inhibitor; Solute carrier family 22 member 11; Solute carrier family 22 member 6; Solute carrier family 22 member 8; Solute carrier family 15 member 1","Indication associated"]
[451,"DB01214","approved","small molecule","Metipranolol","(±)-metipranolol; Acetic acid 4-(2-hydroxy-3-isopropylamino-propoxy)-2,3,6-trimethyl-phenyl ester; Metipranolol","C17H27NO4","CC(C)NCC(O)COC1=C(C)C(C)=C(OC(C)=O)C(C)=C1","A beta-adrenergic antagonist effective for both beta-1 and beta-2 receptors. It is used as an antiarrhythmic, antihypertensive, and antiglaucoma agent.","22664-55-7","309.4006","Indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open angle glaucoma.","Metipranolol is a beta1 and beta2 (non-selective) adrenergic receptor-blocking agent that does not have significant intrinsic sympathomimetic, direct myocardial depressant, or local anesthetic (membrane-stabilizing) activity. Metipranolol is indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma. Metipranolol, when applied topically to the eye, has the action of reducing elevated, as well as normal, intraocular pressure, whether or not accompanied by glaucoma. Elevated intraocular pressure is a major risk factor in the pathogenesis of glaucomatous visual field loss and optic nerve damage. Metipranolol reduces intraocular pressure with little or no effect on pupil size or accommodation in contrast to the miosis which cholinergic agents are known to produce.","Although it is known that metipranolol binds the beta1 and beta2 adrenergic receptors, the mechanism of metipranolol's action is not known. It has no significant intrinsic sympathomimetic activity, and has only weak local anesthetic (membrane-stabilizing) and myocardial depressant activity. It appears that the ophthalmic beta-adrenergic blocking agents reduce aqueous humor production, as demonstrated by tonography and fluorophotometry. A slight increase in aqueous humor outflow may be an additional mechanism.","Beta-2 adrenergic receptor antagonist; Beta-1 adrenergic receptor antagonist","Indication associated"]
[452,"DB01221","approved; vet_approved","small molecule","Ketamine","(+-)-Ketamine; (±)-ketamine; 2-(2-Chloro-phenyl)-2-methylamino-cyclohexanone; 2-(methylamino)-2-(2-chlorophenyl)cyclohexanone; 2-(o-chlorophenyl)-2-(methylamino)-cyclohexanone; DL-ketamine; Ketamine; NMDA; Special K","C13H16ClNO","CNC1(CCCCC1=O)C1=CC=CC=C1Cl","Ketamine is an NMDA receptor antagonist with a potent anesthetic effect. It was developed in 1963 as a replacement for phencyclidine (PCP) by Calvin Stevens at Parke Davis Laboratories. It started being used for veterinary purposes in Belgium and in 1964 was proven that compared to PCP, it produced minor hallucinogenic effects and shorter psychotomimetic effects. It was FDA approved in 1970, and from there, it has been used as an anesthetic for children or patients undergoing minor surgeries but mainly for veterinary purposes.","6740-88-1","237.725","Ketamine is indicated as an anesthetic agent for recommended diagnostic and surgical procedures. If skeletal muscle relaxation is needed, it should be combined with a muscle relaxant. If the surgical procedure involves visceral pain, it should be supplemented with an agent that obtunds visceral pain. Ketamine can be used for induction of anesthesia prior other general anesthetic agents and as a supplement of low potency agents.\r\n\r\nReports have indicated a potential use of ketamine as a therapeutic tool for the management of depression when administered in lower doses. These reports have increased the interest for ketamine in this area and several clinical trials are launched for this indication.","Ketamine is a rapid-acting general anesthetic producing an anesthetic state characterized by profound analgesia, normal pharyngeal-laryngeal reflexes, normal or slightly enhanced skeletal muscle tone, cardiovascular and respiratory stimulation, and occasionally a transient and minimal respiratory depression. The anesthetic state produced by Ketamine has been termed as \"dissociative anesthesia\" in that it appears to selectively interrupt association pathways of the brain before producing somesthetic sensory blockade. It may selectively depress the thalamoneocortical system before significantly obtunding the more ancient cerebral centers and pathways (reticular-activating and limbic systems).\r\n\r\nKetamine enhances descending inhibiting serotoninergic pathways and can exert antidepressive effects. These effects are seen in concentrations ten times lower than the needed concentration for anesthetic proposes. The effect of ketamine can be described as analgesic by the prevention of central sensitization in dorsal horn neurons as well as by the inhibition on the synthesis of nitric oxide. Ketamine can present cardiovascular changes and bronchodilatation.","Ketamine interacts with N-methyl-D-aspartate (NMDA) receptors, opioid receptors, monoaminergic receptors, muscarinic receptors and voltage sensitive Ca ion channels. Unlike other general anaesthetic agents, ketamine does not interact with GABA receptors.","Glutamate receptor ionotropic, NMDA 3A antagonist; Neurokinin 1 receptor antagonist; Dopamine D2 receptor agonist&partial agonist; Delta-type opioid receptor binder; Sodium-dependent noradrenaline transporter inhibitor; Kappa-type opioid receptor agonist; Mu-type opioid receptor binder; Muscarinic acetylcholine receptor binder; 5-hydroxytryptamine receptor 2 antagonist; 5-hydroxytryptamine receptor 1 antagonist; 5-hydroxytryptamine receptor 3A potentiator; Alpha-7 nicotinic cholinergic receptor subunit antagonist; Cholinesterase inhibitor; Nitric oxide synthase, brain inhibitor","Indication associated"]
[453,"DB01222","approved","small molecule","Budesonide","(11β,16α)-16,17-(Butylidenebis(oxy))-11,21-dihydroxypregna-1,4-diene-3,20-dione; Budesonide","C25H34O6","[H][C@@]12C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)C=C[C@]12C","Budesonide is a glucocorticoid that is a mix of the 22R and 22S epimer used to treat inflammatory conditions of the lungs and intestines such as asthma, COPD, Crohn's disease, and ulcerative colitis.\r\n\r\nBudesonide was granted FDA approval on 14 February 1994.","51333-22-3","430.5339","Budesonide extended release capsules are indicated for the treatment and maintenance of mild to moderate Crohn’s disease. Various inhaled budesonide products are indicated for prophylactic therapy in asthma and reducing exacerbations of COPD. A budesonide nasal spray is available over the counter for symptoms of hay fever and upper respiratory allergies. Extended-release capsules are indicated to induce remission of mild to moderate ulcerative colitis and a rectal foam is used for mild to moderate distal ulcerative colitis. In addition, a delayed-release capsule formulation of budesonide is indicated to reduce proteinuria in adults with IgA nephropathy at risk of rapid disease progression.","Budesonide is a glucocorticoid used to treat respiratory and digestive conditions by reducing inflammation. It has a wide therapeutic index, as dosing varies highly from patient to patient. Patients should be counselled regarding the risk of hypercorticism and adrenal axis suppression.","The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.\r\n\r\nGlucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10.\r\n\r\nLower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.","Glucocorticoid receptor agonist; Annexin A1 substrate","Therapeutic strategy associated"]
[454,"DB01223","approved","small molecule","Aminophylline","Aminophyllin; Aminophylline; Theophyline ethylenediamine; Theophylline ethylenediamine","C16H24N10O4","NCCN.CN1C2=C(NC=N2)C(=O)N(C)C1=O.CN1C2=C(NC=N2)C(=O)N(C)C1=O","Aminophylline is a drug combination that contains theophylline and ethylenediamine in a 2:1 ratio. Once in the body, theophylline is released and acts as a phosphodiesterase inhibitor, adenosine receptor blocker, and histone deacetylase activator. Similar to other theophyllines, aminophylline is indicated for the treatment of lung diseases such as asthma, chronic bronchitis, and COPD. The majority of aminophylline medications are discontinued and the remaining medications on the market are in short supply.","317-34-0","420.4264","For the treatment of bronchospasm due to asthma, emphysema and chronic bronchitis.","Aminophylline is the ethylenediamine salt of theophylline. Theophylline stimulates the CNS, skeletal muscles, and cardiac muscle. It relaxes certain smooth muscles in the bronchi, produces diuresis, and causes an increase in gastric secretion.","Aminophylline is the ethylenediamine salt of theophylline. After ingestion, theophylline is released from aminophylline, and theophylline relaxes the smooth muscle of the bronchial airways and pulmonary blood vessels and reduces airway responsiveness to histamine, methacholine, adenosine, and allergen. Theophylline competitively inhibits type III and type IV phosphodiesterase (PDE), the enzyme responsible for breaking down cyclic AMP in smooth muscle cells, possibly resulting in bronchodilation. Theophylline also binds to the adenosine A2B receptor and blocks adenosine mediated bronchoconstriction. In inflammatory states, theophylline activates histone deacetylase to prevent transcription of inflammatory genes that require the acetylation of histones for transcription to begin.","cGMP-inhibited 3',5'-cyclic phosphodiesterase A inhibitor; Adenosine receptor A1 antagonist; Adenosine receptor A3 antagonist; Histone deacetylase 2 activator","Therapeutic strategy associated"]
[455,"DB01224","approved","small molecule","Quetiapine","2-[2-(4-Dibenzo[b,f][1,4]thiazepin-11-yl-1-piperazinyl)ethoxy]ethanol; Quetiapine","C21H25N3O2S","OCCOCCN1CCN(CC1)C1=NC2=CC=CC=C2SC2=CC=CC=C12","Initially approved by the FDA in 1997, quetiapine is a second-generation atypical antipsychotic used in schizophrenia, major depression, and bipolar disorder. Quetiapine demonstrates a high level of therapeutic efficacy and low risk of adverse effects during long-term treatment. It is well-tolerated and a suitable option for some patients with high sensitivity to other drugs, such as  and .","111974-69-7","383.507","Quetiapine is used in the symptomatic treatment of schizophrenia.  In addition, it may be used for the management of acute manic or mixed episodes in patients with bipolar I disorder, as a monotherapy or combined with other drugs. It may be used to manage depressive episodes in bipolar disorder. In addition to the above indications, quetiapine is used in combination with antidepressant drugs for the treatment of major depression.\r\n\r\nSome off-label uses for this drug include the management of post-traumatic stress disorder (PTSD), generalized anxiety disorder, and psychosis associated with Parkinson's disease.\r","Quetiapine improves the positive and negative symptoms of schizophrenia and major depression by acting on various neurotransmitter receptors, such as the serotonin and dopamine receptors. In bipolar disorder, it improves both depressive and manic symptoms.\r\n\r\n**A note on suicidality in young patients and administration in the elderly**\r\n\r\nQuetiapine can cause suicidal thinking or behavior in children and adolescents and should not be given to children under 10 years of age. It is important to monitor for suicidality if this drug is given to younger patients. In addition, this drug is not indicated for the treatment of psychosis related to dementia due to an increased death rate in elderly patients taking this drug.","Although the mechanism of action of quetiapine is not fully understood, several proposed mechanisms exist. In schizophrenia, its actions could occur from the antagonism of dopamine type 2 (D2) and serotonin 2A (5HT2A) receptors. In bipolar depression and major depression, quetiapine's actions may be attributed to the binding of this drug or its metabolite to the norepinephrine transporter. Additional effects of quetiapine, including somnolence, orthostatic hypotension, and anticholinergic effects, may result from the antagonism of H1 receptors, adrenergic α1 receptors, and muscarinic M1 receptors, respectively.","5-hydroxytryptamine receptor 2A antagonist; Dopamine D2 receptor antagonist; 5-hydroxytryptamine receptor 1A antagonist&partial agonist; 5-hydroxytryptamine receptor 1B ligand; 5-hydroxytryptamine receptor 1D ligand; 5-hydroxytryptamine receptor 1E ligand; 5-hydroxytryptamine receptor 2C ligand; 5-hydroxytryptamine receptor 3A ligand; 5-hydroxytryptamine receptor 6 antagonist; 5-hydroxytryptamine receptor 7 ligand; Dopamine D1 receptor antagonist; Dopamine D5 receptor ligand; Dopamine D3 receptor ligand; Dopamine D4 receptor ligand; Histamine H1 receptor antagonist; Alpha-1 adrenergic receptors antagonist; Alpha-2A adrenergic receptor antagonist; Alpha-2B adrenergic receptor antagonist; Alpha-2C adrenergic receptor antagonist; Muscarinic acetylcholine receptor M1 antagonist; Muscarinic acetylcholine receptor M2 ligand; Muscarinic acetylcholine receptor M3 antagonist; Muscarinic acetylcholine receptor M4 ligand; Muscarinic acetylcholine receptor M5 ligand","Indication associated"]
[456,"DB01225","approved","small molecule","Enoxaparin",{"$nulls":3},"Enoxaparin is a common low-molecular-weight heparin (LMWH) used in the prevention and management of various thromboembolic disorders. Initially approved by the FDA in 1993, it is administered by a subcutaneous or intravenous injection and marketed by several pharmaceutical companies. Enoxaparin markedly reduces the incidence of venous thromboembolism in hospitalized patients when compared to unfractionated , without increasing the risk of serious bleeding.","9005-49-6",null,"Enoxaparin is indicated for the prevention of ischemic complications in unstable angina and in non Q-wave myocardial infarction; it is indicated in conjunction with percutaneous intervention and/or other treatment for the management of acute ST elevation myocardial infarction. \r\n\r\nEnoxaparin is also indicated in the prophylaxis of DVT in abdominal surgery, hip replacement, knee replacement, or medical patients with severely restricted mobility during acute illness. Additionally, enoxaparin is indicated for the inpatient treatment of DVT with or without pulmonary embolism and the treatment of outpatient DVT without pulmonary embolism.\r","This drug has an immediate onset of action. Enoxaparin increases Thrombin Time (TT) and activated partial thromboplastin time (aPTT), preventing and reducing thromboembolic complications such as DVT, pulmonary embolism, and ischemic cardiac complications. Administered at 1.5 mg/kg subcutaneously in a pharmacodynamic study, enoxaparin led to a higher ratio of anti-Factor Xa to anti-Factor IIa activity (mean ±SD, 14.0±3.1) (based on areas under anti-Factor activity versus time curves) when compared to that of heparin (mean ±SD, 1.22±0.13). Increases in the TT and aPTT were 1.8 times those of the control group.  Enoxaparin at 1 mg/kg subcutaneously every 12 hours led to aPTT values of 45 seconds or less in most patients. Average aPTT prolongation time on Day 1 was approximately 16% higher than on Day 4 of enoxaparin therapy.\r\n\r\nCaution is advised during treatment with enoxaparin - the risk of hemorrhage and thrombocytopenia is increased. In pregnant women with prosthetic mechanic heart valves, the risk of thromboembolism is increased. \r","Enoxaparin binds to antithrombin III, a serine protease inhibitor, forming a complex that irreversibly inactivates factor Xa, which is frequently used to monitor anticoagulation in the clinical setting. Following factor Xa inactivation, enoxaparin is released and binds to other anti-thrombin molecules. Factor IIa (thrombin) is directly inhibited by enoxaparin, however with less potency than unfractionated heparin (UFH).  Due to the cascade of effects resulting from enoxaparin binding, thrombin is unable to convert fibrinogen to fibrin and form a clot, preventing thromboembolic events. \r\n \r","Antithrombin-III potentiator; Coagulation factor X inhibitor; Prothrombin inhibitor","Indication associated"]
[457,"DB01228","approved; investigational; withdrawn","small molecule","Encainide","(±)-2'-[2-(1-methyl-2-piperidyl)ethyl]-p-anisanilide; (±)-4-methoxy-N-(2-(2-(1-methyl-2-piperidinyl)ethyl)phenyl)benzamide; 4-methoxy-2'-[2-(1-methyl-2-piperidyl)ethyl]benzanilide; 4-Methoxy-N-{2-[2-(1-methyl-piperidin-2-yl)-ethyl]-phenyl}-benzamide","C22H28N2O2","COC1=CC=C(C=C1)C(=O)NC1=CC=CC=C1CCC1CCCCN1C","All drug products containing encainide hydrochloride. Encainide hydrochloride, formerly marketed as Enkaid capsules, was associated with increased death rates in patients who had asymptomatic heart rhythm abnormalities after a recent heart attack. The manufacturer of Enkaid capsules voluntarily withdrew the product from the US market on December 16, 1991.","66778-36-7","352.4699","Encainide is a class Ic antiarrhythmic agent which was used for management of irregular heartbeats, such as atrial fibrillation, atrial flutter, ventricular tachycardia, and ventricular fibrillation.","Used to treat irregular heartbeats, encainide decreases excitability, conduction velocity, and automaticity as a result of slowed atrial, atrioventricular (AV) nodal, His-Purkinje, and intraventricular conduction. It causes a slight but significant prolongation of refractory periods in these tissues. The greatest effect is on the His-Purkinje system. Encainide decreases the rate of rise of the action potential without markedly affecting its duration.","Encainide is a sodium channel blocker, binding to voltage gated sodium channels. It stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses. Ventricular excitability is depressed and the stimulation threshold of the ventricle is increased during diastole.","Sodium channel protein type 5 subunit alpha inhibitor","Indication associated"]
[458,"DB01229","approved; vet_approved","small molecule","Paclitaxel","5beta,20-Epoxy-1,2-alpha,4,7beta,10beta,13alpha-hexahydroxytax-11-en-9-one 4,10-diacetate 2-benzoate 13-ester with (2R,3S)-N-benzoyl-3-phenylisoserine; Paclitaxel; Taxol A","C47H51NO14","[H][C@]12[C@H](OC(=O)C3=CC=CC=C3)[C@]3(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)C4=CC=CC=C4)C4=CC=CC=C4)C(C)=C([C@@H](OC(C)=O)C(=O)[C@]1(C)[C@@H](O)C[C@H]1OC[C@@]21OC(C)=O)C3(C)C","Paclitaxel is a chemotherapeutic agent marketed under the brand name Taxol among others. Used as a treatment for various cancers, paclitaxel is a mitotic inhibitor that was first isolated in 1971 from the bark of the Pacific yew tree which contains endophytic fungi that synthesize paclitaxel. It is available as an intravenous solution for injection and the newer formulation contains albumin-bound paclitaxel marketed under the brand name Abraxane.","33069-62-4","853.9061","Used in the treatment of Kaposi's sarcoma and cancer of the lung, ovarian, and breast. Abraxane® is specfically indicated for the treatment of metastatic breast cancer and locally advanced or metastatic non-small cell lung cancer.","Paclitaxel is a taxoid antineoplastic agent indicated as first-line and subsequent therapy for the treatment of advanced carcinoma of the ovary, and other various cancers including breast cancer. Paclitaxel is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. In addition, paclitaxel induces abnormal arrays or \"bundles\" of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis.","Paclitaxel interferes with the normal function of microtubule growth. Whereas drugs like colchicine cause the depolymerization of microtubules in vivo, paclitaxel arrests their function by having the opposite effect; it hyper-stabilizes their structure. This destroys the cell's ability to use its cytoskeleton in a flexible manner. Specifically, paclitaxel binds to the &beta; subunit of tubulin. Tubulin is the \"building block\" of mictotubules, and the binding of paclitaxel locks these building blocks in place. The resulting microtubule/paclitaxel complex does not have the ability to disassemble. This adversely affects cell function because the shortening and lengthening of microtubules (termed dynamic instability) is necessary for their function as a transportation highway for the cell. Chromosomes, for example, rely upon this property of microtubules during mitosis. Further research has indicated that paclitaxel induces programmed cell death (apoptosis) in cancer cells by binding to an apoptosis stopping protein called Bcl-2 (B-cell leukemia 2) and thus arresting its function.","Tubulin beta-1 chain inhibitor; Apoptosis regulator Bcl-2 inhibitor; Microtubule-associated protein 4; Microtubule-associated protein 2; Microtubule-associated protein tau; Nuclear receptor subfamily 1 group I member 2 inducer","Therapeutic strategy associated"]
[459,"DB01233","approved; investigational","small molecule","Metoclopramide","2-methoxy-4-amino-5-chloro-N,N-(dimethylaminoethyl)benzamide; 2-methoxy-5-chloroprocainamide; 4-amino-5-chloro-2-methoxy-N-(β-diethylaminoethyl)benzamide; 4-amino-5-chloro-N-(2-(diethylamino)ethyl)-o-anisamide; Metoclopramide","C14H22ClN3O2","CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC","Diabetic gastroparesis is a condition that causes frequent nausea and vomiting, which has a negative impact on quality of life and poses a significant burden on the healthcare system. Metoclopramide is a dopamine antagonist used to treat nausea and vomiting that may be associated with diabetic gastroparesis in addition to gastroesophageal reflux disease (GERD). It can also be used to prevent nausea or vomiting associated with chemotherapy or certain surgical or diagnostic procedures. \r\n\r\nOne unique property of this drug is that it does not increase gastric acid secretion. It is available in the oral tablet form or in solution, and can also be administered through the intravenous route. Metoclopramide was initially approved by the FDA in 1980.","364-62-5","299.796","Metoclopramide in the oral tablet form is used for symptomatic treatment of both acute and recurrent diabetic gastroparesis, in addition to the treatment of gastroesophageal reflux disease (GERD) in patients who have failed to respond to traditional therapy. A nasal spray formulation is also indicated to treat adults with acute, recurrent diabetic gastroparesis.\r\n\r\nIn the intravenous injection form, it is indicated for the above conditions as well as for the prevention of vomiting that may follow emetogenic chemotherapy or nausea and vomiting after surgery. Intravenous metoclopramide facilitates intubation of the small bowel and stimulates gastric emptying and barium flow in patients who require radiological examination of the stomach or small intestine.  In some cases, the delay of gastrointestinal emptying interferes with the radiographic visualization of the gastrointestinal tract, and metoclopramide is used to facilitate emptying in these cases, allowing for adequate diagnostic visualization.\r\n\r\nSome off-label uses of metoclopramide include the management of radiation-induced nausea and vomiting, gastric bezoars, intractable hiccups, and migraine pain.","Metoclopramide increases gastric emptying by decreasing lower esophageal sphincter (LES) pressure. It also exerts effects on the area postrema of the brain, preventing and relieving the symptoms of nausea and vomiting. In addition, this drug increases gastrointestinal motility without increasing biliary, gastric, or pancreatic secretions.\r\n\r\nBecause of its antidopaminergic activity, metoclopramide can cause symptoms of tardive dyskinesia (TD), dystonia, and akathisia, and should therefore not be administered for longer than 12 weeks.","Metoclopramide causes antiemetic effects by inhibiting dopamine D2 and serotonin 5-HT3 receptors in the chemoreceptor trigger zone (CTZ) located in the area postrema of the brain. Administration of this drug leads to prokinetic effects via inhibitory actions on presynaptic and postsynaptic D2 receptors, agonism of serotonin 5-HT4 receptors, and antagonism of muscarinic receptor inhibition. This action enhances the release of acetylcholine, causing increased lower esophageal sphincter (LES) and gastric tone, accelerating gastric emptying and transit through the gut. Metoclopramide antagonizes the dopamine D2 receptors. Dopamine exerts relaxant effect on the gastrointestinal tract through binding to muscular D2 receptors.","Dopamine D2 receptor antagonist; Muscarinic acetylcholine receptor M1 agonist; 5-hydroxytryptamine receptor 4 agonist; 5-hydroxytryptamine receptor 3A antagonist","Indication associated"]
[460,"DB01234","approved; investigational; vet_approved","small molecule","Dexamethasone","1-Dehydro-16alpha-methyl-9alpha-fluorohydrocortisone; 1-Dehydro-16α-methyl-9α-fluorohydrocortisone; 16alpha-Methyl-9alpha-fluoro-1-dehydrocortisol; 16α-Methyl-9α-fluoro-1-dehydrocortisol; 9alpha-Fluoro-16alpha-methylprednisolone; 9α-Fluoro-16α-methylprednisolone; Dexamethasone","C22H29FO5","[H][C@@]12C[C@@H](C)[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])CCC2=CC(=O)C=C[C@]12C","Dexamethasone, or MK-125, is a corticosteroid fluorinated at position 9 used to treat endocrine, rheumatic, collagen, dermatologic, allergic, ophthalmic, gastrointestinal, respiratory, hematologic, neoplastic, edematous, and other conditions. Developed in 1957, it is structurally similar to other corticosteroids like  and .\r\n\r\nDexamethasone was granted FDA approval on 30 October 1958. In a press release for the Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial on 16 June 2020, dexamethasone was recommended for use in COVID-19 patients with severe respiratory symptoms. Dexamethasone reduced deaths by approximately one third in patients requiring ventilation and by one fifth in those requiring oxygen.","50-02-2","392.4611","Dexamethasone and  otic suspension is indicated for bacterial infections with inflammation in acute otitis media and acute otitis externa. Intramuscular and intravenous injections are indicated for a number of endocrine, rheumatic, collagen, dermatologic, allergic, ophthalmic, gastrointestinal, respiratory, hematologic, neoplastic, edematous, and other conditions. Oral tablets are indicated for the treatment of multiple myeloma. An intravitreal implant is indicated for some forms of macular edema and non-infectious posterior uveitis affecting the posterior of the eye. Various ophthalmic formulations are indicated for inflammatory conditions of the eye.","Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals. Dexamethasone's duration of action varies depending on the route. Corticosteroids have a wide therapeutic window as patients may require doses that are multiples of what the body naturally produces. Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.","The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.\r\n\r\nGlucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10.\r\n\r\nLower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.","Glucocorticoid receptor agonist; Nuclear receptor subfamily 0 group B member 1 stimulator; Annexin A1 agonist; Nitric oxide synthase, inducible negative modulator; Nuclear receptor subfamily 1 group I member 2 agonist","Therapeutic strategy associated"]
[461,"DB01240","approved","small molecule","Epoprostenol","(5Z,13E)-(15S)-6,9alpha-Epoxy-11alpha,15-dihydroxyprosta-5,13-dienoate; (5Z,9α,11α,13E,15S)-6,9-epoxy-11,15-dihydroxyprosta-5,13-dien-1-oic acid; Epoprostenol; PGI2; PGX; Prostacyclin; Prostaglandin I2; Prostaglandin X; Vasocyclin","C20H32O5","[H][C@]12C[C@@H](O)[C@H](\\C=C\\[C@@H](O)CCCCC)[C@@]1([H])C\\C(O2)=C\\CCCC(O)=O","A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from prostaglandin endoperoxides in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension.","35121-78-9","352.4651","For the long-term intravenous treatment of primary pulmonary hypertension and pulmonary hypertension associated with the scleroderma spectrum of disease in NYHA Class III and Class IV patients who do not respond adequately to conventional therapy.","Epoprostenol has two major pharmacological actions: (1) direct vasodilation of pulmonary and systemic arterial vascular beds, and (2) inhibition of platelet aggregation. In animals, the vasodilatory effects reduce right and left ventricular afterload and increase cardiac output and stroke volume. The effect of epoprostenol on heart rate in animals varies with dose. At low doses, there is vagally mediated brudycardia, but at higher doses, epoprostenol causes reflex tachycardia in response to direct vasodilation and hypotension. No major effects on cardiac conduction have been observed. Additional pharmacologic effects of epoprostenol in animals include bronchodilation, inhibition of gastric acid secretion, and decreased gastric emptying. No available chemical assay is sufficiently sensitive and specific to assess the in vivo human pharmacokinetics of epoprostenol.","Prostaglandins are present in most body tissues and fluids and mediate many biological functions. Epoprostenol (PGI2) is a member of the family of prostaglandins that is derived from arachidonic acid. The major pharmacological actions of epoprostenol is ultimately inhibition of platelet aggregation. Prostacycline (PGI2) from endothelial cells activate G protein-coupled receptors on platelets and endothelial cells. This activation causes adenylate cyclase to produce cyclic AMP which inhibits further platelet activation and activates protein kinase A. Cyclic AMP also prevents coagulation by preventing an increase in intracellular calcium from thromboxane A2 binding. PKA then continues the cascade by phosphorylating and inhibiting myosin light-chain kinase which leads to smooth muscle relaxation and vasodilation. Notably, PGI2 and TXA2 work as physiological antagonists.","P2Y purinoceptor 12 agonist; Prostacyclin receptor agonist; Prostacyclin synthase inducer","Therapeutic strategy associated"]
[462,"DB01242","approved; investigational; vet_approved","small molecule","Clomipramine","3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N,N-dimethyl-1-propanamine; 3-(3-chloro-5H-dibenzo[b,F]azepin-5-yl)-N,N-dimethylpropan-1-amine; 3-Chloroimipramine; Chlorimipramine; Clomipramine; Monochlorimipramine","C19H23ClN2","CN(C)CCCN1C2=CC=CC=C2CCC2=C1C=C(Cl)C=C2","Clomipramine, the 3-chloro analog of imipramine, is a dibenzazepine-derivative tricyclic antidepressant (TCA). TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, clomipramine does not affect mood or arousal, but may cause sedation. In depressed individuals, clomipramine exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Tertiary amine TCAs, such as clomipramine, are more potent inhibitors of serotonin reuptake than secondary amine TCAs, such as nortriptyline and desipramine. TCAs also down-regulate cerebral cortical &beta;-adrenergic receptors and sensitize post-synaptic serotonergic receptors with chronic use. The antidepressant effects of TCAs are thought to be due to an overall increase in serotonergic neurotransmission. TCAs also block histamine-H<sub>1</sub> receptors, &alpha;<sub>1</sub>-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively. See toxicity section below for a complete listing of side effects. Clomipramine may be used to treat obsessive-compulsive disorder and disorders with an obsessive-compulsive component (e.g. depression, schizophrenia, Tourette’s disorder). Unlabeled indications include panic disorder, chronic pain (e.g. central pain, idiopathic pain disorder, tension headache, diabetic peripheral neuropathy, neuropathic pain), cataplexy and associated narcolepsy, autistic disorder, trichotillomania, onchophagia, stuttering, premature ejaculation, and premenstrual syndrome. Clomipramine is rapidly absorbed from the gastrointestinal tract and demethylated in the liver to its primary active metabolite, desmethylclomipramine.","303-49-1","314.852","May be used to treat obsessive-compulsive disorder and disorders with an obsessive-compulsive component (e.g. depression, schizophrenia, Tourette’s disorder).\r\nUnlabeled indications include: depression, panic disorder, chronic pain (e.g. central pain, idiopathic pain disorder, tension headache, diabetic peripheral neuropathy, neuropathic pain), cataplexy and associated narcolepsy (limited evidence), autistic disorder (limited evidence), trichotillomania (limited evidence), onchophagia (limited evidence), stuttering (limited evidence), premature ejaculation, and premenstrual syndrome.","Clomipramine, a tricyclic antidepressant, is the 3-chloro derivative of Imipramine. It was thought that tricyclic antidepressants work exclusively by inhibiting the re-uptake of the neurotransmitters norepinephrine and serotonin by nerve cells. However, this response occurs immediately, yet mood does not lift for around two weeks. It is now thought that changes occur in receptor sensitivity in the cerebral cortex and hippocampus. The hippocampus is part of the limbic system, a part of the brain involved in emotions. Presynaptic receptors are affected: &alpha;<sub>1</sub> and &beta;<sub>1</sub> receptors are sensitized, &alpha;<sub>2</sub> receptors are desensitized (leading to increased noradrenaline production). Tricyclics are also known as effective analgesics for different types of pain, especially neuropathic or neuralgic pain.","Clomipramine is a strong, but not completely selective serotonin reuptake inhibitor (SRI), as the active main metabolite desmethyclomipramine acts preferably as an inhibitor of noradrenaline reuptake. &alpha;<sub>1</sub>-receptor blockage and &beta;-down-regulation have been noted and most likely play a role in the short term effects of clomipramine. A blockade of sodium-channels and NDMA-receptors might, as with other tricyclics, account for its effect in chronic pain, in particular the neuropathic type.","Sodium-dependent serotonin transporter inhibitor; 5-hydroxytryptamine receptor 2A antagonist; 5-hydroxytryptamine receptor 2B antagonist; 5-hydroxytryptamine receptor 2C antagonist; Sodium-dependent noradrenaline transporter inhibitor; Glutathione S-transferase P inhibitor","Indication associated"]
[463,"DB01244","approved; withdrawn","small molecule","Bepridil","Bepadin; Bepridil","C24H34N2O","CC(C)COCC(CN(CC1=CC=CC=C1)C1=CC=CC=C1)N1CCCC1","A long-acting, non selective, calcium channel blocker with significant anti-anginal activity. The drug produces significant coronary vasodilation and modest peripheral effects. It has antihypertensive and selective anti-arrhythmia activities and acts as a calmodulin antagonist. It is no longer marketed in the United States, as it has been implicated in causing ventricular arrhythmias (ie. Torsade de pointes).","64706-54-3","366.5396","For the treatment of hypertension, and chronic stable angina (classic effort-associated angina).","Bepridil is a calcium channel blocker that has well characterized anti-anginal properties and known but poorly characterized type 1 anti-arrhythmic and anti-hypertensive properties. It is not related chemically to other calcium channel blockers such as diltiazem hydrochloride, nifedipine and verapamil hydrochloride.","Bepridil has inhibitory effects on both the slow calcium (L-type) and fast sodium inward currents in myocardial and vascular smooth muscle, interferes with calcium binding to calmodulin, and blocks both voltage and receptor operated calcium channels. Bepridil inhibits the transmembrane influx of calcium ions into cardiac and vascular smooth muscle. This has been demonstrated in isolated myocardial and vascular smooth muscle preparations in which both the slope of the calcium dose response curve and the maximum calcium-induced inotropic response were significantly reduced by bepridil. In cardiac myocytes <i>in vitro</i>, bepridil was shown to be tightly bound to actin. Bepridil regularly reduces heart rate and arterial pressure at rest and at a given level of exercise by dilating peripheral arterioles and reducing total peripheral resistance (afterload) against which the heart works.","Voltage-dependent P/Q-type calcium channel subunit alpha-1A inhibitor; Voltage-dependent T-type calcium channel subunit alpha-1H inhibitor; Voltage-dependent calcium channel subunit alpha-2/delta-2 inhibitor; Sodium/potassium-transporting ATPase subunit alpha-1 inhibitor; Potassium voltage-gated channel subfamily KQT member 1 inhibitor; Troponin C, slow skeletal and cardiac muscles other; Calmodulin binder; Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B inhibitor; Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A inhibitor; Potassium voltage-gated channel subfamily H member 2 inhibitor","Therapeutic strategy associated"]
[464,"DB01247","approved","small molecule","Isocarboxazid","Isocarboxazid","C12H13N3O2","CC1=CC(=NO1)C(=O)NNCC1=CC=CC=C1","Isocarboxazid has the formula 1-benzyl-2-(5-methyl-3-isoxazolylcarbonyl)hydrazine-isocarboxazid. It is a monoamine oxidase inhibitor. It is used in the treatment of major depression, dysthymic disorder, atypical disorder, panic disorder and the phobic disorders. It was first introduced by Roche pharmaceuticals, further developed by Validus pharms Inc and first FDA approved as a prescription drug on July 1st, 1959.","59-63-2","231.2505","Isocarboxazid is indicated for the treatment of the enduring and debilitating symptoms of depression that have not responded to other antidepressant drugs. Depression is a common but serious mood disorder. The patient will present changes in its feelings, thoughts, and ability to handle everyday activities. For a mood disorder to be considered as depression, the symptoms should be present for at least two weeks.","In vivo and in vitro studies demonstrated isocarboxazid-driven inhibition of MAO in the brain, heart, and liver. The reduced MAO activity, caused by isocarboxazid, results in an increased concentration of serotonin, epinephrine, norepinephrine, and dopamine in storage sites throughout the central nervous system (CNS) and sympathetic nervous system. The increase of one or more monoamines is the basis for the antidepressant activity of MAO inhibitors like isocarboxazid.","Isocarboxazid works by irreversibly blocking the action of monoamine oxidases (MAO) in the nervous system. MAO subtypes A and B are involved in the metabolism of serotonin and catecholamine neurotransmitters such as epinephrine, norepinephrine, and dopamine. Isocarboxazid, as a nonselective MAO inhibitor, binds irreversibly to monoamine oxidase-A (MAO-A) and monoamine oxidase-B (MAO-B). Isocarboxacid, like other monoamine oxidase inhibitors, are unique psychopharmacological agents whose clinical effect is related to the direct action of the monoamine oxidases to transform them into reactive metabolites.","Amine oxidase [flavin-containing] A inhibitor; Amine oxidase [flavin-containing] B inhibitor","Indication associated"]
[465,"DB01248","approved; investigational","small molecule","Docetaxel","Docetaxel; Docetaxel anhydrous; N-Debenzoyl-N-(tert-butoxycarbonyl)-10-deacetylpaclitaxel; N-Debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol; TXL","C43H53NO14","[H][C@@]1(C[C@@]2(O)[C@@H](OC(=O)C3=CC=CC=C3)[C@]3([H])[C@@]4(CO[C@@H]4C[C@H](O)[C@@]3(C)C(=O)[C@H](O)C(=C1C)C2(C)C)OC(C)=O)OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C1=CC=CC=C1","Docetaxel is a clinically well established anti-mitotic chemotherapy medication used mainly for the treatment of breast, ovarian, and non-small cell lung cancer. Docetaxel reversibly binds to tubulin with high affinity in a 1:1 stoichiometric ratio","114977-28-5","807.8792","For the treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy. Also used as a single agent in the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of prior platinum-based chemotherapy. It is also used in combination with prednisone, in the treatment of patients with androgen independent (hormone refractory) metastatic prostate cancer. Furthermore, docetaxel has uses in the treatment of gastric adenocarinoma and head and neck cancer.","Docetaxel is a taxoid antineoplastic agent. It promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. In addition, docetaxel induces abnormal arrays or \"bundles\" of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis.","Docetaxel interferes with the normal function of microtubule growth. Whereas drugs like colchicine cause the depolymerization of microtubules in vivo, docetaxel arrests their function by having the opposite effect; it hyper-stabilizes their structure. This destroys the cell's ability to use its cytoskeleton in a flexible manner. Specifically, docetaxel binds to the &beta;-subunit of tubulin. Tubulin is the \"building block\" of microtubules, and the binding of docetaxel locks these building blocks in place. The resulting microtubule/docetaxel complex does not have the ability to disassemble. This adversely affects cell function because the shortening and lengthening of microtubules (termed dynamic instability) is necessary for their function as a transportation highway for the cell. Chromosomes, for example, rely upon this property of microtubules during mitosis. Further research has indicated that docetaxel induces programmed cell death (apoptosis) in cancer cells by binding to an apoptosis stopping protein called Bcl-2 (B-cell leukemia 2) and thus arresting its function.","Tubulin beta-1 chain; Apoptosis regulator Bcl-2; Microtubule-associated protein 2; Microtubule-associated protein 4; Microtubule-associated protein tau; Nuclear receptor subfamily 1 group I member 2 binder","Therapeutic strategy associated"]
[466,"DB01250","approved","small molecule","Olsalazine","Olsalazine","C14H10N2O6","OC(=O)C1=CC(=CC=C1O)\\N=N\\C1=CC=C(O)C(=C1)C(O)=O","Olsalazine is an anti-inflammatory drug used in the treatment of Inflammatory Bowel Disease and Ulcerative Colitis. Olsalazine is a derivative of salicylic acid. Inactive by itself (it is a prodrug), it is converted by the bacteria in the colon to mesalamine. Mesalamine works as an anti-inflammatory agent in treating inflammatory diseases of the intestines.","15722-48-2","302.239","For the treatment of Inflammatory Bowel Disease and Ulcerative Colitis.","Olsalazine is an anti-inflammatory drug used in the treatment of Inflammatory Bowel Disease and Ulcerative Colitis. Olsalazine reduces the bowel inflammation, diarrhea (stool frequency), rectal bleeding, and abdominal pain. Olsalazine is thought to work like balsalazide, delivering mesalazine or 5-aminosalicylic acid past the small intestine to the large intestine to act on the site of disease.","Orally administered olsalazine is converted to mesalamine which is thought to be the therapeutically active agent in the treatment of ulcerative colitis. The mechanism of action of mesalamine (and sulfasalazine) is unknown, but appears to be topical rather than systemic. Mucosal production of arachidonic acid (AA) metabolites, both through the cyclooxygenase pathways, i.e., prostanoids, and through the lipoxygenase pathways, i.e., leukotrienes (LTs) and hydroxyelcosatetraenoic acids (HETEs) is increased in patients with chronic inflammatory bowel disease, and it is possible that mesalamine diminishes inflammation by blocking cyclooxygenase and inhibiting prostaglandin (PG) production in the colon.","Thiopurine S-methyltransferase inhibitor; Interferon gamma","Therapeutic strategy associated"]
[467,"DB01251","approved; investigational","small molecule","Gliquidone","Gliquidone","C27H33N3O6S","COC1=CC2=C(C=C1)C(C)(C)C(=O)N(CCC1=CC=C(C=C1)S(=O)(=O)NC(=O)NC1CCCCC1)C2=O","Gliquidone is a sulfonylurea drug used to treat diabetes mellitus type 2. It is an ATP-dependent K+ (KATP) channel blocker. This block causes a depolarization which leads to activation of voltage-dependent Ca channels and Ca2+ influx, and eventually increases insulin release.","33342-05-1","527.632","Used in the treatment of diabetes mellitus type 2.","Gliquidone is an anti-diabetic drug in the sulfonylurea class. In patients with diabetes mellitus, there is a deficiency or absence of a hormone manufactured by the pancreas called insulin. Insulin is the main hormone responsible for the control of sugar in the blood. Gliquidone is an antidiabetic medication which is used in those patients with adult maturity onset or non-insulin dependent diabetes (NIDDM). It works by lowering blood sugar levels by stimulating the production and release of insulin from the pancreas. It also promotes the movement of sugar from the blood into the cells in the body which need it.\r","The mechanism of action of gliquidone in lowering blood glucose appears to be dependent on stimulating the release of insulin from functioning pancreatic beta cells, and increasing sensitivity of peripheral tissues to insulin. Gliquidone likely binds to ATP-sensitive potassium channel receptors on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Membrane depolarization stimulates calcium ion influx through voltage-sensitive calcium channels. This increase in intracellular calcium ion concentration induces the secretion of insulin.","ATP-binding cassette sub-family C member 8 inhibitor; ATP-sensitive inward rectifier potassium channel 8 inhibitor","Indication associated"]
[468,"DB01252","investigational","small molecule","Mitiglinide","Mitiglinide","C19H25NO3","[H][C@@](CC(=O)N1C[C@@]2([H])CCCC[C@@]2([H])C1)(CC1=CC=CC=C1)C(O)=O","Mitiglinide is a drug for the treatment of type 2 diabetes. It may stimulate insulin secretion in beta-cells by closing off ATP dependant potassium ion channels.","145375-43-5","315.413","For the treatment of type 2 diabetes.","Mitiglinide belongs to the meglitinide class of blood glucose-lowering drugs. It is approved for use in Japan but has not yet gained FDA approval.","Mitiglinide is thought to stimulate insulin secretion by binding to and blocking ATP-sensitive K(+) (K(ATP)) channels (Kir6.2/SUR1 complex, KATP channels) in pancreatic beta-cells. Closure of potassium channels causes depolarization which stimulates calcium influx through voltage-gated calcium channels. High intracellular calcium subsequently triggers the exocytosis of insulin granules.","ATP-binding cassette sub-family C member 8 inhibitor; Peroxisome proliferator-activated receptor gamma agonist","Target associated"]
[469,"DB01255","approved; investigational","small molecule","Lisdexamfetamine","Lisdexamfetamine","C15H25N3O","C[C@@H](CC1=CC=CC=C1)NC(=O)[C@@H](N)CCCCN","Also known as _Vyvanse_, lisdexamfetamine (L-lysine-d-amphetamine) is a prodrug of the psychostimulant d-amphetamine . It is paired with the essential amino acid _L-lysine_. Lisdexamfetamine dimesylate increases attention span and decreases restlessness in children and adults who are overactive/hyperactive, cannot concentrate for long periods, or are easily distracted or impulsive .\r\n\r\nAs a central nervous system stimulant, lisdexamfetamine is utilized as an adjunct therapy in the treatment of attention deficit hyperactivity disorder (ADHD). As a prodrug, lisdexamfetamine was specifically engineered as an abuse-resistant product .  The mechanism by which this occurs is through delayed release after ingestion (unlike some other psychostimulant drugs, which may be abused). After oral administration and absorption, enzyme hydrolysis after contact with red blood cells metabolize lisdexamfetamine into L- lysine, a naturally occurring essential amino acid and active _d-amphetamine_, which is responsible for the drug’s pharmacological effects. Gastrointestinal pH does not affect this conversion, and the addition of the L-lysine slows the amount of d-amphetamine available in the circulation and central nervous system .","608137-32-2","263.3785","For the treatment of Attention-deficit/hyperactivity disorder (ADHD) and for moderate to severe binge eating disorder in adults , .\r\n\r\nThis drug is not indicated for weight loss. Use of other sympathomimetic drugs for weight loss is associated with serious cardiovascular effects. The safety and effectiveness of this drug for the treatment of obesity have not yet been determined .\r","Lisdexamfetamine dimesylate is a prodrug of _d-amphetamine_. Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulating properties . This agent works primarily by inducing the release of the neurotransmitters dopamine and norepinephrine from their storage areas in presynaptic nerve terminals . Both of these transmitters contribute to alertness, increased concentration, in addition to effort and motivation.\r","Lisdexamfetamine is a prodrug of dextroamphetamine. The active form of this drug blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space. The parent drug, lisdexamfetamine, does not bind to the sites for the reuptake of norepinephrine and dopamine in vitro . The mechanism of therapeutic action in attention deficit hyperactivity disorder (ADHD) is not fully understood , . Amphetamines have been recently found to target the trace amine-associated receptor 1 (TAAR1), which was recently discovered. This may explain some of its effects on the extraneuronal space , ,.   Ultimately, the ability of this agent to increase synaptic concentrations of the catecholamine neurotransmitters noradrenaline and dopamine in the prefrontal cortex (PFC), and in the striatum, results in several behavioral changes , .","Trace amine-associated receptor 1 agonist","Indication associated"]
[470,"DB01260","approved; investigational","small molecule","Desonide","11β,21-dihydroxy-16α,17-[(1-methylethylidene)bis(oxy)]pregna-1,4-diene-3,20-dione; 11β,21-dihydroxy-16α,17-isopropylidenedioxypregna-1,4-diene-3,20-dione; 11β,21-dihydroxy-16α,17α-isopropylidenedioxypregna-1,4-diene-3,20-dione; 16α-hydroxyprednisole-16,17-acetonide; 16α-hydroxyprednisolone-16α,17-acetonide; 16α,17α-isopropylidenedioxyprednisolone; Desfluorotriamcinolone acetonide; Desonide","C24H32O6","[H][C@@]12C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)C=C[C@]12C","A nonfluorinated corticosteroid anti-inflammatory agent used topically for dermatoses.","638-94-8","416.5073","For the relief of the inflammatory and pruritic manifestations of corticosteroid responsive dermatose.","Desonide is a synthetic nonfluorinated corticosteroid for topical dermatologic use. The corticosteroids constitute a class of primarily synthetic steroids used topically as anti-inflammatory and antipruritic agents.","Like other topical corticosteroids, desonide has anti-inflammatory, antipruritic and vasoconstrictive properties. The drug binds to cytosolic glucocorticoid receptors. This complex migrates to the nucleus and binds to genetic elements on the DNA. This activates and represses various genes. However corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2.","Glucocorticoid receptor agonist","Therapeutic strategy associated"]
[471,"DB01269","approved; investigational","biotech","Panitumumab","ABX-EGF; Panitumumab",null,null,"Panitumumab (ABX-EGF) is a recombinant human IgG2 monoclonal antibody that binds specifically to the human epidermal growth factor receptor (EGFR). This drug is an antineoplastic agent.\r\n\r\nPanitumumab was granted FDA approval on 27 September 2006.","339177-26-3",null,"For the treatment of EGFR-expressing, metastatic colorectal carcinoma that is refractory to fluoropyrimidine-, oxaliplatin-, and irinotecan- containing chemotherapy regimens.","Panitumumab is a recombinant, human IgG2 kappa monoclonal antibody that binds specifically to the human Epidermal Growth Factor Receptor (EGFR). EGFR is a transmembrane glycoprotein that belongs to the subfamily of type I receptor tyrosine kinases. Although EGFR is expressed in normal cells, the overexpression of EGFR is detected in many human cancers, including those of the colon and rectum. Interaction of EGFR with its normal ligands causes phosphorylation and activation of a series of intracellular proteins that will in turn regulate the transcription of genes involved with cellular growth and survival, motility, and prolieration. Signal transduction through EGFR leads to the activation of the wild type KRAS gene, but the presence of an activating somatic mutation of the KRAS gene within a cancer cell can result in the dysregulation of signaling pathways and resistance to EGFR inhibitor therapy.","Panitumumab binds specifically to EGFR on both normal and tumor cells, and competitively inhibits the binding of ligands for EGFR. Nonclinical studies show that binding of panitumumab to the EGFR prevents ligand-induced receptor autophosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, decreased pro-inflammatory cytokine and vascular growth factor production, and internalization of the EGFR.","Epidermal growth factor receptor suppressor","Therapeutic strategy associated"]
[472,"DB01270","approved","biotech","Ranibizumab","Ranibizumab; rhuFab V2",null,null,"Ranibizumab is a recombinant humanized IgG1 kappa isotype monoclonal antibody fragment designed for intraocular use. Ranibizumab binds to and inhibits the biologic activity of human vascular endothelial growth factor A (VEGF-A). Ranibizumab has a molecular weight of approximately 48 kilodaltons and is produced by an E. coli expression system in a nutrient medium containing the antibiotic tetracycline (tetracycline is not detectable in the final product). Ranibizumab is marketed under the name Lucentis® and was recently approved under the name Susvimo as an intraocular implantation. It is indicated for the treatment of macular edema after retinal vein occlusion, age-related macular degeneration (wet), and diabetic macular edema.","347396-82-1",null,"For the treatment of patients with macular edema after retinal vein occlusion, age-related macular degeneration (wet), and diabetic macular edema.\r","Ranibizumab is a recombinant humanized IgG1 kappa isotype monoclonal antibody fragment designed for intraocular use. Ranibizumab is a VEGF-A antagonist that binds to and inhibits the biologic activity of active forms of human VEGF-A, including the cleaved form (VEGF<sub>110</sub>). VEGF-A has been shown to cause neovascularization (angiogenesis) and an increase in vascular permeability, which is thought to contribute to the progression of the neovascular form of age-related macular degeneration (AMD).","Ranibizumab binds to the receptor binding site of active forms of VEGF-A, including the biologically active, cleaved form of this molecule, VEGF<sub>110</sub>. The binding of ranibizumab to VEGF-A prevents the interaction of VEGF-A with its receptors (VEGFR1 and VEGFR2) on the surface of endothelial cells, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation.","Vascular endothelial growth factor A","Indication associated"]
[473,"DB01274","approved; investigational","small molecule","Arformoterol","(-)-formoterol; (R,R)-formoterol; Arformoterol","C19H24N2O4","COC1=CC=C(C[C@@H](C)NC[C@H](O)C2=CC(NC=O)=C(O)C=C2)C=C1","Arformoterol is a bronchodilator. It works by relaxing muscles in the airways to improve breathing. Arformoterol inhalation is used to prevent bronchoconstriction in people with chronic obstructive pulmonary disease, including chronic bronchitis and emphysema. The use of arformoterol is pending revision due to safety concerns in regards to an increased risk of severe exacerbation of asthma symptoms, leading to hospitalization as well as death in some patients using long acting beta agonists for the treatment of asthma.","67346-49-0","344.4049","A bronchodilator used for the long term, symptomatic treatment of reversible bronchoconstriction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema.","Arformoterol, the active (R,R)-enantiomer of formoterol, is a selective long-acting β2-adrenergic receptor agonist (beta2-agonist) that has two-fold greater potency than racemic formoterol (which contains both the (S,S) and (R,R)-enantiomers). The (S,S)-enantiomer is about 1,000-fold less potent as a β2-agonist than the (R,R)-enantiomer. Arformoterol seems to have little or no effect on β1-adrenergic receptors.","While it is recognized that β2-receptors are the predominant adrenergic receptors in bronchial smooth muscle and β1-receptors are the predominant receptors in the heart, data indicate that there are also β2-receptors in the human heart comprising 10% to 50% of the total beta-adrenergic receptors. The precise function of these receptors has not been established, but they raise the possibility that even highly selective β2-agonists may have cardiac effects. The pharmacologic effects of β2-adrenoceptor agonist drugs, including arformoterol, are at least in part attributable to stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3&prime;,5&prime;-adenosine monophosphate (cyclic AMP). Increased intracellular cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibition of release of proinflammatory mediators from cells, especially from mast cells. In vitro tests show that arformoterol is an inhibitor of the release of mast cell mediators, such as histamine and leukotrienes, from the human lung. Arformoterol also inhibits histamine-induced plasma albumin extravasation in anesthetized guinea pigs and inhibits allergen-induced eosinophil influx in dogs with airway hyper-response.","Beta-2 adrenergic receptor agonist","Therapeutic strategy associated"]
[474,"DB01275","approved","small molecule","Hydralazine","(1Z)-1(2H)-Phthalazinone hydrazone; (2H)-Phthalazinone hydrazone; 1-Hydrazinophthalazine; 1-Phthalazinylhydrazine; 6-Hydralazine; Hydralazin; Hydralazine; Hydrallazine; Hydrazinophthalazine; Hydrazone 1(2H)-phthalazinone; Hypophthalin; Idralazina; Phthalazin-1-ylhydrazine","C8H8N4","NNC1=NN=CC2=CC=CC=C12","Originally developed in the 1950s as a malaria treatment, hydralazine showed antihypertensive ability and was soon repurposed. Hydralazine is a hydrazine derivative vasodilator used alone or as adjunct therapy in the treatment of hypertension and only as adjunct therapy in the treatment of heart failure. Hydralazine is no longer a first line therapy for these indications since the development of newer antihypertensive medications.\r\n\r\nHydralazine hydrochloride was FDA approved on 15 January 1953.","86-54-4","160.1759","Hydralazine is indicated alone or adjunct to standard therapy to treat essential hypertension. A combination product with isosorbide dinitrate is indicated as an adjunct therapy in the treatment of heart failure.","Hydralazine interferes with calcium transport to relax arteriolar smooth muscle and lower blood pressure. Hydralazine has a short duration of action of 2-6h. This drug has a wide therapeutic window, as patients can tolerate doses of up to 300mg. Patients should be cautioned regarding the risk of developing systemic lupus erythematosus syndrome.","Hydralazine may interfere with calcium transport in vascular smooth muscle by an unknown mechanism to relax arteriolar smooth muscle and lower blood pressure. The interference with calcium transport may be by preventing influx of calcium into cells, preventing calcium release from intracellular compartments, directly acting on actin and myosin, or a combination of these actions. This decrease in vascular resistance leads to increased heart rate, stroke volume, and cardiac output.\r\n\r\nHydralazine also competes with protocollagen prolyl hydroxylase (CPH) for free iron. This competition inhibits CPH mediated hydroxylation of HIF-1α, preventing the degradation of HIF-1α. Induction of HIF-1α and VEGF promote proliferation of endothelial cells and angiogenesis.","Membrane primary amine oxidase inhibitor; Prolyl 4-hydroxylase subunit alpha-1 inhibitor; Hypoxia-inducible factor 1-alpha inducer","Indication associated"]
[475,"DB01277","approved; investigational","biotech","Mecasermin","Human somatomedin C; Mecasermin; Mecasermin recombinant; Mechano growth factor",null,null,"Mecasermin contains recombinant-DNA-engineered human insulin-like growth factor-1 (rhIGF-1). IGF-1 consists of 70 amino acids in a single chain with three intramolecular disulfide bridges and a molecular weight of 7649 daltons. The amino acid sequence of the product is identical to that of endogenous human IGF-1. The rhIGF-1 protein is synthesized in bacteria (E. coli) that have been modified by the addition of the gene for human IGF-1.","68562-41-4",null,"For the long-term treatment of growth failure in pediatric patients with Primary IGFD or with GH gene deletion who have developed neutralizing antibodies to GH . It is not indicated to treat Secondary IGFD resulting from GH deficiency, malnutrition, hypothyroidism or other causes; it is not a substitute for GH therapy.","Mecasermin is a biosynthetic (recombinant DNA origin) form of human insulin-like growth factor 1 (IGF-1) designed to replace natural IGF-1 in pediatric patients who are deficient, promoting normalized statural growth. Growth hormones (GH) bind to growth hormone receptors (GHR) in the liver and other tissues, which stimulates the synthesis of IGF-1. In target tissues, IGF-1 activates the IGF-1 receptor, resulting in intracellular signals that stimulate growth . Although many actions of the GH are mediated through IGF-1, the precise roles of GH and IGF-1 have not been fully elucidated. Patients with severe primary IGF-1 deficiency (Primary IGFD) fail to produce adequate levels of IGF-1, due to disruption of the GH pathway used to promote IGF-1 release (possible GH pathway disruptions include mutations in the GHR, post-GHR signaling pathway, and IGF-1 gene defects).","Mecasermin supplies recombinant-DNA-origin IGF-1, which binds to the Type I IGF-1 receptor. This receptor exerts intra-cellular signaling activity in a number of processes involved in statural growth, including mitogenesis in multiple tissue types, chondrocyte growth and division along cartilage growth plates, and increases in organ growth.","Insulin-like growth factor 1 receptor agonist; Insulin-like growth factor-binding protein 3; Insulin receptor; Cation-independent mannose-6-phosphate receptor","Indication associated"]
[476,"DB01278","approved; investigational","small molecule","Pramlintide","Pramlintide","C171H267N51O53S2","[H]N[C@@H](CCCCN)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@@]([H])(NC(=O)[C@H](C)NC(=O)[C@@]([H])(NC(=O)[C@H](CC(N)=O)NC1=O)[C@@H](C)O)[C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@]([H])([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@]([H])([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@]([H])([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@]([H])([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(N)=O","Pramlintide is a relatively new adjunct treatment for diabetes (both type 1 and 2), developed by Amylin Pharmaceuticals. It is derived from amylin, a hormone that is released into the bloodstream, in a similar pattern as insulin, after a meal. Like insulin, amylin is deficient in individuals with diabetes.","151126-32-8","3949.44","For the treatment of type 1 and type 2 diabetes mellitus as an adjunct to preprandial insulin therapy in patients without adequate glycemic control of insulin therapy.","Pramlintide is a synthetic analog of amylin, a glucoregulatory hormone that is synthesized by pancreatic β-cells and released into the bloodstream, in a similar pattern as insulin, after a meal. Like insulin, amylin is deficient in individuals with diabetes. It is provided as an acetate salt. Pramlintide is a 37-amino acid polypeptide that differs structurally from human amylin by the replacement of alanine, serine, and serine at positions 25, 28, and 29 respectively with proline.","Pramlintide is an amlyinomimetic, a functional analog of the naturally occurring pancreatic hormone amylin. Amylin has activity in a number of gastrointestinal and glucodynamic systems, and by mimicking its activity, pramlintide acts to improve glycemic control through modulation of the rate of gastric emptying, prevention of post-prandial rise in glucagon levels, and by increasing sensations of satiety, thereby reducing caloric intake and potentiating weight loss. There appears to be at least three distinct receptor complexes that bind with high affinity to amylin. All three complexes contain the calcitonin receptor at the core, plus one of three Receptor activity-modifying proteins, RAMP1, RAMP2, or RAMP3.","Calcitonin receptor agonist; Receptor activity-modifying protein 1 agonist; Receptor activity-modifying protein 2 agonist; Receptor activity-modifying protein 3 agonist","Therapeutic strategy associated"]
[477,"DB01280","approved; investigational","small molecule","Nelarabine","2-Amino-9-beta-D-arabinofuranosyl-6-methoxy-9H-purine; Nelarabine; Nelzarabine","C11H15N5O5","COC1=NC(N)=NC2=C1N=CN2[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O","Nelarabine is an antineoplastic agent that is typically employed to treat acute T-cell lymphoblastic leukemia. Nelarabine is a purine nucleoside analog converted to its corresponding arabinosylguanine nucleotide triphosphate (araGTP), resulting in inhibition of DNA synthesis and cytotoxicity.","121032-29-9","297.2673","For the treatment of pediatric and adult patients with acute T-cell lymphoblastic leukemia and T-cell lymphoblastic lymphoma whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens.","Nelarabine is a prodrug of the cytotoxic deoxyguanosine analogue 9-&szlig;-D-arabinofuranosylguanine (ara-G). Nelarabine is demethylated by adenosine deaminase (ADA) to ara-G. Ara-G is then transported into cells, where it undergoes three phosphorylation steps, resulting in the formation of ara-G triphosphate (ara-GTP). In the first phosphorylation step, ara-G is converted to ara-G monophosphate (ara-GMP). Ara-GMP is then monophosphorylated by deoxyguanosine kinase and deoxycytidine kinase to ara-G diphosphate, and then subsequently to the active ara-G triphosphate (ara-GTP). Ara-GTP is the one that exerts the pharmacological effect. Pre-clinical studies have demonstrated that targeted T-cells possess marked sensitivity to the agent.","Once nelarabine is metabolized into ara-GTP, the metabolite accumulates in leukemic blasts and incorporates into DNA to exert its S phase-specific cytotoxic effects, leading to the induction of fragmentation and apoptosis. Ara-GTP competes with endogenous deoxyGTP (dGTP) for incorporation into DNA. Once ara-GTP is incorporated at the 3' end of DNA, further DNA elongation is inhibited, which signals apoptosis and leads to cellular destruction. Additional cytotoxic activities may exist, but these are not fully understood.","DNA incorporation into and destabilization; DNA polymerase alpha catalytic subunit inhibitor","Therapeutic strategy associated"]
[478,"DB01281","approved","biotech","Abatacept","Abatacept; Abatacept recombinant",null,null,"Abatacept is a soluble fusion protein, which links the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) to the modified Fc (hinge, CH2, and CH3 domains) portion of human immunoglobulin G1 (IgG1). Structurally, abatacept is a glycosylated fusion protein with a MALDI-MS molecular weight of 92,300 Da and it is a homodimer of two homologous polypeptide chains of 357 amino acids each. It is produced through recombinant DNA technology in mammalian CHO cells. The drug has activity as a selective co-stimulation modulator with inhibitory activity on T lymphocytes. Although approved for the treatment of rheumatoid arthritis, Repligen has entered a slightly different formulation of CTLA4-Ig into clinical trials (RG2077).","332348-12-6",null,"Abatacept is indicated in adult patients for the treatment of moderately-to-severely active rheumatoid arthritis and for the treatment of active psoriatic arthritis. In patients two years of age and older, abatacept is also indicated for the treatment of moderately-to-severely active juvenile idiopathic arthritis.\r\n\r\nAbatacept is also indicated for the prophylaxis of acute graft-versus-host disease, in combination with  and a calcineurin inhibitor such as , in patients two years of age and older who are undergoing hematopoietic stem cell transplantation from a matched or 1 allele-mismatched unrelated donor.","Abatacept is the first in a new class of drugs known as Selective Co-stimulation Modulators. Known as a recombinant fusion protein, the drug consists of the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to a modified Fc portion of human immunoglobulin G<sub>1</sub> (IgG<sub>1</sub>. The Fc portion of the drug consists of the hinge region, the C<sub>H</sub>2 domain, and the C<sub>H</sub>3 domain of IgG<sub>1</sub>. Although there are multiple pathways and cell types involved in the pathogenesis of rheumatoid arthritis, evidence suggests that T-cell activation may play an important role in the immunopathology of the disease. Ordinarily, full T-cell activation requires binding of the T-cell receptor to an antigen-MHC complex on the antigen-presenting cell as well as a co-stimulatory signal provided by the binding of the CD28 protein on the surface of the T-cell with the CD80/86 proteins on the surface of the antigen-presenting cell. CTLA4 is a naturally occurring protein which is expressed on the surface of T-cells some hours or days after full T-cell activation and is capable of binding to CD80/86 on antigen-presenting cells with much greater affinity than CD28. Binding of CTLA4-Ig to CD80/86 provides a negative feedback mechanism which results in T-cell deactivation. Abatacept was developed by Bristol-Myers-Squibb and is licensed in the US for the treatment of Rheumatoid Arthritis in the case of inadequate response to anti-TNF-alpha therapy.","Abatacept is a selective costimulation modulator, like CTLA-4, the drug has shown to inhibit T-cell (T lymphocyte) activation by binding to CD80 and CD86, thereby blocking interaction with CD28. Blockade of this interaction has been shown to inhibit the delivery of the second co-stimulatory signal required for optimal activation of T-cells. This results in the inhibition of autoimmune T-Cell activation that has been implcated in the pathogenesis of rheumatoid arthritis.","T-lymphocyte activation antigen CD80 antagonist; T-lymphocyte activation antigen CD86 antagonist","Indication associated"]
[479,"DB01283","approved; investigational","small molecule","Lumiracoxib","2-((2-chloro-6-fluorophenyl)amino)-5-methylbenzeneacetic acid","C15H13ClFNO2","CC1=CC=C(NC2=C(Cl)C=CC=C2F)C(CC(O)=O)=C1","Lumiracoxib is a COX-2 selective non-steroidal anti-inflammatory drug (NSAID). On August 11, 2007, Australia's Therapeutic Goods Administration (TGA, the Australian equivalent of the FDA) cancelled the registration of lumiracoxib in Australia due to concerns that it may cause liver failure. New Zealand and Canada have also followed suit in recalling the drug.","220991-20-8","293.721","For the acute and chronic treatment of the signs and symptoms of osteoarthritis of the knee in adults.","Lumiracoxib has a different structure from the standard COX-2 inhibitors (e.g. celecoxib). It more closely resembles the structure of diclofenac (one chlorine substituted by fluorine, the phenylacetic acid has another methyl group in meta position), making it a member of the arylalkanoic acid family of NSAIDs. It binds to a different site on the COX-2 receptor than the standard COX-2 inhibitors. It displays extremely high COX-2 selectivity.","The mechanism of action of lumiracoxib is due to inhibition of prostaglandin synthesis via inhibition of cyclooygenase-2 (COX-2). Lumiracoxib does not inhibit COX-1 at therapeutic concentrations.","Prostaglandin G/H synthase 2 inhibitor; Prostaglandin G/H synthase 1 inhibitor","Indication associated"]
[480,"DB01289","investigational","small molecule","Glisoxepide","Glisoxepide","C20H27N5O5S","CC1=CC(=NO1)C(=O)NCCC1=CC=C(C=C1)S(=O)(=O)NC(=O)NN1CCCCCC1","Glisoxepide is one of the sulphonamide-derived oral antidiabetic drugs. It inhibits the uptake of bile acids into isolated rat hepatocytes. However it inhibits taurocholate uptake only in the absence of sodium ions. Glisoxepide uptake could be further inhibited by blockers of the hepatocellular monocarboxylate transporter, by the loop diuretic bumetanide, by 4,4'-diisothiocyano-2,2'-stilbenedisulfonate (DIDS) and by sulphate.  These results are consistent with the transport of glisoxepide via the transport system for the unconjugated bile acid cholate.","25046-79-1","449.524","For the treatment of diabetes mellitus type 2.","Glisoxepide is a sulfonylurea agent. It stimulates beta cells of the islet of Langerhans in the pancreas to release insulin. It also enhances peripheral insulin sensitivity. Overall it potentiates insulin release and improves insulin dynamics.","Glisoxepide is a hypoglycemic sulphonylurea agent. The sulphonylureas are a family of drugs based on a common sulphonylurea core. These drugs act via augmentation of secretion of insulin from pancreatic beta-cells. Sulphonylureas may also cause a reduction in serum glucagon and potentiate the action of insulin at the extrapancreatic tissues.  Glisoxepide functions as a non-selective K(ATP) channel blocker.  It is thought to stimulate insulin secretion by closing the ATP-sensitive K(+) (K(ATP)) channels (Kir6.2/SUR1 complex, KATP channels) in pancreatic beta-cells. This inhibits a tonic, hyperpolarizing efflux of potassium, thus causing the electric potential over the membrane to become more positive. This depolarization opens voltage-gated Ca2+ channels. The rise in intracellular calcium leads to increased fusion of insulin granulae with the cell membrane, and therefore increased secretion of (pro)insulin.","ATP-sensitive inward rectifier potassium channel 8 inhibitor","Indication associated"]
[481,"DB01294","approved; vet_approved","small molecule","Bismuth subsalicylate","2-Hydroxy-benzo[1,3,2]dioxabismin-4-one; Basic bismuth salicylate; Bismuth oxide salicylate; Bismuth oxysalicylate; Bismuth subsalicylate; Pink bismuth; Wismutsubsalicylat","C7H5BiO4","O[Bi]1OC(=O)C2=CC=CC=C2O1","Bismuth subsalicylate is an antacid and anti-diarrheal agent. Exhibiting antibacterial and gastroprotective properties, bismuth subsalicylate is an insoluble salt of  linked to trivalent . Each molecule of bismuth subsalicylate contains 58% bismuth and 42% salicylate by weight. Bismuth subsalicylate has been around for over 100 years: it was originally developed in 1901 for hygienic use and sanitation for cholera infection.\r\n\r\nBismuth subsalicylate was first approved by the FDA in 1939 and is now mainly used to relieve nausea, diarrhea, and gastrointestinal discomfort. It is an active ingredient found in Pepto-Bismol, a common over-the-counter medication that is used to temporarily treat discomforts of the stomach and gastrointestinal tract. Bismuth subsalicylate is a component of HELIDAC Therapy (bismuth subsalicylate, , and ), which is a treatment regimen indicated for the eradication of _H. pylori_ for treatment of patients with _H. pylori_ infection and duodenal ulcer disease.","14882-18-9","362.0926","Bismuth subsalicylate is indicated to temporarily relieve diarrhea, travelers' diarrhea, and upset stomach due to overindulgence in food and drink, including heartburn, indigestion, nausea, gas, belching, and fullness.\r\n\r\nBismuth subsalicylate is a component of HELIDAC Therapy (bismuth subsalicylate, , and ), which is a treatment regimen indicated for the eradication of _H. pylori_ for treatment of patients with _H. pylori_ infection and duodenal ulcer disease.","Bismuth subsalicylate is an antacid and antimicrobial, gastroprotective, anti-secretory, and anti-inflammatory actions. It works to reduce the severity and incidence of flatulence and diarrhea, and consequently relieving gastrointestinal discomfort. In one study, bismuth subsalicylate was prevented traveler's diarrhea with a protection rate >60%.\r\n\r\nOrganobismuth compounds, formed by the breakdown of bismuth subsalicylate in the gastrointestinal tract, inhibit the growth of _Helicobacter pylori_ and other bacteria implicated in gastrointestinal disorders, and some fungi. In one study, bismuth subsalicylate was shown to eradicate up to 90% of _H. pylori_ infection when used as part of a quadruple therapy regimen containing a proton pump inhibitor, tetracycline, and metronidazole. Bismuth subsalicylate exhibited antimicrobial activity against _Clostridium difficile_, enterotoxigenic _Escherichia coli_ O157:H7, _norovirus_, and other common enteric pathogens such as _Salmonella_ and _Shigella_.","The exact mechanism of bismuth subsalicylate is not fully understood. Bismuth subsalicylate is an insoluble complex that constitutes salicylic acid and trivalent bismuth. Once orally administered, bismuth subsalicylate hydrolyzes in the stomach into bismuth oxychloride, which is minimally absorbed into the bloodstream, and salicylic acid, which is almost completely absorbed. Bismuth interacts with other anions and compounds, such as hydrochloric acid, bicarbonate, phosphate, and hydrogen sulfide, in the gastrointestinal tract to form bismuth salts such as bismuth oxychloride, bismuth subcarbonate, bismuth phosphate, and bismuth sulfide. Bismuth salts possess bactericidal and antimicrobial activity, mainly by preventing bacteria from binding and growing on the mucosal cells of the stomach. It has no effects on normal gut flora. By preventing bacteria from binding to mucosal cells, bismuth subsalicylate prevents intestinal secretion and fluid loss, promotes fluid and electrolyte reabsorption, reduces gastrointestinal inflammation, and promotes the healing of pre-existing ulcer in the stomach. Salicylic acid from dissociated bismuth subsalicylate adds to the anti-inflammatory actions of bismuth salts by inhibiting the cyclooxygenase enzyme and limiting the formation of prostaglandin, a pro-inflammatory mediator. Bismuth subsalicylate exhibits cytoprotective and demulcent activity, which makes it an effective drug in peptic ulcer disease. It blocks the adhesion of H. pylori to the gastric epithelial cells and blocks the bacteria's enzyme activities, including phospholipase, protease, and urease.",null,"Therapeutic strategy associated"]
[482,"DB01295","experimental","small molecule","Bevantolol","(±)-bevantolol; 1-((2-(3,4-dimethoxyphenyl)ethyl)amino)-3-(3-methylphenoxy)-2-propanol; 1-(3,4-dimethoxyphenethylamino)-3-(m-tolyloxy)-2-propanol; 1-(3,4-dimethoxyphenethylamino)-3-m-tolyloxy-propan-2-ol; 1-[2-(3,4-Dimethoxy-phenyl)-ethylamino]-3-m-tolyloxy-propan-2-ol","C20H27NO4","COC1=C(OC)C=C(CCNCC(O)COC2=CC=CC(C)=C2)C=C1","Bevantolol is a beta-1 adrenoceptor antagonist that has been shown to be as effective as other beta blockers for the treatment of angina pectoris and hypertension. Mechanism of Action Animal experiments confirm both agonist and antagonist effects on alpha-receptors, in addition to antagonist activity at beta-1 receptors.","59170-23-9","345.4327","For the treatment of angina pectoris and hypertension.","Bevantolol is a beta-1 adrenoceptor antagonist that has been shown to be as effective as other beta blockers for the treatment of angina pectoris and hypertension.","Animal experiments confirm both agonist and antagonist effects on alpha-receptors, in addition to antagonist activity at beta-1 receptors. By binding and antagonizing beta-1 receptors Bevantolol inhibits the normal normal epinephrine-mediated sympathetic actions such as increased heart rate. This has the effect of decreasing preload and blood pressure.","Beta-1 adrenergic receptor antagonist; Beta-2 adrenergic receptor antagonist; Alpha-1A adrenergic receptor antagonist","Indication associated"]
[483,"DB01296","approved; investigational","small molecule","Glucosamine","2-amino-2-deoxy-D-glucose; Chitosamine; D-Glucosamine; Glucosamine","C6H13NO5","N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O","Osteoarthritis (OA) is a progressive and degenerative joint disease marked by loss of cartilage, bone changes, and synovial membrane inflammation. Treatment with chondroprotective drugs, such as glucosamine sulfate may offer additional benefits to nonsteroidal anti-inflammatory drugs treating the painful symptoms of OA. Glucosamine is commonly used over the counter as a treatment for arthritic joint pain, although its acceptance as a medical therapy varies due to contradictory and findings with unclear clinical significance during clinical trials. It is currently not approved as a prescription product by the FDA, but is widely available over the counter.","3416-24-8","179.1711","Glucosamine is generally used over the counter in the symptomatic treatment of osteoarthritis and joint pain, frequently combined with chondroitin sulfate and/or ibuprofen.","The administration of glucosamine, in theory, provides a building block towards the synthesis of glycosaminoglycans, slowing the progression of osteoarthritis and relieving symptoms of joint pain. Studies to this date examining the efficacy of glucosamine sulfate have been inconclusive. Glycosaminoglycans contribute to joint cartilage elasticity, strength, and flexibility. A systematic review of various studies and guidelines determined that modest improvements were reported for joint pain and function in patients taking glucosamine. A consistent joint space narrowing was observed, but with an unclear clinical significance.","The mechanism of action of glucosamine in joint health is unclear, however there are several possible mechanisms that contribute to its therapeutic effects. Because glucosamine is a precursor for glycosaminoglycans, and glycosaminoglycans are a major component of joint cartilage, glucosamine supplements may help to rebuild cartilage and treat the symptoms of arthritis.  Some in vitro studies show evidence that glucosamine reduces inflammation via inhibition of interferon gamma  and Nuclear factor kappa B subunit 65 (NF-κB p65), improving the symptoms of arthritis and joint pain. Clinical relevance is unknown at this time.","Interferon gamma inhibitor; Transcription factor p65 inhibitor","Indication associated"]
[484,"DB01303","approved","small molecule","Oxtriphylline","Choline theophyllinate; Choline theophylline; Oxtriphylline; Theocolin","C12H21N5O3","C[N+](C)(C)CCO.CN1C2=C([N-]C=N2)C(=O)N(C)C1=O","Oxtriphylline is the choline salt form of . Once in the body, theophylline is released and acts as a phosphodiesterase inhibitor, adenosine receptor blocker, and histone deacetylase activator. Its main physiological reponse is to dilate the bronchioles. As such, oxytriphylline is indicated mainly for asthma, bronchospasm, and COPD (i.e. all the same indications as the other theophyllines). It is marketed under the name Choledyl SA, and several forms of oxytriphylline have been discontinued. In the US, oxtriphylline is no longer available.","4499-40-5","283.3268","Used to treat the symptoms of asthma, bronchitis, COPD, and emphysema.","Oxtriphylline is a bronchodilator. Oxtriphylline works in several ways: it relaxes muscles in your lungs and chest to allow more air in, decreases the sensitivity of your lungs to allergens and other substances that cause inflammation, and increases the contractions of your diaphragm to draw more air into the lungs.","Oxtriphylline is a choline salt of theophylline. After ingestion, theophylline is released from oxytriphylline, and theophylline relaxes the smooth muscle of the bronchial airways and pulmonary blood vessels and reduces airway responsiveness to histamine, methacholine, adenosine, and allergen. Theophylline competitively inhibits type III and type IV phosphodiesterase (PDE), the enzyme responsible for breaking down cyclic AMP in smooth muscle cells, possibly resulting in bronchodilation. Theophylline also binds to the adenosine A2B receptor and blocks adenosine mediated bronchoconstriction. In inflammatory states, theophylline activates histone deacetylase to prevent transcription of inflammatory genes that require the acetylation of histones for transcription to begin.\r","cGMP-inhibited 3',5'-cyclic phosphodiesterase A inhibitor; cAMP-specific 3',5'-cyclic phosphodiesterase 4A inhibitor; Adenosine receptor A2a antagonist; Adenosine receptor A1 antagonist; Histone deacetylase 2 activator","Therapeutic strategy associated"]
[485,"DB01306","approved","biotech","Insulin aspart","Aspart; Aspart Insulin; B28-Aspart-Insulin; Insulin aspart; Insulin aspart protamine; Insulin aspart protamine recombinant; Insulin aspart recombinant; Insulin X14; Insulin, aspart protamine, human; Insulin, aspart, human; Insulin,aspart protamine",null,null,"Insulin aspart is a rapid-acting form of insulin used for the treatment of hyperglycemia caused by Type 1 and Type 2 Diabetes. Insulin is typically prescribed for the management of diabetes mellitus to mimic the activity of endogenously produced human insulin, a peptide hormone produced by beta cells of the pancreas that promotes glucose metabolism. Insulin is released from the pancreas following a meal to promote the uptake of glucose from the blood into internal organs and tissues such as the liver, fat cells, and skeletal muscle. Absorption of glucose into cells allows for its transformation into glycogen or fat for storage. Insulin also inhibits hepatic glucose production, enhances protein synthesis, and inhibits lipolysis and proteolysis among many other functions.\r\n\r\nInsulin is an important treatment in the management of Type 1 Diabetes (T1D) which is caused by an autoimmune reaction that destroys the beta cells of the pancreas, resulting in the body not being able to produce or synthesize the insulin needed to manage circulating blood sugar levels. As a result, people with T1D rely primarily on exogenous forms of insulin, such as insulin aspart, to lower glucose levels in the blood. Insulin is also used in the treatment of Type 2 Diabetes (T2D), another form of diabetes mellitus that is a slowly progressing metabolic disorder caused by a combination of genetic and lifestyle factors that promote chronically elevated blood sugar levels. Without treatment or improvement in non-pharmacological measures such as diet and exercise to lower blood glucose, high blood sugar eventually causes cellular resistance to endogenous insulin, and in the long term, damage to pancreatic islet cells. Insulin is typically prescribed later in the course of T2D, after trying several oral medications such as , , or  have been tried, when sufficient damage has been caused to pancreatic cells that the body is no longer able to produce insulin on its own. \r\n\r\nMarketed as the brand name product NovoRapid, insulin aspart begins to exert its effects within 15 minutes of subcutaneous administration, while peak levels occur 30 to 90 minutes after administration. Due to its duration of action of around 5 hours, NovoRapid is considered \"bolus insulin\" as it provides high levels of insulin in a short period of time to mimic the release of endogenous insulin from the pancreas after meals. Bolus insulin is often combined with once daily, long-acting \"basal insulin\" such as , , and  to provide low concentrations of background insulin that can keep blood sugar stable between meals or overnight. Use of basal and bolus insulin together is intended to mimic the pancreas' production of endogenous insulin, with a goal of avoiding any periods of hypoglycemia.\r\n\r\nInsulin aspart is a recombinant, biosynthetic, fast-acting insulin analogue. Compared to human insulin, it has a single amino acid substitution at position B28 where proline is replaced with aspartic acid. This substitution decreases its propensity to form hexamers and gives it a higher rate of absorption following subcutaneous administration compared to native insulin. Insulin aspart is produced in a genetically modified strain of _Saccharomyces cerevisiae_ (baker's yeast)\r\n\r\nWithout an adequate supply of insulin to promote absorption of glucose from the bloodstream, blood sugar levels can climb to dangerously high levels and can result in symptoms such as fatigue, headache, blurred vision, and increased thirst. If left untreated, the body starts to break down fat, instead of glucose, for energy which results in a build-up of ketone acids in the blood and a syndrome called ketoacidosis, which is a life-threatening medical emergency. In the long term, elevated blood sugar levels increase the risk of heart attack, stroke, and diabetic neuropathy.","116094-23-6",null,"Insulin aspart is indicated to improve glycemic control in adults and children with diabetes mellitus.","Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, a basal level of insulin is supplemented with insulin spikes following meals. Postprandial insulin spikes are responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin aspart is a rapid-acting insulin analogue used to mimic postprandial insulin spikes in diabetic individuals. The onset of action of insulin aspart is 10-15 minutes. Its activity peaks 60-90 minutes following subcutaneous injection and its duration of action is 4-5 hours.","Insulin aspart binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism and catabolism. In humans, insulin is stored in the form of hexamers; however, only insulin monomers are able to interact with IR. Substitution of the proline residue at B28 with aspartic acid reduces the tendency to form hexamers and results in a faster rate of absorption and onset of action and shorter duration of action.","Insulin receptor agonist; Insulin-like growth factor 1 receptor activator","Indication associated"]
[486,"DB01307","approved","biotech","Insulin detemir","Detemir; Insulin detemir; Insulin detemir recombinant; Insulin,detemir,human",null,null,"Insulin detemir is a long-acting form of insulin used for the treatment of hyperglycemia caused by Type 1 and Type 2 Diabetes. Insulin is typically prescribed for the management of diabetes mellitus to mimic the activity of endogenously produced human insulin, a peptide hormone produced by beta cells of the pancreas that promotes glucose metabolism. Insulin is released from the pancreas following a meal to promote the uptake of glucose from the blood into internal organs and tissues such as the liver, fat cells, and skeletal muscle. Absorption of glucose into cells allows for its transformation into glycogen or fat for storage. Insulin also inhibits hepatic glucose production, enhances protein synthesis, and inhibits lipolysis and proteolysis among many other functions.\r\n\r\nInsulin is an important treatment in the management of Type 1 Diabetes (T1D) which is caused by an autoimmune reaction that destroys the beta cells of the pancreas, resulting in the body not being able to produce or synthesize the insulin needed to manage circulating blood sugar levels. As a result, people with T1D rely primarily on exogenous forms of insulin, such as insulin detemir, to lower glucose levels in the blood. Insulin is also used in the treatment of Type 2 Diabetes (T2D), another form of diabetes mellitus that is a slowly progressing metabolic disorder caused by a combination of genetic and lifestyle factors that promote chronically elevated blood sugar levels. Without treatment or improvement in non-pharmacological measures such as diet and exercise to lower blood glucose, high blood sugar eventually causes cellular resistance to endogenous insulin, and in the long term, damage to pancreatic islet cells. Insulin is typically prescribed later in the course of T2D, after several oral medications such as , , or  have been tried, when sufficient damage has been caused to pancreatic cells that the body is no longer able to produce insulin on its own. \r\n\r\nMarketed as the brand name product Levemir, insulin detemir has a duration of action of 16-24 hours allowing for once-daily dosing, typically at bedtime. Due to its duration of action, Levemir is considered \"basal insulin\" as it provides low concentrations of background insulin that can keep blood sugar stable between meals or overnight. Basal insulin is often combined with short-acting \"bolus insulin\" such as , , and  to provide higher doses of insulin required following meals. Use of basal and bolus insulin together is intended to mimic the pancreas' production of endogenous insulin, with a goal of avoiding any periods of hypoglycemia.\r\n\r\nInsulin detemir is produced using recombinant DNA technology in yeast cells. This insulin analogue has a 14-C fatty acid, myristic acid, bound to the lysine amino acid at position B29. The myristoyl side chain increases self-association and albumin binding. This along with slow systemic absorption from the injection site prolongs distribution of the hormone into tissues and results in a long duration of action. \r\n\r\nWithout an adequate supply of insulin to promote absorption of glucose from the bloodstream, blood sugar levels can climb to dangerously high levels and can result in symptoms such as fatigue, headache, blurred vision, and increased thirst. If left untreated, the body starts to break down fat, instead of glucose, for energy which results in a build-up of ketone acids in the blood and a syndrome called ketoacidosis, which is a life-threatening medical emergency. In the long term, elevated blood sugar levels increase the risk of heart attack, stroke, and diabetic neuropathy.","169148-63-4",null,"Insulin detemir is indicated to improve glycemic control in adults and children with diabetes mellitus.","Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, the pancreas produces a continuous supply of low levels of basal insulin along with spikes of insulin following meals. Increased insulin secretion following meals is responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by the liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin detemir is a long-acting insulin analogue with a flat and predictable action profile. It is used to mimic the basal levels of insulin in diabetic individuals. The onset of action of insulin detemir is 1 to 2 hours and its duration of action is up to 24 hours. Interestingly, it has a lower affinity (30%) for the insulin receptor than human insulin.","Insulin detemir binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signalling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism and catabolism.\r\nInsulin detemir’s long duration of action appears to be a result of slow systemic absorption from the injection site and delayed distribution to target tissues. The myristic acid side chain on insulin detemir increases self-association and gives it a high binding affinity to serum albumin. These features slow its distribution into target tissues and prolong its duration of action.","Insulin receptor agonist; Insulin-like growth factor 1 receptor activator","Indication associated"]
[487,"DB01309","approved","biotech","Insulin glulisine","Insulin glulisine; Insulin Glulisine (recombinant DNA origin); Insulin glulisine recombinant",null,null,"Insulin glulisine is a short-acting form of insulin used for the treatment of hyperglycemia caused by Type 1 and Type 2 Diabetes. Insulin is typically prescribed for the management of diabetes mellitus to mimic the activity of endogenously produced human insulin, a peptide hormone produced by beta cells of the pancreas that promotes glucose metabolism. Insulin is released from the pancreas following a meal to promote the uptake of glucose from the blood into internal organs and tissues such as the liver, fat cells, and skeletal muscle. Absorption of glucose into cells allows for its transformation into glycogen or fat for storage. Insulin also inhibits hepatic glucose production, enhances protein synthesis, and inhibits lipolysis and proteolysis among many other functions.\r\n\r\nInsulin is an important treatment in the management of Type 1 Diabetes (T1D) which is caused by an autoimmune reaction that destroys the beta cells of the pancreas, resulting in the body not being able to produce or synthesize the insulin needed to manage circulating blood sugar levels. As a result, people with T1D rely primarily on exogenous forms of insulin, such as insulin glulisine, to lower glucose levels in the blood. Insulin is also used in the treatment of Type 2 Diabetes (T2D), another form of diabetes mellitus that is a slowly progressing metabolic disorder caused by a combination of genetic and lifestyle factors that promote chronically elevated blood sugar levels. Without treatment or improvement in non-pharmacological measures such as diet and exercise to lower blood glucose, high blood sugar eventually causes cellular resistance to endogenous insulin, and in the long term, damage to pancreatic islet cells. Insulin is typically prescribed later in the course of T2D, after trying several oral medications such as , , or  have been tried, when sufficient damage has been caused to pancreatic cells that the body is no longer able to produce insulin on its own. \r\n\r\nMarketed as the brand name product Apidra, insulin glulisine begins to exert its effects within 15 minutes of subcutaneous administration, while peak levels occur 30 to 90 minutes after administration. Due to its duration of action of around 5 hours, Apidra is considered \"bolus insulin\" as it provides high levels of insulin in a short period of time to mimic the release of endogenous insulin from the pancreas after meals. Bolus insulin is often combined with once daily, long-acting \"basal insulin\" such as , , and  to provide low concentrations of background insulin that can keep blood sugar stable between meals or overnight. Use of basal and bolus insulin together is intended to mimic the pancreas' production of endogenous insulin, with a goal of avoiding any periods of hypoglycemia.\r\n\r\nInsulin glulisine is a biosynthetic, rapid-acting human insulin analogue produced in a non-pathogenic laboratory strain of _Escherichia coli_ (K12). This recombinant hormone differs from native human insulin in that the amino acid asparagine at position B3 is replaced by lysine and the lysine at position B29 is replaced by glutamic acid. These structural modifications decrease hexamer formation, stabilize insulin glulisine monomers and increase the rate of absorption and onset of action compared to human insulin.\r\n\r\nWithout an adequate supply of insulin to promote absorption of glucose from the bloodstream, blood sugar levels can climb to dangerously high levels and can result in symptoms such as fatigue, headache, blurred vision, and increased thirst. If left untreated, the body starts to break down fat, instead of glucose, for energy which results in a build-up of ketone acids in the blood and a syndrome called ketoacidosis, which is a life-threatening medical emergency. In the long term, elevated blood sugar levels increase the risk of heart attack, stroke, and diabetic neuropathy.","207748-29-6",null,"Insulin glulisine is indicated to improve glycemic control in adults and pediatric patients with diabetes mellitus.","Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, a basal level of insulin is supplemented with insulin spikes following meals. Postprandial insulin spikes are responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin glulisine is a rapid-acting insulin analogue used to mimic postprandial insulin spikes in diabetic individuals. The onset of action of insulin glulisine is approximately 15 minutes. Its activity peaks 60 minutes following subcutaneous injection and its duration of action is 2-4 hours.","Insulin glulisine binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism and catabolism. In humans, insulin is stored in the form of hexamers; however, only insulin monomers are able to interact with IR. Substitution of the arginine at position B3 for lysine and replacement of the B29 lysine with glutamic acid decreases the propensity to form hexamers, stabilizes the hormone in monomeric form and results in a rapid rate of absorption and short duration of action.","Insulin receptor agonist; Insulin-like growth factor 1 receptor activator","Indication associated"]
[488,"DB01319","approved","small molecule","Fosamprenavir","FOS-APV; Fosamprenavir","C25H36N3O9PS","CC(C)CN(C[C@@H](OP(O)(O)=O)[C@H](CC1=CC=CC=C1)NC(=O)O[C@H]1CCOC1)S(=O)(=O)C1=CC=C(N)C=C1","Fosamprenavir is a prodrug of amprenavir, an inhibitor of human immunodeficiency virus (HIV) protease.","226700-79-4","585.607","Indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-1) infection, as well as postexposure prophylaxis of HIV infection in individuals who have had occupational or nonoccupational exposure to potentially infectious body fluids of a person known to be infected with HIV when that exposure represents a substantial risk for HIV transmission. The use of fosamprenavir is pending revision due to a potential association between the drug and myocardial infarction and dyslipidemia in HIV infected adults.","Fosamprenavir is hydrolyzed by cellular phosphatases to the antiretroviral protease inhibitor amprenavir. This hydrolysis allows for the slow release of amprenavir, reducing the number of pills a patient must take.","Fosamprenavir is a prodrug that is rapidly hydrolyzed to amprenavir by cellular phosphatases in the gut epithelium as it is absorbed. Amprenavir is an inhibitor of HIV-1 protease. During HIV replication, HIV protease cleaves viral polypeptide products of the Gag and Gag-Pol genes to form structural proteins of the virion core and essential viral enzymes. Amprenavir interferes with this process by binding to the active site of HIV-1 protease, thereby preventing the processing of viral Gag and Gag-Pol polyprotein precursors, resulting in the formation of immature non-infectious viral particles.","Human immunodeficiency virus type 1 protease inhibitor","Therapeutic strategy associated"]
[489,"DB01321","investigational","small molecule","Josamycin","JM; Josamycin; Kitasamycin A3; Leucomycin A3; leucomycin V 3-acetate 4B-(3-methylbutanoate); leucomycin V 3-acetate 4β-(3-methylbutanoate); Turimycin A5","C42H69NO15","CO[C@H]1[C@@H](CC(=O)O[C@H](C)C\\C=C\\C=C\\[C@H](O)[C@H](C)C[C@H](CC=O)[C@@H]1O[C@@H]1O[C@H](C)[C@@H](O[C@H]2C[C@@](C)(O)[C@@H](OC(=O)CC(C)C)[C@H](C)O2)[C@@H]([C@H]1O)N(C)C)OC(C)=O","A macrolide antibiotic from Streptomyces narbonensis. The drug has antimicrobial activity against a wide spectrum of pathogens.","16846-24-5","827.995","For the treatment of bacterial infections.","Josamycin is a macrolide antibiotic from <i>Streptomyces narbonensis</i>. The drug has antimicrobial activity against a wide spectrum of pathogens.","The mechanism of action of macrolides such as Josamycin is via inhibition of bacterial protein biosynthesis by binding reversibly to the subunit 50S of the bacterial ribosome, thereby inhibiting translocation of peptidyl tRNA. This action is mainly bacteriostatic, but can also be bactericidal in high concentrations. Macrolides tend to accumulate within leukocytes, and are therefore actually transported into the site of infection.","50S ribosomal protein L4 inhibitor","Indication associated"]
[490,"DB01324","approved","small molecule","Polythiazide","Polythiazide","C11H13ClF3N3O4S3","CN1C(CSCC(F)(F)F)NC2=CC(Cl)=C(C=C2S1(=O)=O)S(N)(=O)=O","A thiazide diuretic with actions and uses similar to those of hydrochlorothiazide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p826)","346-18-9","439.882","Polythiazide is a thiazide diuretic used to decrease edema and decrease blood pressure.","As a thiazide diuretic, Polythiazide inhibits the sodium-chloride symporter  which decreases solute reabsorption leading to a retention of water in the urine, as water normally follows solutes. More frequent urination is due to the increased loss of water that has not been retained from the body as a result of a concomitant relationship with sodium loss from the convoluted tubule. The short-term anti-hypertensive action is based on the fact that thiazides decrease preload, decreasing blood pressure","As a diuretic, polythiazide inhibits active chloride reabsorption at the early distal tubule via the thiazide-sensitive Na-Cl cotransporter (TSC), resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like polythiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of polythiazide may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle.","Solute carrier family 12 member 3 inhibitor","Therapeutic strategy associated"]
[491,"DB01325","approved","small molecule","Quinethazone","Quinethazon; Quinethazone","C10H12ClN3O3S","CCC1NC(=O)C2=CC(=C(Cl)C=C2N1)S(N)(=O)=O","Quinethazone, marketed as Hydromox, is a thiazide diuretic indicated for hypertension. Patients may experience adverse reactions such as dizziness, dry mouth, nausea, and hypokalemia.","73-49-4","289.739","Used to treat hypertension.","Quinethazone is a thiazide diuretic used to treat hypertension.  It inhibits Na<sup>+</sup>/Cl<sup>-</sup> reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue.","As a diuretic, quinethazone inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like quinethazone also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of quinethazone is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle.","Carbonic anhydrase 1 inhibitor; Carbonic anhydrase 2 inhibitor; Solute carrier family 12 member 1 inhibitor; Solute carrier family 12 member 2 inhibitor; Solute carrier family 12 member 3 inhibitor","Therapeutic strategy associated"]
[492,"DB01327","approved","small molecule","Cefazolin","(6R,7R)-3-{[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl}-8-oxo-7-[(1H-tetrazol-1-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; Cefamezin; Cefazolin; Cephamezine; Cephazolidin; Cephazolin; Cephazoline; CEZ","C14H14N8O4S3","[H][C@]12SCC(CSC3=NN=C(C)S3)=C(N1C(=O)[C@H]2NC(=O)CN1C=NN=N1)C(O)=O","A semisynthetic cephalosporin analog with broad-spectrum antibiotic action due to inhibition of bacterial cell wall synthesis. It attains high serum levels and is excreted quickly via the urine.","25953-19-9","454.507","Mainly used to treat bacterial infections of the skin. It can also be used to treat moderately severe bacterial infections involving the lung, bone, joint, stomach, blood, heart valve, and urinary tract. It is clinically effective against infections caused by staphylococci and streptococci species of Gram positive bacteria. May be used for surgical prophylaxis; if required metronidazole may be added to cover B. fragilis.","Cefazolin (also known as cefazoline or cephazolin) is a semi-synthetic first generation cephalosporin for parenteral administration. Cefazolin has broad-spectrum antibiotic action due to inhibition of bacterial cell wall synthesis. It attains high serum levels and is excreted quickly via the urine.","In vitro tests demonstrate that the bactericidal action of cephalosporins results from inhibition of cell wall synthesis. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins.","Penicillin-binding protein 1A inhibitor; Penicillin-binding protein 1B inhibitor; Penicillin-binding protein 1C inhibitor; Penicillin-binding protein 2 inhibitor; Peptidoglycan synthase FtsI inhibitor; Serum paraoxonase/arylesterase 1 inhibitor; Interleukin-15 inhibitor; Interleukin-2 inhibitor","Indication associated"]
[493,"DB01328","approved; investigational","small molecule","Cefonicid","(6R,7R)-7-{[(2R)-2-hydroxy-2-phenylacetyl]amino}-8-oxo-3-({[1-(sulfomethyl)-1H-tetrazol-5-yl]sulfanyl}methyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; Cefonicid","C18H18N6O8S3","[H][C@]12SCC(CSC3=NN=NN3CS(O)(=O)=O)=C(N1C(=O)[C@H]2NC(=O)[C@H](O)C1=CC=CC=C1)C(O)=O","A second-generation cephalosporin administered intravenously or intramuscularly. Its bactericidal action results from inhibition of cell wall synthesis. It is used for urinary tract infections, lower respiratory tract infections, and soft tissue and bone infections.","61270-58-4","542.566","For the treatment of bacterial infections caused by susceptible microorganisms.","Cefonicid is a second-generation cephalosporin administered intravenously or intramuscularly. Its bactericidal action results from inhibition of cell wall synthesis. It is used for urinary tract infections, lower respiratory tract infections, and soft tissue and bone infections.","Cefonicid, like the penicillins, is a beta-lactam antibiotic. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins.","Penicillin-binding protein 1A inhibitor; Peptidoglycan synthase FtsI inhibitor; Penicillin-binding protein 1B inhibitor; D-alanyl-D-alanine carboxypeptidase DacB inhibitor; Penicillin-binding protein 2 inhibitor","Indication associated"]
[494,"DB01329","approved; investigational","small molecule","Cefoperazone","(6R,7R)-7-[[2-[(4-ethyl-2,3-dioxopiperazine-1-carbonyl)amino]-2-(4-hydroxyphenyl)acetyl]amino]-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; Cefoperazone","C25H27N9O8S2","[H][C@]12SCC(CSC3=NN=NN3C)=C(N1C(=O)[C@@]2([H])NC(=O)[C@H](NC(=O)N1CCN(CC)C(=O)C1=O)C1=CC=C(O)C=C1)C(O)=O","Cefoperazone is a semisynthetic broad-spectrum cephalosporin proposed to be effective against <i>Pseudomonas</i> infections. It is a third-generation antiobiotic agent and it is used in the treatment of various bacterial infections caused by susceptible organisms in the body, including respiratory tract infections, peritonitis, skin infections, endometritis, and bacterial septicemia. While its clinical use has been discontinued in the U.S., cefoperazone is available in several European countries most commonly under the product name, Sulperazon.","62893-19-0","645.67","Indicated for the treatment of following infections caused by susceptible bacteria:\r\n\r\n1) Respiratory tract infections caused by _S. pneumoniae_, _H. influenzae_, _S. aureus_ (penicillinase and non-penicillinase producing strains), _S. pyogenes_ (Group A beta-hemolytic streptococci), _P. aeruginosa_, _Klebsiella pneumoniae_, _E. coli_, _Proteus mirabilis_, and Enterobacter species.\r\n\r\n2) Peritonitis and other intra-abdominal infections caused by _E. coli_, _P. aeruginosa_, and anaerobic gram-negative bacilli (including _Bacteroides fragilis_).\r\n\r\n3) Bacterial septicemia caused by _S. pneumoniae_, _S. agalactiae_, _S. aureus_, _Pseudomonas aeruginosa_, _E. coli_, _Klebsiella_ spp., _Klebsiella pneumoniae_, Proteus species (indole-positive and indole-negative), _Clostridium_ spp. and anaerobic gram-positive cocci.\r\n\r\n4) Infections of the skin and skin structures caused by S. aureus (penicillinase and non-penicillinase producing strains), S. pyogenes, and P. aeruginosa.\r\n\r\n5) Pelvic Inflammatory Disease, Endometritis, and Other Infections of the Female Genital Tract caused by N. gonorrhoeae, S. epidermidis, S. agalactiae, E. coli, Clostridium spp., Bacteroides species (including Bacteroides fragilis), and anaerobic gram-positive cocci.\r\n\r\n6) Urinary tract infections caused by Escherichia coli and Pseudomonas aeruginosa.\r\n\r\n7) Enterococcal Infections. Although cefoperazone has been shown to be clinically effective in the treatment of infections caused by enterococci in cases of peritonitis and other intra-abdominal infections, infections of the skin and skin structures, pelvic inflammatory disease, endometritis and other infections of the female genital tract, and urinary tract infections, the majority of clinical isolates of enterococci tested are not susceptible to cefoperazone but fall just at or in the intermediate zone of susceptibility, and are moderately resistant to cefoperazone. However, _in vitro_ susceptibility testing may not correlate directly with _in vivo_ results. Despite this, cefoperazone therapy has resulted in clinical cures of enterococcal infections, chiefly in polymicrobial infections. Cefoperazone should be used in enterococcal infections with care and at doses that achieve satisfactory serum levels of cefoperazone.","Cefoperazone is a third generation cephalosporin antibiotic. Cefoperazone exerts its bactericidal effect by inhibiting the bacterial cell wall synthesis","Like all beta-lactam antibiotics, cefoperazone binds to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, causing the inhibition of the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins.","Peptidoglycan synthase FtsI inhibitor; Penicillin-binding protein 1B inhibitor; Penicillin-binding protein 2 inhibitor; Penicillin-binding protein 1A inhibitor; Penicillin-binding protein 1B inhibitor; D-alanyl-D-alanine carboxypeptidase DacC inhibitor; Penicillin-binding protein 1A inhibitor; D-alanyl-D-alanine carboxypeptidase DacA inhibitor; D-alanyl-D-alanine carboxypeptidase DacB inhibitor","Indication associated"]
[495,"DB01330","approved","small molecule","Cefotetan","(6R,7S)-7-(4-(carbamoylcarboxymethylene)-1,3-dithiethane-2-carboxamido)-7-methoxy-3-(((1-methyl-1H-tetrazol-5- yl)thio)methyl)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2- carboxylic acid; Cefotetan","C17H17N7O8S4","[H][C@]12SCC(CSC3=NN=NN3C)=C(N1C(=O)[C@]2(NC(=O)C1SC(S1)=C(C(N)=O)C(O)=O)OC)C(O)=O","A semisynthetic cephamycin antibiotic that is administered intravenously or intramuscularly. The drug is highly resistant to a broad spectrum of beta-lactamases and is active against a wide range of both aerobic and anaerobic gram-positive and gram-negative microorganisms.","69712-56-7","575.619","For prophylaxis and treatment of bacterial infections.","Cefotetan is a semisynthetic cephamycin antibiotic that is administered intravenously or intramuscularly. The drug is highly resistant to a broad spectrum of beta-lactamases and is active against a wide range of both aerobic and anaerobic gram-positive and gram-negative microorganisms.","The bactericidal action of cefotetan results from inhibition of cell wall synthesis by binding and inhibiting the bacterial penicillin binding proteins which help in the cell wall biosynthesis.","Penicillin-binding protein 3 inhibitor","Indication associated"]
[496,"DB01340","approved","small molecule","Cilazapril","Cilazapril anhydrous","C22H31N3O5","CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@H]1CCCN2CCC[C@H](N2C1=O)C(O)=O","Cilazapril is an ACE inhibtor class drug used in the treatment of hypertension and heart failure. It belongs to the angiotensin-converting enzyme inhibitors (ACE inhibitors) class of drugs.  It is a prodrug that is hydrolyzed after absorption to its main metabolite cilazaprilat. It is branded as Inhibace in Canada and other countries, Vascace and Dynorm in a number of European countries, among many other names. None of these varieties are available in the United States.","88768-40-5","417.4986","Cilazapril is an ACE inhibtor class drug used in the treatment of hypertension and heart failure.","Cilazapril inhibits the production angiotensin II. By doing so, it decreases sodium and water reabsorption (via aldosterone) and it decreases vasoconstriction. The combined effect of this is a decrease in vascular resistance, and therefore, blood pressure. The absolute bioavailability of cilazaprilat after oral administration of cilazapril is 57% based on urinary recovery data. (The absolute bioavailability of cilazaprilat after oral administration of cilazaprilat is 19%.) Ingestion of food immediately before the administration of cilazapril reduces the average peak plasma concentration of cilazaprilat by 29%, delays the peak by one hour and reduces the bioavailability of cilazaprilat by 14%. These pharmacokinetic changes have little influence on plasma ACE inhibition.","Cilazapril is a pyridazine ACE inhibitor. It competes with angiotensin I for binding at the angiotensin-converting enzyme, blocking the conversion of angiotensin I to angiotensin II. As angiotensin II is a vasoconstrictor and a negative feedback mediator for renin activity, lower angiotensin II levels results in a decrease in blood pressure, an increase in renin activity, and stimulation of baroreceptor reflex mechanisms. Kininase II, an enzyme which degrades the vasodilator bradykinin, is identical to ACE and may also be inhibited.","Angiotensin-converting enzyme inhibitor","Indication associated"]
[497,"DB01342","experimental","small molecule","Forasartan","Forasartan","C23H28N8","CCCCC1=NN(CC2=CN=C(C=C2)C2=CC=CC=C2C2=NNN=N2)C(CCCC)=N1","Forasartan, a specific angiotensin II antagonist, is used alone or with other antihypertensive agents to treat hypertension. Forasartan competes with angiotensin II for binding at the AT1 receptor subtype. As angiotensin II is a vasoconstrictor which also stimulates the synthesis and release of aldosterone, blockage of its effects results in a decreases in systemic vascular resistance.","145216-43-9","416.522","For the treatment of hypertension.","Forasartan, a specific angiotensin II antagonist, is used alone or with other antihypertensive agents to treat hypertension. By inhibiting angiotensin II receptors, this drug leads to a decrease in sodium reabsorption (which decreases water content of blood) and a decrease in vasoconstriction. Combined, this has the effect of lowering blood pressure.","Forasartan competes with angiotensin II for binding at the AT<sub>1</sub> receptor subtype. As angiotensin II is a vasoconstrictor which also stimulates the synthesis and release of aldosterone, blockage of its effects results in a decreases in systemic vascular resistance. Also, since angiotensin causes vasoconstriction, the inhibition of this receptor decreases vasoconstriction, which consequently also decreases vascular resistnace.","Type-1 angiotensin II receptor antagonist","Target associated"]
[498,"DB01347","experimental","small molecule","Saprisartan","Saprisartan","C25H22BrF3N4O4S","CCC1=NC(C2CC2)=C(N1CC1=CC2=C(OC(=C2Br)C2=CC=CC=C2NS(=O)(=O)C(F)(F)F)C=C1)C(N)=O","Saprisartan is an AT1 receptor antagonist. It is based on medications of losartan's prototypical chemical structure. The mode of (functional) AT1 receptor antagonism has been characterized as insurmountable/noncompetitive for saprisartan.  It is very likely that slow dissociation kinetics from the AT1 receptor underlie insurmountable antagonism .","146623-69-0","611.431","Saprisartan is used in the treatment of hypertension and heart failure.","By inhibiting the angiotensin II receptor, this drug leades to a decrease in sodium reabsorption and a decrease in vasoconstriction. This has the combined effect of decreasing blood pressure.","Saprisartan is a selective, potent, orally active and long-acting nonpeptide Angiotensin II type 1 (AT1) receptor antagonist. Saprisartan blocks the renin-angiotensin-aldosterone system (RAAS) at the level of the AT1 receptor that mediates most, if not all, of the important actions of Ang II.  Saprisartan binds reversibly to the AT1 receptors in vascular smooth muscle and the adrenal gland. As angiotensin II is a vasoconstrictor, which also stimulates the synthesis and release of aldosterone, blockage of its effects results in decreases in systemic vascular resistance. AT1 receptor antagonists avoid the nonspecificity of the Ang I converting enzyme (ACE) inhibitors.","Type-1 angiotensin II receptor antagonist","Target associated"]
[499,"DB01348","approved","small molecule","Spirapril","Spirapril","C22H30N2O5S2","CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@@H](C)C(=O)N1CC2(C[C@H]1C(O)=O)SCCS2","Spirapril is an ACE inhibitor antihypertensive drug used to treat hypertension. Spirapril is converted to the active spiraprilat after administration. ACE inhibitors are used primarily in treatment of hypertension and congestive heart failure.","83647-97-6","466.614","Spirapril is an ACE inhibitor class drug used to treat hypertension.","Spirapril is an angiotensin-converting enzyme (ACE) inhibitor. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. By blocking ACE, spirapril decreases angiotensin II which is a vasoconstrictor and inducer of aldosterone. So by inhibiting the enzymes, aldosterone secreation is decreased (so less sodium is reabsorbed) and there is a decrease in vasoconstriction. Combined, this leades to a decrease in blood pressure.","Spiraprilat, the active metabolite of spirapril, competes with angiotensin I for binding at the angiotensin-converting enzyme, blocking the conversion of angiotensin I to angiotensin II. Inhibition of ACE results in decreased plasma angiotensin II. As angiotensin II is a vasoconstrictor and a negative-feedback mediator for renin activity, lower concentrations result in a decrease in blood pressure and stimulation of baroreceptor reflex mechanisms, which leads to decreased vasopressor activity and to decreased aldosterone secretion. Spiraprilat may also act on kininase II, an enzyme identical to ACE that degrades the vasodilator bradykinin.","Angiotensin-converting enzyme inhibitor","Indication associated"]
[500,"DB01349","experimental","small molecule","Tasosartan","Tasosartan","C23H21N7O","CC1=NC(C)=C2CCC(=O)N(CC3=CC=C(C=C3)C3=CC=CC=C3C3=NNN=N3)C2=N1","Tasosartan is a long-acting angiotensin II (AngII) receptor blocker. Its long duration of action has been attributed to its active metabolite enoltasosartan. It is used to treat patients with essential hypertension.","145733-36-4","411.4591","Tasosartan is infrequently in the treatment of hypertension and heart failure.","By blocking the angiotensin II (AT1) receptor, the drug ultimately causes vasodilation, reduced secretion of vasopressin (ADH), reduced production and secretion of aldosterone, amongst other actions leading to the combined effect of a reduction of blood pressure.","Tasosartan is a selective, potent, orally active and long-acting nonpeptide Angiotensin II type 1 (AT1) receptor antagonist. Tasosartan blocks the renin-angiotensin-aldosterone system (RAAS) at the level of the AT1 receptor that mediates most, if not all, of the important actions of Ang II.  Tasosartan binds reversibly to the AT1 receptors in vascular smooth muscle and the adrenal gland. As angiotensin II is a vasoconstrictor, which also stimulates the synthesis and release of aldosterone, blockage of its effects results in decreases in systemic vascular resistance. AT1 receptor antagonists avoid the nonspecificity of the Ang I converting enzyme (ACE) inhibitors.","Type-1 angiotensin II receptor antagonist; Type-2 angiotensin II receptor antagonist","Target associated"]
[501,"DB01356","experimental","small molecule","Lithium cation","Li(+); Lithium ion; Lithium, ion; Lithium, ion (li1+)","Li","[Li+]","Lithium was used during the 19th century to treat gout. Lithium salts such as lithium carbonate (Li2CO3), lithium citrate, and lithium orotate are mood stabilizers. They are used in the treatment of bipolar disorder, since unlike most other mood altering drugs, they counteract both mania and depression. Lithium can also be used to augment other antidepressant drugs. It is also sometimes prescribed as a preventive treatment for migraine disease and cluster headaches. The active principle in these salts is the lithium ion Li+, which having a smaller diameter, can easily displace K+ and Na+ and even Ca+2, in spite of its greater charge, occupying their sites in several critical neuronal enzymes and neurotransmitter receptors.","7439-93-2","6.941","Lithium, in its salt forms, is used as a mood stabilizer and for the treatment of depression and mania. It is most frequently prescribed in the treatment of bipolar disorder.","Although lithium has been used for over 50 years in treatment of bipolar disorder, the mechanism of action is still unknown. Lithium's therapeutic action may be due to a number of effects, ranging from inhibition of enzymes such as glycogen synthase kinase 3, inositol phosphatases, or modulation of glutamate receptors.","The precise mechanism of action of Li+ as a mood-stabilizing agent is currently unknown. It is possible that Li+ produces its effects by interacting with the transport of monovalent or divalent cations in neurons. An increasing number of scientists have come to the conclusion that the excitatory neurotransmitter glutamate is the key factor in understanding how lithium works. Lithium has been shown to change the inward and outward currents of glutamate receptors (especially GluR3), without a shift in reversal potential. Lithium has been found to exert a dual effect on glutamate receptors, acting to keep the amount of glutamate active between cells at a stable, healthy level, neither too much nor too little.  It is postulated that too much glutamate in the space between neurons causes mania, and too little, depression. Another mechanism by which lithium might help to regulate mood include the non-competitive inhibition of an enzyme called inositol monophosphatase.  Alternately lithium's action may be enhanced through the deactivation of the GSK-3B enzyme.  The regulation of GSK-3B by lithium may affect the circadian clock.  GSK-3 is known for phosphorylating and thus inactivating glycogen synthase. GSK-3B has also been implicated in the control of cellular response to damaged DNA. GSK-3 normally phosphorylates beta catenin, which leads to beta catenin degratation. When GSK-3 is inhibited, beta catenin increases and transgenic mice with overexpression of beta catenin express similar behaviour to mice treated with lithium. These results suggest that increase of beta catenin may be a possible pathway for the therapeutic action of lithium.","Glycogen synthase kinase-3 beta inhibitor; Inositol monophosphatase 1 inhibitor; Inositol monophosphatase 2 inhibitor; Glutamate receptor 3 potentiator","Indication associated"]
[502,"DB01359","approved; investigational","small molecule","Penbutolol","(2S)-1-(tert-butylamino)-3-(2-cyclopentylphenoxy)propan-2-ol; Penbutolol","C18H29NO2","CC(C)(C)NC[C@H](O)COC1=CC=CC=C1C1CCCC1","Penbutolol is a drug in the beta-blocker class used to treat hypertension. Penbutolol binds both beta-1 and beta-2 adrenergic receptors, rendering it a non-selective beta-blocker. Penbutolol can act as a partial agonist at beta adrenergic receptors, since it is a sympathomimetric drug. Penbutolol also demonstrates high binding affinity to the 5-hydroxytryptamine receptor 1A with antagonistic effects. This binding characteristic of penbutolol is being investigated for its implications in Antidepressant Therapy. Penbutolol is contraindicated in patients with cardiogenic shock, sinus bradycardia, second and third degree atrioventricular conduction block, bronchial asthma, and those with known hypersensitivity.","38363-40-5","291.4284","Penbutolol is indicated in the treatment of mild to moderate arterial hypertension. It may be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics.Penbutolol is contraindicated in patients with cardiogenic shock, sinus bradycardia, second and third degree atrioventricular conduction block, bronchial asthma, and those with known hypersensitivity.","Penbutolol is a ß-1, ß-2 (nonselective) adrenergic receptor antagonist. Experimental studies showed a dose-dependent increase in heart rate in reserpinized (norepinephrine-depleted) rats given penbutolol intravenously at doses of 0.25 to 1.0 mg/kg, suggesting that penbutolol has some intrinsic sympathomimetic activity. In human studies, however, heart rate decreases have been similar to those seen with propranolol.","Penbutolol acts on the β1 adrenergic receptors in both the heart and the kidney. When β1 receptors are activated by catecholamines, they stimulate a coupled G protein that leads to the conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP). The increase in cAMP leads to activation of protein kinase A (PKA), which alters the movement of calcium ions in heart muscle and increases the heart rate. Penbutolol blocks the catecholamine activation of β1 adrenergic receptors and decreases heart rate, which lowers blood pressure.","Beta-1 adrenergic receptor antagonist&partial agonist; Beta-2 adrenergic receptor antagonist&partial agonist; 5-hydroxytryptamine receptor 1A antagonist; 5-hydroxytryptamine receptor 1B antagonist","Indication associated"]
[503,"DB01369","approved","small molecule","Quinupristin","Quinupristin","C53H67N9O10S","[H][C@@]12CCCN1C(=O)[C@@H](CC)NC(=O)[C@@H](NC(=O)C1=NC=CC=C1O)[C@@H](C)OC(=O)[C@@H](NC(=O)[C@]1([H])CC(=O)[C@]([H])(CS[C@@H]3CN4CCC3CC4)CN1C(=O)[C@H](CC1=CC=C(C=C1)N(C)C)N(C)C2=O)C1=CC=CC=C1","Quinupristin/dalfopristin is a combination of two antibiotics used to treat infections by staphylococci and by vancomycin-resistant Enterococcus faecium. Dalfopristin inhibits the early phase of protein synthesis in the bacterial ribosome and quinupristin inhibits the late phase of protein synthesis. The combination of the two components acts synergistically and is more effective in vitro than each component alone.","120138-50-3","1022.23","For the treatment of bacterial infections (usually in combination with dalfopristin).","Quinupristin is a streptogramin antibiotic, derived from pristinamycin I. By inhibiting the bacterial ribosomal subunits, protein synthesis is inhibited thus leading to eventual bacterial cell death or stasis.","Quinupristin inhibits the late phase of protein synthesis in the bacterial ribosome. Dalfopristin binds to the 23S portion of the 50S ribosomal subunit, and changes the conformation it, enhancing the binding of quinupristin by a factor of about 100. In addition, it inhibits peptidyl transferase. Quinupristin binds to a nearby site on the 50S ribosomal subunit and prevents elongation of the polypeptide as well as causing incomplete chains to be released.","23S ribosomal RNA inhibitor; 50S ribosomal protein L10 inhibitor; 50S ribosomal protein L22 inhibitor","Indication associated"]
[504,"DB01377","approved","small molecule","Magnesium oxide","Magnesia; Magnesium oxide","MgO","[O--].[Mg++]","Magnesium oxide is an inorganic compound that occurs in nature as the mineral periclase. In aqueous media combines quickly with water to form magnesium hydroxide. It is used as an antacid and mild laxative and has many nonmedicinal uses.","1309-48-4","40.304","Indicated for over-the-counter use as a supplement for cardiovascular and neuromuscular health, and as an antacid for relief of acid indigestion and upset stomach.",null,"The term \"Milk of Magnesia\" was first used to describe a white aqueous, mildly alkaline suspension of magnesium hydroxide formulated at about 8%w/v. Milk of magnesia is primarily used to alleviate constipation, but can also be used to relieve indigestion and heartburn. When taken internally by mouth as a laxative, the osmotic force of the magnesia suspension acts to draw fluids from the body and to retain those already within the lumen of the intestine, serving to distend the bowel, thus stimulating nerves within the colon wall, inducing peristalsis and resulting in evacuation of colonic contents. Magnesium supplements have also been shown to reduce platelet aggregation by inhibiting in the influx of calcium, a crucial component of platelet aggregation.",null,"Therapeutic strategy associated"]
[505,"DB01380","approved; investigational","small molecule","Cortisone acetate","Cortisone 21-acetate; Cortisone acetate; Cortone acetate","C23H30O6","[H][C@@]12CC[C@](O)(C(=O)COC(C)=O)[C@@]1(C)CC(=O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C","Cortisone acetate was first isolate in 1935 and became more widely researched in 1949. Since then, glucocorticoids such as cortisone acetate have been used to treat a number of inflammatory conditions such as endocrine, rheumatic, collagen, dermatologic, allergic, ophthalmic, respiratory, hematologic, neoplastic, edematous, and gastrointestinal diseases and disorders.\r\n\r\nCortisone acetate was granted FDA approval on 13 June 1950.","50-04-4","402.4807","Cortisone acetate is indicated to treat a wide variety of endocrine, rheumatic, collagen, dermatologic, allergic, ophthalmic, respiratory, hematologic, neoplastic, edematous, and gastrointestinal diseases and disorders.","Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals. The duration of action is moderate as it is generally given once daily. Corticosteroids have a wide therapeutic window as patients may require doses that are multiples of what the body naturally produces. Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.","The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.\r\nGlucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10.\r\nLower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.","Glucocorticoid receptor agonist; Annexin A1 inducer","Therapeutic strategy associated"]
[506,"DB01381","approved; investigational; nutraceutical","biotech","Ginkgo biloba","Common ginkgo leaf; Ginkgo; Ginkgo biloba extract; Ginkgo biloba leaf; Ginkgo biloba leaf dry extract; Ginkgo biloba leaf tincture; Ginkgo extract; Ginkgo folium; Ginkgo leaf; Ginkgo macrophylla leaf; Maidenhair extract; Maidenhair tree leaf; Pterophyllus salisburiensis leaf; Salisburia adiantifolia leaf; Salisburia biloba leaf; Salisburia ginkgo leaf; Salisburia macrophylla leaf; Tanakan; Yinxingye",null,null,"_Ginkgo biloba_ extract contains a group of terpene lactones (notably, ginkgolides and diterpenes) and ginkgo flavone glycosides (notably, ginkgetin, bilobetin, and sciadopitysin) that have antioxidant and vasoactive properties. Most of the studies that investigate the effect of _ginkgo biloba_ use the standardized extract of _Ginkgo biloba_ (EGb) 761 (EGb761), which was developed by a German pharmaceutical company in 1964. EGb761 contains 6% terpene lactones and 24% flavonoid glycosides. Flavonoids include quercetin, rutin, kaempferol, and isorhamnetin. Lactones include ginkgolide A, ginkgolide B, ginkgolide C, bilobalide, and ginkgotoxin, a lactone that is structurally related to . _Ginkgo biloba_ is an herbal plant that is now cultivated worldwide. It is originally native to China, and _ginkgo biloba_ extract has been used in traditional Chinese medicine for centuries.\r\n\r\nAfter its nootropic properties were discovered, _ginkgo biloba_ has gained attention as a therapeutic ingredient for memory and concentration enhancement in cognitive impairment and neurogenerative diseases, such as dementia. _Ginkgo biloba_ was investigated in preliminary studies for a variety of therapeutic purposes such as improving cardiovascular health, sexual dysfunction, psychiatric disorders, skin disorders, and glaucoma. _Ginkgo biloba_ is found in a number of homeopathic and over-the-counter herbal products and dietary supplements, but it has no approved therapeutic indications by regulatory bodies, such as the FDA, EMA, and Health Canada. _Ginkgo folium_, the leaf extract of _Ginkgo biloba_, is considered an anti-dementia drug by the World Health Organization.","90045-36-6",null,"_Ginkgo biloba_ does not currently have any approved therapeutic indications, and there is insufficient evidence to support its unapproved use. It is available in over-the-counter herbal products mostly for oral use, to improve memory and cognitive problems.","_Ginkgo biloba_ is a herbal ingredient with demonstrated antioxidant, vasoactive, antiapoptotic, anti-inflammatory, antiplatelet, and fibrinolytic properties. _Ginkgo biloba_ has been investigated for use in a variety of medical conditions, but the most extensively studied area is in the context of cognitive impairment and neurodegenerative disorders. _Ginkgo biloba_ was examined as a potential nootropic agent or cognitive enhancer but research findings supporting the therapeutic efficacy of _ginkgo biloba_ extract (EGb) in dementia remain controversial. Some clinical studies of dementia that were up to one year long showed that EGb improves the cognitive performance and social functioning of patients. However, other studies did not support its clinical benefit for patients with cognitive impairment and dementia. Numerous meta-analysis studies showed insufficient evidence of the effectiveness of EGb in reducing both all-cause dementia incidence and Alzheimer's disease-associated dementia incidence in elderly patients with normal cognition or with mild cognitive impairment. Additionally, there is no up-to-date evidence that demonstrates the benefit of the long-term use of standardized EGb in reducing the risk of progression to Alzheimer's disease. A 2012 meta-analysis did not support the use of EGb in enhancing cognitive function in healthy adults.\r\n\r\nIn the context of cardiovascular diseases, a limited number of studies showed that EGb improved mortality or neurological recovery in the post-stroke period, reduced cognitive and neurological impairment after acute ischemic stroke, and improved blood flow in the coronary artery in patients with coronary artery disease. However, a systemic review found no statistical or clinically significant benefit of EGb for patients with peripheral arterial disease or hypertension. Overall, there is a lack of strong evidence in the use of EGb for the treatment or prevention of cardiovascular diseases.\r\n\r\nIn a small trial, the use of EGb as an adjunctive treatment with citalopram improved depressive symptoms and cognitive function in patients with depression. _Ginkgo biloba_ was also investigated as a potential treatment for antidepressant-induced sexual dysfunction. Another study showed EGb improving the symptoms of tardive dyskinesia. There is insufficient evidence to prove the effectiveness of EGb in these psychiatric disorders. Limited studies have investigated the role of _ginkgo biloba_ in the treatment of vertigo, tinnitus, vitiligo, macular degeneration, and glaucoma, as well as the prevention of acute mountain sickness. As results are either preliminary or controversial, more quality research is warranted.","Two key active ingredients in _ginkgo biloba_ are terpene lactones (notably ginkgolides and diterpenes) and ginkgo flavone glycosides (notably ginkgetin, bilobetin, and sciadopitysin), which are present at varying concentrations. _Ginkgo biloba_ extract EGb 761 is the standardized extract of _ginkgo biloba_ used in studies, which contains 6% terpenoids and 24% flavonoid glycosides. Animal studies have shown that _ginkgo biloba_ works on several neurotransmitter pathways and brain structures. Flavones were shown to inhibit lipid peroxidation; inhibit the uptake of serotonin, dopamine, and norepinephrine; and inhibit platelet aggregation. Terpene lactones may also act as potent antagonists of the platelet-activating factor and may possess anti-ischemic and fibrinolytic effects. They were also shown to downregulate adrenal peripheral benzodiazepine receptors and increase adrenocorticotropic hormone levels. _Ginkgo biloba_ also reversibly inhibits monoamine oxidase A; and modestly inhibits anticholinesterase activity, leading to enhanced cholinergic transmission in the brain. \r\n\r\nSeveral studies suggest that _ginkgo biloba_ exerts neuroprotective effects by reducing free radical production in the prefrontal cortex, which may explain its improvement on short-term memory. _Ginkgo biloba_ extract acts as a free radical scavenger, protecting neurons from oxidative damage and apoptosis related to aging, cerebral ischemia, and neurodegenerative disorders. _Ginkgo biloba_ also inhibits amyloid-β neurotoxicity and protects against hypoxic challenges and increased oxidative stress. One study showed that bilobalide, a terpene lactone, delays the onset of hypoxic glycolysis. _Ginkgo biloba_ has the potential to regulate metabolism, stabilize the membrane, and promote vasodilation. In the arterial endothelium, EGb stimulated the release of endogenous relaxing factors, such as endothelium-derived relaxing factor and prostacyclin. In the inflammatory environment that causes tissue damage, EGb promoted nitric oxide production, leading to enhanced peripheral and cerebral blood flow.","Sodium-dependent noradrenaline transporter inhibitor; Phospholipase A2, membrane associated inhibitor; Glycine receptor subunit alpha-1 antagonist; Gamma-aminobutyric acid receptor subunit alpha-1 negative modulator; Gamma-aminobutyric acid receptor subunit beta-2 negative modulator; Gamma-aminobutyric acid receptor subunit gamma-2 negative modulator; Amine oxidase [flavin-containing] A inhibitor; Nitric oxide synthase, inducible inhibitor","Therapeutic strategy associated"]
[507,"DB01382","approved; investigational","small molecule","Glymidine","Glidiazine; Glycodiazine; Glymidine","C13H15N3O4S","COCCOC1=CN=C(NS(=O)(=O)C2=CC=CC=C2)N=C1","Glycodiazine is used with diet to lower blood glucose by increasing the secretion of insulin from pancreas and increasing the sensitivity of peripheral tissues to insulin. The mechanism of action of glycodiazine in lowering blood glucose appears to be dependent on stimulating the release of insulin from functioning pancreatic beta cells, and increasing sensitivity of peripheral tissues to insulin. Glycodiazine likely binds to ATP-sensitive potassium channel receptors on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Membrane depolarization stimulates calcium ion influx through voltage-sensitive calcium channels. This increase in intracellular calcium ion concentration induces the secretion of insulin. It is used for the concomitant use with insulin for the treatment of noninsulin-dependent (type 2) diabetes mellitus.","339-44-6","309.341","Glycodiazine is used concomitantly with insulin for the treatment of noninsulin-dependent (type 2) diabetes mellitus.","Glycodiazine is used with diet to lower blood glucose by increasing the secretion of insulin from pancreas and increasing the sensitivity of peripheral tissues to insulin.","The mechanism of action of glycodiazine in lowering blood glucose appears to be dependent on stimulating the release of insulin from functioning pancreatic beta cells, and increasing sensitivity of peripheral tissues to insulin. Glycodiazine likely binds to ATP-sensitive potassium channel receptors on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Membrane depolarization stimulates calcium ion influx through voltage-sensitive calcium channels. The rise in intracellular calcium leads to increased fusion of insulin granulae with the cell membrane, and therefore increased secretion of (pro)insulin.","ATP-sensitive inward rectifier potassium channel 1 other/unknown; ATP-binding cassette sub-family C member 8 inducer","Indication associated"]
[508,"DB01384","experimental","small molecule","Paramethasone","Paramethasone","C22H29FO5","[H][C@@]12C[C@@H](C)[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])C[C@H](F)C2=CC(=O)C=C[C@]12C","A glucocorticoid with the general properties of corticosteroids. It has been used by mouth in the treatment of all conditions in which corticosteroid therapy is indicated except adrenal-deficiency states for which its lack of sodium-retaining properties makes it less suitable than hydrocortisone with supplementary fludrocortisone. (From Martindale, The Extra Pharmacopoeia, 30th ed, p737)","53-33-8","392.4611","For the treatment of all conditions in which corticosteroid therapy is indicated except adrenal-deficiency states for which its lack of sodium-retaining properties makes it less suitable than hydrocortisone with supplementary fludrocortisone.","Paramethasone is a glucocorticoid with the general properties of corticosteroids. Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger a variety of important cardiovascular, metabolic, immunologic and homeostatic effects. Glucocorticoids are distinguished from mineralocorticoids and sex steroids by having different receptors, target cells, and effects. Technically, the term corticosteroid refers to both glucocorticoids and mineralocorticoids, but is often used as a synonym for glucocorticoid. Glucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-alpha, the most important of which is the IL-2. Reduced cytokine production limits T cell proliferation. Glucocorticoids also suppress humoral immunity, causing B cells to express lower amounts of IL-2 and IL-2 receptors. This diminishes both B cell clonal expansion and antibody synthesis. The diminished amounts of IL-2 also leads to fewer T lymphocyte cells being activated.","Glucocorticoids such as paramethasone can inhibit leukocyte infiltration at the site of inflammation, interfere with mediators of inflammatory response, and suppress humoral immune responses. The antiinflammatory actions of glucocorticoids are thought to involve phospholipase A2 inhibitory proteins, lipocortins, which control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes. Paramethasone reduces inflammatory reaction by limiting the capillary dilatation and permeability of the vascular structures. These compounds restrict the accumulation of polymorphonuclear leukocytes and macrophages and reduce the release of vasoactive kinins. Recent research suggests that corticosteroids may inhibit the release of arachidonic acid from phospholipids, thereby reducing the formation of prostaglandins. Prednisolone is a glucocorticoid receptor agonist. On binding, the corticoreceptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing an increase or decrease in expression of specific target genes, including suppression of IL2 (interleukin 2) expression.","Glucocorticoid receptor agonist","Therapeutic strategy associated"]
[509,"DB01390","approved","small molecule","Sodium bicarbonate","Baking soda; Bicarbonate of soda; Carbonic acid monosodium salt; NaHCO3; Sodium acid carbonate; Sodium bicarbonate; Sodium hydrogen carbonate; Sodium hydrogencarbonate","CHNaO3","[Na+].OC([O-])=O","Sodium bicarbonate is a white, crystalline powder that is commonly used as a pH buffering agent, an electrolyte replenisher, systemic alkalizer and in topical cleansing solutions.","144-55-8","84.0066","Sodium bicarbonate is used for the treatment of metabolic acidosis which may occur in severe renal disease, uncontrolled diabetes, circulatory insufficiency due to shock or severe dehydration, extracorporeal circulation of blood, cardiac arrest and severe primary lactic acidosis. Also is indicated in severe diarrhea which is often accompanied by a significant loss of bicarbonate. Further indicated in the treatment of certain drug intoxications, including barbiturates (where dissociation of the barbiturateprotein complex is desired), in poisoning by salicylates or methyl alcohol and in hemolytic reactions requiring alkalinization of the urine to diminish nephrotoxicity of blood pigments.","Intravenous sodium bicarbonate therapy increases plasma bicarbonate, buffers excess hydrogen ion concentration, raises blood pH and reverses the clinical manifestations of acidosis.","Sodium bicarbonate is a systemic alkalizer, which increases plasma bicarbonate, buffers excess hydrogen ion concentration, and raises blood pH, thereby reversing the clinical manifestations of acidosis. It is also a urinary alkalizer, increasing the excretion of free bicarbonate ions in the urine, thus effectively raising the urinary pH. By maintaining an alkaline urine, the actual dissolution of uric acid stones may be accomplished. Sodium bicarbonate acts as an antacid and reacts chemically to neutralize or buffer existing quantities of stomach acid but has no direct effect on its output. This action results in increased pH value of stomach contents, thus providing relief of hyperacidity symptoms.","Hydrogen ions neutralizer","Indication associated"]
[510,"DB01392","approved; investigational; vet_approved","small molecule","Yohimbine","(+)-yohimbine; (16α,17α)-17-hydroxyyohimban-16-carboxylic acid methyl ester; 17α-hydroxyyohimban-16α-carboxylic acid methyl ester; Yohimbic acid methyl ester; Yohimbine","C21H26N2O3","[H][C@@]12CC[C@H](O)[C@H](C(=O)OC)[C@@]1([H])C[C@]1([H])N(CCC3=C1NC1=CC=CC=C31)C2","A plant alkaloid with alpha-2-adrenergic blocking activity. Yohimbine has been used as a mydriatic and in the treatment of impotence. It is also alleged to be an aphrodisiac.","146-48-5","354.4427","Indicated as a sympatholytic and mydriatic. Impotence has been successfully treated with yohimbine in male patients with vascular or diabetic origins and psychogenic origins.","Yohimbine is an indolalkylamine alkaloid with chemical similarity to reserpine. Yohimbine blocks presynaptic alpha-2 adrenergic receptors. Its action on peripheral blood vessels resembles that of reserpine, though it is weaker and of short duration. Yohimbine's peripheral autonomic nervous system effect is to increase parasympathetic (cholinergic) and decrease sympathetic (adrenergic) activity. It is to be noted that in male sexual performance, erection is linked to cholinergic activity and to alpha-2 adrenergic blockade which may theoretically result in increased penile inflow, decreased penile outflow or both. Yohimbine exerts a stimulating action on the mood and may increase anxiety. Such actions have not been adequately studied or related to dosage although they appear to require high doses of the drug. Yohimbine has a mild anti-diuretic action, probably via stimulation of hypothalmic center and release of posterior pituitary hormone. Reportedly Yohimbine exerts no significant influence on cardiac stimulation and other effects mediated by (beta)-adrenergic receptors. Its effect on blood pressure, if any, would be to lower it; however, no adequate studies are at hand to quantitate this effect in terms of Yohimbine dosage.","Yohimbine is a pre-synaptic alpha 2-adrenergic blocking agent. The exact mechanism for its use in impotence has not been fully elucidated. However, yohimbine may exert its beneficial effect on erectile ability through blockade of central alpha 2-adrenergic receptors producing an increase in sympathetic drive secondary to an increase in norepinephrine release and in firing rate of cells in the brain noradrenergic nuclei. Yohimbine-mediated norepinephrine release at the level of the corporeal tissues may also be involved. In addition, beneficial effects may involve other neurotransmitters such as dopamine and serotonin and cholinergic receptors.","Alpha-2A adrenergic receptor antagonist; Alpha-2B adrenergic receptor antagonist; Alpha-2C adrenergic receptor antagonist; 5-hydroxytryptamine receptor 1A partial agonist; 5-hydroxytryptamine receptor 1B partial agonist; 5-hydroxytryptamine receptor 1D partial agonist; Dopamine D2 receptor antagonist; Dopamine D3 receptor antagonist; 5-hydroxytryptamine receptor 2A antagonist; 5-hydroxytryptamine receptor 2C antagonist; ATP-sensitive potassium channel inhibitor; 5-hydroxytryptamine receptor 2B antagonist","Indication associated"]
[511,"DB01394","approved","small molecule","Colchicine","Colchicine","C22H25NO6","COC1=CC2=C(C(OC)=C1OC)C1=CC=C(OC)C(=O)C=C1[C@H](CC2)NC(C)=O","First approved by the FDA in 1961, colchicine is an alkaloid drug commonly used in the management of gout, a condition associated with the painful deposition of urate crystals in the joints. It is derived from a plant belonging to the Lily family, known as Colchicum autumnale, or \"autumn crocus\". Other than its use in gout, colchicine has been approved for managing exacerbations of Familial Mediterranean Fever (FMF), a hereditary autoinflammatory condition.","64-86-8","399.443","Colchicine is indicated for the prophylaxis and treatment of gout flares. It is also indicated in Familial Mediterranean fever (FMF) in children and adults of 4 years of age and older. It is important to note that this medication is not a pain reliever to be used for other painful conditions. Consider analgesics for this purpose. Some off-label uses of colchicine include the treatment of the manifestations of Behcet's syndrome, pericarditis, and postpericardiotomy syndrome.","Colchicine reduces the pain resulting from gout and reduces flares of Familial Mediterranean fever by interfering with inflammatory pathways. This drug has a narrow therapeutic index.","The exact mechanism of action of colchicine has not been fully established, however likely occurs via the downstream inhibition of inflammation caused by tubulin disruption. Studies have implied that that colchicine causes disruption of the inflammasome complex that is present in both monocytes and neutrophils, which normally leads to the activation of interleukin-1, an important mediator of inflammation. In addition to the above actions, colchicine acts to interfere with pathways including neutrophil adhesion and recruitment, superoxide production, the RhoA/Rho effector kinase (ROCK) pathway, as well as a type of nuclear factor κΒ (NF-κΒ) pathway, reducing inflammation. \r\n\r\nOn a molecular level, colchicine can be described as an anti-mitotic drug, blocking the mitotic activity cells in the metaphase part of the cell cycle. Specifically, colchicine binds to tubulin, forming complexes that bind to microtubules. This stops their elongation. At low concentrations, colchicine stops microtubule growth and, at elevated concentrations, colchicine causes the depolymerization of microtubules.","Tubulin beta chain inhibitor&binder","Therapeutic strategy associated"]
[512,"DB01395","approved","small molecule","Drospirenone","1,2-Dihydrospirorenone; 6β,7β;15β,16β-Dimethylene-3-oxo-17α-pregn-4-ene-21,17-carbolactone; Dehydrospirorenone; Drospirenone; DRSP","C24H30O3","[H][C@@]12C[C@]1([H])[C@@]1([H])[C@]3([H])[C@]4([H])C[C@]4([H])[C@@]4(CCC(=O)O4)[C@@]3(C)CC[C@]1([H])[C@@]1(C)CCC(=O)C=C21","Drospirenone is a synthetic progestin commonly found in the popular oral contraceptive, Yaz in combination with . Most recently, it was approved by both Health Canada and the FDA in combination with  as an oral contraceptive therapy.  Aside from its contraceptive effects, drospirenone is used with estrogens to control acne and premenstrual dysphoric disorder (PMDD).\r\n\r\nDrospirenone has been the subject of widespread safety concern due to the possibility of an increased risk of venous thromboembolism associated with its use. In 2012, however, a safety statement by the FDA concluded that the increase in the risk of thromboembolism resulting from the use of drospirenone remains unclear, as studies regarding this risk are conflicting. Some studies have demonstrated a significantly increased risk and some demonstrating no risk of thromboembolic events.  In its statement, the FDA has mentioned that increased risk of venous thromboembolism with oral contraceptives such as drospirenone exists but remains lower than the risk of this condition during pregnancy and during the postpartum period, and this should be considered when assessing potential risks of hormonal contraceptive use.","67392-87-4","366.4932","Drospirenone, in combination with ethinyl estradiol or estetrol, is indicated as an oral contraceptive for the prevention of pregnancy. In addition to its use for contraceptive effects, this combination is used to treat moderate acne vulgaris and the symptoms of premenstrual dysphoric disorder.  The drug has approved indications for combination with estrogens for the treatment of menopause-associated symptoms, such as vasomotor symptoms and vulvovaginal atrophy. Drospirenone combined with estrogen may also may aid in the prevention of osteoporosis in women who have been post-menopausal for at least a year and are not candidates for other therapies.   It can sometimes be found in preparations containing estrogen and folic acid for folic acid replenishment during oral contraception.\r\n\r\nWhen used for the treatment of acne vulgaris, drospirenone-containing contraceptives should only be used in women ≥14 years of age who have experienced menarche, desire oral contraception, and do not have any contraindications to oral contraceptives. Off-label uses for this drug include the treatment of menstrual irregularities, dysmenorrhea, hirsutism, and endometriosis.","Drospirenone inhibits the maturation of follicles and inhibits ovulation, preventing pregnancy.  It has antiandrogen effects, improving acne and hirsutism. When combined with ethinyl estradiol, it has been shown to have favorable effects on the plasma lipid profile. Due to its similarity to naturally occurring progesterone, drospirenone is thought to be associated with a lower incidence of progesterone contraceptive related adverse effects, such as breast tenderness and mood swings.\r\n\r\n**A note on venous thromboembolism risk and antimineralcorticoid effects**\r\n\r\nAs with other oral contraceptives, the risk of venous thromboembolism and cardiovascular events may be increased when drospirenone is taken. The risk is especially higher in smokers and women aged 35 and older. Women taking this drug should be advised not to smoke. In addition, drospirenone, due to its antimineralcorticoid effects, may increase the risk of hyperkalemia. Patients at high risk for hyperkalemia should not be administered this drug. Consult the official prescribing information for detailed and updated information on the cardiovascular and other risks associated with drospirenone use.","Drospirenone and ethinyl estradiol in combination suppress the release of follicle stimulating hormone (FSH) and luteinizing hormone (LH), preventing ovulation. Other changes induced by this drug which may aid in the prevention of pregnancy include alterations in cervical mucus consistency, hindering sperm movement, and lowering the chance of embryo implantation.\r\n\r\nDrospirenone is an analog of the diuretic spironolactone, which exerts anti-mineralocorticoid activity, blocking aldosterone receptors, which increases sodium and water excretion. Studies in animals have demonstrated that drospirenone administration leads to antiandrogenic activity. This activity helps to oppose the effects of naturally occurring androgens, inhibiting the binding of dihydrotestosterone (DHT) to its receptor, and preventing androgen synthesis in the ovaries, helping to treat acne and hirsutism. Drospirenone may also decrease the level of edema in sebaceous follicle during the second half of the menstrual cycle, when acne often appears.","Progesterone receptor agonist; Mineralocorticoid receptor antagonist; Androgen receptor antagonist; Glucocorticoid receptor binder","Indication associated"]
[513,"DB01401","approved","small molecule","Choline magnesium trisalicylate",null,"C26H29MgNO10","[Mg++].C[N+](C)(C)CCO.OC1=CC=CC=C1C([O-])=O.OC1=CC=CC=C1C([O-])=O.OC1=CC=CC=C1C([O-])=O","Choline magnesium trisalicylate is a non-acetylated salicylate used widely as a nonsteroidal anti-inflammatory drug. Trisalicylate significantly reduces methotrexate renal clearance, displacing methotrexate from protein, increasing the fraction unbound by 28% .","64425-90-7","539.814","Choline magnesium trisalicylate is used to reduce pain and inflammation caused by conditions such as arthritis. This medication is also used to treat fever in adults.","Trisalicylate-choline is a non-steroidal anti-inflammatory drug (NSAID) that contains a combination of choline salicylate and magnesium salicylate. Does not affect platelet aggregation.","Inhibits prostaglandin synthesis; acts on the hypothalamus heat-regulating center to reduce fever; blocks the generation of pain impulses","Prostaglandin G/H synthase 1 inhibitor; Prostaglandin G/H synthase 2 inhibitor","Therapeutic strategy associated"]
[514,"DB01407","approved; investigational; vet_approved","small molecule","Clenbuterol","(±)-clenbuterol; 1-(4-Amino-3,5-dichloro-phenyl)-2-tert-butylamino-ethanol; 4-amino-3,5-dichloro-α-(((1,1-dimethylethyl)amino)methyl)benzenemethanol; 4-amino-α-((tert-butylamino)methyl)-3,5-dichlorobenzyl alcohol","C12H18Cl2N2O","CC(C)(C)NCC(O)C1=CC(Cl)=C(N)C(Cl)=C1","A substituted phenylaminoethanol that has beta-2 adrenomimetic properties at very low doses. It is used as a bronchodilator in asthma.","37148-27-9","277.19","Used as a bronchodilator in the treatment of asthma patients.","Clenbuterol is a substituted phenylaminoethanol that has beta-2 adrenomimetic properties at very low doses. It is used as a bronchodilator in asthma. Although approved for use in some countries, as of fall, 2006, clenbuterol is not an ingredient of any therapeutic drug approved by the U.S. Food and Drug Administration.","Clenbuterol is a Beta(2) agonist similar in some structural respects to salbutamol. Agonism of the beta(2) receptor stimulates adenylyl cyclase activity which ultimately leads to downstream effects of smooth muscle relaxation in the bronchioles.","Beta-2 adrenergic receptor agonist; Beta-1 adrenergic receptor agonist; Beta-3 adrenergic receptor agonist; Beta-nerve growth factor stimulator; Tumor necrosis factor other/unknown","Target associated"]
[515,"DB01410","approved; investigational","small molecule","Ciclesonide","Ciclesonide","C32H44O7","[H][C@@]12C[C@@]3([H])[C@]4([H])CCC5=CC(=O)C=C[C@]5(C)[C@@]4([H])[C@@H](O)C[C@]3(C)[C@@]1(O[C@@H](O2)C1CCCCC1)C(=O)COC(=O)C(C)C","Ciclesonide is a glucocorticoid used to treat obstructive airway diseases. It is marketed under the brand name Alvesco.","126544-47-6","540.697","For the treatment of nasal symptoms associated with seasonal and perennial allergic rhinitis in adults and adolescents 12 years of age and older.","Ciclesonide is a pro-drug that is enzymatically hydrolyzed to a pharmacologically active metabolite, C21-desisobutyryl-ciclesonide (des-ciclesonide or RM1) following intranasal application. Des-ciclesonide has anti-inflammatory activity with affinity for the glucocorticoid receptor that is 120 times higher than the parent compound. The precise mechanism through which ciclesonide affects allergic rhinitis symptoms is not known. Corticosteroids have been shown to have a wide range of effects on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, and cytokines) involved in allergic inflammation.","Glucocorticoids such as ciclesonide can inhibit leukocyte infiltration at the site of inflammation, interfere with mediators of inflammatory response, and suppress humoral immune responses. The antiinflammatory actions of glucocorticoids are thought to involve phospholipase A2 inhibitory proteins, lipocortins, which control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes. Ciclesonide reduces inflammatory reaction by limiting the capillary dilatation and permeability of the vascular structures. These compounds restrict the accumulation of polymorphonuclear leukocytes and macrophages and reduce the release of vasoactive kinins. Recent research suggests that corticosteroids may inhibit the release of arachidonic acid from phospholipids, thereby reducing the formation of prostaglandins. Ciclesonide is a glucocorticoid receptor agonist. On binding, the corticoreceptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing an increase or decrease in expression of specific target genes, including suppression of IL2 (interleukin 2) expression.","Glucocorticoid receptor agonist","Therapeutic strategy associated"]
[516,"DB01411","investigational","small molecule","Pranlukast","Pranlukast","C27H23N5O4","O=C(NC1=C2OC(=CC(=O)C2=CC=C1)C1=NNN=N1)C1=CC=C(OCCCCC2=CC=CC=C2)C=C1","Pranlukast is a cysteinyl leukotriene receptor-1 antagonist. It antagonizes or reduces bronchospasm caused, principally in asthmatics, by an allergic reaction to accidentally or inadvertently encountered allergens.","103177-37-3","481.512","Used as an adjunct to the standard therapy of inhaled steroids with inhaled long- and/or short-acting beta-agonists.","Pranlukast is a cysteinyl leukotriene receptor-1 antagonist.","Pranlukast selectively antagonizes leukotriene D<sub>4</sub> (LTD<sub>4</sub>) at the cysteinyl leukotriene receptor, CysLT<sub>1</sub>, in the human airway. Pranlukast inhibits the actions of LTD<sub>4</sub> at the CysLT<sub>1</sub> receptor, preventing airway edema, smooth muscle contraction, and enhanced secretion of thick, viscous mucus.","Cysteinyl leukotriene receptor 1 antagonist; Tumor necrosis factor other/unknown; Interleukin-5 antagonist; Eosinophil cationic protein other/unknown; Nuclear factor NF-kappa-B p105 subunit other/unknown; Mucin-2 other/unknown","Target associated"]
[517,"DB01413","approved; investigational","small molecule","Cefepime","(6R,7R)-7-{[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl]amino}-3-[(1-methylpyrrolidinium-1-yl)methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate; Cefepime","C19H24N6O5S2","CO\\N=C(/C(=O)N[C@@H]1C(=O)N2[C@]1([H])SCC(C[N+]1(C)CCCC1)=C2C([O-])=O)C1=CSC(N)=N1","Cefepime is a fourth-generation cephalosporin antibiotic developed in 1994. Cefepime is active against Gram-positive and Gram-negative bacteria, with greater activity against both than third-generation antibiotics. Cefepime is usually reserved to treat severe nosocomial pneumonia, infections caused by multi-resistant microorganisms (e.g. Pseudomonas aeruginosa) and empirical treatment of febrile neutropenia.","88040-23-7","480.561","For the treatment of pneumonia (moderate to severe) caused by <i>Streptococcus pneumoniae</i>, including cases associated with concurrent bacteremia, <i>Pseudomonas aeruginosa</i>, <i>Klebsiella pneumoniae</i>, or <i>Enterobacter</i> species. Also for empiric treatment of febrile neutropenic patients and uncomplicated and complicated urinary tract infections (including pyelonephritis) caused by <i>Escherichia coli</i> or <i>Klebsiella pneumoniae</i>, when the infection is severe, or caused by <i>Escherichia coli</i>, <i>Klebsiella pneumoniae</i>, or <i>Proteus mirabilis</i>, when the infection is mild to moderate, including cases associated with concurrent bacteremia with these microorganisms. Also for the treatment of uncomplicated skin and skin structure infections caused by <i>Staphylococcus aureus</i> (methicillin-susceptible strains only) or <i>Streptococcus pyogenes</i> and complicated intra-abdominal infections (used in combination with metronidazole) caused by <i>Escherichia coli</i>, viridans group streptococci, <i>Pseudomonas aeruginosa</i>, <i>Klebsiella pneumoniae</i>, <i>Enterobacter</i> species, or <i>Bacteroides fragilis</i>.","Cefepime is a fourth-generation cephalosporin antibiotic developed in 1994. Cefepime is active against Gram-positive and Gram-negative bacteria, with greater activity against both than third-generation antibiotics. Cefepime has good activity against important pathogens including Pseudomonas aeruginosa, Staphylococcus aureus, Enterobacteriaceae, and multiple drug resistant Streptococcus pneumoniae. Whereas other cephalosporins are degraded by many plasmid- and chromosome-mediated beta-lactamases, cefepime is stable and is a front line agent when infection with Enterobacteriaceae is known or suspected","Cephalosporins are bactericidal and have the same mode of action as other beta-lactam antibiotics (such as penicillins). Cephalosporins disrupt the synthesis of the peptidoglycan layer of bacterial cell walls. The peptidoglycan layer is important for cell wall structural integrity, especially in Gram-positive organisms. The final transpeptidation step in the synthesis of the peptidoglycan is facilitated by transpeptidases known as penicillin binding proteins (PBPs).","Penicillin-binding protein 2 inhibitor; Peptidoglycan synthase FtsI inhibitor; Penicillin-binding protein 3 inhibitor; Penicillin-binding protein 2 inhibitor","Indication associated"]
[518,"DB01414","experimental; vet_approved","small molecule","Cefacetrile","Cefacetrile; Cephacetrile","C13H13N3O6S","[H][C@]12SCC(COC(C)=O)=C(N1C(=O)[C@H]2NC(=O)CC#N)C(O)=O","A derivative of 7-aminocephalosporanic acid.","10206-21-0","339.324","Cefacetrile is a broad-spectrum first generation cephalosporin antibiotic effective in Gram-positive and Gram-negative bacterial infections.","Cefacetrile is effective against many Gram-positive bacterial strains and somewhat less effective against Gram-negative species. It works by inhibition of bacterial cell wall synthesis. It attains high serum levels and is excreted quickly via the urine.","In vitro tests demonstrate that the bactericidal action of cephalosporins results from inhibition of cell wall synthesis. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins.","Penicillin-binding protein 1A inhibitor; Penicillin-binding protein 1B inhibitor","Indication associated"]
[519,"DB01418","approved; investigational","small molecule","Acenocoumarol","3-(alpha-(4'-Nitrophenyl)-beta-acetylethyl)-4-hydroxycoumarin; 3-(alpha-(p-Nitrophenol)-beta-acetylethyl)-4-hydroxycoumarin; 3-(alpha-Acetonyl-4-nitrobenzyl)-4-hydroxycoumarin; 3-(alpha-Acetonyl-p-nitrobenzyl)-4-hydroxycoumarin; 3-(alpha-p-Nitrophenyl-beta-acetylethyl)-4-hydroxycoumarin; 4-Hydroxy-3-(1-(4-nitrophenyl)-3-oxobutyl)-2H-1-benzopyran-2-one; 4-Hydroxy-3-[1-(4-nitrophenyl)-3-oxobutyl]-2H-chromen-2-one; Acenocoumarin; Acenocoumarol; Acenocumarolo; Acenokumarin; Nicoumalone; Nicumalon; Nitrophenylacetylethyl-4-hydroxycoumarine; Nitrovarfarian; Nitrowarfarin","C19H15NO6","CC(=O)CC(C1=CC=C(C=C1)[N+]([O-])=O)C1=C(O)C2=CC=CC=C2OC1=O","Acenocoumarol is a coumarin derivative used as an anticoagulant. Coumarin derivatives inhibit the reduction of vitamin K by vitamin K reductase. This prevents carboxylation of vitamin K-dependent clotting factors, II, VII, IX and X, and interferes with coagulation. Hematocrit, hemoglobin, international normalized ratio and liver panel should be monitored. Patients on acenocoumarol are prohibited from giving blood.","152-72-7","353.3255","For the treatment and prevention of thromboembolic diseases. More specifically, it is indicated for the prevention of cerebral embolism, deep vein thrombosis, pulmonary embolism, thromboembolism in infarction and transient ischemic attacks. It is used for the treatment of deep vein thrombosis and myocardial infarction.","Acenocoumarol inhibits the reduction of vitamin K by vitamin K reductase. This prevents carboxylation of certain glutamic acid residues near the N-terminals of clotting factors II, VII, IX and X, the vitamin K-dependent clotting factors. Glutamic acid carboxylation is important for the interaction between these clotting factors and calcium. Without this interaction, clotting cannot occur. Both the extrinsic (via factors VII, X and II) and intrinsic (via factors IX, X and II) are affected by acenocoumarol.","Acenocoumarol inhibits vitamin K reductase, resulting in depletion of the reduced form of vitamin K (vitamin KH2). As vitamin K is a cofactor for the carboxylation of glutamate residues on the N-terminal regions of vitamin K-dependent clotting factors, this limits the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulant proteins. The synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S is inhibited resulting in decreased prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.","Vitamin K epoxide reductase complex subunit 1 inhibitor","Indication associated"]
[520,"DB01419","approved","small molecule","Antrafenine","Antrafenine","C30H26F6N4O2","FC(F)(F)C1=CC(=CC=C1)N1CCN(CCOC(=O)C2=CC=CC=C2NC2=C3C=CC(=CC3=NC=C2)C(F)(F)F)CC1","Antrafenine is a piperazine derivative drug that acts as an analgesic and anti-inflammatory drug with similar efficacy to naproxen. It is not widely used as it has largely been replaced by newer drugs.","55300-29-3","588.5435","Antrafenine is used as an anti-inflammatory and analgesic agent for the relief of mild to moderate pain.","Its mode of action is not fully understood; however, its ability to inhibit prostaglandin synthesis may be involved in the anti-inflammatory effect.","Antrafenine is believed to be associated with the inhibition of cyclooxygenase activity. Two unique cyclooxygenases have been described in mammals. The constitutive cyclooxygenase, COX-1, synthesizes prostaglandins necessary for normal gastrointestinal and renal function. The inducible cyclooxygenase, COX-2, generates prostaglandins involved in inflammation. Inhibition of COX-1 is thought to be associated with gastrointestinal and renal toxicity while inhibition of COX-2 provides anti-inflammatory activity.","Prostaglandin G/H synthase 1 inhibitor; Prostaglandin G/H synthase 2 inhibitor","Therapeutic strategy associated"]
[521,"DB01424","approved; withdrawn","small molecule","Aminophenazone","(Dimethylamino)phenazone; 1-Phenyl-2,3-dimethyl-4-(dimethylamino)-5-pyrazolone; 1-Phenyl-2,3-dimethyl-4-dimethylaminopyrazol-5-one; 1,5-Dimethyl-4-dimethylamino-2-phenyl-3-pyrazolone; 2,3-Dimethyl-4-dimethylamino-1-phenyl-5-pyrazolone; 3-Keto-1,5-dimethyl-4-dimethylamino-2-phenyl-2,3-dihydropyrazole; 4-(Dimethylamino)-1,2-dihydro-1,5-dimethyl-2-phenyl-3H-pyrazol-3-one; 4-(Dimethylamino)-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one; 4-(Dimethylamino)antipyrine; 4-Dimethylamino-1-phenyl-2,3-dimethylpyrazolone; 4-Dimethylamino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one; 4-Dimethylamino-2,3-dimethyl-1-phenyl-5-pyrazolone; 4-Dimethylaminoantipyrine; 4-Dimethylaminophenazone; Aminofenazone; Aminophenazone; Aminopyrine; Dimethylaminoantipyrine; Dimethylaminoazophene; Dimethylaminophenazone; Dimethylaminophenyldimethylpyrazolone; Dipyrine","C13H17N3O","CN(C)C1=C(C)N(C)N(C1=O)C1=CC=CC=C1","Aminophenazone is a pyrazolone with analgesic, anti-inflammatory, and antipyretic properties that carries a risk of agranulocytosis. In biomedical applications, radiolabelled (13C-labeled) aminophenazone has been used in breath tests to measure the cytochrome P-450 metabolic activity in liver function tests.","58-15-1","231.2936","Formerly widely used as an antipyretic and analgesic in rheumatism, neuritis, and common colds. Currently used to measure total body water.","Aminophenazone exhibits analgesic, anti-inflammatory, and antipyretic properties.","Aminophenazone is metabolized very slowly by normal newborn babies. In older infants, a higher amount of exhaled 13-CO2 is observed.",null,"Therapeutic strategy associated"]
[522,"DB01427","approved","small molecule","Amrinone","Amrinone; Inamrinone","C10H9N3O","NC1=CC(=CNC1=O)C1=CC=NC=C1","Amrinone (or inamrinone) is a type 3 pyridine phosphodiesterase inhibitor. It is used in the treatment of congestive heart failure.","60719-84-8","187.198","Used in the treatment of congestive heart failure.","Amrinone is a positive inotropic cardiotonic with vasodilator properties, phosphodiesterase inhibitory activity, and the ability to stimulate calcium ion influx into the cardiac cell.","Amrinone is a phosphodiesterase inhibitor (PDE3), resulting in increased cAMP and cGMP which leads to an increase in the calcium influx like that caused by beta-agonists resulting in increased inotropic effect.","cGMP-inhibited 3',5'-cyclic phosphodiesterase A inhibitor; Tumor necrosis factor inhibitor; cGMP-inhibited 3',5'-cyclic phosphodiesterase B inhibitor; cAMP-specific 3',5'-cyclic phosphodiesterase 4 (PDE4) inhibitor; cAMP-specific 3',5'-cyclic phosphodiesterase 3 inhibitor","Target associated"]
[523,"DB01436","approved; nutraceutical","small molecule","Alfacalcidol","(5Z,7E)-9,10-seco-5,7,10(19)-cholestatrien-1α,3β-diol; 1-hydroxycholecalciferol; 1alpha-hydroxycholecalciferol; 1α-hydroxy-vitamin D3; 1α-hydroxycholecalciferol; 1α-hydroxyvitamin D3; 9,10-secocholesta-5,7,10(19)-triene-1α,3β-diol","C27H44O2","CC(C)CCC[C@@H](C)[C@@]1([H])CC[C@@]2([H])\\C(CCC[C@]12C)=C\\C=C1\\C[C@@H](O)C[C@H](O)C1=C","Alfacalcidol, or 1-alpha-hydroxycholecalciferol or 1-alpha-hydroxyvitamin D3, is a non-endogenous analogue of . It plays an essential function in calcium homeostasis and bone metabolism. Alfacaldisol is activated by the enzyme 25-hydroxylase in the liver to mediate its effects in the body, or most importantly, the kidneys and bones. The pharmacological actions of alfacalcidol are prolonged than vitamin D because a negative feedback mechanism regulates the final activation step of vitamin D in the kidneys.\r\n\r\nAlfacalcidol is available in oral and intravenous formulations. In Canada, it is marketed as ONE-ALPHA, which manages hypocalcemia, secondary hyperparathyroidism, and osteodystrophy in adults with chronic renal failure. In approving European countries, alfacalcidol is also indicated for managing nutritional and malabsorptive rickets and osteomalacia, vitamin D-dependent rickets and osteomalacia, and hypophosphataemic vitamin D resistant rickets and osteomalacia.","41294-56-8","400.6371","Alfacalcidol is indicated in adult patients with chronic renal failure for the management of hypocalcemia, secondary hyperparathyroidism, or osteodystrophy.\r\n\r\nAlfacalcidol is indicated in the management of nutritional and malabsorptive rickets and osteomalacia, vitamin D-dependent rickets and osteomalacia, and hypophosphataemic vitamin D resistant rickets and osteomalacia.","Alfacalcidol works to increase serum levels of calcium by stimulating intestinal calcium absorption, reabsorption of calcium from bone, and possibly the renal reabsorption of calcium. It also modestly promotes intestinal phosphorus absorption. In patients with renal failure, alfacalcidol increased intestinal calcium and phosphorus absorption in a dose-related manner. This increase in calcium and phosphorus levels occurs within three days following drug administration: this effect was reversed within three days of drug discontinuation. In patients with chronic renal failure, serum calcium levels were elevated while parathyroid hormone and alkaline phosphatase levels returned to normal levels within five days following alfacalcidol administration. Since alfacalcidol suppresses parathyroid hormone, a reduction in parathyroid hormone levels is achieved more rapidly in patients on intermittent intravenous therapy, with significant reductions occurring within three months of therapy. In patients receiving daily oral therapy of alfacalcidol, the time it takes alfacalcidol to normalize plasma calcium levels may be up to several months, possibly reflecting calcium being utilized for bone mineralization. In patients with nutritional osteomalacia, alfacalcidol increased calcium absorption with six hours of oral administration and the effects peaked at 24 hours.","In conditions like chronic renal failure, renal bone disease, hypoparathyroidism, and vitamin D dependent rickets, the kidneys' capacity for 1α-hydroxylation is impaired, leading to reduced production of endogenous 1,25-dihydroxyvitamin D and aberrated mineral metabolism. As an active and potent analog of vitamin D, alfacalcidol works to restore the functions and activities of endogenous 1,25-dihydroxyvitamin D.","Vitamin D3 receptor agonist; 25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial; Retinoic acid receptor RXR-alpha","Indication associated"]
[524,"DB01440","approved; illicit; investigational","small molecule","gamma-Hydroxybutyric acid","3-carboxypropoxy acid; 4-hydroxy-butyric acid; 4-hydroxybutanoate; 4-hydroxybutanoic acid; 4-Hydroxybutyric acid; gamma-Hydroxybutyrate; GHB; oxy-n-butyric acid; Oxybate; γ-Hydroxybutyric acid","C4H8O3","OCCCC(O)=O","Gamma hydroxybutyric acid, commonly abbreviated GHB, is a therapeutic drug which is illegal in multiple countries. It is currently regulated in the US and sold by Jazz Pharmaceuticals under the name Xyrem. However, it is important to note that GHB is a designated Orphan drug (in 1985). Today Xyrem is a Schedule III drug; however GHB remains a Schedule I drug and the illicit use of Xyrem falls under penalties of Schedule I. GHB is a naturally occurring substance found in the central nervous system, wine, beef, small citrus fruits and almost all other living creatures in small amounts. It is used illegally under the street names Juice, Liquid Ecstasy or simply G, either as an intoxicant, or as a date rape drug. Xyrem is a central nervous system depressant that reduces excessive daytime sleepiness and cataplexy in patients with narcolepsy.","591-81-1","104.1045","Used as a general anesthetic, to treat conditions such as insomnia, clinical depression, narcolepsy, and alcoholism, and to improve athletic performance.","GHB predominantly works at two distinct binding sites in the central nervous system: it works as an agonist at the newly-characterized excitatory GHB receptor, while acting as a weak agonist at the inhibitory GABAB receptor. Since it is a naturally occurring substance, its physiological action is similar to that of some endogenous neurotransmitters in mammalian brain. GHB is probably synthesized from GABA in GABAergic neurons, and released when the neurons fire.","GHB is present at much higher concentrations in the brain, where it activates GABA-B receptors to exert its sedative effects. With high affinity, GHB binds to excitatory GHB receptors that are densely expressed throughout the brain, including the cotex and hippocampus. There is some evidence in research that upon activation of GHB receptors in some brain areas, the excitatory neurotransmitter glutamate is released. GHB stimulates dopamin release at low concentrations by acting on the GHB receptor, and the release of dopamine occurs in a biphasic manner. At higher concentrations, GHB inhibits dopamine release by acting on the GABA-B receptors, which is followed by GHB receptor signaling and increased release of dopamine. This explains the paradoxical mix of sedative and stimulatory properties of GHB, as well as the so-called \"rebound\" effect, experienced by individuals using GHB as a sleeping agent, wherein they awake suddenly after several hours of GHB-induced deep sleep. It is proposed that overtime, the level of GHB in the brain decreases below the threshold for significant GABA-B receptor activation, leading to preferential activation of GHB receptor over GABA-B receptors and enhanced wakefulness.","Gamma-hydroxybutyrate (GHB) receptor agonist; Gamma-aminobutyric acid receptor subunit beta-1 agonist","Indication associated"]
[525,"DB01452","approved; illicit; investigational","small molecule","Diamorphine","(5α,6α)-7,8-Didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol diacetate (ester); 3,6-Diacetylmorphine; 7,8-Dihydro-4,5-alpha-epoxy-17-methylmorphinan-3,6-alpha-diol diacetate; Diacetylmorphine; Diamorphine; Heroin; O,O'-Diacetylmorphine","C21H23NO5","[H][C@@]12C=C[C@H](OC(C)=O)[C@@H]3OC4=C(OC(C)=O)C=CC5=C4[C@]13CCN(C)[C@@H]2C5","Diamorphine (heroin) is a narcotic analgesic that may be habit-forming. It is a controlled substance (opium derivative) listed in the U.S. Code of Federal Regulations, Title 21 Parts 329.1, 1308.11 (1987). Sale is forbidden in the United States by Federal statute. (Merck Index, 11th ed) Internationally, diamorphine is controlled under Schedules I and IV of the Single Convention on Narcotic Drugs. As heroin, it is illegal to manufacture, possess, or sell in the United States and the UK. However, under the name diamorphine, heroin is a legal prescription drug in the United Kingdom.","561-27-3","369.411","Diamorphine, as a prescription medication in the United Kingdom, is indicated for use in the treatment of severe pain associated with surgical procedures, myocardial infarction or pain in the terminally ill and for the relief of dyspnoea in acute pulmonary edema .","The onset of heroin's effects is dependent on the method of administration. Taken orally, heroin is totally metabolized in vivo via extensive first-pass metabolism into morphine before crossing the blood-brain barrier; so the effects are the same as orally administered morphine . Take by injection, diamorphine's acetyl groups facilitate rapid crossing into the brain . Once in the brain, heroin is rapidly metabolized into morphine by removal of the acetyl groups, therefore making it a prodrug for the delivery of morphine . Subsequently, whether eliciting actions peripherally (on smooth muscle, skeletal muscle, kidney, lung, liver, or spleen tissue , for example) or on the central nervous system, it is ultimately the morphine metabolite of heroin that then binds with opioid receptors and produces the narcotic opioid effects commonly associated with the substance .","When administered orally, diamorphine experiences extensive first-pass metabolism by way of deacetylation to generate the active metabolites 6-monoacetylmorphine (6-MAM) and morphine . Alternatively, when given as an injection the acetyl groups present in the diamorphine/diacetylmorphine compound confer the substance lipophilicity that facilitates diamorphine's rapid crossing of the blood-brain-barrier . Once in the brain, diamorphine is metabolised via deacetylation to the active 6-MAM and morphine metabolites as well . Despite diamorphine possessing little to no opioid agonist activity itself, its rapid transit across the blood-brain-barrier elicits a far faster onset of activity in comparison to the extensive first-pass metabolism of oral administration . Regardless, the metabolism of diamorphine to morphine makes heroin a prodrug for the delivery of morphine .\r\n\r\nMorphine is subsequently a mu-opioid agonist. It acts on endogenous mu-opioid receptors that are spread in discrete packets throughout the brain, spinal cord and gut in almost all mammals . Morphine, along with other opioids, are agonists to four endogenous neurotransmitters . They are beta-endorphin, dynorphin, leu-enkephalin, and met-enkephalin . The body responds to morphine in the brain by reducing (and sometimes stopping) production of the endogenous opioids when morphine is present . Endorphins are regularly released in the brain and nerves, attenuating pain. Their other functions are still obscure, but are probably related to the effects produced by morphine besides analgesia (antitussin, anti-diarrheal) .\r\n\r\nNevertheless, morphine ultimately elicits the majority of its analgesic activity by binding to mu opioid receptors in both the central and peripheral nervous systems . The overall effect of morphine is activation of descending inhibitory pathways of the central nervous system as well as inhibition of nociceptive afferent neurons of the peripheral nervous system, which results in an overall reduction of the nociceptive pain transmission .","Mu-type opioid receptor agonist; Kappa-type opioid receptor agonist; Delta-type opioid receptor agonist; Liver carboxylesterase 1","Therapeutic strategy associated"]
[526,"DB01489","experimental; illicit","small molecule","Camazepam","Camazepam","C19H18ClN3O3","CN(C)C(=O)OC1N=C(C2=CC=CC=C2)C2=C(C=CC(Cl)=C2)N(C)C1=O","Camazepam is a benzodiazepine which is a dimethyl carbamate ester of tamzepam, a metabolite of diazepam. Similarly to other drugs in its class, it has antxiolytic, anticonvulsant, hypnotic, and skeletal muscle relaxant properties. However, unlike other benzodiapeines camazepam is predominantly anxiolytic and is relatively weak as an anticonvulsant, hypnotic and skeletal muscle relaxant.\r\n\r\nCamazepam also has less side effects, such as impaired cognition and reaction times, compared to other benzodiazepines. However, impairment of cognition and disrupted sleep patterns will occur at doses higher than 40mg of carazepam. Camazepam is also believed to increase attention, and is associated with skin disorders.  \r\n\r\nIn the United States camazepam is regulated as a Schedule IV controlled substance.","36104-80-0","371.818","Camazepam has been used in placebo controlled studies for the treatment of patients suffering from anxiety and depression.",null,"Camazepam has been shown to bind competitively to benzodiazepine receptors in the brain with a relatively low affinity in animal models. This binding of benzodiazepine receptors by camazepam and its active metabolites is responsible for its anticonvulsant effects. Notably, only three metabolites were shown to exert anticonvulsant activity, temazepam, oxazepam, and hydroxy camazepam. \r\n\r\nThe anxiolytic properties of camazepam are also attributed to their ability to bind benzodiazepine receptors, also known as GABA receptors.  When benzodiazepines bind to GABA receptors they increase the efficiency with which the inhibitory neurotransmitter GABA binds.","GABA(A) Receptor positive allosteric modulator; GABA(A) Receptor Benzodiazepine Binding Site ligand","Indication associated"]
[527,"DB01550","experimental; illicit; withdrawn","small molecule","Fenproporex","Fenproporex","C12H16N2","CC(CC1=CC=CC=C1)NCCC#N","Fenproporex is an orally active stimulant drug, which was developed in the 1960s. It is used as an appetite suppressant and a treatment for obesity. It is listed as an illicit substance in many countries due to addiction issues and listed as a prohibited substance by the World Anti-Doping Agency. Structurally, fenproporex (N-2-cyanoethylamphetamine) falls within the phenylethamine and amphetamine chemical class of drugs. The N-2-cyanoethyl substituent was once believed to be resistant to cleavage, because fenproporex -- once recommended as an obesity treatment for patients with cardiovascular disease -- was originally claimed to lack stimulant properties. Contrary to the claim, research has demonstrated easy in vivo cleavage of the N-2-cyanothyl substituent to yield amphetamine as a metabolite.  However, in clinical practice, central nervous system stimulative effects are less notorious than with some other agents such as diethylpropion and mazindol. \r\n\r\nIn the United States fenproporex was never approved by the FDA for clinical use due to a lack of efficacy and safety data, and is listed as a drug in Schedule IV of the Controlled Substances Act. In 2006 and 2009, the FDA issued warnings that it had been detected in diet pills sold online, and imported from foreign manufacturers.\r\n\r\nDespite being banned in the United States, fenproporex has been described as the second most commonly consumed appetite suppressant worldwide,  with fenproporex containing anorectics still being commonly prescribed in South America. Little is known about the specific hazards of amphetamine based diet pills, however case reports have noted side effects such as chest pain, palpitations, headaches, and insomnia. In addition, placebo controlled studies have shown that participants using fenproporex experience more joint pain, sweating, blurred vision and tremor.","16397-28-7","188.2688","Fenproporex is used as an appetite suppressant, and anti-obesity agent ; however, due to substance abuse potential, it is an illicit substance in many countries. In some countries, such as Brazil, it is still prescribed -- often in the form of diet pills (ie. Brazilian Diet Pills) which combine amphetamines, benzodiazepines, antidepressants, diuretics and laxatives. \r\n\r\nIn the United States the sale of such diet pills has been banned due to concerns over side effects, and the risk of potentially fatal overdose.\r\nHowever, internet sales and illicit markets has lead to international availability. It has been found by primary care physicians that Brazilian immigrant women utilized imported diet pills at particularly high rates, and sometimes suffered from side effects requiring hospitalization or experienced a loss of employment.","Fenproporex was first claimed to not exert a stimulant effect on the body, however research into its metabolism has shown that it is converted into a considerable amount of amphetamine in the body, which leads to stimulant effects.","Fenproporex is an amphetamine based anorectic which is rapidly metabolized into amphetamine in the body. Both acute and chronic fenproporex administration has been shown to increase brain energy metabolism in young rats, by increasing the activity of citrate synthase, malate dehydrogenase, succinate dehydrogenase, creatine kinase and complexes I,II, III, and IV. \r\n\r\nAmphetamine based drugs are also known to reduce food intake. They are addictive substances due to their ability to increase dopamine release, however their anorectic effects are believed to be a result of noradrenergic neurotransmission. Activation of the alpha 1 and beta 2 adrenoceptors has been shown to decrease food intake, and drugs which release norepinephrine or block norepinephrine reuptake can activate these receptors.  \r\n\r\nThe alpha 1 and beta 2 adrenoceptors are noted to be clinically important receptors in weight regulation.",null,"Indication associated"]
[528,"DB01556","illicit; withdrawn","small molecule","Chlorphentermine","4-Chloro-a,a-dimethylbenzeneethanamine; 4-Chloro-a,a-dimethylphenethylamine; a,a-Dimethyl-p-chlorophenethylamine; Chlorphentermine","C10H14ClN","CC(C)(N)CC1=CC=C(Cl)C=C1","A sympathomimetic agent that was formerly used as an anorectic. It has properties similar to those of dextroamphetamine. It has been implicated in lipid storage disorders and pulmonary hypertension. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1223)","461-78-9","183.678","Used as an appetite suppressant.","Chlorphentermine is a relatively weak stimulant with little abuse potential. It presents a prominent serotonergic profile leading to pulmonary hypertension and cardiac fibrosis after prolonged use. Thus, this drug is no longer used.",null,null,"Therapeutic strategy associated"]
[529,"DB01563","approved; illicit; investigational; vet_approved","small molecule","Chloral hydrate","1,1,1-trichloro-2,2-dihydroxyethane; 1,1,1-trichloro-2,2-ethanediol; 2,2,2-trichloro-1,1-ethanediol; Chloral hydrate; chloral monohydrate; trichloroacetaldehyde hydrate","C2H3Cl3O2","OC(O)C(Cl)(Cl)Cl","A hypnotic and sedative used in the treatment of insomnia. The safety margin is too narrow for chloral hydrate to be used as a general anesthetic in humans, but it is commonly used for that purpose in animal experiments. It is no longer considered useful as an anti-anxiety medication.","302-17-0","165.403","Mainly used as a hypnotic in the treatment of insomnia; however, it is only effective as a hypnotic for short-term use. May be used as a routine sedative preoperatively to decrease anxiety and cause sedation and/or sleep with respiration depression or cough reflex.",{"$nulls":3},"Indication associated"]
[530,"DB01577","approved; illicit","small molecule","Metamfetamine","(+)-(S)-N-α-dimethylphenethylamine; (S)-N,α-dimethylbenzeneethanamine; (αS)-N,α-dimethylbenzeneethanamine; d-1-phenyl-2-methylaminopropane; d-deoxyephedrine; d-desoxyephedrine; d-N-methylamphetamine; d-phenylisopropylmethylamine; Dextromethamphetamine; Metamfetamine; Methamphetamine; methyl-β-phenylisopropylamine","C10H15N","CN[C@@H](C)CC1=CC=CC=C1","Metamfetamine (methamphetamine) is a psychostimulant and sympathomimetic drug. It is a member of the amphetamine group of sympathomimetic amines. Methamphetamine can induce effects such as euphoria, increased alertness and energy, and enhanced self-esteem. It is a scheduled drug in most countries due to its high potential for addiction and abuse.","537-46-2","149.2328","For the treatment of Attention Deficit Disorder with Hyperactivity (ADHD) and exogenous obesity.","Methamphetamine is a potent central nervous system stimulant which affects neurochemical mechanisms responsible for regulating heart rate, body temperature, blood pressure, appetite, attention, mood and responses associated with alertness or alarm conditions. The acute effects of the drug closely resemble the physiological and psychological effects of an epinephrine-provoked fight-or-flight response, including increased heart rate and blood pressure, vasoconstriction (constriction of the arterial walls), bronchodilation, and hyperglycemia (increased blood sugar). Users experience an increase in focus, increased mental alertness, and the elimination of fatigue, as well as a decrease in appetite.","Methamphetamine enters the brain and triggers a cascading release of norepinephrine, dopamine and serotonin. To a lesser extent methamphetamine acts as a dopaminergic and adrenergic reuptake inhibitor and in high concentrations as a monamine oxidase inhibitor (MAOI). The mechanism of action involved in producing the beneficial behavioral changes seen in hyperkinetic children receiving methamphetamine is unknown.","Sodium-dependent dopamine transporter negative modulator; Sodium-dependent serotonin transporter negative modulator; Sodium-dependent noradrenaline transporter negative modulator; Synaptic vesicular amine transporter inhibitor; Chromaffin granule amine transporter inhibitor; Trace amine-associated receptor 1 agonist; Alpha-2A adrenergic receptor agonist; Alpha-2B adrenergic receptor agonist; Alpha-2C adrenergic receptor agonist; Amine oxidase [flavin-containing] A inhibitor; Amine oxidase [flavin-containing] B inhibitor","Indication associated"]
[531,"DB01579","approved; illicit","small molecule","Phendimetrazine","(2S,3S)-3,4-dimethyl-2-phenylmorpholine; Phendimetrazine","C12H17NO","C[C@H]1[C@@H](OCCN1C)C1=CC=CC=C1","Phendimetrazine is a weight loss medication. Phendimetrazine is chemically related to amphetamines and is a Schedule III drug under the Convention on Psychotropic Substances and in the US since 1970.","634-03-7","191.274","Used in the management of exogenous obesity as a short term adjunct (a few weeks) in a regimen of weight reduction based on caloric restriction.","Phendimetrazine is a phenylalkylamine sympathomimetic amine with pharmacological activity similar to the prototype drugs of this class used in obesity, the amphetamines. Actions include central nervous system stimulation and elevation of blood pressure. Tachyphylaxis and tolerance has been demonstrated with all drugs of this class in which these phenomena have been looked for. Drugs of this class used in obesity are commonly known as ''anorectics or anorexigenics.\" It has not been established, however, that the action of such drugs in treating obesity is primarily one of appetite suppression. Other central nervous system actions or metabolic effects, may be involved.","Phendimetrazine may act in a similar way to amphetamines in that it activates the alpha-adrenergic system to induce an appetite suppressive and metabolic increase effect. The drug also acts as a norepinephrine-dopamine releasing agent (NDRA). It can bind to and reverse the NET.","Alpha-1A adrenergic receptor agonist; Sodium-dependent noradrenaline transporter negative modulator; Alpha-1B adrenergic receptor agonist","Therapeutic strategy associated"]
[532,"DB01580","approved","small molecule","Oxprenolol","Oxprenolol","C15H23NO3","CC(C)NCC(O)COC1=CC=CC=C1OCC=C","A beta-adrenergic antagonist used in the treatment of hypertension, angina pectoris, arrhythmias, and anxiety.","6452-71-7","265.348","Used in the treatment of hypertension, angina pectoris, arrhythmias, and anxiety.","Oxprenolol is a non-selective beta blocker with some intrinsic sympathomimetic activity. Oxprenolol is a lipophilic molecule and hence, it is able to cross the blood-brain barrier. As such, it is associated with a higher incidence of CNS-related side effects than hydrophilic ligands such as atenolol, sotalol and nadolol. Oxprenolol is an potent beta-blocker and should not be administered to asthmatics because it can cause irreversible airway failure and inflammation.","Like other beta-adrenergic antagonists, oxprenolol competes with adrenergic neurotransmitters such as catecholamines for binding at sympathetic receptor sites. Like propranolol and timolol, oxprenolol binds at beta(1)-adrenergic receptors in the heart and vascular smooth muscle, inhibiting the effects of the catecholamines epinephrine and norepinephrine and decreasing heart rate, cardiac output, and systolic and diastolic blood pressure. It also blocks beta-2 adrenergic receptors located in bronchiole smooth muscle, causing vasoconstriction. By binding beta-2 receptors in the juxtaglomerular apparatus, oxprenolol inhibits the production of renin, thereby inhibiting angiotensin II and aldosterone production. Oxprenolol therefore inhibits the vasoconstriction and water retention due to angiotensin II and aldosterone, respectively.","Beta-1 adrenergic receptor antagonist; Beta-2 adrenergic receptor antagonist; Beta-3 adrenergic receptor","Indication associated"]
[533,"DB01582","approved; investigational; vet_approved","small molecule","Sulfamethazine","2-(4-Aminobenzenesulfonamido)-4,6-dimethylpyrimidine; 2-(p-Aminobenzenesulfonamido)-4,6-dimethylpyrimidine; 2-Sulfanilamido-4,6-dimethylpyrimidine; 4-Amino-N-(2,6-dimethyl-4-pyrimidinyl)benzenesulfonamide; 4-Amino-N-(4,6-dimethyl-pyrimidin-2-yl)-benzenesulfonamide; 4-amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide; 4,6-Dimethyl-2-sulfanilamidopyrimidine; 6-(4'-Aminobenzol-sulfonamido)-2,4-dimethylpyrimidin; N-(4,6-Dimethyl-2-pyrimidyl)sulfanilamide; N(1)-(4,6-Dimethyl-2-pyrimidinyl)sulfanilamide; N(1)-(4,6-Dimethyl-2-pyrimidyl)sulfanilamide; SMZ; Sulfadimethyldiazine; Sulfadimethylpyrimidine; Sulfadimidine; Sulfamethazine; Sulfamezathine; Sulphadimethylpyrimidine; Sulphamethazine","C12H14N4O2S","CC1=CC(C)=NC(NS(=O)(=O)C2=CC=C(N)C=C2)=N1","A sulfanilamide anti-infective agent. It has a spectrum of antimicrobial action similar to other sulfonamides.","57-68-1","278.33","For the treatment bacterial infections causing bronchitis, prostatitis and urinary tract infections.","Sulfamethazine is a sulfonamide drug that inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid (PABA) for binding to dihydropteroate synthetase (dihydrofolate synthetase). Sulfamethazine is bacteriostatic in nature. Inhibition of dihydrofolic acid synthesis decreases the synthesis of bacterial nucleotides and DNA.","Sulfonamides inhibit the enzymatic conversion of pteridine and p-aminobenzoic acid (PABA) to dihydropteroic acid by competing with PABA for binding to dihydrofolate synthetase, an intermediate of tetrahydrofolic acid (THF) synthesis. THF is required for the synthesis of purines and dTMP and inhibition of its synthesis inhibits bacterial growth. Pyrimethamine and trimethoprim inhibit dihydrofolate reductase, another step in THF synthesis, and therefore act synergistically with the sulfonamides.","Dihydropteroate synthase inhibitor","Indication associated"]
[534,"DB01583","approved","small molecule","Liotrix","Levothyroxine Sodium mixture with Liothyronine Sodium; Liotrix; Liotrix (T4;T3)","C30H21I7N2Na2O8","[Na+].[Na+].N[C@@H](CC1=CC(I)=C(OC2=CC(I)=C(O)C=C2)C(I)=C1)C([O-])=O.N[C@@H](CC1=CC(I)=C(OC2=CC(I)=C(O)C(I)=C2)C(I)=C1)C([O-])=O","Liotrix is a synthetically derived thyroid hormone replacement preparation. It consists of levothyroxine sodium (thyroxine, T4) and liothyronine sodium (triiodothyronine, T3) in a 4 to 1 ratio by weight. Liotrix was developed when it was believed that serum levels of both T4 and T3 were maintained by direct thyroidal secretion. It is now known that the thyroid gland secretes approximately ten times more T4 than T3 and that 80% of serum T3 is derived from deiodination of T4 in peripheral tissues. Administration of levothyroxine alone is sufficient for maintaining serum T4 and T3 levels in most patients and combination hormone replacement therapy generally offers no therapeutic advantage. In fact, administration of T3 may result in supratherapeutic levels of T3.","8065-29-0","1471.8072","May be used to treat primary, secondary or tertiary hypothyroidism. May also be used to suppress thyroid stimulating hormone (TSH) secretion in patients with simple (nontoxic) goiter, subacute or chronic lymphocytic thyroiditis multinodular goiter, and in the management of thyroid cancer. May be used in conjunction with other antithyroid agents to treat thyrotoxicosis to prevent goitrogenesis and hypothyroidism. May also be used for differential diagnosis of suspected mild hyperthyroidism or thyroid gland autonomy.","Thyroid hormone drugs are natural or synthetic preparations containing T<sub>4</sub> or T<sub>3</sub> or both. T<sub>4</sub> and T<sub>3</sub> are produced in the human thyroid gland by the iodination and coupling of the amino acid tyrosine. Liotrix is a synthetic preparation of T4 and T3 in a 4:1 weight-based ratio. These hormones enhance oxygen consumption by most tissues of the body and increase the basal metabolic rate and the metabolism of carbohydrates, lipids and proteins. Thus, they exert a profound influence on every organ system in the body and are of particular importance in the development of the central nervous system.","The hormones, T<sub>4</sub> and T<sub>3</sub>, are tyrosine-based hormones produced by the thyroid gland. Iodine is an important component in their synthesis. The major secreted form of thyroid hormone is T4. T4 is converted T3, the more active thyroid hormone, by deiodinases in peripheral tissues. T3 acts in the body to increase basal metabolic rate, alter protein synthesis and increase the body's sensitivity to catecholamines (such as adrenaline). Thyroid hormones are essential for proper development and differentiation of all cells of the human body. T<sub>4</sub> and T<sub>3</sub> regulate protein, fat and carbohydrate metabolism to varying extents. The most pronounced effect of the hormones is in altering how human cells use energetic compounds. The thyroid hormone derivatives bind to the thyroid hormone receptors initially to initiate their downstream effects.","Thyroid hormone receptor alpha agonist; Thyroid hormone receptor beta agonist","Target associated"]
[535,"DB01584","approved; withdrawn","biotech","Thyroglobulin",{"$nulls":3},"Thyroglobulin (also known as Tg) is an enzyme thyroid hormone used by the thyroid gland to produce the thyroid hormones thyroxine (T4) and triiodothyronine (T3). The active form of thyroxine, triiodothyronine, is produced both within the thyroid gland and periphery by 5'-deiodinase. Patients with Hashimoto's thyroiditis or Graves' disease, frequently develop antibodies against thyroglobulin. Thyroglobulin is used to treat hypothyroidism.","9010-34-8",null,"For the treatment of hypothyroidism (deficiency in the production of thyroid hormone).",{"$nulls":3},"Indication associated"]
[536,"DB01590","approved","small molecule","Everolimus","40-O-(2-hydroxyethyl)-rapamycin; 42-O-(2-Hydroxyethyl)rapamycin","C53H83NO14","[H][C@@]1(C[C@@H](C)[C@]2([H])CC(=O)[C@H](C)\\C=C(C)\\[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)\\C=C\\C=C\\C=C(C)\\[C@H](C[C@]3([H])CC[C@@H](C)[C@@](O)(O3)C(=O)C(=O)N3CCCC[C@@]3([H])C(=O)O2)OC)CC[C@@H](OCCO)[C@@H](C1)OC","Everolimus is a derivative of Rapamycin (sirolimus), and works similarly to Rapamycin as an mTOR (mammalian target of rapamycin) inhibitor. It is currently used as an immunosuppressant to prevent rejection of organ transplants. In a similar fashion to other mTOR inhibitors Everolimus' effect is solely on the mTORC1 protein and not on the mTORC2 protein.","159351-69-6","958.24","Everolimus is indicated for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer (advanced HR+ BC) in combination with exemestane, after failure of treatment with letrozole or anastrozole.\r\nIndicated for the treatment of adult patients with progressive neuroendocrine tumors of pancreatic origin (PNET) with unresectable, locally advanced or metastatic disease.\r\nIndicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib.\r\nIndicated for the treatment of adult patients with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery.\r\nIndicated in pediatric and adult patients with tuberous sclerosis complex (TSC) for the treatment of subependymal giant cell astrocytoma (SEGA) that requires therapeutic intervention but cannot be curatively resected.",null,"Everolimus is a mTOR inhibitor that binds with high affinity to the FK506 binding protein-12 (FKBP-12), thereby forming a drug complex that inhibits the activation of mTOR. This inhibition reduces the activity of effectors downstream, which leads to a blockage in the progression of cells from G1 into S phase, and subsequently inducing cell growth arrest and apoptosis. Everolimus also inhibits the expression of hypoxia-inducible factor, leading to a decrease in the expression of vascular endothelial growth factor. The result of everolimus inhibition of mTOR is a reduction in cell proliferation, angiogenesis, and glucose uptake.","Serine/threonine-protein kinase mTOR inhibitor","Therapeutic strategy associated"]
[537,"DB01597","approved; investigational","small molecule","Cilastatin","(L)-7-(2-Amino-2-carboxy-ethylsulfanyl)-2-[(2,2-dimethyl-cyclopropanecarbonyl)-amino]-hept-2-enoic acid; (Z)-(S)-6-carboxy-6-[(S)-2,2-dimethylcyclopropanecarboxamido]hex-5-enyl-L-cysteine; (Z)-7-((R)-2-Amino-2-carboxy-ethylsulfanyl)-2-[((S)-2,2-dimethyl-cyclopropanecarbonyl)-amino]-hept-2-enoic acid; Cilastatin","C16H26N2O5S","CC1(C)C[C@@H]1C(=O)N\\C(=C/CCCCSC[C@H](N)C(O)=O)C(O)=O","Cilastatin is an inhibitor of renal dehydropeptidase, an enzyme responsible for both the metabolism of thienamycin beta-lactam antibiotics as well as conversion of leukotriene D4 to leukotriene E4. Since the antibiotic, , is one such antibiotic that is hydrolyzed by dehydropeptidase, cilastatin is used in combination with imipenem to prevent its metabolism. The first combination product containing both drugs was approved by the FDA in November of 1985 under the trade name Primaxin, marketed by Merck & Co. A newer triple-drug product was approved in July 2019 under the trade name Recarbrio which also contains .","82009-34-5","358.453","Cilastatin is indicated, in combination with  with or without , for the treatment of bacterial infections including respiratory, skin, bone, gynecologic, urinary tract, and intra-abdominal as well as septicemia and endocarditis.","Cilastatin is a chemical compound which inhibits the human enzyme dehydropeptidase. Renal Dehydropeptidase degrades the antibiotic . Cilastatin is therefore combined intravenously with imipenem in order to protect it from dehydropeptidase and prolong its antibacterial effect. However, cilastatin in and of itself does not have any antibacterial activity. The increased renal excretion of unchanged imipenem appears to prevent proximal tubular necrosis associated with high doses of imipenem.","Cilastatin is a renal dehydropeptidase-I inhibitor. Since the antibiotic, imipenem, is hydrolyzed by dehydropeptidase-I, which resides in the brush border of the renal tubule, cilastatin is administered with imipenem to block the metabolism of imipenem.","Dipeptidase 1 inhibitor","Indication associated"]
[538,"DB01598","approved","small molecule","Imipenem","(5R,6S)-3-((2-(Formimidoylamino)ethyl)thio)-6-((R)-1-hydroxyethyl)-7-oxo-1-azabicyclo(3.2.0)hept-2-ene-2-carboxylic acid; (5R,6S)-3-(2-Formimidoylamino-ethylsulfanyl)-6-((R)-1-hydroxy-ethyl)-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid; Imipenem; Imipenem anhydrous; N-formimidoyl thienamycin; N-formimidoylthienamycin","C12H17N3O4S","[H][C@]12CC(SCC\\N=C\\N)=C(N1C(=O)[C@]2([H])[C@@H](C)O)C(O)=O","Imipenem is a semisynthetic thienamycin that has a wide spectrum of antibacterial activity against gram-negative and gram-positive aerobic and anaerobic bacteria, including many multiresistant strains. It is stable to many beta-lactamases. Similar compounds include , known for having greater activity against Gram negative bacteria, and the newer  which exhibits a longer half-life due to increased binding to plasma proteins. Imipenem is commonly used in combination with  and is now available in a triple-drug product with cilastatin and  which was recently approved by the FDA. Imipenem was first approved by the FDA in November 1985 as the combination product Primaxin marketed by Merck & Co.","64221-86-9","299.346","Imipenem is indicated, in combination with  with or without , for the treatment of bacterial infections including respiratory, skin, bone, gynecologic, urinary tract, and intra-abdominal as well as septicemia and endocarditis.","Imipenem is a beta-lactam antibiotic belongings to the subgroup of carbapenems. Imipenem is active against aerobic and anaerobic Gram positive as well as Gram negative bacteria including <i>Pseudomonas aeruginosa</i> and the <i>Enterococcus</i>. It exerts a bactericidal effects by disrupting cell wall synthesis.","Imipenem acts as an antimicrobial through the inhibition of cell wall synthesis of various gram-positive and gram-negative bacteria. This inhibition of cell wall synthesis in gram-negative bateria is attained by binding to penicillin-binding proteins (PBPs). In E. coli and selected strains of P. aeruginosa, imipenem has shown to have the highest affinity to PBP-2, PBP-1a, and PBP-1b. This inhibition of PBPs prevents the bacterial cell from adding to the peptidoglycan polymer which forms the bacterial cell wall eventually leading to cell death.","Penicillin-binding protein 2 inhibitor; Penicillin-binding protein 1B inhibitor; Penicillin-binding protein 1A inhibitor; Penicillin-binding protein 3 inhibitor; Penicillin-binding protein 4","Indication associated"]
[539,"DB01600","approved","small molecule","Tiaprofenic acid","2-(5-Benzoyl-thiophen-2-yl)-propionic acid; 5-benzoyl-α-methyl-2-thiopheneacetic acid; 5-benzoyl-α-methylthiophene-2-acetic acid; Tiaprofenic acid; α-methyl-5-benzoyl-2-thienylacetic acid","C14H12O3S","CC(C(O)=O)C1=CC=C(S1)C(=O)C1=CC=CC=C1","Tiaprofenic acid is a non-steroidal anti-inflammatory drug employed in the treatment of pain, particularly arthritis pain. It belongs to the _arylpropionic acid_ (profen) group of nonsteroidal anti-inflammatory drugs (NSAIDs).","33005-95-7","260.308","Tiaprofenic acid is used to treat pain, especially arthritic pain.","Tiaprofenic acid is a non-steroidal anti-inflammatory drug of the arylpropionic acid (profen) class, used to treat pain, especially arthritic pain. The typical adult dose is 300mg twice daily. This drug is not recommended for use in the pediatric population.","Tiaprofenic acid belongs to a group of medicines called non-steroidal anti-inflammatory drugs (NSAIDs). It works by blocking the production of a chemical (prostaglandin) which the body produces in response to injury or certain diseases. This prostaglandin would otherwise go on to cause swelling, pain and inflammation.","Prostaglandin G/H synthase 2 inhibitor; Prostaglandin G/H synthase 1 inhibitor","Therapeutic strategy associated"]
[540,"DB01602","approved; investigational","small molecule","Bacampicillin","1-[(ethoxycarbonyl)oxy]ethyl (2S,5R,6R)-6-{[(2R)-2-amino-2-phenylacetyl]amino}-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate; 1'-ethoxycarbonyloxyethyl-(6-D-α-aminophenylacetamido)penicillanate; Bacampicillin","C21H27N3O7S","[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)[C@H](N)C1=CC=CC=C1)C(=O)OC(C)OC(=O)OCC","Bacampicillin is a prodrug of ampicillin and is microbiologically inactive. It is absorbed following oral administration. During absorption from the gastrointestinal tract, bacampicillin is hydrolyzed by esterases present in the intestinal wall. It is microbiologically active as ampicillin, and exerts a bactericidal action through the inhibition of the biosynthesis of cell wall mucopeptides.  It is used to cure infection of upper and lower respiratory tract; skin and soft tissue; urinary tract and acute uncomplicated gonococcal urethritis etc.","50972-17-3","465.52","For infections at the following sites: upper and lower respiratory tract; skin and soft tissue; urinary tract and acute uncomplicated gonococcal urethritis, when due to sensitive strains of the following organisms:  Gram-positive: streptococci (including <i>S. faecalis</i> and <i>S. pneumoniae</i>) and nonpenicillinase-producing staphylococci; Gram-negative: <i>H. influenzae</i>, <i>N. gonorrhoeae</i>, <i>E. coli</i>, <i>P. mirabilis</i>, <i>Salmonellae</i> and <i>Shigellae</i>.","Bacampicillin is a prodrug of ampicillin and is microbiologically inactive.","During absorption from the gastrointestinal tract, bacampicillin is hydrolyzed by esterases present in the intestinal wall. It is microbiologically active as ampicillin, and exerts a bactericidal action through the inhibition of the biosynthesis of cell wall mucopeptides.","Penicillin-binding protein inhibitor","Indication associated"]
[541,"DB01604","approved","small molecule","Pivampicillin","Ampicillin pivaloyloxymethyl ester; Pivaloylampicillin; Pivaloyloxymethyl ampicillinate; Pivampicillin","C22H29N3O6S","[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)[C@H](N)C1=CC=CC=C1)C(=O)OCOC(=O)C(C)(C)C","Pivalate ester analog of ampicillin.","33817-20-8","463.547","or the treatment of respiratory tract infections (including acute bronchitis, acute exacerbations of chronic bronchitis and pneumonia); ear, nose and throat infections; gynecological infections; urinary tract infections (including acute uncomplicated gonococcal urethritis) when caused by non penicillinase-producing susceptible strains of the following organisms: gram-positive organisms, e.g., streptococci, pneumococci and staphylococci; gram-negative organisms, e.g., H. influenzae, N. gonorrhoeae, E. coli, P. mirabilis.","Pivampicillin is the pivaloyloxymethyl ester of (the semi-synthetic penicillin) ampicillin. It is an inactive pro-drug, which is converted during its absorption from the gastrointestinal tract to the microbiologically active ampicillin, together with formaldehyde and pivalic acid, by non-specific esterases present in most body tissues. Amounts in excess of 99% of the pivampicillin absorbed are converted to ampicillin within 15 minutes of absorption.","Ampicillin (the active metabolite of pivampicillin) has a bactericidal action resulting from inhibition of cell wall mucopeptide biosynthesis.","Penicillin-binding protein 1A inhibitor","Indication associated"]
[542,"DB01606","approved","small molecule","Tazobactam","Tazobactam","C10H12N4O5S","[H][C@@]12CC(=O)N1[C@@H](C(O)=O)[C@](C)(CN1C=CN=N1)S2(=O)=O","Tazobactam is an antibiotic of the beta-lactamase inhibitor class that prevents the breakdown of other antibiotics by beta-lactamase enzyme producing organisms. It is combined with  and  for the treatment of a variety of bacterial infections.\r\n\r\nPiperacillin-tazobactam was initially approved by the FDA in 1994, and ceftolozane-tazobactam was approved by the FDA in 2014, providing wider antibacterial coverage for gram-negative infections. In June 2019, ceftolozane-tazobactam was approved by the FDA for treating hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia, which are significant causes of morbidity and mortality in hospitalized patients.","89786-04-9","300.291","Tazobactam is used in combination with piperacillin or ceftolozane to broaden the spectrum of piperacillin antibacterial action, treating susceptible infections. As with any other antibiotic, tazobactam should only be used for infections that are either proven or strongly suspected to be susceptible to the tazobactam containing drug.\r\n\r\n**Tazobactam-piperacillin**\r\n\r\nWhen combined with piperacillin, it is used to treat a variety of infections, including those caused by aerobic and facultative gram-positive and gram-negative bacteria, in addition to gram-positive and gram-negative anaerobes. Some examples of infections treated with piperacillin-tazobactam include cellulitis, diabetic foot infections, appendicitis, and postpartum endometritis infections. Certain gram-negative bacilli infections with beta-lactamase producing organisms cannot be treated with piperacillin-tazobactam, due to a gene mutation conferring antibiotic resistance.\r\n\r\n**Tazobactam-ceftolozane**\r\n\r\nTazobactam-ceftolozane combined with metronidazole is used to treat complicated urinary tract infections (UTI) and complicated intra-abdominal infections, as well as ventilator-associated bacterial pneumonia and hospital-acquired bacterial pneumonia.. This combination increases efficacy against infections with gram-negative bacilli.","Tazobactam inhibits the action of bacterial beta-lactamase producing organisms, which are normally resistant to beta-lactam antibiotics. This augments the effects of antibiotics which would otherwise not be effective in treating certain infections.  These antibiotics contain a beta-lactam ring in their chemical structure, which is destroyed by beta-lactam resistant organisms. When combined with other antibiotics, a variety of infections, including serious and life-threatening infections may be treated.","Tazobactam broadens the spectrum of piperacillin and ceftolozane by making them effective against organisms that express beta-lactamase and would normally degrade them. This occurs through the irreversible inhibition of beta-lactamase enzymes. In addition, tazobactam may bind covalently to plasmid-mediated and chromosome-mediated beta-lactamase enzymes. Tazobactam is predominantly effective against the OHIO-1, SHV-1, and TEM groups of beta-lactamases, but may also inhibit other beta-lactamases.\r\n\r\nTazobactam shows little antibacterial activity by itself, and for this reason, is generally not administered alone.\r","Beta-lactamase TEM inhibitor; Beta-lactamase Ohio-1 inhibitor; Beta-lactamase SHV-1 inhibitor","Indication associated"]
[543,"DB01607","approved; investigational; vet_approved","small molecule","Ticarcillin","(2S,5R,6R)-6-{[(2R)-2-carboxy-2-thiophen-3-ylacetyl]amino}-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; Ticarcillin; α-carboxy-3-thienylmethylpenicillin","C15H16N2O6S2","[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)[C@H](C(O)=O)C1=CSC=C1)C(O)=O","An antibiotic derived from penicillin similar to carbenicillin in action.","34787-01-4","384.427","For the treatment of bacterial infections.","Ticarcillin is a semisynthetic antibiotic with a broad spectrum of bactericidal activity against many gram-positive and gram-negative aerobic and anaerobic bacteria. Ticarcillin is, however, susceptible to degradation by ß-lactamases, and therefore, the spectrum of activity does not normally include organisms which produce these enzymes.","Ticarcillin's principal mechanism of action revolves around its capacity to prevent the cross-linking of peptidoglycan during bacterial cell wall synthesis. Consequently, when the offending bacteria attempt to undergo cell division, cell death occurs.","Penicillin binding protein 2a inhibitor","Indication associated"]
[544,"DB01611","approved","small molecule","Hydroxychloroquine","(±)-hydroxychloroquine; 2-((4-((7-chloro-4-quinolyl)amino)pentyl)ethylamino)ethanol; 2-(N-(4-(7-chlor-4-chinolylamino)-4-methylbutyl)ethylamino)ethanol; 7-chloro-4-(4-(ethyl(2-hydroxyethyl)amino)-1-methylbutylamino)quinoline; 7-chloro-4-(4-(N-ethyl-N-β-hydroxyethylamino)-1-methylbutylamino)quinoline; 7-chloro-4-[4-(N-ethyl-N-β-hydroxyethylamino)-1-methylbutylamino]quinoline; 7-chloro-4-[5-(N-ethyl-N-2-hydroxyethylamino)-2-pentyl]aminoquinoline; Oxichlorochine; Oxichloroquine","C18H26ClN3O","CCN(CCO)CCCC(C)NC1=C2C=CC(Cl)=CC2=NC=C1","Hydroxychloroquine is a racemic mixture consisting of an R and S enantiomer. Hydroxychloroquine is an aminoquinoline like . It is a commonly prescribed medication in the treatment of uncomplicated malaria, rheumatoid arthritis, chronic discoid lupus erythematosus, and systemic lupus erythematosus. Hydroxychloroquine is also used for the prophylaxis of malaria in regions where chloroquine resistance is unlikely. It was developed during World War II as a derivative of  with less severe side effects. Chloroquine and hydroxychloroquine are both being investigated for the treatment of SARS-CoV-2.\r\n\r\n**The FDA emergency use authorization for hydroxychloroquine and  in the treatment of COVID-19 was revoked on 15 June 2020.**\r\n\r\nHydroxychloroquine was granted FDA approval on 18 April 1955.\r\n\r\nA recent study reported a fatality in the group being treated with hydroxychloroquine for COVID-19.","118-42-3","335.872","Hydroxychloroquine is indicated for the prophylaxis of malaria where chloroquine resistance is not reported, treatment of uncomplicated malaria (caused by _P. falciparum_, _P. malariae_, _P. ovale_, or _P. vivax_), chronic discoid lupus erythematosus, systemic lupus erythematosus, acute rheumatoid arthritis, and chronic rheumatoid arthritis.","Hydroxychloroquine affects the function of lysozomes in humans as well as plasmodia. Altering the pH of the lysozomes reduces low affinity self antigen presentation in autoimmue diseases and interferes with the ability of plasmodia to proteolyse hemoglobin for their energy requirements. Hydroxychloroquine has a long duration of action as it may be taken on a weekly basis for some indications. Hydroxychloroquine may lead to severe hypoglycemia and so diabetic patients are advised to monitor their blood glucose levels. Hydroxychloroquine is not effective against malaria in areas where chloroquine resistance has been reported.","The exact mechanisms of hydroxychloroquine are unknown. It has been shown that hydroxychloroquine accumulates in the lysosomes of the malaria parasite, raising the pH of the vacuole. This activity interferes with the parasite's ability to proteolyse hemoglobin, preventing the normal growth and replication of the parasite. Hydroxychloroquine can also interfere with the action of parasitic heme polymerase, allowing for the accumulation of the toxic product beta-hematin.\r\n\r\nHydroxychloroquine accumulation in human organelles also raise their pH, which inhibits antigen processing, prevents the alpha and beta chains of the major histocompatibility complex (MHC) class II from dimerizing, inhibits antigen presentation of the cell, and reduces the inflammatory response. Elevated pH in the vesicles may alter the recycling of MHC complexes so that only the high affinity complexes are presented on the cell surface. Self peptides bind to MHC complexes with low affinity and so they will be less likely to be presented to autoimmune T cells. Hydroxychloroquine also reduces the release of cytokines like interleukin-1 and tumor necrosis factor, possibly through inhibition of Toll-like receptors.\r\n\r\nThe raised pH in endosomes, prevent virus particles (such as SARS-CoV and SARS-CoV-2) from utilizing their activity for fusion and entry into the cell.\r\n\r\nHydroxychloroquine inhibits terminal glycosylation of ACE2, the receptor that SARS-CoV and SARS-CoV-2 target for cell entry. ACE2 that is not in the glycosylated state may less efficiently interact with the SARS-CoV-2 spike protein, further inhibiting viral entry.","DNA cross-linking/alkylation; Toll-like receptor 7 antagonist; Toll-like receptor 9 antagonist; Angiotensin-converting enzyme 2 modulator","Therapeutic strategy associated"]
[545,"DB01612","approved","small molecule","Amyl Nitrite","1-nitropentane; n-Amyl nitrite; n-pentyl nitrite; Nitramyl; pentyl nitrite","C5H11NO2","CCCCCON=O","Amyl Nitrite is an antihypertensive medicine. Amyl nitrite is employed medically to treat heart diseases such as angina and to treat cyanide poisoning. Its use as a prescription medicine comes from its ability to lower blood pressure. As an inhalant, it also has psychoactive effect which has led to illegal drug use.","8017-89-8","117.1463","For the rapid relief of angina pectoris.","Amyl nitrite, in common with other alkyl nitrites, is a potent vasodilator. It expands blood vessels, resulting in lowering of the blood pressure. Alkyl nitrite functions as a source of nitric oxide, which signals for relaxation of the involuntary muscles. Adverse effects are related to this pharmacological activity and include hypotension, headache, flushing of the face, tachycardia, dizziness, and relaxation of involuntary muscles, especially the blood vessel walls and the anal sphincter.","Amyl nitrite's antianginal action is thought to be the result of a reduction in systemic and pulmonary arterial pressure (afterload) and decreased cardiac output because of peripheral vasodilation, rather than coronary artery dilation. Amyl nitrite is a source of nitric oxide, which accounts for the mechanism described above. As an antidote (to cyanide poisoning), amyl nitrite promotes formation of methemoglobin, which combines with cyanide to form nontoxic cyanmethemoglobin.","Atrial natriuretic peptide receptor 1 agonist","Indication associated"]
[546,"DB01616","approved; investigational","small molecule","Alverine","Alverine; Bis(gamma-phenylpropyl)ethylamine; Di(phenylpropyl)ethylamine; N-Ethyl-3-phenyl-N-(3-phenylpropyl)-1-propanamine; N-Ethyl-3,3'-diphenyldipropylamine; N-Ethyl-N-(3-phenylpropyl)benzenepropanamine; N,N-Bis(3-phenylpropyl)ethylamine; Phenopropamine; Phenpropamine","C20H27N","CCN(CCCC1=CC=CC=C1)CCCC1=CC=CC=C1","Alverine is a smooth muscle relaxant used to relieve cramps or spasms of the stomach and intestines. It is therefore useful in treating irritable bowel syndrome (IBS) and similar conditions. It can also be used to help relieve period pain.","150-59-4","281.4351","Used to relieve cramps or spasms of the stomach and intestines. It is also useful in treating irritable bowel syndrome (IBS) and similar conditions. It can also be used to help relieve period pain. Alverine citrate is also under investigation to increase the cytotoxic effects of the proteasome inhibitor MG132 on breast cancer cells.","Alverine is a smooth muscle relaxant. Smooth muscle is a type of muscle that is not under voluntary control; it is the muscle present in places such as the gut and uterus. Alverine acts directly on the muscle in the gut, causing it to relax. This prevents the muscle spasms which occur in the gut in conditions such as irritable bowel syndrome and diverticular disease. Diverticular disease is a condition in which small pouches form in the gut lining. These pouches can trap particles of food and become inflamed and painful. In irritable bowel syndrome the normal activity of the gut muscle is lost. The muscle spasms result in symptoms such as heartburn, abdominal pain and bloating, constipation or diarrhoea. By relaxing the gut muscle, alverine citrate relieves the symptoms of this condition. Alverine also relaxes the smooth muscle in the womb (uterus). It is therefore also used to treat painful menstruation, which is caused by muscle spasms in the uterus (dysmenorrhea).",null,"5-hydroxytryptamine receptor 1A antagonist","Therapeutic strategy associated"]
[547,"DB01625","approved; vet_approved","small molecule","Isopropamide","Isopropamide","C23H33N2O","CC(C)[N+](C)(CCC(C(N)=O)(C1=CC=CC=C1)C1=CC=CC=C1)C(C)C","Isopropamide iodide is a long-acting quaternary anticholinergic drug. It is used in the treatment of peptic ulcer and other gastrointestinal disorders marked by hyperacidity and hypermotility.","7492-32-2","353.5209","For the treatment of a wide range of gastrointestinal disorders, including such conditions as peptic ulcer, gastritis, hyperchlorhydria, functional diarrhea, irritable or spastic colon, pyloroduodenal irritability, pylorospasm, acute nonspecific gastroenteritis, biliary dyskinesia and chronic cholelithiasis, duodenitis, gastrointestinal spasm; it may also be used to treat genitourinary spasm.","Isopropamide is a long-acting quaternary anticholinergic drug. It is used in the treatment of peptic ulcer and other gastrointestinal disorders marked by hyperacidity and hypermotility.","Anticholinergics are a class of medications that inhibit parasympathetic nerve impulses by selectively blocking the binding of the neurotransmitter acetylcholine to its receptor in nerve cells. The nerve fibers of the parasympathetic system are responsible for the involuntary movements of smooth muscles present in the gastrointestinal tract. Inhibition here decreases acidity and motility, aiding in the treatment of gastrointestinal disorders.","Muscarinic acetylcholine receptor M3 antagonist; Muscarinic acetylcholine receptor M4 antagonist","Indication associated"]
[548,"DB01626","approved","small molecule","Pargyline","Pargyline","C11H13N","CN(CC#C)CC1=CC=CC=C1","Pargyline is a monoamine oxidase inhibitor with antihypertensive properties.","555-57-7","159.2276","For the treatment of moderate to severe hypertension.","Pargyline is a monoamine oxidase B (MAO-B) inhibitor with antihypertensive properties. Patients taking pargyline must avoid concurrent consumption of tyramine-containing foods such as bleu cheese and beer, as this can lead to a hypertensive crisis.","MAOIs act by inhibiting the activity of monoamine oxidase, thus preventing the breakdown of monoamine neurotransmitters and thereby increasing their availability. There are two isoforms of monoamine oxidase, MAO-A and MAO-B. MAO-A preferentially deaminates serotonin, melatonin, epinephrine and norepinephrine. MAO-B preferentially deaminates phenylethylamine and trace amines. Pargyline functions by inhibiting the metabolism of catecholamines and tyramine within presynaptic nerve terminals. Catecholamines cause general physiological changes that prepare the body for physical activity (fight-or-flight response). Some typical effects are increases in heart rate, blood pressure, blood glucose levels, and a general reaction of the sympathetic nervous system.","Amine oxidase [flavin-containing] B inhibitor; Amine oxidase [flavin-containing] A inhibitor","Therapeutic strategy associated"]
[549,"DB01627","approved; vet_approved","small molecule","Lincomycin","Cillimycin; LCM; Lincomycin; Lincomycinum","C18H34N2O6S","[H][C@]1(C[C@@H](CCC)CN1C)C(=O)N[C@H]([C@@H](C)O)[C@H]1O[C@H](SC)[C@H](O)[C@@H](O)[C@H]1O","Lincomycin is a lincosamide antibiotic first isolated from the soil bacterium _Streptomyces lincolnensis_ in Lincoln, Nebraska. Clinical use of lincomycin has largely been superseded by its semisynthetic derivative  due to its higher efficacy and a wider range of susceptible organisms, though lincomycin remains in use.\r\n\r\nLincomycin was approved by the FDA on December 29, 1964.","154-21-2","406.54","Lincomycin is indicated for the treatment of serious bacterial infections by susceptible strains of streptococci, pneumococci, and staphylococci in patients who are allergic to penicillins or for situations in which a penicillin is deemed inappropriate. As with all antibacterial agents, lincomycin should only be used to treat infections proven or strongly suspected to be caused by susceptible bacteria.","Lincomycin is a lincosamide antibiotic derived as a natural fermentation product from _Streptomyces lincolnensis_. Like , lincomycin is active against Gram-positive cocci and bacilli as well as Gram-negative cocci and some other organisms such as _Haemophilus_ spp. It is also effective against anaerobic bacteria, though in this regard  is generally more potent. Prescribing information highlights that the range of clinically confirmed effectiveness is largely limited to _Staphylococcus_ spp. and _Streptococcus_ spp., with additional activity noted _in vitro_.\r\n\r\nLincomycin should be used with caution due to its association with severe cutaneous hypersensitivity reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, and acute generalized exanthematous pustulosis, and its potential to precipitate _Clostridium difficile_ associated diarrhea (CDAD), which may lead to fatal colitis. Special care should therefore be exercised when used in elderly patients, individuals with a history of gastrointestinal disease, and those with a history of asthma or significant allergies. Lincomycin for injection may contain benzyl alcohol as a preservative, which has been associated with gasping syndrome in pediatric patients. The serum half-life is extended in patients with hepatic/renal impairment and may require dose adjustments and additional monitoring. Like all antibiotics, lincomycin use may cause overgrowth of non-susceptible organisms, which should be considered.","Lincomycin contains the unusual amino acid moiety propyl hygric acid linked to the sugar moiety α-methylthiolincosamine (α-MTL) that, like other lincosamides, functions as a structural analogue of the 3' end of L-Pro-Met-tRNA and deacylated-tRNA to interact with the 23S rRNA of the 50S bacterial ribosomal subunit. Detailed investigations into the mechanism of the related lincosamide  suggested a two-phase binding, instantaneously to the A-site with a shift in equilibrium towards the P-site over several seconds. This shift appears to be due to rotation of the propyl hygric acid moiety, while the α-MTL remains relatively stationary. Recent crystal structures of lincomycin in complex with the 50S ribosomal subunit of _Staphylococcus aureus_ show that the α-MTL moiety forms hydrogen bonds with C2611, A2058, G2505, A2059, and G2503 of the 23S rRNA while the propyl hygric acid moiety interacts only through van der Waals contacts, suggesting it may be free to rotate similar to . This mechanism is supported by the observation that the most common resistance mechanism, which also affects macrolides and streptogramin B (MSLB resistance) involves methylation of A2058; other resistance mechanisms similarly target residues such as A2058, A2059, and C2611.","23S ribosomal RNA binder","Indication associated"]
[550,"DB01628","approved; investigational","small molecule","Etoricoxib","5-chloro-2-(6-methylpyridin-3-yl)-3-(4-(methylsulfonyl)phenyl)pyridine; 5-Chloro-3-(4-methanesulfonyl-phenyl)-6'-methyl-[2,3']bipyridinyl; 5-chloro-6'-methyl-3-(p-(methylsulfonyl)phenyl)-2,3'-bipyridine","C18H15ClN2O2S","CC1=NC=C(C=C1)C1=C(C=C(Cl)C=N1)C1=CC=C(C=C1)S(C)(=O)=O","Etoricoxib is a new COX-2 selective inhibitor. Current therapeutic indications are: treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, chronic low back pain, acute pain and gout. Like any other COX-2 selective inhibitor, Etoricoxib selectively inhibits isoform 2 of cyclo-oxigenase enzyme (COX-2) to reduce the generation of prostaglandins (PGs) from arachidonic acid. It is approved in more than 60 countries worldwide but not in the US.","202409-33-4","358.842","For the treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, chronic low back pain, acute pain and gout.","Etoricoxib is a COX-2 selective inhibitor (approximately 106 times more selective for COX-2 inhibition over COX-1).","Like any other COX-2 selective inhibitor Etoricoxib selectively inhibits isoform 2 of cyclo-oxigenase enzyme (COX-2), preventing production of prostaglandins (PGs) from arachidonic acid.","Prostaglandin G/H synthase 2 inhibitor","Indication associated"]
[551,"DB01669","experimental","small molecule","Virginiamycin M1","Mikamycin A; Ostreogrycin A; Pristinamycin IIA; Streptogramin A; Virginiamycin factor M1; Virginiamycin M1","C28H35N3O7","CC(C)[C@H]1OC(=O)C2=CCCN2C(=O)C2=COC(=N2)CC(=O)C[C@H](O)\\C=C(/C)\\C=C\\CNC(=O)\\C=C\\[C@H]1C","Pristinamycin IIA is a macrolide antibiotic, a member of the streptogramin A group of antibiotics, and one component of pristinamycin. It is produced by Streptomyces graminofaciens and other bacteria.","21411-53-0","525.5934","For the treatment of bacterial infections.",null,"Virginiamycin M1 is a macrocyclic lactone antibiotic that acts syngeristically with the structurally unrelated cyclic depsipeptides more commonly known as the virginiamycins B (ostreogrycin B or streptogramin B) and S to inhibit peptide elongation. This is achieved by blocking formation of a peptide bond between the growing peptide chain (peptidyl-tRNA) linked to the 50S ribosome and aminoacyl-tRNA. Virginiamycin M1 has proven to be highly active against Gram positive bacteria, particularly methicillin-resistant S. aureus.","Streptogramin A acetyltransferase","Indication associated"]
[552,"DB01708","approved; investigational; nutraceutical","small molecule","Prasterone","3-beta-hydroxy-5-androsten-17-one; 3beta-hydroxyandrost-5-en-17-one; 3β-hydroxyandrost-5-en-17-one; Dehydroandrosterone; Dehydroepiandrosterone; Dehydroisoandrosterone; DHEA; Prasterone","C19H28O2","[H][C@@]12CCC(=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC=C2C[C@@]([H])(O)CC[C@]12C","Prasterone, also known as dehydroepiandrosterone (DHEA) is a major C19 steroid produced by the adrenal cortex. It is also produced in small quantities in the testis and the ovary. Dehydroepiandrosterone (DHEA) can be converted to testosterone; androstenedione; estradiol; and estrone. Most of DHEA is sulfated (dehydroepiandrosterone sulfate) before secretion.\r\n\r\nIn the United States, DHEA or DHEAS have been advertised with claims that they may be beneficial for a wide variety of ailments. DHEA and DHEAS are readily available in the United States, where they are marketed as over-the-counter dietary supplements. In November 2016, DHEA was approved (as Intrarosa) to treat women experiencing moderate to severe pain during sexual intercourse (dyspareunia), a symptom of vulvar and vaginal atrophy (VVA), due to menopause.\r\n\r\nIn Canada, a prescription is required to buy DHEA.","53-43-0","288.4244","DHEA is taken as a supplement for a variety of unsubstantiated indications. The following indications have shown promise and are backed up by some scientific evidence: schizophrenia (DHEA may be more effective in women than men); improving the appearance of older people’s skin (taking DHEA by mouth seems to increase skin thickness and moisture, and decrease facial “age spots” in elderly men and women); improving ability to achieve an erection in men with sexual dysfunction. Additionally, DHEA has shown promise in improving symptoms of lupus (SLE). Taking DHEA by mouth along with conventional treatment may help reduce the number of times symptoms flare up and may allow a reduction in the dose of prescription drugs needed. DHEA may also help SLE symptoms such as muscle ache and mouth ulcers. DHEA also seems to strengthen bones in SLE patients being treated with high-dose steroids (corticosteroids).\r\nDHEA also shows promise in the treatment of osteoporosis. Taking DHEA by mouth daily seems to improve bone mineral density (BMD) in older women and men with osteoporosis or osteopenia (pre-osteoporosis). DHEA may also increase BMD in young women with the eating disorder called anorexia nervosa. DHEA is often prescribed in India for the induction of ovulation to improve chances of pregnancy.","DHEA is naturally produced from cholesterol through two cytochrome P450 enzymes. Cholesterol is converted to pregnenolone by the enzyme P450 scc (side chain cleavage); then another enzyme, CYP17A1, converts pregnenolone to 17α-Hydroxypregnenolone and then to DHEA. DHEA is increased by exercise and calorie restriction. Some theorize that the increase in endogenous DHEA brought about by calorie restriction is partially responsible for the longer life expectancy known to be associated with calorie restriction.","DHEA can be understood as a prohormone for the sex steroids. DHEAS may be viewed as buffer and reservoir. As most DHEA is produced by the zona reticularis of the adrenal cortex, it is argued that there is a role in the immune and stress response. DHEAS/DHEA are useful to detect excess adrenal activity as seen in adrenal cancer or hyperplasia, including certain forms of congenital adrenal hyperplasia as it is produced nearly entirely by the adrenal glands. Women with polycystic ovary syndrome tend to have elevated levels of DHEAS.","Estrogen receptor alpha binder; Estrogen receptor beta activator; GABA(A) Receptor antagonist; NMDA receptor agonist; Androgen receptor agonist; Peroxisome proliferator-activated receptor alpha activator; Sigma non-opioid intracellular receptor 1 agonist; Nuclear receptor subfamily 1 group I member 2 activator; Nuclear receptor subfamily 1 group I member 3 activator","Target associated"]
[553,"DB01764","approved","small molecule","Dalfopristin","Dalfopristin","C34H50N4O9S","CCN(CC)CCS(=O)(=O)[C@@H]1CCN2[C@H]1C(=O)O[C@H](C(C)C)[C@H](C)\\C=C\\C(=O)NC\\C=C\\C(\\C)=C\\[C@@H](O)CC(=O)CC1=NC(=CO1)C2=O","Dalfopristin is a combination of two antibiotics (Dalfopristin and quinupristin) used to treat infections by staphylococci and by vancomycin-resistant Enterococcus faecium. It is not effective against Enterococcus faecalis infections. Dalfopristin inhibits the early phase of protein synthesis in the bacterial ribosome and quinupristin inhibits the late phase of protein synthesis.","112362-50-2","690.85","For the treatment of bacterial infections (usually in combination with quinupristin).","Dalfopristin is a streptogramin antibiotic, derived from pristinamycin IIA.","The site of action of dalfopristin is the bacterial ribosome. Dalfopristin \r\nhas been shown to inhibit the early phase of protein synthesis.\r","Streptogramin A acetyltransferase inhibitor","Indication associated"]
[554,"DB01783","approved; nutraceutical; vet_approved","small molecule","Pantothenic acid","(+)-Pantothenic acid; D-pantothenic acid; Pantothenate; Vitamin B5","C9H17NO5","CC(C)(CO)[C@@H](O)C(=O)NCCC(O)=O","Pantothenic acid, also called pantothenate or vitamin B5 (a B vitamin), is a water-soluble vitamin discovered by Roger J. Williams in 1919. For many animals, pantothenic acid is an essential nutrient as it is required to synthesize coenzyme-A (CoA), as well as to synthesize and metabolize proteins, carbohydrates, and fats. Pantothenic acid is the amide between pantoic acid and β-alanine and commonly found as its alcohol analog, the provitamin panthenol, and as calcium pantothenate. Small quantities of pantothenic acid are found in nearly every food, with high amounts in whole-grain cereals, legumes, eggs, meat, royal jelly, avocado, and yogurt. Pantothenic acid is an ingredient in some hair and skin care products. Only the dextrorotatory (D) isomer of pantothenic acid possesses biological activity. while the levorotatory (L) form may antagonize the effects of the dextrorotatory isomer.","79-83-4","219.235","Studied for the treatment of many uses such as treatment of testicular torsion, diabetic ulceration, wound healing, acne, obesity, diabetic peripheral polyneuropathy. It has also been investigated for its hypolipidemic effects and as cholesterol lowering agent.","Pantothenic acid is used in the synthesis of coenzyme A (CoA). CoA is thought to act as a carrier molecule, allowing the entry of acyl groups into cells. This is of critical importance as these acyl groups are used as substrates in the tricarboxylic acid cycle to generate energy and in the synthesis of fatty acids, cholesterol, and acetylcholine. Additionally, CoA is part of acyl carrier protein (ACP), which is required in the synthesis of fatty acids in addition to CoAs use as a substrate. \r\n\r\nPantothenic acid in the form of CoA is also required for acylation and acetylation, which, for example, are involved in signal transduction and enzyme activation and deactivation, respectively.\r\n\r\nSince pantothenic acid participates in a wide array of key biological roles, it may have numerous wide-ranging effects.","Pantothenic acid is incorporated into COENZYME A and protects cells against peroxidative damage by increasing the level of GLUTATHIONE.","Pantothenate kinase","Indication associated"]
[555,"DB01827","experimental","small molecule","2,3,5,6-Tetrafluoro-4-Methoxy-Benzamide",null,"C8H5F4NO2","COC1=C(F)C(F)=C(C(N)=O)C(F)=C1F",null,null,"223.1244",{"$nulls":3},"Galectin-3","Target associated"]
[556,"DB01890","experimental","small molecule","N,N-Bis(3-(D-gluconamido)propyl)deoxycholamide","D-Gluconamide, N,N'-((((3alpha,5beta,12alpha)-3,12-dihydroxy-24-oxocholan-24-yl)imino)di-3,1-propanediyl)bis-; Deoxy-bigchap; N,N-Bis(3-(D-gluconamido)propyl)deoxycholamide; N,N'-((((3alpha,5beta,12alpha)-3,12-Dihydroxy-24-oxocholan-24-yl)imino)di-3,1-propandiyl)bis-D-gluconamide","C42H75N3O15","[H][C@@]1(CC[C@@]2([H])[C@]3([H])CC[C@]4([H])C[C@H](O)CC[C@]4(C)[C@@]3([H])C[C@H](O)[C@]12C)[C@H](C)CCC(=O)N(CCCNC(=O)[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO)CCCNC(=O)[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO",null,"86303-23-3","862.056",{"$nulls":3},"Insulin-like growth factor I; Peroxisome proliferator-activated receptor alpha","Target associated"]
[557,"DB01992","investigational; nutraceutical","small molecule","Coenzyme A","3'-phosphoadenosine-(5')diphospho(4')pantatheine; CoA; CoA-SH; CoASH; HSCoA","C21H36N7O16P3S","CC(C)(COP(O)(=O)OP(O)(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1OP(O)(O)=O)N1C=NC2=C1N=CN=C2N)[C@@H](O)C(=O)NCCC(=O)NCCS","Coenzyme A (CoA, CoASH, or HSCoA) is a coenzyme, well known for it's role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All genomes sequenced to date encode enzymes that use coenzyme A as a substrate, and around 4% of cellular enzymes use it, or a thioester form of it, as a substrate. It is used as a supplement for the hypothetical treatment of acne.","85-61-0","767.534",{"$nulls":3},"Acetyl-coenzyme A synthetase; Acyl-CoA-binding protein; Formyl-coenzyme A transferase; Carnitine O-acetyltransferase; Crotonobetainyl-CoA:carnitine CoA-transferase; Formate acetyltransferase 1; Malate synthase G; 3-hydroxy-3-methylglutaryl-coenzyme A reductase; Phosphopantetheine adenylyltransferase; Holo-[acyl-carrier-protein] synthase; Protease synthase and sporulation negative regulatory protein PAI 1; Gentamicin 3'-acetyltransferase; Galactoside O-acetyltransferase; 3-hydroxy-3-methylglutaryl-coenzyme A reductase; Fatty acid metabolism regulator protein; Histone acetyltransferase KAT5; 2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-succinyltransferase; Acetyl-CoA acetyltransferase, cytosolic; Acetyl-CoA acetyltransferase; Streptogramin A acetyltransferase; Citrate synthase, mitochondrial; 3-oxoacyl-[acyl-carrier-protein] synthase 3; Formyl-coenzyme A transferase; Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex; Pantothenate kinase; Acetyl transferase; Uncharacterized N-acetyltransferase YvbK; Aminoglycoside N(6')-acetyltransferase type 1; Acyl-CoA hydrolase; Uncharacterized acyl-CoA thioester hydrolase HI_0827; 3-oxoacyl-[acyl-carrier-protein] synthase 3; Mycothiol acetyltransferase; Histone acetyltransferase KAT2A; Acyl-CoA hydrolase; Histone acetyltransferase KAT2B; 1,4-Dihydroxy-2-naphthoyl-CoA synthase; Citrate synthase; Aminoglycoside 2'-N-acetyltransferase; Aac(6')-Ii protein; 4'-phosphopantetheinyl transferase sfp; Uncharacterized protein; Serine acetyltransferase; Citrate synthase; 4-hydroxybenzoyl-CoA thioesterase; Bifunctional protein GlmU","Target associated"]
[558,"DB02106","experimental","small molecule","[3,5-Dibromo-4-(4-Hydroxy-3-Phenethylcarbamoyl-Phenoxy)-Phenyl]-Acetic Acid",null,"C23H23Br2NO5","OC(O)CC1=CC(Br)=C(OC2=CC(C(O)NCCC3=CC=CC=C3)=C(O)C=C2)C(Br)=C1",null,null,"553.24",{"$nulls":3},"Thyroid hormone receptor beta","Target associated"]
[559,"DB02187","experimental","small molecule","Equilin","1,3,5,7-Estratetraen-3-ol-17-one; 7-Dehydroestrone; Dihydroequilenin; Equilin","C18H20O2","[H][C@@]12CCC(=O)[C@@]1(C)CC[C@]1([H])C3=C(CC=C21)C=C(O)C=C3","An estrogenic steroid produced by horses. It has a total of four double bonds in the A- and B-ring. High concentration of equilin is found in the urine of pregnant mares.","474-86-2","268.3502","For the treatment of moderate to severe vasomotor symptoms associated with the menopause, atrophic vaginitis, osteoporosis, hypoestrogenism due to hypogonadism, castration, primary ovarian failure, breast cancer (for palliation only), and Advanced androgen-dependent carcinoma of the prostate (for palliation only)","Equilin is a component of Premarin (conjugated estrogens), a mixture of the water soluble salts of sulfate esters from estrone, equilin, 17 alpha-dihydroequilin, and other related steroids, may be derived from pregnant equine urine or yam and soy plants. Estrogens are important in the development and maintenance of the female reproductive system and secondary sex characteristics. They promote growth and development of the vagina, uterus, and fallopian tubes, and enlargement of the breasts. Indirectly, they contribute to the shaping of the skeleton, maintenance of tone and elasticity of urogenital structures, changes in the epiphyses of the long bones that allow for the pubertal growth spurt and its termination, growth of axillary and pubic hair, and pigmentation of the nipples and genitals. Decline of estrogenic activity at the end of the menstrual cycle can bring on menstruation, although the cessation of progesterone secretion is the most important factor in the mature ovulatory cycle. However, in the preovulatory or nonovulatory cycle, estrogen is the primary determinant in the onset of menstruation. Estrogens also affect the release of pituitary gonadotropins. The pharmacologic effects of conjugated estrogens are similar to those of endogenous estrogens.","Estrogens enter the cells of responsive tissues (e.g., female organs, breasts, hypothalamus, pituitary) where they interact with a protein receptor, subsequently increasing the rate of synthesis of DNA, RNA, and some proteins. Estrogens decrease the secretion of gonadotropin-releasing hormone by the hypothalamus, reducing the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary.","Estradiol 17-beta-dehydrogenase 1; Estrogen receptor alpha","Indication associated"]
[560,"DB02266","approved","small molecule","Flufenamic acid","Flufenamic acid","C14H10F3NO2","OC(=O)C1=CC=CC=C1NC1=CC(=CC=C1)C(F)(F)F","An anthranilic acid derivative with analgesic, anti-inflammatory, and antipyretic properties. It is used in musculoskeletal and joint disorders and administered by mouth and topically. (From Martindale, The Extra Pharmacopoeia, 30th ed, p16)","530-78-9","281.2299",{"$nulls":3},"Prostaglandin G/H synthase 2; Prostaglandin G/H synthase 1; Aldo-keto reductase family 1 member C3; Androgen receptor; Peroxisome proliferator-activated receptor alpha activator; Peroxisome proliferator-activated receptor gamma agonist","Target associated"]
[561,"DB02342","investigational","small molecule","2-Methoxyestradiol","2-Hydroxyestradiol 2-methyl ether; 2-Hydroxyestradol 2-methyl ether; 2-ME2; 2-methoxy-17β-estradiol; 2-Methoxyestradiol-17beta; 2ME2","C19H26O3","[H][C@@]12CC[C@H](O)[C@@]1(C)CC[C@]1([H])C3=C(CC[C@@]21[H])C=C(O)C(OC)=C3","2-Methoxyestradiol (2ME2) is a drug that prevents the formation of new blood vessels that tumors need in order to grow (angiogenesis). It has undergone Phase 1 clinical trials against breast cancers and preclinical studies suggest that 2ME2 could also be effective against inflammatory diseases such as rheumatoid arthritis.","362-07-2","302.4079","For the treatment of breast cancer and inflammatory diseases such as rheumatoid arthritis.","2-Methoxyestradiol belongs to the family of drugs called angiogenesis inhibitors. It also acts as a vasodilator.","2-Methoxyestradiol is an angiogenesis inhibitor, and has been shown to attack both tumor cells and their blood supply in preclinical testing. 2-methoxyestradiol is a naturally occurring estrogen metabolite but has no undesired estrogenic activity.","Hypoxia-inducible factor 1-alpha; Catechol O-methyltransferase; Cytochrome P450 1A1; Cytochrome P450 1B1; Cytochrome P450 19A1","Indication associated"]
[562,"DB02383","withdrawn","small molecule","Tolrestat","Tolrestat","C16H14F3NO3S","COC1=C(C2=CC=CC(C(=S)N(C)CC(O)=O)=C2C=C1)C(F)(F)F","Tolrestat (INN) (AY-27773) is an aldose reductase inhibitor which was approved for the control of certain diabetic complications. While it was approved for marketed in several countries, it failed a Phase III trial in the U.S. due to toxicity and never received FDA approval. It was sold under the tradename Alredase but was discontinued by Wyeth in 1997 because of the risk of severe liver toxicity and death.","82964-04-3","357.347","For the pharmacological control of certain diabetic complications.",null,null,"Aldose reductase inhibitor; Alcohol dehydrogenase [NADP(+)]; Aldo-keto reductase family 1 member B10","Indication associated"]
[563,"DB02458","experimental","small molecule","S-(2,4-dinitrophenyl)glutathione","dinitrophenyl-S-glutathione; DNP-S-glutathione; DNP-SGc","C16H19N5O10S","[H][C@](N)(CCC(=O)N[C@@]([H])(CSC1=C(C=C(C=C1)N(=O)=O)N(=O)=O)C(=O)NCC(O)=O)C(O)=O",null,"26289-39-4","473.415",{"$nulls":3},"Glutathione S-transferase Mu 1; Glutathione S-transferase Mu 2","Target associated"]
[564,"DB02509","experimental","small molecule","Farnesol",null,"C15H26O","CC(C)=CCC\\C(C)=C/CC\\C(C)=C/CO","A colorless liquid extracted from oils of plants such as citronella, neroli, cyclamen, and tuberose. It is an intermediate step in the biological synthesis of cholesterol from mevalonic acid in vertebrates. It has a delicate odor and is used in perfumery. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)","4602-84-0","222.3663",{"$nulls":3},"Amine oxidase [flavin-containing] B; Bile acid receptor agonist","Target associated"]
[565,"DB02545","experimental","small molecule","Fexaramine",null,"C32H36N2O3","COC(=O)\\C=C\\C1=CC(=CC=C1)N(CC1=CC=C(C=C1)C1=CC=C(C=C1)N(C)C)C(=O)C1CCCCC1",null,"574013-66-4","496.6398",{"$nulls":3},"Bile acid receptor","Target associated"]
[566,"DB02546","approved; investigational","small molecule","Vorinostat","Octanedioic acid hydroxyamide phenylamide; SAHA; SHH; Suberanilohydroxamic acid; Suberoylanilide hydroxamic acid","C14H20N2O3","ONC(=O)CCCCCCC(=O)NC1=CC=CC=C1","Vorinostat (rINN) or suberoylanilide hydroxamic acid (SAHA), is a drug currently under investigation for the treatment of cutaneous T cell lymphoma (CTCL), a type of skin cancer, to be used when the disease persists, gets worse, or comes back during or after treatment with other medicines. It is the first in a new class of agents known as histone deacetylase inhibitors.  A recent study suggested that vorinostat also possesses some activity against recurrent glioblastoma multiforme, resulting in a median overall survival of 5.7 months (compared to 4 - 4.4 months in earlier studies). Further brain tumor trials are planned using combinations of vorinostat with other drugs.","149647-78-9","264.3202","For the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma who have progressive, persistent or recurrent disease on or following two systemic therapies.",null,"Vorinostat inhibits the enzymatic activity of histone deacetylases HDAC1, HDAC2 and HDAC3 (Class I) and HDAC6 (Class II) at nanomolar concentrations (IC<sub>50</sub>&lt; 86 nM). These enzymes catalyze the removal of acetyl groups from the lysine residues of histones proteins. In some cancer cells, there is an overexpression of HDACs, or an aberrant recruitment of HDACs to oncogenic transcription factors causing hypoacetylation of core nucleosomal histones. By inhibiting histone deacetylase, vorinostat causes the accumulation of acetylated histones and induces cell cycle arrest and/or apoptosis of some transformed cells. The mechanism of the antineoplastic effect of vorinostat has not been fully characterized.","Histone deacetylase 1 inhibitor; Histone deacetylase 2 inhibitor; Histone deacetylase 3 inhibitor; Histone deacetylase 6 inhibitor; Histone deacetylase 8; Acetoin utilization protein","Therapeutic strategy associated"]
[567,"DB02638","approved; investigational","small molecule","Terlipressin","Terlipressin","C52H74N16O15S2","NCCCC[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@@H]1CSSC[C@H](NC(=O)CNC(=O)CNC(=O)CN)C(=O)N[C@@H](CC2=CC=C(O)C=C2)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N1)C(=O)NCC(N)=O","Terlipressin is an analogue of vasopressin used as a vasoactive drug in the management of hypotension which has been found to be effective when norepinephrine fails.","14636-12-5","1227.372","Commonly used to stop bleeding of varices in the food pipe (oesophagus).","Terlipressin is a medicine similar to a naturally occurring hormone present in the body, known as antidiuretic hormone (ADH) or vasopressin. ADH has two main effects in the body. Firstly, it causes narrowing of blood vessels (vasoconstriction), thereby limiting blood flow to a particular area of the body. It also acts on receptors in the kidney to retain water in the body, which helps to prevent excessive loss of water in the urine.","Terlipressin, an analogue of vasopressin, acts on three different receptors, vasopressin receptor V1a (which initiates vasoconstriction, liver gluconeogenesis, platelet aggregation and release of factor VIII), vasopressin receptor V1b (which mediates corticotrophin secretion from the pituitary) and vasopressin receptor V2 which controls free water reabsorption in the renal medullar. The binding of terlipressin to the V2 receptor activates adenylate cyclase which causes the release of aquaporin 2 channels into the cells lining the renal medullar duct. This allows water to be reabsorbed down an osmotic gradient so the urine is more concentrated.","Vasopressin V2 receptor agonist; Vasopressin V1b receptor; Vasopressin V1a receptor stimulator","Therapeutic strategy associated"]
[568,"DB02659","approved","small molecule","Cholic Acid","Cholic Acid","C24H40O5","[H][C@@](C)(CCC(O)=O)[C@@]1([H])CC[C@@]2([H])[C@]3([H])[C@]([H])(O)C[C@]4([H])C[C@]([H])(O)CC[C@]4(C)[C@@]3([H])C[C@]([H])(O)[C@]12C","A major primary bile acid produced in the liver and usually conjugated with glycine or taurine. It facilitates fat absorption and cholesterol excretion. \r\nCholic acid, formulated as Cholbam capsules, is approved by the United States Food and Drug Administration as a treatment for children and adults with bile acid synthesis disorders due to single enzyme defects, and for peroxisomal disorders (such as Zellweger syndrome).","81-25-4","408.5714","Oral cholic acid is indicated for: treatment of bile acid synthesis disorders due to single enzyme defects; and as adjunctive treatment of peroxisomal disorders including Zellweger spectrum disorders in patients who exhibit manifestations of liver disease, steatorrhea or complications from decreased fat soluble vitamin absorption.",null,null,"Ferrochelatase, mitochondrial; Alcohol dehydrogenase 1C; Estrogen-related receptor gamma; Gastrotropin; Cytochrome c oxidase subunit 4 isoform 1, mitochondrial; Cytochrome c oxidase subunit 1; Cytochrome c oxidase subunit 2; Cytochrome c oxidase subunit 3; Cytochrome c oxidase subunit 5A, mitochondrial; Cytochrome c oxidase subunit 5B, mitochondrial; Cytochrome c oxidase subunit 6C; Cytochrome c oxidase subunit 7B, mitochondrial; Cytochrome c oxidase subunit 7C, mitochondrial; Cytochrome c oxidase subunit 8A, mitochondrial; Cytochrome c oxidase subunit 6A2, mitochondrial; Cytochrome c oxidase subunit 6B1; Cytochrome c oxidase subunit 7A1, mitochondrial; Phospholipase A2; Liver carboxylesterase 1; Ferrochelatase; Choloylglycine hydrolase; Bile acid receptor; G-protein coupled bile acid receptor 1","Target associated"]
[569,"DB02703","approved; investigational","small molecule","Fusidic acid","Fucidate; Fucidin acid; Fusidate; Fusidic acid; Fusidine; Ramycin","C31H48O6","[H][C@@]12C[C@@H](O)[C@@]3([H])[C@@]4(C)CC[C@@H](O)[C@@H](C)[C@]4([H])CC[C@]3(C)[C@@]1(C)C[C@H](OC(C)=O)\\C2=C(\\CCC=C(C)C)C(O)=O","An antibiotic isolated from the fermentation broth of Fusidium coccineum. (From Merck Index, 11th ed) It acts by inhibiting translocation during protein synthesis. It is often used topically in creams and eyedrops but is available in systemic formulations including tablets and injections.","6990-06-3","516.7092","For the treatment of bacterial infections.","Fusidic acid is a bacteriostatic antibiotic and helps prevent bacterial growth while the immune system clears the infection.","Fusidic acid works by interfering with bacterial protein synthesis, specifically by preventing the translocation of the elongation factor G (EF-G) from the ribosome. It also can inhibit chloramphenicol acetyltransferase enzymes.","Elongation factor G inhibitor; Chloramphenicol acetyltransferase inhibitor; Chloramphenicol acetyltransferase 3 inhibitor","Indication associated"]
[570,"DB02746","experimental","small molecule","Phthalic Acid",null,"C8H6O4","OC(=O)C1=CC=CC=C1C(O)=O",null,"88-99-3","166.1308",{"$nulls":3},"Nicotinate-nucleotide pyrophosphorylase [carboxylating]; Estrogen receptor alpha; Progesterone receptor; Estrogen receptor beta; Peroxisome proliferator-activated receptor alpha; Peroxisome proliferator-activated receptor delta; Peroxisome proliferator-activated receptor gamma; Retinoic acid receptor RXR-alpha; Retinoic acid receptor RXR-beta; Retinoic acid receptor RXR-gamma","Target associated"]
[571,"DB02767","experimental","small molecule","(R)-3-hydroxytetradecanoic acid","(−)-3-hydroxymyristic acid; (3R)-hydroxymyristic acid; (R)-(-)-3-Hydroxytetradecanoic acid; (R)-(−)-3-hydroxytetradecanoic acid; (R)-3-Hydroxymyristic acid; (R)-3-Hydroxytetradecanoic acid; D-(-)-beta-Hydroxymyristic acid; D-(−)-β-hydroxymyristic acid; β-hydroxymyristic acid; β-hydroxytetradecanoic acid","C14H28O3","CCCCCCCCCCC[C@@H](O)CC(O)=O",null,"28715-21-1","244.3703",{"$nulls":3},"Ferrichrome-iron receptor; Protein TonB; Lymphocyte antigen 96; Toll-like receptor 4","Target associated"]
[572,"DB02859","experimental","small molecule","Soraphen A",null,"C29H44O8","[H]\\C1=C([H])/[C@@]([H])(OC)[C@]([H])(CCCC[C@]([H])(OC(=O)[C@@]([H])(C)[C@@]2(O)O[C@]([H])([C@@]([H])(C)[C@]([H])(O)[C@@]2([H])OC)[C@@]1([H])C)C1=CC=CC=C1)OC",null,"122547-72-2","520.6549",{"$nulls":3},"Acetyl-CoA carboxylase 2","Target associated"]
[573,"DB03010","experimental; investigational","small molecule","Patupilone","(−)-epothilone B; Epo B; Epothilone B; Patupilone","C27H41NO6S","[H]\\C(=C(\\C)[C@]1([H])C[C@]2([H])O[C@]2(C)CCC[C@]([H])(C)[C@]([H])(O)[C@@]([H])(C)C(=O)C(C)(C)[C@@]([H])(O)CC(=O)O1)C1=CSC(C)=N1","Epothilone B is a 16-membered macrolide that mimics the biological effects of taxol.","152044-54-7","507.683","Investigated for use/treatment in ovarian cancer, lung cancer, brain cancer, breast cancer, and gastric cancer.",null,"The principal mechanism of the epothilone class is inhibition of microtubule function. Microtubules are essential to cell division, and epothilones therefore stop cells from properly dividing. Epothilone B possess the same biological effects as taxol both in vitro and in cultured cells. This is because they share the same binding site, as well as binding affinity to the microtubule. Like taxol, epothilone B binds to the αβ-tubulin heterodimer subunit. Once bound, the rate of αβ-tubulin dissociation decreases, thus stabilizing the microtubules. Furthermore, epothilone B has also been shown to induce tubulin polymerization into microtubules without the presence of GTP. This is caused by formation of microtubule bundles throughout the cytoplasm. Finally, epothilone B also causes cell cycle arrest at the G2-M transition phase, thus leading to cytotoxicity and eventually cell apoptosis.","Tubulin alpha-3C/D chain; Tubulin beta chain; Tubulin beta-1 chain; Tubulin beta-4B chain; Tubulin beta-4A chain; Tubulin alpha-4A chain; Tubulin beta-3 chain; Tubulin alpha-1C chain; Tubulin alpha-8 chain; Tubulin alpha-1B chain; Tubulin alpha-1A chain","Therapeutic strategy associated"]
[574,"DB03017","approved; experimental","small molecule","Lauric acid","1-undecanecarboxylic acid; ABL; C12 fatty acid; C12:0; Coconut oil fatty acids; DAO; Dodecanoic acid; Dodecoic acid; Dodecylcarboxylate; Dodecylic acid; Duodecyclic acid; Duodecylic acid; Laurostearic acid; n-dodecanoic acid; Undecane-1-carboxylic acid; Vulvic acid","C12H24O2","CCCCCCCCCCCC(O)=O","Lauric acid is an inexpensive, non-toxic and safe to handle compound often used in laboratory investigations of melting-point depression. Lauric acid is a solid at room temperature but melts easily in boiling water, so liquid lauric acid can be treated with various solutes and used to determine their molecular masses.","143-07-7","200.3178",{"$nulls":3},"Alcohol dehydrogenase class-3; 3-oxoacyl-[acyl-carrier-protein] synthase 1; Ferrichrome-iron receptor; Ganglioside GM2 activator; 3-oxoacyl-[acyl-carrier-protein] synthase 3; Genome polyprotein; Genome polyprotein; Genome polyprotein; Hepatocyte nuclear factor 4-alpha; Phospholipase A2, membrane associated; Very low-density lipoprotein receptor; Glycolipid transfer protein; 3-oxoacyl-[acyl-carrier-protein] synthase 2; Lactotransferrin; Protein TonB; Complement component C8 gamma chain; Group IID secretory phospholipase A2; Acyl-homoserine lactone acylase PvdQ; Lymphocyte antigen 96; Toll-like receptor 4; Peroxisome proliferator-activated receptor alpha","Target associated"]
[575,"DB03124","experimental","small molecule","5-[4-(1-Carboxymethyl-2-Oxo-Propylcarbamoyl)-Benzylsulfamoyl]-2-Hydroxy-Benzoic Acid",null,"C20H20N2O9S","[H][C@@](CC(O)=O)(NC(=O)C1=CC=C(CNS(=O)(=O)C2=CC(C(O)=O)=C(O)C=C2)C=C1)C(C)=O",null,null,"464.446",{"$nulls":3},"Caspase-3","Target associated"]
[576,"DB03169","experimental","small molecule","(S)-Hmg-Coa",null,"C27H39N7O20P3S","[H][C@](O)(C([O-])=NCCC([O-])=NCCSC(=O)C[C@@](C)(O)CC([O-])=O)C(C)(C)COP(O)(=O)OP(O)(=O)OC[C@@]1([H])O[C@@]([H])(N2C=NC3=C(N)N=CN=C23)[C@]([H])(O)[C@]1([H])OP([O-])([O-])=O",null,null,"906.62",{"$nulls":3},"3-hydroxy-3-methylglutaryl-coenzyme A reductase; 3-hydroxy-3-methylglutaryl-coenzyme A reductase; 3-hydroxy-3-methylglutaryl CoA synthase","Target associated"]
[577,"DB03176","experimental","small molecule","KB-141","3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenylacetic acid","C17H16Cl2O4","CC(C)C1=CC(OC2=C(Cl)C=C(CC(O)=O)C=C2Cl)=CC=C1O","An anticholesteremic agent.","219691-94-8","355.213",{"$nulls":3},"Thyroid hormone receptor beta; Thyroid hormone receptor alpha","Target associated"]
[578,"DB03181","experimental","small molecule","2-[4-(4-Hydroxy-3-Isopropyl-Phenoxy)-3,5-Dimethyl-Phenyl]-2h-[1,2,4]Triazine-3,5-Dione",null,"C20H21N3O4","CC(C)C1=CC(OC2=C(C)C=C(C=C2C)N2N=CC(=O)NC2=O)=CC=C1O",null,null,"367.3984",{"$nulls":3},"Thyroid hormone receptor beta","Target associated"]
[579,"DB03193","approved; experimental","small molecule","Stearic acid","C18:0; n-octadecanoic acid; Octadecanoic acid; Octadecoic acid; Stearic acid","C18H36O2","CCCCCCCCCCCCCCCCCC(O)=O","Stearic acid (IUPAC systematic name: octadecanoic acid) is one of the useful types of saturated fatty acids that comes from many animal and vegetable fats and oils. It is a waxy solid.","57-11-4","284.4772",{"$nulls":3},"Group IID secretory phospholipase A2; Peroxisome proliferator-activated receptor alpha","Target associated"]
[580,"DB03310","approved; experimental; investigational","small molecule","Glutathione disulfide","Glutathione disulphide; GSSG; Oxidized glutathione; Oxiglutatione","C20H32N6O12S2","N[C@@H](CCC(=O)N[C@@H](CSSC[C@H](NC(=O)CC[C@H](N)C(O)=O)C(=O)NCC(O)=O)C(=O)NCC(O)=O)C(O)=O","A GLUTATHIONE dimer formed by a disulfide bond between the cysteine sulfhydryl side chains during the course of being oxidized.","27025-41-8","612.631",{"$nulls":3},"Glutathione S-transferase Mu 2 activator; Glutathione reductase, mitochondrial substrate; Glutathione peroxidase; Microsomal glutathione S-transferase 1 activator; Glutathione S-transferases (Cytosolic) activator","Target associated"]
[581,"DB03316","experimental","small molecule","1,4-Dioxane","1,4-dioxacyclohexane; 1,4-Dioxan; 1,4-Dioxane; di(ethylene oxide); Dioxan-1,4; Dioxane-1,4; glycol ethylene ether; p-Dioxane; tetrahydro-1,4-dioxin; tetrahydro-p-dioxin; tetrahydro-para-dioxin","C4H8O2","C1COCCO1",null,"123-91-1","88.1051",{"$nulls":3},"Subtilisin Carlsberg; Tumor necrosis factor ligand superfamily member 13B; Epsin-1; Structural polyprotein; Transforming growth factor beta-3","Target associated"]
[582,"DB03338","experimental","small molecule","Heptyl glucoside","1-Heptyl beta-D-glucoside; Heptyl beta-D-glucopyranoside; Heptyl glucoside; n-Heptyl beta-D-glucopyranoside; n-Heptyl beta-D-glucoside","C13H26O6","CCCCCCCO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O",null,"78617-12-6","278.3419",{"$nulls":3},"Peroxisome proliferator-activated receptor delta; Peptidyl-prolyl cis-trans isomerase FKBP1A","Target associated"]
[583,"DB03384","experimental","small molecule","Fica",null,"C11H11FN2OS","FC1=CC2=C(NC(=C2)C(=O)NCCS)C=C1",null,null,"238.281",{"$nulls":3},"Caspase-7","Target associated"]
[584,"DB03461","experimental","small molecule","Nicotinamide adenine dinucleotide phosphate","Codehydrase II; Codehydrogenase II; Coenzyme II; Triphosphopyridine nucleotide","C21H28N7O17P3","NC(=O)C1=CC=C[N+](=C1)[C@@H]1O[C@H](COP([O-])(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](OP(O)(O)=O)[C@@H]2O)N2C=NC3=C2N=CN=C3N)[C@@H](O)[C@H]1O","Nicotinamide adenine dinucleotide phosphate. A coenzyme composed of ribosylnicotinamide 5&#39;-phosphate (NMN) coupled by pyrophosphate linkage to the 5&#39;-phosphate adenosine 2&#39;,5&#39;-bisphosphate. It serves as an electron carrier in a number of reactions, being alternately oxidized (NADP+) and reduced (NADPH). (Dorland, 27th ed)","53-59-8","743.405",{"$nulls":3},"Alcohol dehydrogenase 1B; NADPH--cytochrome P450 reductase; Shikimate dehydrogenase; NADP-dependent isopropanol dehydrogenase; GDP-L-fucose synthase; Aspartate-semialdehyde dehydrogenase; 2,4-dienoyl-CoA reductase [NADPH]; NADP-dependent malic enzyme; NAD(P) transhydrogenase subunit beta; 3-oxoacyl-[acyl-carrier-protein] reductase FabG; Isocitrate dehydrogenase [NADP]; Aldose reductase; Glucose-6-phosphate 1-dehydrogenase; Aldo-keto reductase family 1 member C2; Estradiol 17-beta-dehydrogenase 1; NAD(P) transhydrogenase, mitochondrial; Corticosteroid 11-beta-dehydrogenase isozyme 1; Sepiapterin reductase; Pteridine reductase 1; L-xylulose reductase; Isocitrate dehydrogenase [NADP] cytoplasmic; Dihydrofolate reductase; Aldo-keto reductase family 1 member C1; Nitric oxide synthase, brain; Glucose-6-phosphate 1-dehydrogenase; Dihydrofolate reductase; ADP-L-glycero-D-manno-heptose-6-epimerase; C-1-tetrahydrofolate synthase, cytoplasmic; Aldo-keto reductase family 1 member C3; Flavin reductase (NADPH); Isocitrate dehydrogenase [NADP]; Dihydrofolate reductase; Quinone oxidoreductase; Dehydrogenase/reductase SDR family member 11; 3-hydroxy-3-methylglutaryl-coenzyme A reductase; Malate dehydrogenase, cytoplasmic; Oxidoreductase YdhF; Putative pteridine reductase 2; Estradiol 17-beta-dehydrogenase 8; Alcohol dehydrogenase [NADP(+)]; Putative ketoacyl reductase; 2,4-dienoyl-CoA reductase, mitochondrial; Oxidoreductase, short chain dehydrogenase/reductase family; Prostaglandin F synthase; General stress protein 69; Ferredoxin--NADP reductase; Bifunctional protein MdtA; Alcohol dehydrogenase; NADPH:adrenodoxin oxidoreductase, mitochondrial; Ferredoxin--NADP reductase; 2,5-diketo-D-gluconic acid reductase A; Protein IolS; NADP-dependent glyceraldehyde-3-phosphate dehydrogenase; Prostaglandin reductase 1; Sulfite reductase [NADPH] flavoprotein alpha-component; Aldo-keto reductase family 1 member B10; Alcohol dehydrogenase (NADP(+)); NADP-dependent fatty aldehyde dehydrogenase; Putative dehydrogenase/reductase SDR family member 4-like 2; Aldehyde reductase","Target associated"]
[585,"DB03496","experimental; investigational","small molecule","Alvocidib","Alvocidib freebase; Flavopiridol","C21H20ClNO5","CN1CC[C@@H]([C@H](O)C1)C1=C(O)C=C(O)C2=C1OC(=CC2=O)C1=CC=CC=C1Cl","Alvocidib is a synthetic flavonoid based on an extract from an Indian plant for the potential treatment of cancer. It works by inhibiting cyclin-dependent kinases, arresting cell division and causing apoptosis in non-small lung cancer cells.","146426-40-6","401.84","Investigated for use/treatment in esophageal cancer, leukemia (lymphoid), lung cancer, liver cancer, and lymphoma (unspecified).",null,"Inhibits cyclin-dependent kinases, arresting cell division and causing apoptosis in non-small lung cancer cells.","Cyclin-dependent kinase 2 inhibitor; Cyclin-dependent kinase 5; Cyclin-dependent kinase 9; Cyclin-dependent kinase 1; Cyclin-dependent kinase 6; Epidermal growth factor receptor; Cyclin-dependent kinase 4; Cyclin-dependent kinase 8; Cyclin-dependent kinase 7; Glycogen phosphorylase, muscle form; Glycogen phosphorylase, brain form; Glycogen phosphorylase, liver form","Therapeutic strategy associated"]
[586,"DB03507","experimental","small molecule","6-[3-(4-Morpholinyl)Propyl]-2-(3-Nitrophenyl)-5-Thioxo-5,6,-Dihydro-7h-Thienol[2',3':4,5]Pyrrolo[1,2-C]Imidazol-7-One",null,"C21H20N4O4S2","[O-][N+](=O)C1=CC(=CC=C1)C1=CC2=C(S1)C=C1N2C(=S)N(CCCN2CCOCC2)C1=O",null,null,"456.538",{"$nulls":3},"Tumor necrosis factor receptor superfamily member 1A","Target associated"]
[587,"DB03518","experimental","small molecule","Mevalonic acid","(R)-3,5-dihydroxy-3-methylvaleric acid; (R)-mevalonate; (R)-mevalonic acid; 3,5-Dihydroxy-3-methylvaleric acid","C6H12O4","C[C@@](O)(CCO)CC(O)=O",null,"150-97-0","148.1571",{"$nulls":3},"3-hydroxy-3-methylglutaryl-coenzyme A reductase","Target associated"]
[588,"DB03600","experimental","small molecule","Capric acid","1-nonanecarboxylic acid; Capric acid; Decanoic acid; n-capric acid; n-decanoic acid; n-decylic acid","C10H20O2","CCCCCCCCCC(O)=O","Decanoic acid is a solid. This compound belongs to the straight chain fatty acids. These are fatty acids with a straight aliphatic chain. The proteins that decanoic acid targets include furin, octanoyltransferase, 3-oxoacyl- synthase 1, peptostreptococcal albumin-binding protein, and putative uncharacterized protein tcp14.","334-48-5","172.2646",{"$nulls":3},"3-oxoacyl-[acyl-carrier-protein] synthase 1; Furin; Peptostreptococcal albumin-binding protein; Glycolipid transfer protein; Octanoyltransferase; Putative uncharacterized protein tcp14; Peroxisome proliferator-activated receptor gamma ligand","Target associated"]
[589,"DB03604","investigational","small molecule","Tiratricol","3',3,5-Triiodothyroacetic acid; Tiratricol; Triiodothyroacetic acid","C14H9I3O4","OC(=O)CC1=CC(I)=C(OC2=CC=C(O)C(I)=C2)C(I)=C1","A metabolite of T3 and T4 thyroid hormones; promoted for hyperlipidemia, localized lipodystrophy, and obesity. Tiratricol has been used in trials studying the treatment of Allan-Herndon-Dudley Syndrome.","51-24-1","621.9323",{"$nulls":3},"Thyroid hormone receptor beta","Target associated"]
[590,"DB03619","approved","small molecule","Deoxycholic acid","(3α,5β,12α)-3,12-dihydroxycholan-24-oic acid; 3alpha,12alpha-Dihydroxy-5beta-cholanic acid; 7α-deoxycholic acid; Deoxycholate; Deoxycholic acid; Desoxycholic acid","C24H40O4","[H][C@@]12CC[C@H]([C@H](C)CCC(O)=O)[C@@]1(C)[C@@H](O)C[C@@]1([H])[C@@]2([H])CC[C@]2([H])C[C@H](O)CC[C@]12C","Deoxycholic acid is a a bile acid which emulsifies and solubilizes dietary fats in the intestine, and when injected subcutaneously, it disrupts cell membranes in adipocytes and destroys fat cells in that tissue. In April 2015, deoxycholic acid was approved by the FDA for the treatment submental fat to improve aesthetic appearance and reduce facial fullness or convexity. It is marketed under the brand name Kybella by Kythera Biopharma and is the first pharmacological agent available for submental fat reduction, allowing for a safer and less invasive alternative than surgical procedures.","83-44-3","392.572","For improvement in appearance of moderate to severe fullness associated with submental fat in adults.",null,"As a bile acid, deoxycholic acid emulsifies fat in the gut. Synthetically derived deoxycholic acid, when injected, stimulates a targeted breakdown of adipose cells by disrupting the cell membrane and causing adipocytolysis. This results in an inflammatory reaction and clearing of the adipose tissue remnants by macrophages. Deoxycholic acid's actions are reduced by albumin and tissue-associated proteins, therefore its effect is limited to protein-poor subcutaneous fat tissue. Protein-rich tissues like muscle and skin are unaffected by deoxycholic acid, contributing to its safety profile.","Steroid Delta-isomerase; PpcA; Elongation factor Tu GTP-binding domain-containing protein 1; Choloylglycine hydrolase; Lactaldehyde dehydrogenase; Acriflavine resistance protein B; Cytochrome c oxidase subunit 1; Cytochrome c oxidase subunit 2; Bile acid receptor; Glutathione S-transferase P; G-protein coupled bile acid receptor 1","Therapeutic strategy associated"]
[591,"DB03781","experimental","small molecule","2-[4-(2,4-Dichlorophenoxy)Phenoxy]Propanoic Acid",null,"C15H12Cl2O4","[H][C@](C)(OC1=CC=C(OC2=CC=C(Cl)C=C2Cl)C=C1)C(O)=O",null,null,"327.159",{"$nulls":3},"Acetyl-CoA carboxylase 2","Target associated"]
[592,"DB03785","experimental","small molecule","Mevinolinic acid","Lovastatin acid","C24H38O6","[H][C@]12[C@H](C[C@@H](C)C=C1C=C[C@H](C)[C@@H]2CC[C@@H](O)C[C@@H](O)CC(O)=O)OC(=O)[C@@H](C)CC",null,"75225-51-3","422.5549",{"$nulls":3},"3-hydroxy-3-methylglutaryl-coenzyme A reductase","Target associated"]
[593,"DB03788","experimental","small molecule","GC-24",null,"C24H24O4","CC1=CC(OCC(O)=O)=CC(C)=C1CC1=CC=C(O)C(CC2=CC=CC=C2)=C1",null,null,"376.445",{"$nulls":3},"Thyroid hormone receptor beta","Target associated"]
[594,"DB03796","approved","small molecule","Palmitic Acid","1-hexyldecanoic acid; 1-Pentadecanecarboxylic acid; Hexadecanoate; Hexadecanoic acid; Hexadecoic acid; Hexadecylic acid; Hexaectylic acid; Palmitate; Palmitic Acid; Palmitinic acid","C16H32O2","CCCCCCCCCCCCCCCC(O)=O","A common saturated fatty acid found in fats and waxes including olive oil, palm oil, and body lipids.","57-10-3","256.4241",null,"Palmitic acid is the first fatty acid produced during lipogenesis (fatty acid synthesis) and from which longer fatty acids can be produced. Palmitate negatively feeds back on acetyl-CoA carboxylase (ACC) which is responsible for converting acetyl-ACP to malonyl-ACP on the growing acyl chain, thus preventing further palmitate generation",null,"Glycodelin; Hepatocyte nuclear factor 4-gamma; Lipid binding protein; Cytochrome P450 2C8; Trafficking protein particle complex subunit 3; Fatty acid-binding protein TM_1468; Rhodopsin; Palmitoyl-protein thioesterase 1; Myelin P2 protein; Alpha-lactalbumin; Peroxisome proliferator-activated receptor alpha","Target associated"]
[595,"DB03849","investigational","small molecule","Cilomilast","Ariflo; Cilomilast; cis-4-cyano-4-(3-(cyclopentyloxy)-4-methoxyphenyl)cyclohexanecarboxylic acid","C20H25NO4","COC1=C(OC2CCCC2)C=C(C=C1)[C@]1(CC[C@@H](CC1)C(O)=O)C#N","Cilomilast (Ariflo, SB-207,499) is a drug which was developed for the treatment of respiratory disorders such as asthma and Chronic Obstructive Pulmonary Disease (COPD). It is orally active and acts as a selective Phosphodiesterase-4 inhibitor. Following four clinical trials, the drug proved to be effective in treating COPD, however it has never been marketed due to a poor side effect profile.","153259-65-5","343.4168","Investigated for use/treatment in chronic obstructive pulmonary disease (COPD).",null,"Cilomilast shows high selectivity for cAMP-specific PDE4, an isoenzyme that predominates in pro-inflammatory and immune cells and that is 10-fold more selective for PDE4D than for PDE4A, -B or -C. In vitro, cilomilast suppresses the activity of several pro-inflammatory and immune cells that have been implicated in the pathogenesis of asthma and COPD. Moreover, it is highly active in animal models of these diseases. Cilomilast has been shown to exert potent anti-inflammatory effects both in vitro and in vivo.","cAMP-specific 3',5'-cyclic phosphodiesterase 4D inhibitor; cAMP-specific 3',5'-cyclic phosphodiesterase 4B inhibitor","Therapeutic strategy associated"]
[596,"DB04209","approved; investigational","small molecule","Dequalinium","1,1'-(1,10-Decanediyl)bis(4-amino-2-methylquinolinium) dichloride; 1,1'-Decamethylenebis(4-aminoquinaldinium chloride); Decamethylenebis(4-aminoquinaldinium chloride)","C30H40N4","CC1=CC(N)=C2C=CC=CC2=[N+]1CCCCCCCCCC[N+]1=C(C)C=C(N)C2=C1C=CC=C2","Dequalinium is a quaternary ammonium cation that contains two quaternary quinolinium units linked by an N-decylene chain. It is an antiseptic and disinfectant agent with a broad bactericidal and fungicidal activity. It is most commonly available as a dichloride salt but is available as other various salts as well. It is used in wound dressings and mouth infections and may also have antifungal action, but may associate with skin ulceration. Dequalinium chloride is used as an active ingredient in tablets as Fluomizin for vaginal bacterial infections and in topical bacteriostat formulation as Dequadin. It has been studied for use in treatment of malaria and acute promyelocytic leukemia. Its multiple mode of action is thought to reduce the risk of resistance of pathogens.","6707-58-0","456.6654","Effective local treatment as vaginal tablets for infections such as fluor vaginalis, bacterial vaginosis, aerobic vaginitis, vulvo-vaginal candidiasis and trichomoniasis. Used as a topical antimicrobial agent.","Dequalinium is an antimicrobial against Gram negative and positive bacteria, yeast and protozoa. It primarily mediates this action by increasing the cell permeability with subsequent loss of enzyme activity under a rapid bactericidal and fungicidal action. The enzymatic inactivation initially might be reversible but becomes irreversible after a longer contact time between the drug and bacteria . The bactericidal and fungicidal effect of dequalinium chloride has been demonstrated to occur within 30–60 min . Dequalinium targets a broad spectrum of microorganisms including aerobic and anaerobic bacteria, as well as Candida species.","Dequalinium has a multiple mode of action. It disrupts the cell permeability of the bacteria by absorbing onto the bacterial cell surface and diffusing across the membrane. It also binds to the cytoplasmic membrane with subsequent formation of complexes and protein precipitation and lyses the membrane in adequate concentrations, perturbing osmotic exchange. Loss of normal enzymatic activity is achieved through several different processes. Denaturation of proteins results in inhibition of bacterial cell metabolism. Disruption of bacterial energy production is mediated through inhibition of glucose metabolism and inhibition of mitochondrial ATP synthesis via inhibition of bacterial F1-ATPase. Protein synthesis is also terminated at the level of ribosomes. Bacterial nucleic acids are also affected through direct binding of the drug to DNA in vitro, and precipitation of cytoplasmic material with nucleic acids being the most sensitive . \r\nThe cationic form of dequalinium accumulates in the mitochondria and promotes anticancer activity in human leukemia cells. It mediates a cytotoxic effect by altering redox balance in cells and downregulating Raf/MEK/ERK1/2 and PI3K/Akt signaling pathways in these cells which leads to cell death by apoptosis and/or necrosis . \r\nDequalinium inhibits mycothiol ligase activity in Mycobacterium tuberculosis strains .","Acriflavine resistance protein B; E3 ubiquitin-protein ligase XIAP antagonist&inhibitor; cGMP-gated cation channel alpha-1 blocker; Calcium-activated potassium channel subunit alpha-1 inhibitor; HTH-type transcriptional regulator QacR","Therapeutic strategy associated"]
[597,"DB04224","approved; investigational; vet_approved","small molecule","Oleic Acid",null,"C18H34O2","CCCCCCCC\\C=C\\CCCCCCCC(O)=O","An unsaturated fatty acid that is the most widely distributed and abundant fatty acid in nature. It is used commercially in the preparation of oleates and lotions, and as a pharmaceutical solvent. (Stedman, 26th ed)","112-80-1","282.4614",{"$nulls":3},"Myelin P2 protein; Peroxisome proliferator-activated receptor alpha; Peroxisome proliferator-activated receptor delta; Retinoic acid receptor RXR-alpha; Peroxisome proliferator-activated receptor gamma ligand","Target associated"]
[598,"DB04270","experimental","small molecule","(S)-3-(4-(2-Carbazol-9-Yl-Ethoxy)-Phenyl)-2-Ethoxy-Propionic Acid",null,"C25H25NO4","[H][C@@](CC1=CC=C(OCCN2C3=C(C=CC=C3)C3=C2C=CC=C3)C=C1)(OCC)C(O)=O",null,null,"403.4703",{"$nulls":3},"Peroxisome proliferator-activated receptor gamma","Target associated"]
[599,"DB04335","experimental; investigational","small molecule","Inosine","9-β-D-ribofuranosyl-9H-purin-6-ol; 9-β-D-ribofuranosylhypoxanthine; beta-Inosine; hypoxanthine D-riboside; Hypoxanthosine; INO; Inosine","C10H12N4O5","OC[C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C=NC2=C1NC=NC2=O","A purine nucleoside that has hypoxanthine linked by the N9 nitrogen to the C1 carbon of ribose. It is an intermediate in the degradation of purines and purine nucleosides to uric acid and in pathways of purine salvage. It also occurs in the anticodon of certain transfer RNA molecules. (Dorland, 28th ed)","58-63-9","268.2261","The primary popular claim made for inosine, that it enhances exercise and athletic performance, is refuted by the available research data. There is some preliminary evidence that inosine may have some neurorestorative, anti-inflammatory, immunomodulatory and cardioprotective effects.","Inosine may have neuroprotective, cardioprotective, anti-inflammatory and immunomodulatory activities.","Inosine has been found to have potent axon-promoting effects in vivo following unilateral transection of the corticospinal tract of rats. The mechanism of this action is unclear. Possibilities include serving as an agonist of a nerve growth factor-activated protein kinase (N-Kinase), conversion to cyclic nucleotides that enable advancing nerve endings to overcome the inhibitory effects of myelin, stimulation of differentiation in rat sympathetic neurons, augmentation of nerve growth factor-induced neuritogenesis and promotion of the survival of astrocytes, among others. The mechanism of inosine's possible cardioprotective effect is similarly unclear. Inosine has been reported to have a positive inotropic effect and also to have mild coronary vasodilation activity. Exogenous inosine may contribute to the high-energy phosphate pool of cardiac muscle cells and favorably affect bioenergetics generally. Inosine has also been reported to enhance the myocardial uptake of carbohydrates relative to free fatty acids as well as glycolysis. In cell culture studies, inosine has been found to inhibit the production, in immunostimulated macrophages and spleen cells, of the proinflammatory cytokines, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, interleukin (IL)-12, macrophage-inflammatory protein-1 alpha and interferon (IFN)-gamma. It also suppressed proinflammatory cytokine production and mortality in a mouse endotoxemic model. These actions might account for the possible immunomodulatory, anti-inflammatory and anti-ischemic actions of inosine.","IAG-nucleoside hydrolase; Purine nucleoside phosphorylase; Purine nucleoside phosphorylase DeoD-type","Therapeutic strategy associated"]
[600,"DB04339","approved; investigational","small molecule","Carbocisteine","(L)-2-Amino-3-(carboxymethylthio)propionic acid; (R)-S-(carboxymethyl)cysteine; Carbocisteine; L-3-((carboxymethyl)thio)alanine; L-carbocysteine; S-(carboxymethyl)-(R)-cysteine; S-carboxymethyl-L-cysteine; S-carboxymethylcysteine","C5H9NO4S","N[C@@H](CSCC(O)=O)C(O)=O","Dyspnea and cough are common symptoms of chronic obstructive pulmonary disease (COPD) and other respiratory conditions characterized by increased mucus production. Individuals with COPD have a greater risk of pulmonary infection due to the growth and accumulation of viruses and bacteria in thick bronchial mucus. Carbocisteine is a mucolytic drug that alleviates respiratory symptoms and infections by reducing the viscosity of mucus, allowing it to be expelled.\r\n\r\nSeveral licenses for this drug were withdrawn following serious and fatal paradoxical effects after carbocisteine therapy in children; respiratory dress, dyspnea, and cough aggravation were reported by physicians in France and Italy.  Carbocisteine is currently not FDA or Health Canada approved, but is approved for use in Asia, Europe, and South America.","638-23-3","179.194","Carbocisteine is indicated over the counter and in prescription formulas to clear airway secretions in conditions associated with increased mucus.","Due to its mucolytic effects, carbocisteine significantly reduces sputum viscosity, cough, dyspnea and fatigue. Additionally, it prevents pulmonary infections by decreasing accumulated mucus in the respiratory tract; this is especially beneficial in preventing exacerbations of COPD caused by bacteria and viruses. It has in-vitro anti-inflammatory activity with some demonstrated action against free radicals.","The hypersecretion of mucus characterizes serious respiratory conditions including asthma, cystic fibrosis (CF), and chronic obstructive pulmonary disease (COPD).\r\nIt blocks bacterial adherence to cells, preventing pulmonary infections.  Glycoproteins (fucomucins, sialomucins and sulfomucins) regulate the viscoelastic properties of bronchial mucus. Increased fucomucins can be found in the mucus of patients with COPD. Carbocisteine serves to restore equilibrium between sialomucins and fucomucins, likely by intracellular stimulation of sialyl transferase enzyme, thus reducing mucus viscosity.\r\n\r\nA study found that L-carbocisteine can inhibit damage to cells by hydrogen peroxide (H2O2) by activating protein kinase B (Akt) phosphorylation, suggesting that carbocisteine may have antioxidant effects and prevent apoptosis of lung cells. There is some evidence that carbocisteine suppresses NF-κB and ERK1/2 MAPK signalling pathways, reducing TNF-alpha induced inflammation in the lungs, as well as other inflammatory pathways. An in-vitro study found that L-carbocisteine reduces intracellular adhesion molecule 1 (ICAM-1), inhibiting rhinovirus 14 infection, thereby reducing airway inflammation.","PI-PLC X domain-containing protein 3 inhibitor; Lactosylceramide alpha-2,3-sialyltransferase inducer","Therapeutic strategy associated"]
[601,"DB04348","approved; experimental","small molecule","Taurocholic acid",null,"C26H45NO7S","[H][C@@]1(CC[C@@]2([H])[C@]3([H])[C@H](O)C[C@]4([H])C[C@H](O)CC[C@]4(C)[C@@]3([H])C[C@H](O)[C@]12C)[C@H](C)CCC(=O)NCCS(O)(=O)=O","The product of conjugation of cholic acid with taurine. Its sodium salt is the chief ingredient of the bile of carnivorous animals. It acts as a detergent to solubilize fats for absorption and is itself absorbed. It is used as a cholagogue and cholerectic.","81-24-3","515.703",{"$nulls":3},"Bile salt-activated lipase; Bile acid receptor; Gastrotropin ligand","Target associated"]
[602,"DB04377","experimental","small molecule","Meglutol","3-hydroxy-3-methylglutaric acid; Dicrotalic acid","C6H10O5","CC(O)(CC(O)=O)CC(O)=O","An antilipemic agent which lowers cholesterol, triglycerides, serum beta-lipoproteins and phospholipids. It acts by interfering with the enzymatic steps involved in the conversion of acetate to hydroxymethylglutaryl coenzyme A as well as inhibiting the activity of HYDROXYMETHYLGLUTARYL COA REDUCTASES which is the rate limiting enzyme in the biosynthesis of cholesterol.","503-49-1","162.1406",{"$nulls":3},"3-hydroxy-3-methylglutaryl-coenzyme A reductase","Target associated"]
[603,"DB04447","experimental","small molecule","1,4-Dithiothreitol","2,3-dihydroxy-1,4-dithiobutane","C4H10O2S2","O[C@@H](CS)[C@@H](O)CS","A reagent commonly used in biochemical studies as a protective agent to prevent the oxidation of SH (thiol) groups and for reducing disulphides to dithiols.","3483-12-3","154.251",{"$nulls":3},"Protease synthase and sporulation negative regulatory protein PAI 1; Holo-[acyl-carrier-protein] synthase; Histidinol dehydrogenase; Shikimate dehydrogenase; Galectin-1; Calcium/calmodulin-dependent protein kinase type II subunit alpha; 50S ribosomal protein L27; Retinal dehydrogenase 1; Organic hydroperoxide resistance protein; 3-carboxy-cis,cis-muconate cycloisomerase; Transient receptor potential cation channel subfamily M member 7; Unsaturated glucuronyl hydrolase; Cyclic pyranopterin monophosphate synthase; C protein alpha-antigen; Mitochondrial peptide methionine sulfoxide reductase; Chaperone protein TorD; Axin-1; Peptidyl-prolyl cis-trans isomerase B; Amylosucrase; Thymidylate synthase; Triosephosphate isomerase; Maleylacetoacetate isomerase; 3-hydroxy-3-methylglutaryl-coenzyme A reductase; Listeriolysin regulatory protein","Target associated"]
[604,"DB04465","approved; experimental; investigational","small molecule","Lactose",null,"C12H22O11","OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O","A disaccharide of glucose and galactose in human and cow milk. It is used in pharmacy for tablets, in medicine as a nutrient, and in industry.","63-42-3","342.2965",{"$nulls":3},"Glycosyltransferase 6 domain-containing protein 1; Glycolipid transfer protein; Hydrolase; Endo-1,4-beta-xylanase A; Beta-galactosidase; Galectin-3; Sialidase; Beta-galactosidase","Target associated"]
[605,"DB04519","investigational","small molecule","Caprylic acid","1-heptanecarboxylic acid; C8:0; Caprylic acid; n-caprylic acid; n-octanoic acid; n-Octoic acid; n-octylic acid; Octanoic acid; Octoic acid; Octylic acid","C8H16O2","CCCCCCCC(O)=O","Caprylic acid is an eight-carbon chain fatty acid, also known systematically as octanoic acid. It is found naturally in coconuts and breast milk. It is an oily liquid with a slightly unpleasant rancid-like smell that is minimally soluble in water.","124-07-2","144.2114",{"$nulls":3},"3-oxoacyl-[acyl-carrier-protein] synthase 1; Acyl-CoA thioesterase I; Peroxisome proliferator-activated receptor alpha","Target associated"]
[606,"DB04552","experimental","small molecule","Niflumic acid","NFA; Niflumic acid","C13H9F3N2O2","OC(=O)C1=C(NC2=CC=CC(=C2)C(F)(F)F)N=CC=C1","Niflumic acid is an analgesic and anti-inflammatory agent used in the treatment of rheumatoid arthritis.","4394-00-7","282.218","Used in the treatment of rheumatoid arthritis.","Niflumic acid, a nonsteroidal anti-inflammatory fenamate, is a Ca<sup>2+</sup>-activated Cl<sup>-</sup> channel blocker.","Niflumic acid is able to inhibit both phospholipase A2 as well as COX-2, thereby acting as an antiinflamatory and pain reduction agent.","Phospholipase A2 inhibitor; Prostaglandin G/H synthase 2 inhibitor; Chloride channel protein ClC-Ka inducer; Prostaglandin G/H synthase 1; Cytosolic phospholipase A2; UDP-glucuronosyltransferase 1-9","Therapeutic strategy associated"]
[607,"DB04557","experimental","small molecule","Arachidonic Acid",null,"C20H32O2","CCCCC\\C=C/C\\C=C/C\\C=C/C\\C=C/CCCC(O)=O","An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes.","506-32-1","304.4669",{"$nulls":3},"14 kDa fatty acid-binding protein; Prostaglandin G/H synthase 1; Peroxisome proliferator-activated receptor alpha; Bile acid receptor ligand; Retinoic acid receptor RXR-alpha","Target associated"]
[608,"DB04570","approved; investigational","small molecule","Latamoxef","Festamoxin; Lamoxactam; Latamoxef; Moxalactam","C20H20N6O9S","[H][C@]12OCC(CSC3=NN=NN3C)=C(N1C(=O)[C@]2(NC(=O)C(C(O)=O)C1=CC=C(O)C=C1)OC)C(O)=O","Latamoxef is a broad- spectrum beta-lactam antibiotic similar in structure to the cephalosporins except for the substitution of an oxaazabicyclo moiety for the thiaazabicyclo moiety of certain cephalosporins. It has been proposed especially for the meningitides because it passes the blood-brain barrier and for anaerobic infections.","64952-97-2","520.473","Latamoxef is an oxacephem antibiotic usually grouped with the cephalosporins. It is used to treat bacterial infections. Latamoxef  is primarily indicated in conditions like Bone and joint infection, GI infections, Gynecological infections, Meningitis, Respiratory tract infections, Septicaemia, Skin infections, Soft tissue infections, UTI.","Latamoxef works by inhibiting bacterial cell wall biosynthesis.","Penicillins acylate the penicillin-sensitive transpeptidase C-terminal domain (the penicillin-binding protein) by opening the lactam ring. This inactivation of the enzyme prevents the formation of a cross-link of two linear peptidoglycan strands, inhibiting the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that amoxicllin interferes with an autolysin inhibitor.","Penicillin-binding protein 3 inhibitor; Penicillin-binding protein 1A inhibitor; Penicillin-binding protein 1B inhibitor; D-alanyl-D-alanine carboxypeptidase DacB inhibitor","Indication associated"]
[609,"DB04574","approved","small molecule","Estrone sulfate","Estra-1,3,5 (10)-triene-17-one-3-yl-sulfate; Estrone 3-sulfate; Estrone bisulfate; Estrone hemisulfate; Estrone hydrogen sulfate; Estrone sulphate; Estrone-3-sulphate; Estrone, hydrogen sulfate","C18H22O5S","[H][C@@]12CCC(=O)[C@@]1(C)CC[C@]1([H])C3=C(CC[C@@]21[H])C=C(OS(O)(=O)=O)C=C3","Estrone sulfate (as estropipate) is a form of estrogen. It has several uses such as: alleviate symptoms of menopause as hormone replacement therapy, treatment some types of infertility, treatment of some conditions leading to underdevelopment of female sexual characteristics, treatment of vaginal atrophy, treatment of some types of breast cancer (particularly in men and postmenopausal women), treatment of prostate cancer and prevention of osteoporosis.","481-97-0","350.429","Estropipate is used for the treatment of moderate to severe vasomotor symptoms associated with the monopause, and moderate to severe symptoms of vulval and vaginal atrophy associated with the menopause. It is also used to treat hypoestrogenism due to hypogonadism, castration or primary ovarian failure, and prevent postmenopausal osteoporosis.","Estropipate is an estrogenic substance. It acts as naturally produced estrogen does. Estrogens act through binding to nuclear receptors in estrogen-responsive tissues. Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women.","Estradiol enters target cells freely (e.g., female organs, breasts, hypothalamus, pituitary) and interacts with a target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estradiol upon the target cell. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary.","Estrogen receptor alpha agonist; Estrogen receptor beta agonist","Indication associated"]
[610,"DB04626","experimental; vet_approved","small molecule","Apramycin","4-O-((8R)-2-amino-8-O-(4-amino-4-deoxy-α-D-glucopyranosyl)-2,3,7-trideoxy-7-(methylamino)-D-glycero-α-D-allo-octodialdo-1,5:8,4-dipyranos-1-yl)-2-deoxy-D-streptamine; 4-O-(3α-amino-6α-((4-amino-4-deoxy-α-D-glucopyranosyl)oxy)-2,3,4,5aβ,6,7,8,8aα-octahydro-8β-hydroxy-7β-(methylamino)pyrano(3,2-b)pyran-2α-yl)-2-deoxy-D-streptamine; Apramycin; Nebramycin II","C21H41N5O11","CN[C@H]1[C@@H](O)[C@H]2O[C@H](O[C@@H]3[C@@H](N)C[C@@H](N)[C@H](O)[C@H]3O)[C@H](N)C[C@@H]2O[C@@H]1O[C@H]1O[C@H](CO)[C@@H](N)[C@H](O)[C@H]1O","Apramycin is an aminoglycoside antibiotic and has a bactericidal action against many gram-negative bacteria. Apramycin is a structurally unique antibiotic that contains a bicyclic sugar moiety and a monosubstituted deoxystreptamine. It is not approved for use in humans.","37321-09-8","539.5771","For the treatment of bacterial infections in animals.",null,"Apramycin stands out among aminoglycosides for its mechanism of action which is based on blocking translocation and its ability to bind also to the eukaryotic decoding site despite differences in key residues required for apramycin recognition by the bacterial target. The drug binds in the deep groove of the RNA which forms a continuously stacked helix comprising non-canonical C.A and G.A base pairs and a bulged-out adenine. The binding mode of apramycin at the human decoding-site RNA is distinct from aminoglycoside recognition of the bacterial target, suggesting a molecular basis for the actions of apramycin in eukaryotes and bacteria.","16S ribosomal RNA","Indication associated"]
[611,"DB04689","experimental","small molecule","2-{5-[3-(6-BENZOYL-1-PROPYLNAPHTHALEN-2-YLOXY)PROPOXY]INDOL-1-YL}ETHANOIC ACID",null,"C33H31NO5","CCCC1=C(OCCCOC2=CC3=C(C=C2)N(CC(O)=O)C=C3)C=CC2=C1C=CC(=C2)C(=O)C1=CC=CC=C1",null,null,"521.6029",{"$nulls":3},"Peroxisome proliferator-activated receptor gamma","Target associated"]
[612,"DB04690","experimental","small molecule","Camptothecin","(+)-camptothecin; (+)-camptothecine; (S)-(+)-camptothecin; 20(S)-camptothecine; 21,22-Secocamptothecin-21-oic acid lactone; Camptothecine; D-camptothecin","C20H16N2O4","CC[C@@]1(O)C(=O)OCC2=C1C=C1N(CC3=CC4=CC=CC=C4N=C13)C2=O","Camptothecin is an alkaloid isolated from the stem wood of the Chinese tree, <i>Camptotheca acuminata</i>. This compound selectively inhibits the nuclear enzyme DNA topoisomerase, type I. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity.","7689-03-4","348.352","Investigated for the treatment of cancer.","Camptothecin demonstrated strong anticancer activity in preliminary clinical trials but also low solubility and adverse drug reaction. Camptothecin is believed to be a potent topoisomerase inhibitor that interferes with the essential function of topoisomerase in DNA replication.","Camptothecin binds to the topoisomerase I and DNA complex resulting in a ternary complex, stabilizing it and preventing DNA re-ligation and therefore causes DNA damage which results in apoptosis.","DNA topoisomerase 1","Therapeutic strategy associated"]
[613,"DB04701","experimental","small molecule","S-Methyl glutathione","Glutathione ester; Glutathione S-methyl ester; L-gamma-Glutamyl-S-methyl-L-cysteinylglycine","C11H19N3O6S","CSC[C@H](NC(=O)CC[C@H](N)C(O)=O)C(=O)NCC(O)=O",null,"2922-56-7","321.35",{"$nulls":3},"Glutathione S-transferase Mu 2","Target associated"]
[614,"DB04725","investigational","small molecule","Licofelone","Licofelone","C23H22ClNO2","CC1(C)CN2C(CC(O)=O)=C(C(=C2C1)C1=CC=CC=C1)C1=CC=C(Cl)C=C1","Developed by the German pharmaceutical company, Merckle GmbH, together with EuroAlliance partners Alfa Wassermann and Lacer, licofelone (ML3000) is a dual COX/LOX inhibitor and the first member of this new class of analgesic and anti-inflammatory drugs. It is currently under evaluation as a treatment for osteoarthritis (OA), the most common form of arthritis. Although phase III trials have been successfully completed in OA patients no dates for regulatory submission have yet been given.","156897-06-2","379.879","For the management of osteoarthritis.","Licofelone belongs to a novel class of dual-acting anti-inflammatory drugs called COX/LO inhibitors. This group of drugs simultaneously inhibits the enzymes cyclooxygenase (COX) and 5-lipoxygenase (LO).","Licofelone, through combined 5-LOX/COX-inhibition, reduces levels of inflammatory prostaglandins and leukotrienes.","Group IIE secretory phospholipase A2; Prostaglandin G/H synthase 2; Arachidonate 5-lipoxygenase","Therapeutic strategy associated"]
[615,"DB04743","approved; investigational; withdrawn","small molecule","Nimesulide","Nimesulide","C13H12N2O5S","CS(=O)(=O)NC1=C(OC2=CC=CC=C2)C=C(C=C1)[N+]([O-])=O","Nimesulide is a relatively COX-2 selective, non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. Its approved indications are the treatment of acute pain, the symptomatic treatment of osteoarthritis and primary dysmenorrhoea in adolescents and adults above 12 years old. Due to concerns about the risk of hepatotoxicity, nimesulide has been withdrawn from market in many countries.","51803-78-2","308.31","For the treatment of acute pain, the symptomatic treatment of osteoarthritis and primary dysmenorrhoea in adolescents and adults above 12 years old.","Food, gender and advanced age have negligible effects on nimesulide pharmacokinetics.","The therapeutic effects of Nimesulide are the result of its complete mode of action which targets a number of key mediators of the inflammatory process such as: COX-2 mediated prostaglandins, free radicals, proteolytic enzymes and histamine.","Prostaglandin G/H synthase 2 inhibitor; Group IIE secretory phospholipase A2; Lactotransferrin","Therapeutic strategy associated"]
[616,"DB04801","experimental","small molecule","cis-Vaccenic acid","(Z)-11-octadecenoic acid; (Z)-octadec-11-enoic acid; Asclepic acid; cis-11-octadecenoic acid; cis-octadec-11-enoic acid","C18H34O2","CCCCCC\\C=C/CCCCCCCCCC(O)=O",null,"506-17-2","282.4614",{"$nulls":3},"Peroxisome proliferator-activated receptor delta","Target associated"]
[617,"DB04817","approved; investigational; withdrawn","small molecule","Metamizole",null,"C13H17N3O4S","CN(CS(O)(=O)=O)C1=C(C)N(C)N(C1=O)C1=CC=CC=C1","Metamizole, formerly marketed as Dimethone tablets and injection, Protemp oral liquid, and other drug products, was associated with potentially fatal agranulocytosis. Approvals of the NDA's for dipyrone drug products were withdrawn on June 27, 1977 (see the Federal Register of June 17, 1977 (42 FR 30893)). Withdrawn from the Canadian market in 1963.","50567-35-6","311.36","Used in the past as a powerful painkiller and fever reducer.","Dipyrone is a non-steroidal anti-inflammatory drug (NSAID), commonly used in the past as a powerful painkiller and fever reducer.",null,"Prostaglandin G/H synthase 1","Therapeutic strategy associated"]
[618,"DB04818","withdrawn","small molecule","Iproniazid","Iproniazid","C9H13N3O","CC(C)NNC(=O)C1=CC=NC=C1","Withdrawn from the Canadian market in July 1964 due to interactions with food products containing tyrosine.","54-92-2","179.219","For the treatment of depression (originally intended to treat tuberculosis).","Iproniazid is a monoamine oxidase inhibitor (MAOI) that was developed as the first anti-depressant.",null,null,"Indication associated"]
[619,"DB04831","withdrawn","small molecule","Tienilic acid","(2,3-Dichloro-4-(2-thenoyl)phenoxy)acetic acid; (2,3-Dichloro-4-(2-thiophenecarbonyl)phenoxy)acetic acid; 4-(2-Thienylketo)-2,3-dichlorophenoxyacetic acid; Thienylic acid; Ticrynafen; Tienilic acid","C13H8Cl2O4S","OC(=O)COC1=C(Cl)C(Cl)=C(C=C1)C(=O)C1=CC=CS1","Tienilic acid, or ticrynafen, is a diuretic drug with uric acid-lowering action which was marketed for the treatment of hypertension. It was withdrawn in 1982 after case reports in the United States suggested a link between ticrynafen and hepatitis. (Manier et al., 1982)","40180-04-9","331.171","For the treatment of hypertension.",{"$nulls":3},"Indication associated"]
[620,"DB04832","approved; withdrawn","small molecule","Zimelidine","(Z)-3-(4'-Bromophenyl)-3-(3''-pyridyl)dimethylallylamine; (Z)-zimelidine; cis-zimelidine; Zimeldine","C16H17BrN2","CN(C)C\\C=C(\\C1=CC=C(Br)C=C1)C1=CC=CN=C1","Zimelidine has been banned worldwide due to serious, sometimes fatal, cases of central and/or peripheral neuropathy known as Guillain-Barré syndrome and due to a peculiar hypersensitivity reaction involving many organs including skin exanthema, flu-like symptoms, arthralgias, and sometimes eosinophilia. Additionally, zimelidine was charged to cause an increase in suicidal ideation and/or attempts among depressive patients.","56775-88-3","317.23","For the treatment of depression.","Zimelidine was the first marketed selective serotonin reuptake inhibitor (SSRI) antidepressant. It is a pyridylallylamine, structurally different from other antidepressants.","The antidepressant actions of zimelidine are presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. Zimelidine blocks the reuptake of serotonin at the serotonin reuptake pump of the neuronal membrane, enhancing the actions of serotonin on 5HT1A autoreceptors. SSRIs bind with significantly less affinity to histamine, acetylcholine, and norepinephrine receptors than tricyclic antidepressant drugs.","Sodium-dependent serotonin transporter; Amine oxidase [flavin-containing] B inhibitor; Amine oxidase [flavin-containing] A inhibitor","Indication associated"]
[621,"DB04836","illicit; withdrawn","small molecule","Amineptine","Amineptine","C22H27NO2","OC(=O)CCCCCCNC1C2=CC=CC=C2CCC2=CC=CC=C12","The Food and Drug Administration suspended the marketing authorisation for Survector in 1999 and France withdrew it from the market, however several developing countries continued to produce it up until 2005.","57574-09-1","337.463","For the treatment of depression.","Amineptine is an atypical tricyclic antidepressant.","Amineptine selectively inhibits the reuptake of dopamine and to a lesser extent norepinephrine, thus exerting a powerful and fast-acting antidepressant effect.","Sodium-dependent noradrenaline transporter; Sodium-dependent serotonin transporter","Indication associated"]
[622,"DB04838","approved","small molecule","Cyclandelate","3,3,5-Trimethylcyclohexyl mandelate; 3,5,5-Trimethylcyclohexyl amygdalate; Cyclandelate","C17H24O3","CC1CC(CC(C)(C)C1)OC(=O)C(O)C1=CC=CC=C1","A direct-acting smooth muscle relaxant used to dilate blood vessels. It may cause gastrointestinal distress and tachycardia. Cyclandelate is not approved for use in the U.S. or Canada, but is approved in various European countries.","456-59-7","276.3707","Used in the treatment of various blood vessel diseases (e.g., claudication, arteriosclerosis and Raynaud's disease) and nighttime leg cramps.","Cyclandelate is in a class of drugs called vasodilators. Cyclandelate relaxes veins and arteries, which makes them wider and allows blood to pass through them more easily.","Cyclandelate produces peripheral vasodilation by a direct effect on vascular smooth muscle. Pharmacological action may be due to calcium-channel antagonism.","Voltage-dependent calcium channel subunit alpha-2/delta-1 inhibitor; Liver carboxylesterase 1","Indication associated"]
[623,"DB04840","approved; investigational","small molecule","Debrisoquine","Debrisoquin; Debrisoquine","C10H13N3","NC(=N)N1CCC2=CC=CC=C2C1","An adrenergic neuron-blocking drug similar in effects to guanethidine. It is also noteworthy in being a substrate for a polymorphic cytochrome P-450 enzyme. Persons with certain isoforms of this enzyme are unable to properly metabolize this and many other clinically important drugs. They are commonly referred to as having a debrisoquin 4-hydroxylase polymorphism.","1131-64-2","175.2303","For the treatment of moderate and severe hypertension, either alone or as an adjunct, and for the treatment of renal hypertension.","Debrisoquin is an adrenergic neuron-blocking drug similar in effects to guanethidine. It is a substrate for a polymorphic cytochrome P-450 enzyme. Persons with certain isoforms of this enzyme are unable to properly metabolize this and many other clinically important drugs. They are commonly referred to as having a debrisoquin 4-hydroxylase polymorphism.","Debrisoquin acts at the sympathetic neuroeffector junction by inhibiting or interfering with the release and/or distribution of norepinephrine, rather than acting at the effector cell by inhibiting the association of norepinephrine with its receptors. It is taken up by norepinephrine transporters. It becomes concentrated in NE transmitter vesicles, replacing NE in these vesicles. This leads to a gradual depletion of NE stores in the nerve endings. Once inside the terminal it blocks the release of noradrenaline in response to arrival of an action potential. In contrast to ganglionic blocking agents, debrisoquin suppresses equally the responses mediated by alpha-and beta-adrenergic receptors but does not produce parasympathetic blockade. Since sympathetic blockade results in modest decreases in peripheral resistance and cardiac output, debrisoquin lowers blood pressure in the supine position. It further reduces blood pressure by decreasing the degree of vasoconstriction that normally results from reflex sympathetic nervous activity upon assumption of the upright posture, thus reducing venous return and cardiac output more.","Sodium-dependent noradrenaline transporter inducer","Indication associated"]
[624,"DB04846","approved; investigational","small molecule","Celiprolol","Celiprolol; RS)-N'-{3-acetyl-4-[3-(tert-butylamino)-2-hydroxypropoxy]phenyl}-N,N-diethylurea","C20H33N3O4","CCN(CC)C(=O)NC1=CC=C(OCC(O)CNC(C)(C)C)C(=C1)C(C)=O","Celiprolol is indicated for the management of mild to moderate hypertension and effort-induced angina pectoris. It is simultaneously a selective β1 receptor antagonist, a β2 receptor partial agonist and a weak α2 receptor antagonist. In 2010 a clinical trial has suggested a use for this medication in the prevention of vascular complications of a rare inherited disease called vascular Ehlers–Danlos syndrome. This study demonstrated decreased incidence of arterial rupture or dissection (a specific type of arterial rupture in which the layers of the vessel separate prior to complete failure of the artery wall). Celiprolol is not approved for use by the FDA in the treatment of vascular Ehlers–Danlos syndrome.","56980-93-9","379.501","Celiprolol is indicated for the management of mild to moderate hypertension and effort-induced angina pectoris.",null,"Celiprolol is a vasoactive beta-1 selective adrenoceptor antagonist with partial beta-2 agonist activity. The beta-2 agonist activity is thought to account for its mild vasodilating properties. It lowers blood pressure in hypertensive patients at rest and on exercise. The effects on heart rate and cardiac output are dependent on the pre-existing background level of sympathetic tone.\r\nUnder conditions of stress such as exercise, celiprolol attenuates chronotropic and inotropic responses to sympathetic stimulation. However, at rest minimal impairment of cardiac function is seen.","Beta-1 adrenergic receptor antagonist; Beta-2 adrenergic receptor agonist; Beta-3 adrenergic receptor agonist; Alpha-2A adrenergic receptor antagonist; Alpha-2B adrenergic receptor antagonist; Alpha-2C adrenergic receptor antagonist","Therapeutic strategy associated"]
[625,"DB04852","investigational","small molecule","Implitapide","Implitapide","C35H37N3O2","CC1=NC2=C(C3=CC=CC=C3N2CC2=CC(=CC=C2)[C@H](C2CCCC2)C(=O)N[C@@H](CO)C2=CC=CC=C2)C(C)=C1","Implitapide is a microsomal triglyceride transfer protein (MTP)-inhibitor.","177469-96-4","531.6872","For the treatment of atherosclerosis.","Implitapide is an inhibitor of microsomal triglyceride transfer protein (MTP), a key enzyme involved in the assembly and release of cholesterol and triglyceride from the liver and intestinal tract. It is being investigated for the treatment of atherosclerosis.","MTP mediates triglyceride absorption and chylomicron secretion from the intestine and very-low-density lipoprotein (VLDL) secretion from the liver by linking lipid molecules with apolipoprotein B (apoB). Inhibition of MTP reduces the level of all apoB-containing lipoproteins, including LDL.","Microsomal triglyceride transfer protein large subunit","Indication associated"]
[626,"DB04854","approved","small molecule","Febuxostat","2-(3-cyano-4-isobutoxyphenyl)-4-methyl- 1,3-thiazole-5-carboxylic acid","C16H16N2O3S","CC(C)COC1=C(C=C(C=C1)C1=NC(C)=C(S1)C(O)=O)C#N","Febuxostat is a non-purine xanthine oxidase (XO) inhibitor. In early 2008, febuxostat was granted marketing authorization by the European Commission for the treatment of chronic hyperuricemia and gout. In the following year, the FDA for approved febuxostat for use in the chronic management of hyperuricemia in adult patients with gout who have an inadequate response or intolerance to . Gout is a form of arthritis that is caused by the accumulation of uric acid crystal in or around a joint, leading to inflammation and further deposition of uric acid crystal deposition in bones, joints, tissues, and other organs in the long term. Gout is closely associated with hyperuricemia. Febuxostat works by inhibiting the activity of an enzyme that is responsible for the synthesis of uric acid, thereby reducing serum uric acid levels. \r\n\r\nIn February 2019, a black box warning for febuxostat was added, based on the findings of a post-market clinical study (the CARES trial) where there was an increased risk of cardiovascular (CV) fatal outcomes in patients with gout and known cardiovascular disease treated with febuxostat, when compared to those treated with allopurinol. The manufacturer and the FDA advise health professionals to limit the use of febuxostat to second-line therapy in patients who have inadequate response or intolerance to allopurinol, and to avoid the use of febuxostat in patients with cardiovascular diseases.","144060-53-7","316.375","Febuxostat is indicated for the chronic management of hyperuricemia in adult patients with gout who have an inadequate response to a maximally titrated dose of , who are intolerant to allopurinol, or for whom treatment with allopurinol is not advisable. It is not recommended for the treatment of asymptomatic hyperuricemia  or secondary hyperuricemia.","Febuxostat is a novel, selective xanthine oxidase/dehydrogenase inhibitor that works by decreasing serum uric acid in a dose-dependent manner. In healthy subjects, febuxostat decreased the mean serum uric acid and serum xanthine concentrations, as well as the total urinary uric acid excretion. Febuxostat at daily doses of 40-80 mg reduced the 24-hour mean serum uric acid concentrations by 40 to 55%. Closely related to the drug-induced reduction of serum uric acid levels and mobilization of urate crystals in tissue deposits, febuxostat is associated with gout flares. \r\n\r\nUnlike  and , febuxostat has no inhibitory actions against other enzymes involved in purine and pyrimidine synthesis and metabolism, because it does not structurally resemble purines or pyrimidines.","Gout is a form of acute arthritis that is characterized by the accumulation of crystals of monosodium urate and urate crystals in or around a joint, leading to inflammation and persistent urate crystal deposition in bones, joints, tissues, and other organs that may exacerbate over time. Hyperuricemia is closely related to gout, whereby it may exist for many years before the first clinical attack of gout; thus, aberrated serum uric acid levels and hyperuricemia are believed to be the biochemical aberration involved in the pathogenesis of gout. Xanthine oxidoreductase (XOR) can act as a xanthine oxidase or xanthine dehydrogenase. In humans, it is a critical enzyme for uric acid production as it catalyzes the oxidation reaction steps from hypoxanthine to xanthine and from xanthine to uric acid in the pathway of purine metabolism. Febuxostat potently inhibits XOR, blocking both its oxidase and dehydrogenase activities. With high affinity, febuxostat binds to XOR in a molecular channel leading to the molybdenum-pterin active site, where  demonstrates relatively weak competitive inhibition. \r\n\r\nXOR is mainly found in the dehydrogenase form under normal physiological conditions; however, in inflammatory conditions, XOR can be converted into the xanthine oxidase form, which catalyzes reactions that produce reactive oxygen species (ROS), such as peroxynitrite. ROS contribute to vascular inflammation and alterations in vascular function. As febuxostat can inhibit both forms of XOR, it can inhibit ROS formation, oxidative stress, and inflammation. In a rat model, febuxostat suppressed renal ischemia-reperfusion injury by attenuating oxidative stress.","Xanthine dehydrogenase/oxidase inhibitor","Therapeutic strategy associated"]
[627,"DB04855","approved","small molecule","Dronedarone","Dronedarone; N-(2-butyl-3-(4-(3-(dibutylamino)propoxy)benzoyl)-5-benzofuranyl)-methanesulfonamide; N-(2-butyl-3-(p-(3-(dibutylamino)propoxy)benzoyl)-5-benzofuranyl)methanesulfonamide","C31H44N2O5S","CCCCN(CCCC)CCCOC1=CC=C(C=C1)C(=O)C1=C(CCCC)OC2=C1C=C(NS(C)(=O)=O)C=C2","Dronedarone is a Class III antiarrhythmic drug that works to restore the normal sinus rhythm in patients with paroxysmal or persistent atrial fibrillation. Atrial fibrillation is a common sustained arrhythmia where the treatment primarily focuses on stroke prevention and symptom management. It is managed by rate control, rhythm control, prevention of thromboembolic events, and treatment of the underlying disease. Similar to , dronedarone is a multichannel blocker that works to control rhythm and rate in atrial fibrillation. It meets criteria of all four Vaughan Williams antiarrhythmic drug classes by blocking sodium, potassium, and calcium ion channels and inhibiting β-adrenergic receptors. \r\n\r\nDronedarone is a related benzofuran compound to amiodarone but its chemical structure lacks iodine moieties which are associated with amiodarone-induced thyroid problems. Additionally, the methyl sulfonyl group in its structure renders dronedarone to be more lipophilic with a shorter half-life than amiodarone. This ultimately leads to reduced tissue accumulation of the drug and decreased risk for organ toxicities, such as thyroid and pulmonary toxicities. Commonly marketed as Multaq®, dronedarone was approved by the FDA in July 2009 and Health Canada in August 2009. A safety concern for the risk of drug-induced hepatocellular injury has been issued following marketing of dronedarone.","141626-36-0","556.756","Dronedarone is indicated for the management of atrial fibrillation (AF) in patients in sinus rhythm with a history of paroxysmal or persistent AF to reduce the risk of hospitalization.","Dronedarone is an antiarrhythmic agent that restores normal sinus rhythm and reduces heart rate in atrial fibrillation. In another model, it prevents ventricular tachycardia and ventricular fibrillation. Dronedarone moderately prolongs the QTc interval by about 10 ms on average. Dronedarone decreases arterial blood pressure and reduces oxygen consumption. It reduces myocardial contractility with no change in left ventricular ejection fraction. Dronedarone vasodilates coronary arteries through activation of the nitric oxide pathway. In clinical studies, dronedarone reduced incidence of hospitalizations for acute coronary syndromes and reduced incidence of stroke. Dronedarone exhibits antiadrenergic effects by reducing alpha-adrenergic blood pressure response to epinephrine and beta 1 and beta 2 responses to isoproterenol. \r\n\r\nDronedarone was shown to inhibit triiodothyronine (T3) signalling by binding to TRα1 but much less so to TRβ1. The treatment of dronedarone in patients with severe heart failure and left ventricular systolic dysfunction was associated with increased early mortality related to the worsening of heart failure. In animal studies, the use of dronedarone at doses equivalent to the recommended human doses was associated with fetal harm. In clinical studies and postmarketing reports, dronedarone was shown to cause hepatocellular liver injury and pulmonary toxicities, such as interstitial lung disease, pneumonitis, and pulmonary fibrosis. Compared to its related compound , dronedarone has a faster onset and offset of actions with a shorter elimination half-life and low tissue accumulation.","Atrial fibrillation is the most common type of arrhythmia that is caused by abnormal electrical activity in the atria. In atrial fibrillation, tachyarrhythmia, or fast heart rate, can either be paroxysmal (less than 7 days) or persistent (more than 7 days). Atrial fibrillation causes turbulent and abnormal blood flow through the heart chambers, leading to decreased the effectiveness of the heart to pump blood and an increased likelihood of thrombus formation within the atria which can ultimately dislodge and cause a stroke. \r\n\r\nDronedarone achieves heart rate and rhythm control in atrial fibrillation. _In vitro_, dronedarone decreased the maximum rate of the rise of an action potential in a concentration- and frequency-dependent manner. Cardiac action potentials are generated by ionic currents of multiple voltage-gated ion channels, including potassium, sodium, and calcium channels. Dronedarone is a multichannel blocker that meets the criteria of all four Vaughan Williams antiarrhythmic drug classes but the contribution of each of these activities to the drug's antiarrhythmic effect is unknown. Dronedarone inhibits rapid Na+ currents rate-dependently (class Ib), non-competitively antagonizes α– and β-adrenergic receptors (class II), blocks K+ outward currents (class III) and blocks slow Ca2+ inward currents (class IV). More specifically, it decreases delayed-rectifier K+ current (IKr), slowly activating delayed-rectifier K+ current (IKs), inward rectifier potassium current (IK1), peak Na+ current (INa) and L-type Ca2+ current (ICa (L)). Dronedarone ultimately increases refractory periods, decelerates cardiac conduction, and prolongs cardiac action potential and refractory periods.","Alpha-1A adrenergic receptor antagonist; Alpha-1B adrenergic receptor antagonist; Alpha-1D adrenergic receptor antagonist; Alpha-2A adrenergic receptor antagonist; Alpha-2B adrenergic receptor antagonist; Alpha-2C adrenergic receptor antagonist; Beta-1 adrenergic receptor antagonist; Potassium voltage-gated channel subfamily H member 2 inhibitor; Voltage-dependent L-type calcium channel subunit alpha-1C inhibitor; Voltage-dependent L-type calcium channel subunit alpha-1D inhibitor; Voltage-dependent L-type calcium channel subunit alpha-1F inhibitor; Voltage-dependent L-type calcium channel subunit alpha-1S inhibitor; Voltage-dependent L-type calcium channel subunit beta-1 inhibitor; Voltage-dependent L-type calcium channel subunit beta-2 inhibitor; Voltage-dependent L-type calcium channel subunit beta-3 inhibitor; Voltage-dependent L-type calcium channel subunit beta-4 inhibitor; Potassium channel subfamily K member 2 inhibitor; Sodium channel protein type 5 subunit alpha inhibitor; G protein-activated inward rectifier potassium channel 1 inhibitor; Potassium voltage-gated channel subfamily KQT member 1 inhibitor; Inward rectifier potassium channel inhibitor; Sodium/calcium exchanger 1 inhibitor; Potassium voltage-gated channel subfamily D member 3 inhibitor; Thyroid hormone receptor alpha inhibitor","Therapeutic strategy associated"]
[628,"DB04856","investigational","small molecule","Dexloxiglumide","Dexloxiglumide","C21H30Cl2N2O5","CCCCCN(CCCOC)C(=O)[C@@H](CCC(O)=O)NC(=O)C1=CC(Cl)=C(Cl)C=C1","Dexloxiglumide is a selective cholecystokinin type A (CCKA) receptor antagonist in phase III testing by Rottapharm in Europe only, as U.S. trials have been discontinued. As the D-isomer of loxiglumide, it retains all pharmacological properties of loxiglumide but is more potent.","119817-90-2","461.379","For the treatment of Irritable Bowel Syndrome (IBS) and Gastroesophageal Reflux Disease (GERD).","Dexloxiglumide is a selective cholecystokinin type A (CCKA) receptor antagonist. In October 2003, following the completion of two phase III clinical studies involving dexloxiglumide in women with constipation-predominant irritable bowel syndrome (IBS), Forest Laboratories decided to discontinue development of the drug for this indication. The results of the studies showed that dexloxiglumide did not show statistically significant favorability over placebo. Rotta Research is continuing a phase III trial of a different design in Europe for the IBS indication and also for gastroesophogeal reflux disease.","CCKA antagonists target receptors in the gastrointestinal system to increase gastric emptying and intestinal motility, as well as modulate intestinal sensitivity to distension.","Cholecystokinin receptor type A","Indication associated"]
[629,"DB04861","approved; investigational","small molecule","Nebivolol","Narbivolol; Nebivolol","C22H25F2NO4","OC(CNCC(O)C1CCC2=C(O1)C=CC(F)=C2)C1CCC2=C(O1)C=CC(F)=C2","Nebivolol is a racemic mixture of 2 enantiomers where one is a beta adrenergic antagonist and the other acts as a cardiac stimulant without beta adrenergic activity. Treatment with nebivolol leads to a greater decrease in systolic and diastolic blood pressure than , , or . Nebivolol and other beta blockers are generally not first line therapies as many patients are first treated with thiazide diuretics.\r\n\r\nNebivolol was granted FDA approval on 17 December 2007.","118457-14-0","405.435","Nebivolol is indicated to treat hypertension.","Nebivolol is a selective beta-1 adrenergic receptor antagonist that decreases vascular resistance, increases stroke volume and cardiac output, and does not negatively affect left ventricular function. It has a long duration of action as effects can be seen 48 hours after stopping the medication and a wide therapeutic window as patients generally take 5-40mg daily. Patients should not abruptly stop taking this medication as this may lead to exacerbation of coronary artery disease. Diabetic patients should monitor their blood glucose levels as beta blockers may mask signs of hypoglycemia.","Nebivolol is a highly selective beta-1 adrenergic receptor antagonist with weak beta-2 adrenergic receptor antagonist activity. Blocking beta-1 adrenergic receptors by d-nebivolol leads to decreased resting heart rate, exercise heart rate, myocardial contracility, systolic blood pressure, and diastolic blood pressure. The selectivity of d-nebivolol limits the magnitude of beta blocker adverse effects in the airways or relating to insulin sensitivity. Nebivolol also inhibits aldosterone, and beta-1 antagonism in the juxtaglomerular apparatus also inhibits the release of renin. Decreased aldosterone leads to decreased blood volume, and decreased renin leads to reduced vasoconstriction. l-nebivolol is responsible for beta-3 adrenergic receptor agonist activity that stimulates endothelial nitric oxide synthase, increasing nitric oxide levels; leading to vasodilation, decreased peripheral vascular resistance, increased stroke volume, ejection fraction, and cardiac output. The vasodilation, reduced oxidative stress, and reduced platelet volume and aggregation of nebivolol may lead to benefits in heart failure patients.","Beta-1 adrenergic receptor antagonist; Beta-2 adrenergic receptor antagonist; Beta-3 adrenergic receptor agonist","Therapeutic strategy associated"]
[630,"DB04863","investigational","small molecule","Lefradafiban","Lefradafiban","C23H25N3O6","[H][C@@]1(COC2=CC=C(C=C2)C2=CC=C(C=C2)C(=N)NC(=O)OC)C[C@@H](CC(=O)OC)C(=O)N1","Lefradafiban is an oral platelet glycoprotein IIb/IIIa receptor antagonist being investigated in the treatment of angina.","149503-79-7","439.4611","For the treatment of unstable angina.","Lefradafiban, an orally active prodrug of fradafiban, is a novel glycoprotein (IIb/IIIa) inhibitor for the treatment of unstable angina. Development was discontinued in 2000 due to lack of efficacy.","GPIIb/IIIa inhibitors, such as lefradafiban, block the final common pathway of platelet aggregation.","Integrin alpha-IIb; Integrin beta-3","Therapeutic strategy associated"]
[631,"DB04870","investigational","small molecule","Oleoyl-estrone","Estrone 3-oleate; Estrone monooleate; Estrone oleic acid ester; OE; Oleoyl estrone; Oleoylestrone","C36H54O3","[H][C@@]12CCC(=O)[C@@]1(C)CC[C@]1([H])C3=C(CC[C@@]21[H])C=C(OC(=O)CCCCCCC\\C=C/CCCCCCCC)C=C3","Oleoyl-estrone (OE) is a fatty acid ester of estrone. This hormone occurs naturally and is found circulating in various animal species and humans. It has been shown in animal studies to promote the loss of body fat while maintaining body protein storage, maintaining nitrogen balance.  Body protein loss is an unpleasant effect of fat loss by the restriction of calories, and studies show that this drug appears to avoid this effect.","180003-17-2","534.8122","For the treatment of obesity.","Oleoyl-estrone is a fatty acid ester of estrone, and may be directly involved in the control of body weight (PMID: 8782737).","Based on extensive preclinical studies, it is believed that oleoyl-estrone (OE) works by a dual mechanism of action. Centrally, OE appears to act at the brain's hypothalamus, resetting the body's ponderostat, the &ldquo;food control center&rdquo; in the brain that detects and integrates signals that control both appetite and metabolic behavior. Peripherally, OE also causes reduced storage of fat in &ldquo;white fat&rdquo; tissue and allows skeletal muscle to use fat as an alternate energy source.",null,"Indication associated"]
[632,"DB04871","approved","small molecule","Lorcaserin","Lorcaserin; Lorqess","C11H14ClN","C[C@H]1CNCCC2=CC=C(Cl)C=C12","Lorcaserin (previously APD-356), a highly selective 5HT2C receptor agonist, is used for the treatment of obesity. It has been shown to reduce body weight and food intake in animal models of obesity, and it is thought that targeting the 5HT2C receptor may alter body weight by regulating satiety. Lorcaserin is marketed as a salt form called Belviq, which is lorcaserin hydrochloride.","616202-92-7","195.69","For the treatment of obesity, as an adjunct to a reduced-calorie diet and increased physical activity.","Lorcaserin produced a dose-dependent weight loss over a 12-week period by promoting  satiety and decreasing food consumption.","Although the exact mechanism is unknown, it is believed to involve the selective activation of 5-HT2C receptors in the anorexigenic pro-opiomelanocortin neurons in the arcuate nucleus of the hypothalamus. This results in decreased food intake and satiety by promoting the release of alpha-melanocortin stimulating hormone, which acts on melanocortin-4 receptors.","5-hydroxytryptamine receptor 2C","Therapeutic strategy associated"]
[633,"DB04872","investigational","small molecule","Osanetant","Osanetant","C35H41Cl2N3O2","CN(C(C)=O)C1(CCN(CCC[C@@]2(CCCN(C2)C(=O)C2=CC=CC=C2)C2=CC(Cl)=C(Cl)C=C2)CC1)C1=CC=CC=C1","Developed by Sanofi-Aventis (formerly Sanofi-Synthelabo), osanetant (SR-142801) is an NK3 receptor antagonist which was under development for the treatment of schizophrenia and other Central Nervous System (CNS) disorders. In a review of its R&D portfolio, the company announced in August 2005 that it would cease any further development of osanetant. This follows an earlier decision to discontinue development of eplivanserin for schizophrenia.","160492-56-8","606.625","Potential therapy for schizophrenia, depression and visceral pain.","Osanetant is a neurokinin-3 (NK3) receptor antagonist. Preliminary clinical trials have demonstrated that osanetant is superior to placebo on global assessment of efficacy and measures of positive symptoms in schizophrenia.","The mechanism of action of osanetant is uncertain at this point. Various preclinical data indicate that activation of NK3 receptors enhances the release of biogenic amines, including dopamine and serotonin. NK3 receptor antagonists could block NK3-receptor-mediated activation of these systems.","Neuromedin-K receptor","Indication associated"]
[634,"DB04873","investigational","small molecule","Piboserod","Piboserod","C22H31N3O2","CCCCN1CCC(CNC(=O)C2=C3OCCCN3C3=CC=CC=C23)CC1","Piboserod (SB 207266) is a selective 5-HT(4) receptor antagonist.","152811-62-6","369.5004","For the treatment of atrial fibrillation and irritable bowel syndrome (IBS).","GlaxoSmithKline was investigating piboserod, a 5HT4 antagonist, for the treatment of atrial fibrillation. Phase II trials were ongoing in March 2004, but by December of that year, development had been discontinued. Piboserod had previously being investigated for the treatment of irritable bowel syndrome (IBS), but development for this indication was terminated in 1999.","Piboserod appears to act as a specific antagonist of one of the receptors for 5-hydroxytryptamine, the 5-HT4 receptor. The 5-HT4 receptor antagonists are thought to antagonize both the ability of serotonin to sensitize the peristaltic reflex and 5-HT-induced defecation, at least in animal studies. As 5-HT4 receptors are present in human atrial cells and when stimulated may cause atrial arrhythmias, piboserod was under investigation in clinical trials for atrial fibrillation.","5-hydroxytryptamine receptor 4","Indication associated"]
[635,"DB04874","investigational","small molecule","Picoplatin","(SP-4-3)-Amminedichloro(2-methylpyridine)platinium; Picoplatin","C6H10Cl2N2Pt","N.[Cl-].[Cl-].[Pt++].CC1=CC=CC=N1","Picoplatin is a cytotoxic platinum compound in clinical development for the treatment of patients with solid tumors. It causes apoptosis (cell death) by binding to DNA and interfering with DNA replication and transcription.","181630-15-9","376.147","For the treatment of patients with solid tumors.","Picoplatin is a sterically hindered platinum (II) complex designed to deliver an extended spectrum of anti-cancer activity and overcome platinum resistance.","Picoplatin causes apoptosis (cell death) by binding to DNA and interfering with DNA replication and transcription.","DNA","Therapeutic strategy associated"]
[636,"DB04875","investigational","small molecule","Pralnacasan","Pralnacasan","C26H29N5O7","CCO[C@@H]1OC(=O)C[C@@H]1NC(=O)[C@@H]1CCCN2N1C(=O)[C@H](CCC2=O)NC(=O)C1=NC=CC2=CC=CC=C12","Pralnacasan is an orally bioavailable pro-drug of a potent, non-peptide inhibitor of interleukin-1beta converting enzyme (ICE).","192755-52-5","523.5378","For the treatment of rheumatoid arthritis (RA).","Pralnacasan is a potent, non-peptide inhibitor of interleukin-1beta converting enzyme (ICE). Pralnacasan is an oral, anti-cytokine drug candidate licensed for development by Aventis Pharma from Vertex Pharmaceuticals. In November 2003, Aventis and Vertex Pharmaceuticals announced that they had voluntarily suspended the phase II clinical trials of pralnacasan due to results from an animal toxicity study that demonstrated liver abnormalities after a nine-month exposure to pralnacasan at high doses. While no similar liver toxicity has been seen to date in human trials, the companies will evaluate the animal toxicity results before proceeding with the phase II clinical program.","Pralnacasan inhibits interleukin-1beta converting enzyme (ICE), an enzyme that regulates the production of IL-1 and IFN gamma - intercellular mediators that initiate and sustain the process of inflammation. Inhibiting ICE may be an effective strategy for curtailing damaging inflammatory processes common to a number of acute and chronic conditions, such as rheumatoid arthritis (RA) and osteoarthritis.","Caspase-1","Therapeutic strategy associated"]
[637,"DB04878","investigational","small molecule","Voglibose","Voglibose","C10H21NO7","OCC(CO)N[C@H]1C[C@](O)(CO)[C@@H](O)[C@H](O)[C@H]1O","Voglibose is an alpha-glucosidase inhibitor used for lowering post-prandial blood glucose levels in people with diabetes mellitus. It is made in India by Ranbaxy Labs and sold under the trade name Volix.","83480-29-9","267.2762","For the treatment of diabetes. It is specifically used for lowering post-prandial blood glucose levels thereby reducing the risk of macrovascular complications.","Voglibose, an alpha-glucosidase inhibitor, is a synthetic compound with potent and enduring therapeutic efficacies against disorders of sensory, motor and autonomic nerve systems due to diabetes mellitus. The drug was approved in Japan in 1994 for the treatment of diabetes, and it is under further investigation by Takeda for the treatment of impaired glucose tolerance. Alpha-glucosidase inhibitors are oral anti-diabetic drugs used for diabetes mellitus type 2 that work by preventing the digestion of complex carbohydrates (such as starch). Complex carbohydrates are normally converted into simple sugars (monosaccharides) which can be absorbed through the intestine. Hence, alpha-glucosidase inhibitors reduce the impact of complex carbohydrates on blood sugar.","Alpha-glucosidase inhibitors are saccharides that act as competitive inhibitors of enzymes needed to digest carbohydrates: specifically alpha-glucosidase enzymes in the brush border of the small intestines. The membrane-bound intestinal alpha-glucosidases hydrolyze oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in the small intestine. Acarbose also blocks pancreatic alpha-amylase in addition to inhibiting membrane-bound alpha-glucosidases. Pancreatic alpha-amylase hydrolyzes complex starches to oligosaccharides in the lumen of the small intestine. Inhibition of these enzyme systems reduces the rate of digestion of complex carbohydrates. Less glucose is absorbed because the carbohydrates are not broken down into glucose molecules. In diabetic patients, the short-term effect of these drugs therapies is to decrease current blood glucose levels: the long term effect is a small reduction in hemoglobin-A1c level. (From Drug Therapy in Nursing, 2nd ed)","Maltase-glucoamylase, intestinal inhibitor","Indication associated"]
[638,"DB04883","investigational","small molecule","Darusentan","Darusentan","C22H22N2O6","COC1=CC(OC)=NC(O[C@H](C(O)=O)C(OC)(C2=CC=CC=C2)C2=CC=CC=C2)=N1","Darusentan is a selective endothelin ETA receptor antagonist. It is being evaluated as a treatment for congestive heart failure and hypertension.","171714-84-4","410.4199","For the treatment of congestive heart failure and hypertension.","Darusentan is a selective endothelin ETA receptor antagonist.","The mode of action by which the endothelin receptor antagonists cause a decrease of the BP is not yet totally elucidated; however, peripheral vasodilatation due to blockade of the vasoconstrictor effects of endothelin is the most likely explanation. A reduction of cardiac contractility is considered unlikely. Several studies have been published that investigated the effects of either selective or nonselective endothelin receptor blockade in patients with heart failure. In these studies, application of endothelin antagonists, while decreasing both systemic and pulmonary BP increased cardiac index and did not alter cardiac contractility or heart rate.","Endothelin-1 receptor","Indication associated"]
[639,"DB04885","investigational","small molecule","Cilansetron","Cilansetron","C20H21N3O","CC1=NC=CN1C[C@H]1CCC2=C(C3=CC=CC4=C3N2CCC4)C1=O","Cilansetron is a 5HT-3 antagonist made by Solvay Pharmaceuticals that is currently under trial phase in the EU and US.","120635-74-7","319.4002","For the treatment of symptoms associated with irritable bowel syndrome.","Cilansetron is an orally formulated medication that blocks the action of 5-hydroxy-tryptamine 3 (5-HT3) receptors. Phase III studies of cilansetron had been suspended by Solvay in order to assess whether the drug possesses safety concerns similar to alosetron. Alosetron, also a 5-HT3 antagonist, was withdrawn from the market due to questions regarding its safety. Phase III testing with cilansetron has since resumed. In June 2005 the company announced that they were reviewing the priority of the cilansetron program.","Cilansetron is a potent and selective 5-HT<sub>3</sub> receptor antagonist. 5-HT<sub>3</sub> receptors are nonselective cation channels that are extensively distributed on enteric neurons in the human gastrointestinal tract, as well as other peripheral and central locations. Activation of these channels and the resulting neuronal depolarization affect the regulation of visceral pain, colonic transit and gastrointestinal secretions, processes that relate to the pathophysiology of irritable bowel syndrome (IBS). 5-HT<sub>3</sub> receptor antagonists such as cilansetron inhibit activation of non-selective cation channels which results in the modulation of the enteric nervous system.","5-hydroxytryptamine receptor 3A","Indication associated"]
[640,"DB04889","investigational","small molecule","Bicifadine","Bicifadine","C12H15N","CC1=CC=C(C=C1)C12CC1CNC2","Bicifadine (DOV-220075) is a nonopioid analgesic. It is an inhibitor of both the norepinephrine and serotonin transporters and an NMDA antagonist with a non-narcotic profile. Bicifadine was shown to have potent analgesic activity in vivo and was chosen for further development for the treatment of pain.","71195-57-8","173.2542","For the treatment of pain.","Bicifadine is a chemically distinct molecule with a unique profile of pharmacological activity. Its primary pharmacological action is to enhance and prolong the actions of norepinephrine and serotonin by inhibiting the transport proteins that terminate the physiological actions of the two biogenic amines. Bicifadine is not a narcotic and is well-tolerated and, in preclinical studies, has been shown not to act at any opiate receptor. Bicifadine does not exhibit any anti-inflammatory activity and does not inhibit prostaglandin synthetase in vitro.","Preclinical studies and clinical trials indicate that bicifadine's analgesic properties result through the enhancement and prolongation of norepinephrine and serotonin actions, however other actions may be involved.","Sodium-dependent noradrenaline transporter; Sodium-dependent serotonin transporter; Dopamine D2 receptor","Therapeutic strategy associated"]
[641,"DB04897","approved; investigational","biotech","Lucinactant","ATI-02; KL4-surfactant; Lucinactant",null,null,"Lucinactant is a new synthetic peptide-containing surfactant for intratracheal use. It contains sinapultide, a novel, hydrophobic, 21-amino acid peptide (leucine and lysine repeating units, KL4 peptide) designed to mimic human surfactant protein-B (SB-P). More specifically, it mimics the C-terminal amphipathic helical domain of this protein. It also consists of phospholipids (dipalmitoylphosphatidylcholine, DPPC and palmitoyloleoyl phosphatidylglycerol, POPG) and a fatty acid (palmitic acid). It is completely devoid of animal-derived components. FDA approved on March 6, 2012.","825600-90-6",null,"Intended for the prevention of respiratory distress syndrome (RDS) in premature infants at high risk for RDS.","Lucinactant is a new synthetic surfactant containing a protein that mimics human surfactant protein-B, is effective at preventing respiratory distress syndrome (RDS) and related complications in preterm infants. Lucinactant has been shown to have antiinflammatory properties, is resistant to proteolytic degradation and oxidation, and has no potential for transmitting animal-derived diseases. Lucinactant has proven safe and effective in the prevention of RDS in preterm infants and as a treatment for MAS in full-term infants and for adult ARDS.","Pulmonary surfactant is a lipoprotein complex that is produced naturally in the lungs, where it lines the alveolar epithelium and serves to reduce surface tension, which facilitates alveoli expansion and allows gas exchange. Human surfactants contain phospholipids, predominantly dipalmitoylphosphatidylcholine (DPPC), in addition to surfactant proteins A, B, C and D. Surfactant is also a physical barrier to inhaled particle and noxious agents, enhances particle clearance, is involved in host defense against infection and possesses antiinflammatory properties. Several serious respiratory disorders have been associated with a loss or lack of endogenous surfactant. Lucinactant was designed to mimic the essential endogenous human surfactant protein B (SP-B).",null,"Therapeutic strategy associated"]
[642,"DB04900","investigational","biotech","Thymalfasin","Thymalfasin; Thymosin alpha1 (human)",null,null,"Thymalfasin is a chemically synthesized version of thymosin alpha 1 that is identical to human thymosin alpha 1. Thymosin alpha 1 is an acetylated polypeptide. Thymosin alpha 1 is now approved in 35 developing countries for the treatment of Hepatitis B and C. It is also used to boost the immune response in the treatment of other diseases.","62304-98-7",null,"Indicated as an adjuvant for influenza vaccine in elderly patients and as an adjuvant for both influenza and hepatitis B vaccines in chronic hemodialysis patients who failed to achieve adequate antibody titers from previous immunization.","Thymalfasin is a 28-amino acid polypeptide produced synthetically but originally isolated from thymosin fraction 5, a bovine thymus extract containing a number of immunologically active peptides. In vitro studies have shown that Thymalfasin can influence T-cell production and maturation, stimulate production of Th1 cytokines such as interferon-gamma and interleukin-2, and activate natural killer cell-mediated cytotoxicity.","The mechanism of action of thymalfasin is not completely understood but is thought to be related to its immunomodulating activities, centered primarily around augmentation of T-cell function. In various in vitro assays, thymosin alpha 1 has been shown to promote T-cell differentiation and maturation; for example, CD4+, CD8+, and CD3+ cells have all been shown to be increased. Thymosin alpha 1 has also been shown to increase production of IFN-g, IL-2, IL-3, and expression of IL-2 receptor following activation by mitogens or antigens, increase NK cell activity, increase production of migratory inhibitory factor (MIF), and increase antibody response to T-cell dependent antigens. Thymosin alpha 1 has also been shown to antagonize dexamethasone-induced apoptosis of thymocytes in vitro. In vivo administration of thymosin alpha 1 to animals immunosuppressed by chemotherapy, tumor burden, or irradiation showed that thymosin alpha 1 protects against cytotoxic damage to bone marrow, tumor progression and opportunistic infections, thereby increasing survival time and number of survivors. Many of the in vitro and in vivo effects of thymosin alpha 1 have been interpreted as influences on either differentiation of pluripotent stem cells to thymocytes or activation of thymocytes into activated T-cells. Thymalfasin also has been shown in vitro to upregulate expression of toll like receptors (TLR) including TLR2 and TLR9 in mouse and human dendritic cells, as well as activate NF-kB and JNK/P38/AP1 pathways. Thymalfasin's activation of dendritic cells provides another possible pathway explaining thymalfasin's immunomodulatory and antiviral effects.",null,"Therapeutic strategy associated"]
[643,"DB04901","investigational","biotech","Galiximab","Anti-CD80 monoclonal antibody; Galiximab",null,null,"Galiximab is a chimeric monoclonal antibody which is used as an immunosuppressive drug.","357613-77-5",null,"Investigated for use/treatment in lymphoma (non-hodgkin's), psoriasis and psoriatic disorders, bone metastases, multiple myeloma, prostate cancer, and rheumatoid arthritis.","Galiximab is a monoclonal antibody that is being studied in the treatment of follicular non-Hodgkin lymphoma. Monoclonal antibodies are made in the laboratory and can locate and bind to cancer cells. Galiximab binds to the protein CD80, which is found on certain normal and cancerous white blood cells.","Galiximab, an IgG(1) anti-CD80 antibody, binds to CD80, a costimulatory molecule involved in T-cell activation. Reduction in lesional, activated T cells induces improvement in psoriatic plaques.","T-lymphocyte activation antigen CD80 antibody","Indication associated"]
[644,"DB04915","investigational","small molecule","Idronoxil","3-(4-hydroxyphenyl)-2H-chromen-7-ol; Dehydroequol; Haginin E; Idronoxil; Phenoxodiol","C15H12O3","OC1=CC=C(C=C1)C1=CC2=C(OC1)C=C(O)C=C2","Idronoxil is a substance that is being studied in the treatment of cancer. It belongs to the family of drugs called signal transduction inhibitors.","81267-65-4","240.254","Intended for the treatment of various forms of cancer.","Phenoxodiol inhibits proliferation of many cancer cell lines and induces apoptosis by disrupting FLICE-inhibitory protein, FLIP, expression and by caspase-dependent and -independent degradation of the X-linked inhibitor of apoptosis, XIAP. In addition, phenoxodiol sensitizes drug-resistant tumour cells to anticancer drugs including paclitaxel, carboplatin and gemcitabine.","The antiproliferative effects of phenoxodiol are associated with inhibition of plasma membrane electron transport in tumour cell lines and primary immune cells. Results from one study (PMID: 17904534) indicate that plasma membrane electron transport (PMET) may be a primary target for phenoxodiol in tumour cells and in activated T cells.","Ecto-NOX disulfide-thiol exchanger 2","Therapeutic strategy associated"]
[645,"DB04917","investigational","small molecule","Renzapride","Renzapride","C16H22ClN3O2","COC1=C(C=CC(N)=C1Cl)C(=O)NC1CCN2CCCC1C2","Renzapride is currently in Phase III clinical development in the United States for the treatment of constipation-predominant irritable bowel syndrome (IBS-C). It has been suggested that renzapride is effective in the treatment of irritable bowel syndrome with alternating stool pattern. It is being developed by Alizyme of the UK.","112727-80-7","323.818","For the treatment of constipation-predominant irritable bowel syndrome (IBS-C).","Renzapride is a substituted benzamide which acts on the upper gastrointestinal tract. It has been shown to enhance stomach emptying in normal subjects; doses of 2 and 5 mg decreasing by 21 and 37% respectively the volume of gastric contents aspirated 80 min after a test meal. Renzapride was found to reduce the oro-caecal transit time as assessed by the lactulose/breath hydrogen method in a dose related manner from 0.2 to 5 mg; the later dose producing a 62% reduction.","Renzapride is a full serotonin 5-HT4 receptor agonist and partial serotonin 5-HT3 receptor antagonist.","5-hydroxytryptamine receptor 3A; 5-hydroxytryptamine receptor 4","Indication associated"]
[646,"DB04918","approved; investigational","small molecule","Ceftobiprole",null,"C20H22N8O6S2","[H][C@@]1(NC(=O)C(=N/O)\\C2=NSC(N)=N2)C(=O)N2C(C(O)=O)=C(CS[C@]12[H])\\C=C1/CCN(C1=O)[C@]1([H])CCNC1","Ceftobiprole is a cephalosporin antibiotic with activity against methicillin-resistant <i>Staphylococcus aureus</i>. It was discovered by Basilea Pharmaceutica and is being developed by Johnson & Johnson Pharmaceutical Research and Development. Ceftobiprole is the first cephalosporin to demonstrate clinical efficacy in patients with infections due to methicillin-resistant staphylococci and, if approved by regulatory authorities, is expected to be a useful addition to the armamentarium of agents for the treatment of complicated skin infections and pneumonia.","209467-52-7","534.57","For the treatment of serious bacterial infections in hospitalised patients.","Ceftobiprole, a cephalosporin antibiotic, is active against methicillin-resistant <i>Staphylococcus aureus</i>.","Cephalosporins, such as ceftobiprole, are bactericidal and have the same mode of action as other beta-lactam antibiotics (such as penicillins). Cephalosporins disrupt the synthesis of the peptidoglycan layer of bacterial cell walls. The peptidoglycan layer is important for cell wall structural integrity, especially in Gram-positive organisms. The final transpeptidation step in the synthesis of the peptidoglycan is facilitated by transpeptidases known as penicillin binding proteins (PBPs). PBPs bind to the D-Ala-D-Ala at the end of muropeptides (peptidoglycan precursors) to crosslink the peptidoglycan. Beta-lactam antibiotics mimic this site and competitively inhibit PBP crosslinking of peptidoglycan.","MecA; Penicillin-binding protein 2x; Peptidoglycan synthase FtsI","Indication associated"]
[647,"DB04919","investigational","biotech","Alfimeprase","Alfimeprase",null,null,"Alfimeprase is a recombinant analog of fibrolase. Fibrolase is a zinc-containing metalloproteinase isolated from the venom of the southern copperhead snake (<i>Agkistrodon contortrix contortrix</i>). It is a small protein that contains 203 residues (Randolph et al. 1992). Alfimeprase is being developed by Nuvelo.","259074-76-5",null,"Alfimeprase is being evaluated as a potential treatment for acute ischemic stroke, catheter occlusion (CO) and acute peripheral arterial occlusion (PAO).","Alfimeprase is a recombinant direct acting fibrinolytic (rDAF), or blood clot dissolver, that has the potential to rapidly and directly degrade fibrin, a protein that provides the scaffolding for blood clots, when delivered through a catheter to the site of a blood clot.","When delivered locally at the site of a blood clot, alfimeprase has the potential, through a unique mechanism of action, to directly and rapidly degrade fibrin, a protein that provides the scaffolding for blood clots. In addition, alfimeprase's thrombolytic activity appears to be localized to the site of delivery because it is rapidly inactivated by alpha-2 macroglobulin, a naturally occurring protein in the blood, as it moves away from the site of delivery and into the general blood circulation.","Fibrinogen alpha chain; Fibrinogen beta chain","Indication associated"]
[648,"DB04920","approved; investigational","small molecule","Clevidipine","Clevidipine; Clevidipine butyrate","C21H23Cl2NO6","CCCC(=O)OCOC(=O)C1=C(C)NC(C)=C(C1C1=CC=CC(Cl)=C1Cl)C(=O)OC","Clevidipine is a dihydropyridine L-type calcium channel blocker that is selective for vascular smooth muscle and is indicated for blood pressure reduction when oral therapy is not an option.","167221-71-8","456.316","For the reduction of blood pressure when when oral antihypertensive therapy is not feasible or not desirable.","Clevidipine belongs to a well-known class of drugs called dihydropyridine calcium channel antagonists. Clevidpine is the first third generation intravenous dihydropyridine calcium channel blocker. In vitro studies demonstrated that clevidipine acts by selectively relaxing the smooth muscle cells that line small arteries, resulting in arterial dilation, widening of the artery opening, and without reducing central venous pressure or reducing cardiac output.","Possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, clevidipine inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. The resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries and improved oxygen delivery to the myocardial tissue.","Voltage-dependent L-type calcium channel subunit alpha-1F; Voltage-dependent L-type calcium channel subunit alpha-1S; Voltage-dependent L-type calcium channel subunit alpha-1D; Voltage-dependent L-type calcium channel subunit alpha-1C","Indication associated"]
[649,"DB04924","investigational","small molecule","Itopride","Itopride; N-(p-(2-(Dimethylamino)ethoxy)benzyl)veratramide","C20H26N2O4","COC1=CC=C(C=C1OC)C(=O)NCC1=CC=C(OCCN(C)C)C=C1","Itopride is a dopamine D2 antagonist with acetylcholinesterase inhibitory actions.","122898-67-3","358.4314","Investigated for use/treatment in gastrointestinal diseases and disorders (miscellaneous).",null,"Itopride has anticholinesterase (AchE) activity as well as dopamine D2 receptor antagonistic activity. It is well established that M3 receptors exist on the smooth muscle layer throughout the gut and acetylcholine (ACh) released from enteric nerve endings stimulates the contraction of smooth muscle through M3 receptors. The enzyme AChE hydrolyses the released ACh, inactivates it and thus inhibits the gastric motility leading to various digestive disorders. Besides ACh, dopamine is present in significant amounts in the gastrointestinal tract and has several inhibitory effects on gastrointestinal motility, including reduction of lower esophageal sphincter and intragastric pressure. These effects appear to result from suppression of ACh release from the myenteric motor neurons and are mediated by the D2 subtype of dopamine receptors. Itopride, by virtue of its dopamine D2 receptor antagonism, removes the inhibitory effects on Ach release. It also inhibits the enzyme AchE which prevents the degradation of ACh. The net effect is an increase in ACh concentration, which in turn, promotes gastric motility, increases the lower esophageal sphincter pressure, accelerates gastric emptying and improves gastro-duodenal coordination. This dual mode of action of Itopride is unique and different from the actions of other prokinetic agents available in the market.\r","Dopamine D2 receptor; Acetylcholinesterase inhibitor","Therapeutic strategy associated"]
[650,"DB04925","investigational","biotech","Desmoteplase","Desmoteplase; DSPA desmoteplase; rDSPA alpha 1; Salivary plasminogen activator alpha 1, Desmodus rotundus",null,null,"Desmoteplase is a chemical in the saliva of vampire bats. It activates plasminogen to the serine protease, plasmin. Plasmin acts by breaking down fibrin blood clots. When a vampire bat bites its victim, it secretes an enzyme that prevents the blood from clotting. The enzyme is called DSPA (Desmodus rotundus salivary plasminogen activator) and scientists are using DSPA as stroke and heart attack medication. Desmoteplase is a recombinant form of vampire bat DSPA (Salivary plasminogen activator alpha 1).","145137-38-8",null,"Investigated for use/treatment in cerebral ischemia and strokes.","Desmoteplase is a novel thrombolytic agent derived from vampire-bat saliva.  It is genetically related to the clot buster tissue plasminogen activator (t-PA) but is more potent and demonstrates a safer toxicity profile (desmoteplase does not promote kainate- or NMDA-mediated neurotoxicity in vivo). Plasminogen activators are enzymes found in all vertebrate species investigated so far. Their physiological function is the generation of localized proteolysis in the context of tissue remodeling, wound healing and neuronal plasticity.","Desmoteplase targets and destroys fibrin, the structural scaffold of blood clots.","Plasminogen","Indication associated"]
[651,"DB04929","investigational","small molecule","DG031",{"$nulls":3},"DG031, deCODE genetics's lead compound, is being developed for the prevention of myocardial infarction, or heart attack.",null,null,"Investigated for use/treatment in heart disease and myocardial infarction.","DG031 is an inhibitor of 5-lipoxygenase activating protein, or FLAP. deCODE has linked variants in the gene encoding FLAP, and the gene encoding leukotriene A4 hydrolase (LTA4H) to risk of heart attack. These variants appear to confer increased risk of heart attack by increasing the production of leukotriene B4 (LTB4), a potent driver of inflammation produced in atherosclerotic plaques. In Phase II trials completed last year, DG031 was shown to be well tolerated at all doses tested and to reduce the production of LTB4 in a dose-dependent manner. Late last year deCODE discovered that the HapK variant of the LTA4H gene, discovered in Iceland and which confers a moderate increase in risk of heart attack in people of predominantly European ancestry, confers a 250% increase in risk of the disease in African Americans. deCODE licensed DG031 from Bayer AG, which developed it originally for the treatment of asthma. In deCODE’s clinical trials and those conducted previously by Bayer, a total of approximately 2000 people have been dosed with DG031.","DG031 inhibits the activity of the FLAP, or 5-lipoxygenase activating protein, that modulates the activity of the leukotriene pathway.","Arachidonate 5-lipoxygenase-activating protein","Indication associated"]
[652,"DB04932","approved; investigational","biotech","Defibrotide","Defibrotide free acid; Defibrotide free acid (porcine mucosa); Defibrotide free acid (porcine)",null,null,"Defibrotide is the sodium salt of a mixture of single-stranded oligodeoxyribonucleotides derived from porcine mucosal DNA. It has been shown to have antithrombotic, anti-inflammatory and anti-ischemic properties (but without associated significant systemic anticoagulant effects). It is marketed under the brand names Dasovas (FM), Noravid, and Prociclide in a variety of countries. In the USA it is was approved in March, 2016 as Defitelio.","83712-60-1",null,"Indicated for the treatment of severe hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem-cell transplantation (HSCT).","Defibrotide is a deoxyribonucleic acid derivative extracted from mammalian organs, which has been developed for the treatment of a number of vascular disorders. It appears to increase fibrinolysis and may possess antithrombotic, antiatherosclerotic and anti-ischaemic actions, probably due to its ability to selectively increase prostaglandin I2 and E2 levels and to increase tissue plasminogen activator and decrease plasminogen activator inhibitor function. Defibrotide is available as an intravenous and intramuscular preparation, and also as an oral formulation for long term use.","The drug appears to prevent the formation of blood clots and to help dissolve blood clots by increasing levels of prostaglandin I2, E2, and prostacyclin, altering platelet activity, increasing tissue plasminogen activator function, and decreasing activity of tissue plasminogen activator inhibitor. Prostaglandin I2 relaxes the smooth muscle of blood vessels and prevents platelets from adhering to each other. Prostaglandin E2 at certain concentrations also inhibits platelet aggregation. Moreover, the drug provides additional beneficial anti-inflammatory and antiischemic activities as recent sudies have shown. It is yet unclear, if the latter effects can be utilized clinically (e.g., treatment of ischemic stroke).","Adenosine receptor A1; Adenosine receptor A2a; Adenosine receptor A2b","Therapeutic strategy associated"]
[653,"DB04933","investigational","small molecule","Eritoran","Eritoran","C66H126N2O19P2","CCCCCCCCCCCC(=O)CC(=O)N[C@H]1[C@@H](OP(O)(O)=O)O[C@H](CO[C@@H]2O[C@H](COC)[C@@H](OP(O)(O)=O)[C@H](OCC[C@@H](CCCCCCC)OC)[C@H]2NC(=O)CCCCCCCCC\\C=C/CCCCCC)[C@@H](O)[C@@H]1OCCCCCCCCCC","Eritoran is a structural analogue of the lipid A portion of lipopolysaccharide (LPS). It is being developed by Eisai Research Institute of Boston for the treatment of severe sepsis.","185955-34-4","1313.6562","Investigated for use/treatment in sepsis and septicemia.","Eritoran has been shown to down-regulate the intracellular generation of pro-inflammatory cytokines IL-6 and TNF-alpha in human monocytes.","Eritoran is a toll-like receptor 4 inhibitor.","Toll-like receptor 4","Target associated"]
[654,"DB04934","investigational","small molecule","Rifalazil","3'-hydroxy-5'-(4-isobutyl-1-piperazinyl)benzoxazinorifamycin; Rifalazil","C51H64N4O13","CO[C@H]1\\C=C\\O[C@@]2(C)OC3=C(C)C(O)=C4C(=O)C(NC(=O)\\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@@H]1C)=C1OC5=CC(=CC(O)=C5N=C1C4=C3C2=O)N1CCN(CC(C)C)CC1","Rifalazil is a derivative of the antibiotic rifamycin. It is being investigated by ActivBiotics for the treatment of various bacterial infections.","129791-92-0","941.088","Investigated for use/treatment in atherosclerosis, bacterial infection, and peripheral vascular disease.","Rifalazil represents a new generation of ansamycins that contain a unique four-ring structure. Originally rifalazil was developed as a therapeutic agent to replace rifampin as part of a multiple drug regimen in the treatment of tuberculosis. As a result of its superior antimicrobial activity and high intracellular levels, rifalazil has potential to treat indications caused by the intracellular pathogen, <i>Chlamydia trachomatis</i>, which causes non-gonococcal urethritis and cervicitis, often leading to pelvic inflammatory disease. Rifalazil also has potential to treat the related microorganism, <i>Chlamydia pneumoniae</i>, which may be involved in chronic inflammatory processes thought to be partly responsible for atherosclerosis. Due to its favourable antimicrobial spectrum and other positive attributes, rifalazil may also prove valuable in the treatment of gastric ulcer disease, caused by <i>Helicobacter pylori</i>, and antibiotic-associated colitis, the result of toxin production following the growth of <i>Clostridium difficile</i> in the colon. The potential value of rifalazil in the treatment of these indications will be assessed in human clinical trials.","The potent antimycobacterial activity of rifalazil is due to inhibition of bacterial RNA polymerase.","DNA-directed RNA polymerase subunit beta","Therapeutic strategy associated"]
[655,"DB04936","investigational","small molecule","Tagatose","(3S,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-one; D-lyxo-hex-2-ulose; D-lyxo-hexulose; D-tag; D-tagatose; keto-D-tagatose","C6H12O6","OC[C@@H](O)[C@H](O)[C@H](O)C(=O)CO","Tagatose is a functional sweetener. It is a naturally occurring monosaccharide, specifically a hexose. It is commonly found in dairy with a similar texture and sweetened capacity to sucrose but with only a third of the calories. It is approved as a food additive as a low calorie sweetener. Additionally, it is under investigation by Spherix for the treatment of obesity and type II diabetes.","87-81-0","180.1559","Intended for use as a therapeutic adjunct in the treatment of type II diabetes.","Oral tagatose significantly blunts the rise in plasma glucose seen after oral glucose in patients with diabetes mellitus in a dose-dependent manner without significantly affecting insulin levels. The minimal elevation of plasma tagatose levels in normal patients and the adverse gastrointestinal effects seen following larger doses of tagatose support poor absorption of this hexose and suggest that tagatose may act by attenuating glucose absorption in the intestine.","he steps in the metabolism of tagatose are identical to those for fructose or fruit sugar but tagatose is incompletely absorbed. Only 15-20 percent of tagatose is absorbed in the small intestine. The major part of ingested tagatose is fermented in the colon by indigenous microflora, resulting in the production of short-chain fatty acids. The short chain fatty acids are absorbed almost completely and metabolized.",null,"Indication associated"]
[656,"DB04944","investigational","small molecule","Acadesine","Acadesine; AICA-riboside","C9H14N4O5","[H][C@]1(CO)O[C@]([H])([C@H](O)[C@@H]1O)N1C=NC(C(N)=O)=C1N","Acadesine (AICA-riboside) is a purine nucleoside analog with anti-ischemic properties that is currently being studied (Phase 3) for the prevention of adverse cardiovascular outcomes in patients undergoing coronary artery bypass graft (CABG) surgery. It is being developed jointly by PeriCor and Schering-Plough. Acadesine has been granted Orphan Drug Designation for B-CLL in the EU.","2627-69-2","258.2313","Investigated for use/treatment in cardiac reperfusion injury, cardiovascular disorders, and coronary artery disease.","Acadesine has been shown to induce cell death apoptosis selectively in B-cells taken from healthy subjects and patients with B-CLL, with little effect on T-cells. As T-cells have an important role in fighting infection, it is anticipated that patients treated with acadesine will have a reduced risk of serious infections compared to those on current chemotherapies.","The mechanism by which acadesine selectively kills B-cells is not yet fully elucidated. The action of acadesine does not require the tumour suppressor protein p53 like other treatments. This is important, as p53 is often missing or defective in cancerous B-cells. Studies have shown acadesine activates AMPK and induces apoptosis in B-cell chronic lymphocytic leukemia cells but not in T lymphocytes.",null,"Therapeutic strategy associated"]
[657,"DB04949","investigational","biotech","Pexelizumab","5G1.1-sc; h5G1.1-scFv; Pexelizumab",null,null,"Pexelizumab is a humanized monoclonal antibody used as an immunosuppressive drug. It is being investigated by Alexion Pharmaceuticals.","219685-93-5",null,"For the treatment of inflammation during cardiac surgery.","Myocardial injury and dysfunction in acute infarction and during cardiac surgery with cardiopulmonary bypass (CPB) are associated with an undesirable systemic inflammatory response, in which the complement cascade plays a major role. In animal models C5 inhibition has been found to significantly reduce myocardial infarct size and decrease cellular necrosis and apoptosis. Pexelizumab is a humanized, monoclonal, single-chain antibody fragment that inhibits C5, thereby blocking its cleavage into active forms.","Although inflammation is a normal response, continued exposure to foreign surfaces, toxic antigens, and tissue injury results in pathologic local and systemic inflammation (SIRS). This response involves multiple humoral and cellular components, including the coagulation (Factor XII, thrombin, Proteins C and S, platelets) and complement systems, cytokines (TNF-alpha, interleukins), leukocytes, monocytes, adhesion molecules (ICAM-1), and endothelial cells, among others. The complement system is a group of glycoproteins, which, when activated, results in the formation of C3-convertase, which converts C3 to C3a and C3b. C3a cleaves C5 to C5a and C5b. C5b, in conjunction with C6, C7, C8, and C9, forms the membrane attack or terminal complement complex (TCC) C5b-9. Both C5a and C5b-9 activate, promote, and amplify inflammatory components, and likely play central roles in the development of SIRS, tissue injury, reperfusion injury, and apoptosis. Pexelizumab, a recombinant humanized single chain monoclonal antibody to C5, blocks the conversion of C5 to C5a and C5b-9.",null,"Therapeutic strategy associated"]
[658,"DB04951","approved; investigational","small molecule","Pirfenidone","Pirfenidone","C12H11NO","CC1=CN(C(=O)C=C1)C1=CC=CC=C1","Pirfenidone is an orally active small molecule drug that may inhibit collagen synthesis, down regulate production of multiple cytokines and block fibroblast proliferation and stimulation in response to cytokines. Pirfenidone has demonstrated activity in multiple fibrotic conditions, including those of the lung, kidney and liver. It is being investigated by InterMune.","53179-13-8","185.2218","For the treatment of idiopathic pulmonary fibrosis (IPF).","Pirfenidone is a novel agent with anti-inflammatory, antioxidant, and antifibrotic properties. It may improve lung function and reduce the number of acute exacerbations in patients with idiopathic pulmonary fibrosis (IPF).","Although the precise mechanism of action of pirfenidone and its specific molecular targets have yet to be elucidated, the molecule has demonstrated anti-fibrotic, anti-inflammatory, and antioxidant activity. One vital anti-fibrotic mechanism involves suppression of TGF-β1 (transforming growth factor-β1), a key cytokine involved in fibrogenesis and extracellular matrix production. \r\n\r\nThere is also evidence to suggest that pirfenidone has the ability to downregulate the expression of potent pro-inflammatory cytokines including TNF-α, interleukin-1, and interferon gamma. In animal models, pirfenidone can inhibit both the influx of inflammatory cells and the increased pulmonary vascular permeability induced by bleomycin.",null,"Therapeutic strategy associated"]
[659,"DB04952","investigational","small molecule","Ramoplanin","Ramoplanin","C119H154ClN21O40","NCCC[C@H]1NC(=O)[C@@H](CC2=CC=CC=C2)NC(=O)[C@H]([C@@H](O)C)NC(=O)[C@H](NC(=O)[C@H](NC(=O)[C@@H]([C@@H](C)O)NC(=O)[C@@H](CCCN)NC(=O)[C@H](NC(=O)[C@@H](NC(=O)[C@@H](CC(N)=O)NC(=O)\\C=C/C=C\\CC(C)C)[C@@H](OC(=O)[C@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H]([C@@H](C)O)NC(=O)[C@@H](NC1=O)C1=CC=C(C=C1)O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]1O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]1O)C1=CC=C(O)C=C1)C1=CC(Cl)=C(O)C=C1)C(N)=O)C1=CC=C(O)C=C1)C1=CC=C(O)C=C1)C1=CC=C(O)C=C1","Ramoplanin is a novel glycolipodepsipeptide antibiotic under development for the treatment of CDAD.","76168-82-6","2554.066","For the treatment of bacterial infections.","Ramoplanin represents a new class of antibiotics with a novel mechanism of action that is highly effective against <i>Staphylococci</i>.\r","Ramoplanin is the first in a new class of antimicrobials to reach clinical trials. It is a glycolipodepsipeptide produced by the fermentation of <i>Actinoplanes spp.</i>. Ramoplanin blocks bacterial cell wall biosynthesis by interfering with peptidoglycan production. Ramoplanin inhibits the N-acetylglucosaminyltransferase-catalysed conversion of lipid intermediate I to lipid intermediate II, a step that occurs before the transglycosylation and transpeptidation reactions. Ramoplanin’s mechanism of action is distinct from that of glycopeptides. Unlike glycopeptides, ramoplanin does not complex with the D-Ala–D-Ala sequence of cell wall precursors.",null,"Indication associated"]
[660,"DB04954","investigational","small molecule","Tecadenoson","Tecadenoson","C14H19N5O5","OC[C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C=NC2=C(N[C@@H]3CCOC3)N=CN=C12","Tecadenoson is a novel selective A1 adenosine receptor agonist that is currently being evaluated for the conversion of paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm. It is being developed by CV Therapeutics, Inc.","204512-90-3","337.3312","Investigated for use/treatment in arrhythmia and atrial fibrillation.","Tecadenoson is a novel A1 adenosine receptor stimulator. Adenosine is a naturally occurring compound that stimulates all adenosine receptor subtypes in the body, including the A2 adenosine receptor which lowers blood pressure. In non-clinical trials, tecadenoson selectively stimulated the A1 adenosine receptor in the AV node and slowed the speed of electrical conduction across the AV node, reducing the number of electrical impulses that reached the ventricle, without affecting blood pressure. Clinical studies to date with intravenous tecadenoson suggest that it may slow the speed of AV nodal conduction by selectively stimulating the A1 adenosine receptor, and may avoid blood pressure lowering by not stimulating the A2 adenosine receptor. Thus, it may be possible to use intravenous tecadenoson to convert patients from PSVT to normal sinus rhythm without lowering blood pressure or causing adverse events related to vasodilitation such as flushing, palpitations or headache.","Tecadenoson selectively stimulates the A1 adenosine receptor. Stimulation of the A1 adenosine receptor slows the conduction of electrical impulses in the AV node of the heart, a region that controls the transmission of electrical impulses from the atria to the ventricles.","Adenosine receptor A1","Indication associated"]
[661,"DB04956","investigational","biotech","Afelimomab","Afelimomab",null,null,"Afelimomab (also known as Fab 2 or MAK 195F) is an anti-TNF-α monoclonal antibody. Administration of 195F reduces the concentration of interleukin-6 in patients with sepsis.","156227-98-4",null,"Investigated for use/treatment in sepsis and septicemia.","Afelimomab is the F(ab')2 fragment of a murine anti-TNF-alpha antibody, and has been evaluated in clinical trials in septic patients. The results suggest that the drug is well tolerated, and may be of benefit in certain groups of patients with sepsis. Afelimomab is safe, biologically active, and well tolerated in patients with severe sepsis, reduces 28-day all-cause mortality, and attenuates the severity of organ dysfunction in patients with elevated interleukin-6 levels.",null,"Tumor necrosis factor","Target associated"]
[662,"DB04957","investigational","small molecule","Azimilide","Azimilide","C23H28ClN5O3","CN1CCN(CCCCN2C(=O)CN(N=CC3=CC=C(O3)C3=CC=C(Cl)C=C3)C2=O)CC1","Azimilide is an investigational class III anti-arrhythmic drug that blocks fast and slow components of the delayed rectifier cardiac potassium channels. It is not approved for use in any country, but is currently in clinical trials in the United States.","149908-53-2","457.96","Investigated for use/treatment in arrhythmia and atrial fibrillation.","Azimilide is a new class III anti-arrhythmic agent. It is distinguished by a relative lack of reverse use-dependence, excellent oral absorption, no need for dose titration, an option for out-patient initiation, no need for adjustment associated with renal or liver failure and a lack of interaction with warfarin or digoxin. It carries some risk of torsade de pointes and rarely, neutropoenia.","The mechanism of action of azimilide is to block both the slowly conducting (I(Ks)) and rapidly conducting (I(Kr)) rectifier potassium currents in cardiac cells. This differs from other class III agents that block I(Kr) exclusively or in combination with sodium, calcium, or transient outward (I(to)) potassium current channels. It also has blocking effects on sodium (I(Na)) and calcium currents (I(CaL)). Its effects on reentrant circuits in infarct border zones causing ventricular tachyarrhythmias are unknown.","Potassium voltage-gated channel subfamily E member 1; Potassium voltage-gated channel subfamily KQT member 1; Potassium voltage-gated channel subfamily H member 2","Indication associated"]
[663,"DB04963","investigational","biotech","rhGAD65","Recombinant human GAD65; Recombinant human glutamic acid decarboxylase",null,null,"rhGAD65 (recombinant human glutamic acid decarboxylase) is a vaccine being developed to treat insulin dependent type 1 diabetes.",null,null,"Investigated for use/treatment in diabetes mellitus type 1.","The immune system of patients treated with rhGAD65 demonstrate an increase in the secretion of several immunomodulatory substances, dominated by regulatory cytokines, including IL5, IL13, IL10, IL17, IFN-a and TNF-a. Additionally, the activity of T-cells in response to GAD65 is increased with rhGAD65 therapy and subjects receiving rhGAD65 show an up regulation of cytokines in response to GAD65.",null,null,"Indication associated"]
[664,"DB04971","investigational","small molecule","Reglitazar","Reglitazar; Reglixane","C22H20N2O5","CC1=C(CCOC2=CC=C(CC3C(=O)NOC3=O)C=C2)N=C(O1)C1=CC=CC=C1","Reglitazar, an isoxazolidine-3,5-dione derivative, is being developed by Pfizer for the treatment of diabetes. It is the first non-thiazolidenedione to enter clinical trials.","170861-63-9","392.411","For the treatment of diabetes mellitus type 1 and 2.","Reglixane shows a hypoglycemic effect and also a stronger triglyceride-lowering effect than the thiazolidine-2,4-diones. In preclinical studies, reglixane has been shown to prevent several diabetic complications, such as cataract, nephropathy, and neuropathy.","Reglixane is an agonist of peroxisome proliferator-activated receptor (PPAR) gamma and alpha.","Peroxisome proliferator-activated receptor alpha; Peroxisome proliferator-activated receptor gamma","Target associated"]
[665,"DB04974","investigational","small molecule","Rimiducid","Rimiducid","C78H98N4O20","CC[C@H](C(=O)N1CCCC[C@H]1C(=O)O[C@H](CCC1=CC=C(OC)C(OC)=C1)C1=CC(OCC(=O)NCCNC(=O)COC2=CC=CC(=C2)[C@@H](CCC2=CC=C(OC)C(OC)=C2)OC(=O)[C@@H]2CCCCN2C(=O)[C@@H](CC)C2=CC(OC)=C(OC)C(OC)=C2)=CC=C1)C1=CC(OC)=C(OC)C(OC)=C1","Rimiducid is a lipid-permeable tacrolimus analogue and a protein dimerizer. It was designed to overcome limitations of current cellular immunotherapies used for cancer and other blood disorders by enhancing the control of the immune cell activity and function. When administered via chemically-inducible dimerization (CID) technologies, rimiducid binds to switch proteins and dimerizes them, triggering downstream signaling cascade. The combination use of rimiducid with immunotherapies for enhanced therapeutic effectiveness is currently under investigation.","195514-63-7","1411.65","Investigated for use/treatment in bone marrow transplant and graft versus host disease.","Rimiducis is used to activate inducible caspase-9 produced by a modified gene included in some CAR T-cell therapies. This activation produces rapid induction of apoptosis in activated modified T-cells and resolution of the signs and symptoms of graft versus host disease within 24 hours.","Rimiducid binds to a drug binding domain derived from human FK506-binding protein which is present on a modified form of inducible caspase-9. This binding results in dimerization and subsequent activation of caspase-9. This system was designed to function as a \"safety switch\" in CAR T-cell therapy used in hematological cancers. Retroviral vectors used in production of these modified cells preferentially integrate this gene nearby promoters associated with T-cell activation. This results in higher expression of the modified inducible caspase-9 product in activated T-cells. In practice, this allows for specific targeting of these active T-cells by rimiducid which results in a decrease in circulating cell numbers of over 90% in the setting of graft versus host disease. This specificity spares non-alloreactive T-cells and allows for successful reconstitution of the transplanted immune system from these cells. Additionally, these non-alloreactive cells retain their sensitivity to rimiducid.","Serine/threonine-protein kinase mTOR ligand","Therapeutic strategy associated"]
[666,"DB04977","investigational","small molecule","Plitidepsin","Dehydrodidemnin B; Plitidepsin","C57H87N7O15","[H][C@@]12CCCN1C(=O)[C@H](CC(C)C)NC(=O)[C@@H](C)C(=O)[C@@H](OC(=O)C[C@H](O)[C@]([H])(NC(=O)[C@@H](NC(=O)[C@@H](CC(C)C)N(C)C(=O)[C@@H]1CCCN1C(=O)C(C)=O)[C@@H](C)OC(=O)[C@H](CC1=CC=C(OC)C=C1)N(C)C2=O)[C@@H](C)CC)C(C)C","Aplidine is a peptide found in tunicates which shows promise in shrinking tumors in pancreatic, stomach, bladder, and prostate cancers. The specific marine organism is _Aplidium albicans_. Aplidine is also of interest as a potential treatment for some leukemias.","137219-37-5","1110.357","Intended for the treatment of various forms of cancer.",null,"Aplidine inhibits the growth and induces apoptosis in MOLT-4 cells through the indirect inhibition of VEGF secretion which blocks the VEGF/VEGFR-1 autocrine loop necessary for the growth of these cells.",null,"Therapeutic strategy associated"]
[667,"DB04979","investigational","biotech","AVR118",{"$nulls":3},"AVR118 represents a new type of biopolymer chemistry that also possesses novel immunomodulator activity. This non-toxic peptide-nucleic acid, which to date has shown no indication of human toxicity, appears to stimulate the proinflammatory responses required to combat viral infections such as AIDS and human papilloma virus and to dampen aberrant autoimmune-type inflammatory responses. AVR118 is being studied for the promise shown in its ability to mitigate the toxic side effects of other drugs (including those used to treat HIV infection and chemotherapeutic drugs employed in the treatment of cancers); for its ability to stimulate the immune system to attack tumor cells (especially those cancer cells that have been damaged by chemotherapeutic agents) and for its ability to treat cachexia (wasting) in patients with AIDS or cancer.",{"$nulls":3},"AVR118 is a peptide-nucleic acid immunomodulator with proinflammatory, broad-spectrum antiviral, and potential antineoplastic activities.","AVR118 stimulates the peripheral blood mononuclear cell (PBMC) production of the proinflammatory cytokines IFN-y, IL-1b, IL-6 and TNF-a. This agent may reduce HIV-1 p24 antigen; viral reverse transcriptase activity; syncitial cell formation; and viral mRNA in infected PBMCs and human CD4+ lymphocyte H9 cells, and may decrease viral loads and increase CD4+ and CD8+ T-cell counts in HIV patients. In vitro, AVR118 has been shown to induce the maturation of HL60 leukemic cells and to inhibit the invasive and metastatic properties of a highly malignant breast cancer cell line.",null,"Therapeutic strategy associated"]
[668,"DB04980","investigational","small molecule","Lemuteporfin","Lemuteporfin","C44H48N4O10","COC(=O)C1C(=CC=C2\\C3=C\\C4=N\\C(=C/C5=C(C)C(CCC(=O)OCCO)=C(N5)\\C=C5/N=C(/C=C(\\N3)C12C)C(C)=C5CCC(=O)OCCO)\\C(C=C)=C4C)C(=O)OC","Lemuteporfin, under development by QLT Incorporated, is a benzoporphyrin-derived chlorin-like photosensitizer. It is intended for the treatment of beign prostatic hyperplasia.","215808-49-4","792.886","Intended for the treatment of benign prostatic hyperplasia and prostrate disorders.","Trial data accumulated thus far indicate a generally positive tollerability profile and preliminary efficacy.","Lemuteporfin is transported in the plasma primarily by lipoproteins. Once lemuteporfin is activated by light in the presence of oxygen, highly reactive, short-lived singlet oxygen and reactive oxygen radicals are generated. Light activation of lemuteporfin results in local damage to neovascular endothelium, resulting in vessel occlusion. Damaged endothelium is known to release procoagulant and vasoactive factors through the lipo-oxygenase (leukotriene) and cyclo-oxygenase (eicosanoids such as thromboxane) pathways, resulting in platelet aggregation, fibrin clot formation and vasoconstriction.",null,"Therapeutic strategy associated"]
[669,"DB04985","investigational","biotech","Tigapotide","Tigapotide",null,null,"Tigapotide is a synthetic 15-mer peptide that is derived from the natural sequence of amino acids of the prostate secretory protein (PSP94), one of three predominant proteins found in human seminal fluid.","848084-83-3",null,"For the treatment of late stage Hormone Refractory Prostate Cancer (HRPC) for which no effective therapy currently exists.\r\n\r","PCK3145 is a synthetic 15-mer peptide that is derived from the natural sequence of amino acids of the prostate secretory protein (PSP94), one of three predominant proteins found in human seminal fluid. PSP94 expression in the prostate is down regulated in patients with advanced prostate cancer, and believed to be a survival mechanism for the cancer cells. Results from an earlier trial conducted in the U.K. showed PCK3145 to be safe and well tolerated at all doses tested and further suggest that it also plays a role in preventing the metastatic process as measured by its effect on MMP-9 levels, a Gelatinase B enzyme involved in angiogenesis, tumor invasion and metastasis.","The mechanism of action and receptor for PCK3145 suggests PCK3145 to be a signal transduction inhibitor with multiple ways (apoptosis, anti-angiogenesis and anti-metastasis) to restrict disease development.","40S ribosomal protein SA","Therapeutic strategy associated"]
[670,"DB04987","investigational","biotech","P113D",{"$nulls":3},"P113D is a novel 12 amino-acid antimicrobial peptide drug derived from histatins, which are compounds found naturally in human saliva. It is being pursued as a potential treatment for cystic fibrosis by Demegen, Inc.",null,null,"For the potential treatment of cystic fibrosis and bacterial infections.","P113D has demonstrated activity against CF patient clinical isolates of bacteria that are resistant to traditional antibiotics. The compound is stable and maintains activity in sputum of CF patients. P113 was determined to be the smallest histatin fragment which retained antimicrobial activity equivalent to that of the parent compound. Interestingly, synthesizing P113 with D-amino acids gave rise P113D, a compound that was impervious to enzymatic degradation and maintained the antimicrobial activity of the parent compound. P113D also has very potent in vitro activity against a variety of Gram negative and positive bacteria including <i>P. aeruginosa</i>, <i>S. aureus</i>, <i>H. influenzae</i>, <i>S. typhimurium</i>, <i>E. coli</i>, <i>S. epidermidis</i>, <i>S. mutans</i> and <i>S. sobrinus</i>. In the case of <i>P. aeruginosa</i> and <i>S. aureus</i>, antibacterial activity has been demonstrated against a variety of CF patient clinical isolates which are resistant to traditional antibiotics. <i>P. aeruginosa</i> isolates that produce thick alginate secretions (mucoid phenotype) are also susceptible to killing by P113D.","For both bacteria and fungi such as <i>Candida albicans</i>, P113D has been shown to kill cells as opposed to simply inhibiting their growth. It has been demonstrated that P113D acts by binding to the cell surface and increasing the permeability of both the outer and inner membranes of the cells of Gram negative bacteria, killing them within seconds.",null,"Indication associated"]
[671,"DB04991","investigational","small molecule","XL784",{"$nulls":3},"XL784 is a potent inhibitor of the ADAM-10 metalloprotease enzyme, a target of significant interest because of its important role in blood vessel formation and cell proliferation. XL784 was specifically optimized to be MMP-1 sparing, thus potentially enhancing its safety profile and enabling higher dosing compared with other previously studied metalloprotease inhibitors. Results of single dose Phase I clinical trials of XL784 administered orally to 96 healthy volunteers have demonstrated that XL784 has attractive safety and pharmacokinetic profiles. It is being developed by Exelixis, Inc.",null,null,"For treatment in patients with diabetes who have clinically significant proteinuria.","XL784 is a potent inhibitor of the ADAM-10 metalloprotease (MP) enzyme, a target of significant interest because of its important role in blood vessel formation and cell proliferation. XL784 was specifically optimized to spare matrix metalloprotease 1 (MMP1), thus potentially significantly enhancing its safety profile and enabling higher dosing in comparison to other MMP inhibitors. Data from a Phase 1 clinical trial of orally administered XL784 in 70 healthy volunteers showed single doses of the compound to be free of side effects and to have an attractive pharmacokinetic profile. XL784 has been reformulated for chronic administration and has demonstrated dose-proportional absorption, was orally bioavailable and was well tolerated.","XL784 is a potent small molecule inhibitor of the ADAM-10 metalloprotease enzyme, which plays a role in blood vessel formation and cell proliferation that can cause renal fibrosis and impairment.","Disintegrin and metalloproteinase domain-containing protein 10","Therapeutic strategy associated"]
[672,"DB04999","investigational","small molecule","MBO7133",{"$nulls":3},"MB07133 is a HepDirect prodrug of an activated form of cytarabine (araC), an anti-cancer drug that is used to treat leukemia but is ineffective against primary liver cancer. AraC's anti-cancer activity is associated with its ability to be converted to its biologically active form, araCTP. However, araC is only slowly converted to araCTP in the liver or in primary liver tumors due to low levels of an enzyme in the liver that is required for the conversion of araC to araCMP, the first step in the activation pathway of the drug. Higher doses of araC cannot be used to overcome this limitation due to bone marrow toxicity resulting from rapid activation in that tissue. MB07133 uses our HepDirect technology to target a prodrug form of araCMP specifically to the liver. Once in the liver cell, the prodrug is rapidly cleaved, producing araCMP, bypassing the rate-limiting enzyme. Once generated in the target tissue, araCMP is rapidly converted to araCTP, the cancer-killing active form.",null,null,"Investigated for use/treatment in liver cancer.",null,"MB07133 is a novel HepDirect prodrug of cytarabine monophosphate designed to produce the oncolytically active form, cytarabine triphosphate, in the liver tumor where it acts to inhibit cell proliferation and induce apoptosis or cell death.",null,"Therapeutic strategy associated"]
[673,"DB05001","investigational","small molecule","PSN9301",{"$nulls":3},"PSN9301 is an oral small molecule inhibitor of Dipeptidyl Peptidase IV (DP-IV), being developed for the treatment of type 2 diabetes. PSN9301 has a very rapid onset and a relatively short duration of action, and available pre-clinical and clinical data indicate that it may be an ideal product candidate for meal-related dosing.",null,null,"Investigated for use/treatment in diabetes mellitus type 1 and 2.",null,"PSN9301 is an oral small molecule inhibitor of Dipeptidyl Peptidase IV (DP-IV), an enzyme involved in the inactivation of the gut hormone glucagon-like peptide-1 (GLP-1). GLP-1 plays an important role in regulating meal-related blood glucose by increasing the amount of insulin secreted in response to meals. PSN9301 increases GLP-1 activity and causes significant lowering of blood glucose levels. The increase in insulin secretion in response to GLP-1 is glucose-dependent, providing a built in safety mechanism against low blood glucose levels (hypoglycaemia) in response to treatment with DP-IV inhibitors.","Dipeptidyl peptidase 4","Therapeutic strategy associated"]
[674,"DB05003","investigational","small molecule","Imexon","Imexon","C4H5N3O","NC1=NC(=O)N2CC12","Imexon is currently being studied for the treatment of pancreatic, lung, breast, prostate, melanoma, and multiple myeloma cancers. It belongs to the family of drugs called cyanoaziridine derivatives. Also called Amplimexon. Imexon is a cyanoaziridine derivative.\r\nImexon is a thiol-binding small molecule which induces mitochondrial oxidation, a loss of membrane potential and cytochrome C, leading to apoptosis.","59643-91-3","111.102","Investigated for use/treatment in melanoma, multiple myeloma, ovarian cancer, pancreatic cancer, and solid tumors.",null,"Imexon enters the cell and binds to glutathione and other sulfhydryl compounds, effectively preventing them from scavenging the toxic free radicals. So, particularly in the rapidly dividing cancer cell, free radical build-up in the presence of imexon leads to changes in mitochondrial membrane potential and ultimately to the mitochondria swelling and bursting. Mitochondrial proteins, in particular cytochrome c, are released into the cytoplasm and this activates caspase-mediated apoptosis resulting in cancer cell death. This sequence of events has been well characterized and published in several papers in leading cancer journals. Imexon is probably the only cancer drug under development at this time which exploits this mechanism of action.\r\nImexon is an inhibitor of ribonucleotide reductase, a key enzyme in DNA synthesis that is also a target for gemcitabine. Imexon is also a cell cycle inhibitor and in the presence of the drug cells accumulate in S phase.","Ribonucleoside-diphosphate reductase subunit M2; Ribonucleoside-diphosphate reductase large subunit","Therapeutic strategy associated"]
[675,"DB05004","investigational","small molecule","Peptide YY (3-36)","Pyy (3-36) peptide; PYY 3-36; PYY(3-36); PYY3-36",null,null,"Peptide YY (3-36), a synthetic human PYY 3-36, is a compound being evaluated for the treatment of obesity. It reduces appetite and increases satiety in obese patients.","123583-37-9",null,"Investigated for use/treatment in metabolic disease and obesity.",null,"PYY 3-36 acts via the presynaptic Y2 receptor in the ARC. It decreases neuropeptide Y (NPY) release from static hypothalamic explants and thus acts to decrease food intake.","Neuropeptide Y receptor type 2; Neuropeptide Y receptor type 1; Neuropeptide Y receptor type 5; Neuropeptide Y receptor type 4","Indication associated"]
[676,"DB05015","approved; investigational","small molecule","Belinostat","Belinostat","C15H14N2O4S","ONC(=O)\\C=C\\C1=CC=CC(=C1)S(=O)(=O)NC1=CC=CC=C1","Belinostat is a novel agent that inhibits the enzyme histone deacetylase (HDAC) with a sulfonamide-hydroxamide structure. It was developed as an orphan drug to target hematological malignancies and solid tumors by TopoTarget. The safety and efficacy of belinostat is currently being evaluated for use in combination with traditional front-line therapies for the treatment of PTCL. Intravenous administration of the agent is available as Beleodaq as monotherapy and the dosing regimen involves a 21-day cycle. It was US-approved in July 2014 as a therapeutic agent for relapsed or refractory peripheral T-cell lymphoma.","866323-14-0","318.35","Belinostat is indicated for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) with manageable safety profile. It is a potential alternative therapy for patients who did not experience adequate response to first-line drugs for PTCL. It can be used in patients with baseline thrombocytopenia .","Beleodaq is a histone deacetylase (HDAC) inhibitor that exhibits pan-HDAC inhibition and potent growth inhibitory and pro-apoptotic activities in a variety of tumor cells, including PTCL cells, at nanomolar concentrations . None of the trials show any clinically relevant changes caused by Beleodaq on heart rate, PR duration or QRS duration as measures of autonomic state, atrio-ventricular conduction or depolarization; there were no cases of Torsades de Pointes.","Belinostat inhibits the activity of histone deacetylase (HDAC) thus prevents the removal of acetyl groups from the lysine residues of histones and some non-histone proteins. In vitro, belinostat caused the accumulation of acetylated histones and other proteins, increased the expression of tumor-suppressor genes. It ultimately induces cell cycle arrest, inhibition of angiogenesis and/or apoptosis of some transformed cells.","Histone deacetylase inhibitor","Therapeutic strategy associated"]
[677,"DB05017","investigational","small molecule","YSIL6",{"$nulls":3},"YSIL6 is a small-molecule drug in development for the treatment of inflammatory diseases, including rheumatoid arthritis and psoriasis. The molecule works by inhibiting TNF-alpha and IL-6 production in T-cells and macrophages, and by inhibiting T-cell proliferation and migration.",null,null,"Investigated for use/treatment in crohn's disease, psoriasis and psoriatic disorders, and rheumatoid arthritis.",null,"The molecule works by inhibiting TNF-alpha and IL-6 production in T-cells and macrophages, and by inhibiting T-cell proliferation and migration.","Tumor necrosis factor; Interleukin-6","Target associated"]
[678,"DB05025","investigational","small molecule","Arimoclomol","Arimoclomol","C14H20ClN3O3","O[C@@H](CON=C(Cl)C1=C[N+]([O-])=CC=C1)CN1CCCCC1","Arimoclomol is an experimental drug compound developed by CytRx Corporation, a biopharmaceutical company based in Los Angeles, California. The orally administered drug is intended to treat amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, a neurodegenerative disease with no effective treatment.","289893-25-0","313.78","Investigated for use/treatment in amyotrophic lateral sclerosis (ALS), diabetes mellitus type 2, neurologic disorders, and neuropathy (diabetic).",null,"Arimoclomol is designed to stimulate a natural cellular repair pathway by activating compounds called “molecular chaperones.” Arimoclomol uses a unique 'molecular chaperone' co-induction mechanism. The small molecule drug candidate is believed to function by stimulating a normal cellular protein repair pathway through the activation of \"molecular chaperones.\" Since damaged proteins called aggregates are thought to play a role in many diseases, CytRx believes that activation of molecular chaperones could have therapeutic efficacy for a broad range of diseases.","Superoxide dismutase [Cu-Zn]","Indication associated"]
[679,"DB05027","investigational","small molecule","DG041",{"$nulls":3},"DG041 is a novel, first-in-class, orally-administered small molecule developmented for the prevention of arterial thrombosis and its complications. \r\nDG041, an anti-platelet compound, has shown to be a selective and potent antagonist of the EP3 receptor for prostaglandins E2. EP3 is a target that associates with increased risk of various vascular diseases. It block the formation of blood clots mediated through inflammation in atherosclerotic plaques but without increasing bleeding risk.",null,null,"Investigated for use/treatment in peripheral vascular disease.",null,"DG041 is an antagonist of the EP3 receptor for prostaglandins E2 - a receptor involved in peripheral artery disease (PAD). DG041 produces concentration-dependent inhibition of one of the platelet activation pathways and reduces platelet aggregation without increasing bleeding time.\r\nStudies have shown that DG041 dramatically inhibits platelet activation mediated through VASP as well as platelet aggregation. DG041 also reduced levels of another indicator of platelet activation, p-selectin, and several markers of inflammation -- c-reactive protein (CRP), monocyte chemotactic protein 1 (MCP1), and soluble intracellular adhesion molecule (sICAM) -- in a dose-dependent manner.",null,"Therapeutic strategy associated"]
[680,"DB05032","investigational","small molecule","REV131",{"$nulls":3},"rEV131 is in development for allergic rhinitis, asthma and several inflammatory eye diseases. It is a topically delivered small protein that acts as an anti-inflammatory agent.",null,null,"Investigated for use/treatment in allergic reaction, allergic rhinitis, and cataracts.",null,"rEV131 is smaller than therapeutic antibodies and its compact structure gives good bioavailablity by a number of routes including: injected, inhaled, intraperitoneal, topical (ocular and nasal). The molecule is thermo-stable and can be stored in solution for more than 18 months at room temperature without significant loss of activity. This is an attractive feature for a protein drug candidate.\r\n\r\nrEV131 is a novel histamine binding protein that modulates the immediate inflammatory response largely caused by the release of pre-formed histamine from mast cells in the skin. This molecule binds histamine at two active sites, one of which has an affinity for histamine 10 - 100 times higher than any known histamine receptor. This enables rEV131 to out compete the body's natural receptors and prevent histamine from reaching and activating them.\r\n\r\nThere are at least four different natural histamine receptors. The most recently discovered H4 receptor, was described in 2001, and appears to be involved in the late phase inflammatory process. rEV131 is understood to be the only drug candidate in clinical development, which prevents activation of the H4 receptor.\r\n\r\nrEV131 has demonstrated activity against both early and late phase inflammation in clinical and preclinical studies. This differentiates it from approved treatments: anti-histamines used in early phase inflammation and corticosteroid therapies, which are used predominantly in late phase inflammation. A favourable safety profile and a variety of delivery routes provide additional potential advantages for rEV131 over existing therapies.","Histamine H4 receptor","Therapeutic strategy associated"]
[681,"DB05035","investigational","small molecule","Eprotirome","Eprotirome","C18H17Br2NO5","CC(C)C1=C(O)C=CC(OC2=C(Br)C=C(NC(=O)CC(O)=O)C=C2Br)=C1","Eprotirome which is a compound with promising properties for treatment of obesity and dyslipidemia. Eprotirome increases the body’s energy consumption and reduces body weight and markedly reduces blood lipids and blood glucose.","355129-15-6","487.144","Investigated for use/treatment in hyperlipidemia, metabolic disease, and obesity.","KB2115 is liver selectuve TR agonist that can induce pharmacological effects in the liver. It increases energy consumption, reduces body weight and also markedly reduces blood lipids and blood glucose levels at doses not affecting heart rate, bone density or TSH levels.","KB2115 works by selectively stimulating the thyroid hormone\r\nreceptor which is the protein in the body that mediates the effects of thyroid hormone. KB2115 has receptor and tissue selective properties and thereby negative effects on the heart can be avoided.","Thyroid hormone receptor alpha; Thyroid hormone receptor beta","Target associated"]
[682,"DB05044","investigational","small molecule","PSN357",{"$nulls":3},"PSN357 is a glycogen phosphorylase inhibitor (GPI), which is designed to rapidly lower blood glucose levels by preventing glycogen breakdown to glucose in the liver.",null,null,"Investigated for use/treatment in diabetes mellitus type 2.",null,"Psn357 is a novel glycogen phosphorylase inhibitor. It reduces night-time systemic glucose levels by reducing the hepatic glucose output that is thought to play a major role in the pathophysiology of type 2 diabetics.","Glycogen phosphorylase, liver form","Indication associated"]
[683,"DB05045","investigational","small molecule","Obinepitide","(34-L-glutamine)pancreatic hormone (human); Obinepitide","C185H288N54O55S2","CC[C@H](C)[C@H](N=C(O)[C@H](CC1=CC=C(O)C=C1)N=C(O)[C@H](CCCNC(N)=N)N=C(O)[C@H](CCCNC(N)=N)N=C(O)[C@H](CC(C)C)N=C(O)[C@H](CC(O)=O)N=C(O)[C@H](C)N=C(O)[C@H](C)N=C(O)[C@H](CC1=CC=C(O)C=C1)N=C(O)[C@H](CCC(O)=N)N=C(O)[C@H](C)N=C(O)[C@H](CCSC)N=C(O)[C@H](CCC(O)=N)N=C(O)[C@H](CCC(O)=O)N=C(O)[C@@H]1CCCN1C(=O)[C@@H](N=C(O)[C@H](C)N=C(O)[C@H](CC(O)=N)N=C(O)[C@H](CC(O)=O)N=C(O)CN=C(O)[C@@H]1CCCN1C(=O)[C@H](CC1=CC=C(O)C=C1)N=C(O)[C@@H](N=C(O)[C@@H]1CCCN1C(=O)[C@H](CCC(O)=O)N=C(O)[C@H](CC(C)C)N=C(O)[C@@H]1CCCN1C(=O)[C@H](C)N)C(C)C)[C@@H](C)O)C(O)=N[C@@H](CC(O)=N)C(O)=N[C@@H](CCSC)C(O)=N[C@@H](CC(C)C)C(O)=N[C@@H]([C@@H](C)O)C(O)=N[C@@H](CCCNC(N)=N)C(O)=N[C@@H](CCC(O)=N)C(O)=N[C@@H](CCCNC(N)=N)C(O)=N[C@@H](CC1=CC=C(O)C=C1)C(O)=N","Obinepitide is a synthetic analogue of two natural human hormones, PYY and Pancreatic Polypeptide, which normally are released during a meal. These hormones are known to play a role in the regulation of food intake and appetite in man as satiety signal from the GI-tract to the CNS. In obinepitide, the properties of both of these hormones have been implanted into a single molecule.","348119-84-6","4212.78","Investigated for use/treatment in obesity.",null,"TM30338 is a first-in-class compound, which in a single\r\ndrug targets both the Y2 and the Y4 receptor with similar and very high potency. The Y2 and the Y4 receptors have both previously been validated in man as independent appetite suppressive drug targets through the use of the natural hormones. In pre-clinical studies in diet-induced obese animals the dual active TM30338 has demonstrated clear superiority in respect of long term reduction in body weight\r\nreduction as compared, for example, to the natural hormone PYY3-36, which only targets the Y2 receptor.","Neuropeptide Y receptor type 4; Neuropeptide Y receptor type 2","Indication associated"]
[684,"DB05048","investigational","small molecule","Cannabinor",null,"C28H38O6","[H][C@]12C[C@]([H])(C(=O)C[C@@H]1C1=C(O)C=C(C=C1OC(=O)\\C=C\\C(O)=O)C(C)(C)CCCCCC)C2(C)C","Cannabinor, a synthetic CB2-selective agonist, is in Phase 2 clinical testing as an analgesic.","573981-31-4","470.606","Investigated for use/treatment in pain (acute or chronic).",null,"CB2 agonists bind to CB2 receptors, which are located on immune and inflammatory cells. By activating CB2 receptors, CB2 agonists inhibit autoimmune and inflammatory processes and are likely to be useful for treating pain, autoimmune and inflammatory disorders. Pharmos is developing its CB2 agonists as treatments for chronic pain and autoimmune diseases such as multiple sclerosis and rheumatoid arthritis.",null,"Therapeutic strategy associated"]
[685,"DB05049","investigational","small molecule","DDP733",{"$nulls":3},"DDP733 is an oral prokinetic drug which Dynogen is developing as a treatment for both Irritable Bowel Syndrome with constipation (IBS-c) and nocturnal gastroesophageal reflux disease (NGERD). It is a partial agonist of the serotonin type 3 receptor (5-HT3). Serotonin is a neurotransmitter that is known to be involved in the control of the gastrointestinal (GI) system. Preclinical studies of DDP733 established the compound’s prokinetic properties (the ability to promote the motility of the GI tract).",null,null,"Investigated for use/treatment in constipation, gastroesophageal reflux disease (GERD), gastrointestinal diseases and disorders (miscellaneous), and irritable bowel syndrome (IBS).",null,"DDP733 is an agonist of 5-HT3 receptors, a specific sub-type of serotonin receptor. Serotonin, a neurotransmitter, is believed to play an important role in the regulation of gastrointestinal motility.","5-hydroxytryptamine receptor 3A","Indication associated"]
[686,"DB05051","investigational","small molecule","BZL101",{"$nulls":3},"BZL101 is an oral drug designed for the treatment of advanced breast cancer with a novel mechanism of action. BZL101 targets diseased cells while leaving normal cells healthy and intact.",null,null,"Investigated for use/treatment in breast cancer.",null,"BZL101 works by eliciting a cancer cell’s innate mechanism of self-suicide or apoptosis. The drug selectively releases Apoptosis Inducing Factor-1 (AIF1) from a cancer cell’s mitochondrial membrane. AIF then moves to the cell’s nucleus, disintegrating the DNA structure, and fragmenting and killing the cancer cell.",null,"Therapeutic strategy associated"]
[687,"DB05053","investigational","small molecule","MB-07803",null,"C24H37N4O7PS","CCOC(=O)C(C)(C)NP(=O)(NC(C)(C)C(=O)OCC)C1=CC=C(O1)C1=C(SC(N)=N1)C(=O)C(C)(C)C","MB07803 is a second generation gluconeogenesis inhibitor for the treatment of type 2 diabetes. It is designed to block the metabolic pathway in the liver that is responsible for producing glucose.","882757-24-6","556.61","Investigated for use/treatment in diabetes mellitus type 2.",null,"MB07803 is a selective inhibitor of fructose-1, 6-bisphosphatase (FBPase), a regulatory enzyme in the pathway responsible for the production of glucose in the liver, known as the gluconeogenesis pathway. By specifically inhibiting this pathway, liver glucose production should be reduced and blood sugar levels decreased in patients with diabetes, independent of insulin levels and body weight.","Fructose-1,6-bisphosphatase 1","Indication associated"]
[688,"DB05054","investigational","small molecule","AN0128",{"$nulls":3},"AN0128 is a novel compound that contains a boron atom within a borinic acid complex. AN0128 has broad spectrum activity against a wide variety of Gram positive\r\nbacteria, including many that are known skin colonizers. Of particular importance is P. acnes and its causal role in acne vulgaris. The rise in antibiotic\r\nresistance of P. acnes to standard antibiotics necessitates the development of new treatment agents. AN0128 is a good candidate for a topical antibiotic and is currently being developed by Anacor as a novel therapeutic for acne and atopic dermatitis.",null,null,"Investigated for use/treatment in acne, atopic dermatitis, pediatric indications, and psoriasis and psoriatic disorders.",null,"AN0128 inhibits the release of pro-inflammatory cytokines, including TNF- alpha, without affecting the normal immune response.",null,"Therapeutic strategy associated"]
[689,"DB05061","investigational","small molecule","GFT14",{"$nulls":3},"GFT14 is a new class of medicaction for treatment of cardiometabolic disease. GFT14 aims to target mixed dyslipidemia of type IIb (high levels of triglycerides and LDL-C) as one of the major indications of cardiometabolic disease.\r\nGFT14 is destined to improve the condition of patients at risk from cardiovascular disease by a simultaneous and favorable action on the plasmatic lipids (rise of HDL- cholesterol et lowering of triglycerides) and on other risk factors such as hypertension or diabetes. Orally absorbed GFT14 has absolutely no structural link with current treatments for dyslipidemia (statin or fibrate based). The risks of medical interaction are weak and GFT14 may be easily combined with statins or other antidiabetic molecules (glitazones).",null,null,"Investigated for use/treatment in cardiovascular disorders and hyperlipidemia.",null,"GFT14 is a synthetic modified triglyceride that agonizes PPAP alpha. It raises HDL-C and lowers triglycerides.",null,"Indication associated"]
[690,"DB05064","investigational","small molecule","INCB13739",{"$nulls":3},"INCB13739 is developed as a new treatment for type 2 diabetes. \r\nIt is an orally available small molecule inhibitor of 11beta-HSD1 (11-beta hydroxysteroid dehydrogenase type 1). 11beta-HSD1 is an enzyme that appears to be critical to the development of type 2 diabetes.",null,null,"Investigated for use/treatment in diabetes mellitus type 2 and diabetes prevention.","11beta-HSD1 is an enzyme that converts cortisone into the potent biologically active hormone cortisol. This conversion occurs intra-cellularly within several key metabolic tissues including the liver, adipose, muscle and pancreas. Cortisol acts as an antagonist of insulin action, and 11beta-HSD1 mediated production of cortisol has been hypothesized to contribute to human insulin resistance and type 2 diabetes. INCB13739 inhibits 11beta-HSD1 and has the potential to provide a broad spectrum impact on the multiple components seen in patients with type 2 diabetes.","INCB13739 is an inhibitor of 11beta-HSD1 (11-beta hydroxysteroid dehydrogenase type 1). 11beta-HSD1 is an enzyme that appears to be critical to the development of type 2 diabetes. INCB13739 completely inhibits the production of intra-adipose and intra-hepatic cortisol by 11beta-HSD1, while maintaining normal systemic cortisol levels, which are essential for immune function and response to stress.","Corticosteroid 11-beta-dehydrogenase isozyme 1","Therapeutic strategy associated"]
[691,"DB05068","investigational","small molecule","ATG002",{"$nulls":3},"ATG002 is a completely new approach to treating chronic wounds such as diabetic foot ulcers, which is based upon stimulation of angiogenesis in the wound bed to help drive the wound-healing process. Unlike protein-derived growth factors, ATG002 is a small molecule that, applied topically, effectively penetrates through the wound and into surrounding tissues.",null,null,"Investigated for use/treatment in diabetic foot ulcers and wounds.",null,"ATG002 is an agonist of the nicotinic acetylcholine (nACh) receptor pathway (pro-angiogenic drugs). It stimulates the nACh receptor pathway and could be useful in promoting angiogenesis in disease conditions where there is an insufficient supply of blood.",null,"Indication associated"]
[692,"DB05072","investigational","small molecule","AV608",{"$nulls":3},"AV608 is a NK-1 antagonist. It is developed for the treatment of Social anxiety disorder (SAD), irritable bowel syndrome (IBS) and overactive bladder (OAB).",null,null,"Investigated for use/treatment in anxiety disorders, irritable bowel syndrome (IBS), and urinary incontinence.",null,"An extensive body of scientific literature supports the potential therapeutic application of NK-1 antagonists to the treatment of anxiety disorders. At a biological level, there is a close anatomical association between Substance P, NK-1 receptors and monoamines. More specifically, ~50% of ascending serotonin neurons in the brain also co-express substance P, and norepinephrine cell bodies in the locus coeruleus express NK-1 receptors. In addition, it has been demonstrated that NK-1 receptor blockade can alter the firing pattern of both serotonin and norepinephrine neurons and increase hippocampal neurogenesis. At a functional level, NK-1 antagonists (including AV608) have broadly demonstrated activity in nearly all of the traditionally used preclinical assays to identify anxiolytic agents, including those assays that are predictive for both benzodiazepines and selective serotonin reuptake inhibitors (SSRIs). Clinically, anxiety remains a high priority target for Industry, as evidenced by recent development activity in this area.\r\n It is known that the human intestinal mucosa expresses NK-1 receptors. These receptors are also found in the smooth muscle, arterioles, venules and cells associated with lymph nodules and co-localized with substance P, which is found throughout the gastrointestinal tract. Nerve fibers, including sensory fibers, come into close contact with mast cells, which also express NK-1 receptors. Furthermore, approximately 80% of visceral sensory afferents in the gut express substance P, and it is known that NK-1 receptors in the spinal cord mediate visceral hyperalgesia. Tachykinins are potent secretagogues at the small and large intestinal mucosa in several animal models as well as in the human colon, where there is a direct NK-1 receptor mediated response. Perhaps most important with respect to IBS is the observation that stimulation of sensory fibers or mast cells in the human intestinal tract causes the release of substance P and a consequent increase in epithelial ion transport through the activation of NK-1 receptors. The response to colorectal distension has often been used as a proxy for IBS. In this model, colorectal distension increases abdominal flinching, which is an indicator of pain. This procedure also activates a rectocolonic inhibitory reflex characterized by a decrease in colonic pressure and an increase in fluid transport. Several authors have now observed that NK-1 receptors mediate this rectocolonic inhibitory reflex. Decreased colonic pressure is related to increased colonic transit and these findings are therefore consistent with reports that stress increases intestinal transit, an effect blocked by NK-1 receptor antagonists.\r\nOveractive bladder is a common and distressing condition that has a profound effect on the daily living of affected individuals. This common cause of urinary incontinence describes a cluster of symptoms typified by urinary urgency, frequency, and urge urinary incontinence. Whereas the currently available anticholinergic drugs used to treat overactive bladder act on efferent nerves to counteract overactive bladder, essentially after it occurs, NK-1 antagonists appear to have promising therapeutic potential in their ability to affect the afferent nerves that modulate bladder contraction. A key potential advantage of NK-1 antagonists is that there may be essentially no decrement of detrusor contractility and no urinary retention risk, as is seen with current anticholinergic agents. This is because NK-1 antagonists inhibit sensory afferent nerves but not efferent nerves, which are important for normal and complete voiding of urine. Furthermore, NK-1 antagonists have a more favorable tolerability profile than observed with anticholinergic medications.","Neurokinin 1 receptor","Therapeutic strategy associated"]
[693,"DB05075","investigational","small molecule","TG-100801",null,"C33H30ClN5O3","CC1=C2N=C(NC3=CC=C(OCCN4CCCC4)C=C3)N=NC2=CC(=C1)C1=CC(OC(=O)C2=CC=CC=C2)=CC=C1Cl","TG100801 is a topically applied kinase inhibitor in macular degeneration patients. It is administered noninvasively as an eye drop and is designed to suppress VEGF mediated leakage and additional kinase targets associated with inflammation, edema, and angiogenesis which are the pathological hallmarks of AMD and other back of the eye diseases including diabetic macular edema and proliferative diabetic retinopathy.","867331-82-6","580.09","Investigated for use/treatment in macular degeneration.","In cell based assays, following topical instillation, TG100572, the active drug produced by conversion of TG100801 as it penetrates the eye, was shown to induce apoptosis in proliferating endothelial cells responsible for neovasculariztion and to inhibit inflammatory-mediated processes as measured by endotoxin-induced nitric oxide release in vitro.","TG100801 is the first topically applied, multitargeted vascular endothelial growth factor receptor (VEGFR)/Src kinase inhibitor to advance into the clinic. TG100801 significantly reduced VEGF mediated retinal leakage and choroidal neovascularization in relevant pre-clinical models of macular degeneration. In cell based assays, following topical instillation, TG100572, the active drug produced by conversion of TG100801 as it penetrates the eye, was shown to induce apoptosis in proliferating endothelial cells responsible for neovasculariztion and to inhibit inflammatory-mediated processes as measured by endotoxin-induced nitric oxide release in vitro.","Vascular endothelial growth factor receptor 1; Vascular endothelial growth factor receptor 2; Vascular endothelial growth factor receptor 3; Tyrosine-protein kinase CSK","Therapeutic strategy associated"]
[694,"DB05077","investigational","small molecule","SLV319",{"$nulls":3},"SLV319 belongs to a novel class of agents called CB1 antagonists, which work by blocking the cannabinoid type 1 (CB1) receptor. It is developed for the treatment of obesity and other metabolic disorders.",null,null,"Investigated for use/treatment in obesity.",null,"SLV319 belongs to a novel class of agents called CB1 antagonists, which work by blocking the cannabinoid type 1 (CB1) receptor.  Clinical and preclinical studies involving this class of drug have shown that blocking the cannabinoid type 1 (CB1) receptor results in reduced food intake..","Cannabinoid receptor 1","Indication associated"]
[695,"DB05080","investigational","small molecule","OBE101",{"$nulls":3},"OBE101 is a new weight loss drug developed by Obecure Ltd. It is a new formulation that is based on the vertigo medication, Betahistine. Obecure is repurposing betahistine, which is an H1 receptor agonist and partial H3 receptor antagonist for the treatment of obese individuals and for other weight management indications.",null,null,"Investigated for use/treatment in adverse effects (drug), hyperlipidemia, and obesity.",null,"OBE101 is a H1 receptor agonist and partial H3 receptor antagonist. Because inhibition of H1 receptors increases feeding, agonism of H1 receptors by OBE101 should reduce feeding. By also partially antagonizing H3, OBE101 impedes a negative feedback loop that essentially prolongs stimulation of the H1 receptors.","Histamine H1 receptor; Histamine H3 receptor","Indication associated"]
[696,"DB05084","approved; investigational","biotech","Abaloparatide","Abaloparatide",null,null,"Abaloparatide is an analog of PTHrP (parathyroid hormone-related protein). It was approved in April 28, 2017 by the FDA (as Tymlos) for the treatment of postmenopausal women with osteoporosis at high risk for fracture. Abaloparatide is a synthetic peptide that is related to hPTHrP and has demonstrated in preclinical testing the potential to widen the anabolic window for bone therapeutics, stimulating bone formation with a limited effect on bone resorption and mineral mobilization. This could enable improved convenience over currently available anabolic therapies, resulting in greater compliance and, ultimately, greater benefit to patients.","247062-33-5",null,"Investigated for use/treatment in postmenopausal osteoporosis to reduce vertebral and/or non-vertebral fractures.","Abaloparatide (BA058), a proprietary analog of human parathyroid hormone-related protein (hPTHrP), is currently undergoing clinical trials by the company for the treatment of osteoporosis in postmenopausal women. PTHrP is a critical peptide for promoting new bone formation, with a distinct role from parathyroid hormone, or PTH, which primarily regulates calcium homeostasis and bone resorption. Clinical studies show increased bone mineral density (BMD) and levels of bone formation markers in a dose-response relationship.","In target cells, abaloparatide acts as an agonist on PTH type 1 receptor (PTH1R) and activates both G protein–mediated cAMP signaling and β-arrestin-mediated ERK-1/2 signaling pathways with similar potency. Abaloparatide binds to RG conformation of PTH1R with greater selectivity that results in more transient cell signalling responses.","Parathyroid hormone/parathyroid hormone-related peptide receptor ligand","Indication associated"]
[697,"DB05088","investigational","small molecule","Tetrathiomolybdate","Thiomolybdate; Tiomolibdate ion","MoS4","[S-][Mo]([S-])(=S)=S","Tetrathiomolybdate is an oral, small-molecule, anticopper agent that is highly specific for lowering the levels of free copper in serum. COPREXA has completed pivotal clinical trials for the treatment of neurologic Wilson's disease. It is also developed for fibrotic disorders based upon the rationale that the fibrotic disease process is dependent upon the availability of free copper in the body.","16330-92-0","224.19","Investigated for use/treatment in liver disease and pulmonary fibrosis.","Tetrathiomolybdate demonstrated the ability to reduce toxic free copper levels and substantially improve clinical neurologic outcomes in Wilson’s patients. Studies also showed it is capable of specifically inhibiting chronic fibrotic disease processes in the lung.","Tetrathiomolybdate has demonstrated the ability to inhibit fibrosis in a number of well established animal models through the sequestration of available copper and inhibition of key fibrotric cytokines, including secreted protein acid rich in cysteine (SPARC), NFkappaB, TGF-beta, FGF-2, IL-1, IL-6, IL-8, and connective tissue growth factor (CTGF).","Amyloid beta A4 protein","Therapeutic strategy associated"]
[698,"DB05093","investigational","small molecule","AX200",{"$nulls":3},"AX200, which has been developed for the treatment of stroke, is the most advanced drug candidate and is halfway through the process of gaining clinical approval. The expression of the endogenous AX200 protein in the brain is increased after brain damage. Thus, if this drug administered in the acute phase of stroke, the brain’s own protective action is supported. And this is where the double neurotherapeutic approach is most beneficial: AX200 stops neuronal cell death in the acute phase of stroke, while stimulating simultaneously the regeneration of nervous tissue through the induction of neuro- and arteriogenesis and supporting the reorganisation of the nervous system.",null,null,"Investigated for use/treatment in cardiovascular disorders and strokes.",null,"The AX200 protein is produced at highly elevated levels in\r\nthe brain, as part of an endogenous protective mechanism after brain damage. Thus, if this drug administered in the acute phase of stroke, the brain’s own protective action is further boosted. This offers a highly beneficial, dual neurotherapeutic approach which has been discovered by SYGNIS. AX200 stops neuronal cell death in the acute phase of stroke, and in addition, it stimulates the regeneration of the already damaged nervous tissue through the induction of new nerve cells and blood vessels and the reorganisation of neuronal networks.",null,"Indication associated"]
[699,"DB05095","investigational","small molecule","Cimicoxib","Cimicoxib","C16H13ClFN3O3S","COC1=C(F)C=C(C=C1)C1=C(Cl)N=CN1C1=CC=C(C=C1)S(N)(=O)=O","Cimicoxib is a selective COX-2 inhibitor being developed by Affectis as a treatment for depression and schizophrenia. If approved, Cimicoxib would be the first drug in decades to treat depression by a new mechanism of action.","265114-23-6","381.809","Investigated for use/treatment in depression.",null,"Depression and schizophrenia are inflammatory diseases. Increased levels of pro-inflammatory cytokines and prostaglandin E (PGE) have repeatedly been described in major depression. COX-2 inhibitors inhibit production of both. Cimicoxib is a selective COX-2 inhibitor. The mechanism by which some COX-2 inhibitors work in depression could be linked to their anti-inflammatory mechanisms.","Prostaglandin G/H synthase 2","Therapeutic strategy associated"]
[700,"DB05098","investigational","small molecule","Leptin",{"$nulls":3},"Although leptin is a circulating signal that reduces appetite, in general, obese people have an unusually high circulating concentration of leptin. These people are said to be resistant to the effects of leptin, in much the same way that people with type 2 diabetes are resistant to the effects of insulin. Thus, obesity develops when people take in more energy than they use over a prolonged period of time, and this excess food intake is not driven by hunger signals, occurring in spite of the anti-appetite signals from circulating leptin. The high sustained concentrations of leptin from the enlarged fat stores result in the cells that respond to leptin becoming desensitized.","169494-85-3",null,"Investigated for use/treatment in lipodystrophy and obesity.",null,"It is unknown whether leptin can cross the blood-brain barrier to access receptor neurons, because the blood-brain barrier is somewhat absent in the area of the median eminence, close to where the NPY neurons of the arcuate nucleus are. If it does cross the blood-brain barrier, it is unknown whether this occurs via an active or passive process. It is generally thought that leptin might enter the brain at the choroid plexus, where there is intense expression of a form of leptin receptor molecule that might act as a transport mechanism.\r\n\r\nOnce leptin has bound to the Ob-Rb receptor, it activates the molecule stat3, which is phosphorylated and travels to the nucleus, it is presumed, to effect changes in gene expression. One of the main effects on gene expression is the down-regulation of the expression of endocannabinoids, responsible—among their many other functions—for increasing appetite. There are other intracellular pathways activated by leptin, but less is known about how they function in this system. Neuronal receptors remodel in response to leptin to have a different number and different types of synapses.\r\n\r\nAlthough leptin is a circulating signal that reduces appetite, in general, obese people have an unusually high circulating concentration of leptin. These people are said to be resistant to the effects of leptin, in much the same way that people with type 2 diabetes are resistant to the effects of insulin. Thus, obesity develops when people take in more energy than they use over a prolonged period of time, and this excess food intake is not driven by hunger signals, occurring in spite of the anti-appetite signals from circulating leptin. The high sustained concentrations of leptin from the enlarged fat stores result in the cells that respond to leptin becoming desensitized.\r\n\r\nIn mice, leptin is also required for male and female fertility. In mammals generally, and in humans in particular, puberty in females is linked to a critical level of body fat. When fat levels fall below this threshold (as in anorexia), the ovarian cycle stops and females stop menstruating.\r\n\r\nLeptin is also strongly linked with angiogenesis, increasing VEGF levels.","Leptin receptor","Therapeutic strategy associated"]
[701,"DB05099","approved; investigational","biotech","Ancrod","Ancrod",null,null,"Ancrod, marketed as Viprinex, is a defibrinogenating agent derived from Malayan pit viper venom. The defribrinogenation of blood results in an anticoagulant effect. Currently, Viprinex®/ancrod is not approved or marketed in any country, but is being investigated as a stroke treatment in worldwide clinical trials. In January 2005, the U.S. FDA granted a 'fast-track status' for investigation of ancrod use in patients suffering from acute ischemic stroke, a life threatening condition caused by the blockage of blood vessels supplying blood and oxygen to portions of the brain, for which phase III trials are currently being conducted.","9046-56-4",null,"Ancrod is indicated for the treatment of deep vein thrombosis (DVT), central retinal branch vein thrombosis, pripaism, pulmonary hypertension of embolic origin, embolism after insertion of prosthetic cardiac valves, rethrombosis after thrombolytic therapy, rethrombosis after vascular surgery, and prevention of DVT after repair of a fractured neck of a femur.","The decreased viscosity is directly attributable to lowered fibrinogen levels and leads to important improvements in blood flow and perfusion of the microcirculation. Ancrod decreases the blood viscosity in affected arteries, leads to less intense pain, improves physical limb mobility, facilitates physical and ergo therapy, and decreases the likelihood of local thrombotic events.","Ancrod's anticoagulant effects are through the rapid removal of fibrinogen from the blood within hours following ancrod administration. Ancrod specifically cleaves only the alpha chain of fibrinogen, producing the characteristic fibrinopeptides A, AP and AY, not the B-fibrinopeptide. The resulting fibrin polymers are imperfectly formed and much smaller in size (1 to 2 µm long) than the fibrin polymers produced by the action of thrombin. These ancrod-induced microthrombi are friable, unstable, urea-soluble and have significantly degraded a-chains. They do not cross-link to form thrombi. They are markedly susceptible to digestion by plasmin and are rapidly removed from circulation by either reticuloendothelial phagocytosis or normal fibrinolysis, or both. Blood viscosity is reduced by 30-40%.\r\nAncrod does not activate plagminogen and does not degrade preformed, fully cross-linked thrombin fibrin. Consequently, unlike fibrinolytic agents, ancrod can be used postoperatively. \r\nAncrod does not activate Factor XIII, produce platelet aggregation, or release ADP, ATP, potassium, or serotonin from platelets.\r","Fibrinogen alpha chain","Therapeutic strategy associated"]
[702,"DB05103","investigational","small molecule","AN-9","Pivaloyloxymethyl butyrate; Pivaloyloxymethylbutyrate; Pivanex","C10H18O4","CCCC(=O)OCOC(=O)C(C)(C)C","Pivaloyloxymethyl butyrate (AN-9), an acyloxyalkyl ester prodrug of butyric acid (BA), exhibited low toxicity and significant anticancer activity in vitro and in vivo. It shows greater potency than BA at inducing malignant cell differentiation and tumor growth inhibition and has demonstrated more favorable toxicological, pharmacological, and pharmaceutical properties than BA in preclinical studies.","122110-53-6","202.25","Investigated for use/treatment in liver cancer, lung cancer, melanoma, and leukemia (lymphoid).",null,"Pivaloyloxymethyl butyrate is a histone deacetylase inhibitor analog of butyric acid that causes apoptosis of cancer cells through signaling cellular differentiation. It is rapidly and extensively transported intracellularly because of its high lipophilicity, where it undergoes esterase-mediated hydrolysis to form pivalic acid, formaldehyde, and BA.",null,"Therapeutic strategy associated"]
[703,"DB05104","investigational","small molecule","Asimadoline","Asimadoline","C27H30N2O2","CN([C@H](CN1CC[C@H](O)C1)C1=CC=CC=C1)C(=O)C(C1=CC=CC=C1)C1=CC=CC=C1","Asimadoline is a proprietary small molecule therapeutic, originally discovered by Merck KGaA of Darmstadt, Germany. Asimadoline was originally developed to treat peripheral pain such as arthritis. Asimadoline is an orally administered agent that acts as a kappa opioid receptor agonist. It has shown encouraging clinical efficacy for the treatment of IBS in a barostat study in IBS patients and has the potential for treating other gastrointestinal diseases.","153205-46-0","414.5393","Investigated for use/treatment in irritable bowel syndrome (IBS).",null,"Asimadoline is an orally administered agent that acts as a kappa opioid receptor agonist. Kappa opioid receptors are found mostly in the digestive tract and are believed to play an important role in control of visceral pain and bowel motility. As such, kappa opioid agonists are ideal candidates to relieve the pain, discomfort an impaired motility common to IBS and other gastrointestinal disorders.","Kappa-type opioid receptor","Indication associated"]
[704,"DB05115","investigational","small molecule","NN344",{"$nulls":3},"NN344 is a neutral, soluble long-acting human insulin analogue with 24 hour coverage by once daily injection. NN344 has a very flat and predictable action profile. The product is intended for basal insulin treatment of diabetes mellitus.",null,null,"Investigated for use/treatment in diabetes mellitus type 1 and 2.",null,"NN344 binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of NN344 to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor is able to autophosphorylate and phosphorylate numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. These activated proteins, in turn, lead to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC) which play a critical role in metabolism and catabolism.","Insulin receptor","Indication associated"]
[705,"DB05118","investigational","small molecule","R1204",{"$nulls":3},"R1204 is G-protein-coupled receptor modulator. It is developed for the treatment of depression.",null,null,"Investigated for use/treatment in depression.",null,"R1204 is G-protein-coupled receptor modulator which is involved in the regulation of mood and behavior.",null,"Indication associated"]
[706,"DB05119","investigational","small molecule","Rilapladib","Rilapladib","C40H38F5N3O3S","COCCN1CCC(CC1)N(CC1=CC=C(C=C1)C1=CC=C(C=C1)C(F)(F)F)C(=O)CN1C(SCC2=C(F)C(F)=CC=C2)=CC(=O)C2=C1C=CC=C2","Rilapladib is the third genomics-derived small molecule drug arising from the Human Genome Sciences-GlaxoSmithKline collaboration to enter clinical development. It is a lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor. Lp-PLA2 is an enzyme associated with the formation of atherosclerotic plaques.","412950-08-4","735.81","Investigated for use/treatment in atherosclerosis and cardiovascular disorders.",null,"Rilapladib is a Lp-PLA2 inhibitor. Lp-PLA2 has been found to be enriched in the highly atherogenic lipoprotein subfraction of small dense LDL, which is susceptible to oxidative modification. Moreover, enzyme levels are increased in patients with hyperlipidaemia, stroke, Type 1 and Type 2 diabetes mellitus, as well as in post-menopausal women. As such, plasma Lp-PLA2 levels tend to be elevated in those individuals who are considered to be at risk of developing accelerated atherosclerosis and clinical cardiovascular events. Thus, inhibition of the Lp-PLA2 enzyme would be expected to stop the build up of this fatty streak (by inhibition of the formation of lysophosphatidylcholine), and so be useful in the treatment of atherosclerosis.","Platelet-activating factor acetylhydrolase","Indication associated"]
[707,"DB05120","investigational","small molecule","AT1391",{"$nulls":3},"AT1391 is a daily insulin skin patch designed to provide continuous basal levels of insulin for patients with diabetes.",null,null,"Investigated for use/treatment in diabetes mellitus type 1 and 2.",null,"Insulin binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor is able to autophosphorylate and phosphorylate numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. These activated proteins, in turn, lead to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC) which play a critical role in metabolism and catabolism.","Insulin receptor","Indication associated"]
[708,"DB05122","investigational","small molecule","R1295",{"$nulls":3},"R1295 is an integrin antagonist currently in clinical trials for the treatment of rheumatoid arthritis. Integrins are associated to the pathology seen in some of the autoimmune diseases such as rheumatoid arthritis.",null,null,"Investigated for use/treatment in rheumatoid arthritis.",null,"R1295 is an integrin antagonist. As leukocyte integrins are key molecules in immune-mediated and inflammatory processes,   R1295 may treat human inflammatory diseases such as rheumatoid arthritis.","Integrin alpha-4; Integrin beta-4; Integrin beta-7","Therapeutic strategy associated"]
[709,"DB05125","investigational","small molecule","SC12267",{"$nulls":3},"SC12267 is a novel, small molecule agent from the class of DMARDs (disease modifying anti-rheumatic drug) for the therapy of autoimmune diseases such as rheumatoid arthritis or multiple sclerosis. Through highly selective inhibition of pyrimidine biosynthesis, it controls the growth of rapidly proliferating cells, especially of lymphocytes, which are important for the immune response.",null,null,"Investigated for use/treatment in multiple sclerosis and rheumatoid arthritis.",null,"SC12267, a novel, selective and orally available, small molecule inhibitor of dihydroorotate dehydrogenase\r\n(DHODH), interferes with cell proliferation through blocking the synthesis pathway of pyrimidines. Its mode-of-\r\naction is of therapeutic relevance for the treatment of autoimmune disorders such as rheumatoid arthritis and\r\nmultiple sclerosis.","Dihydroorotate dehydrogenase (quinone), mitochondrial","Indication associated"]
[710,"DB05126","investigational","small molecule","PYM50018",{"$nulls":3},"PYM50018 is a patented, orally active, neuroprotective and neuroregenerative compound. It is developed for the treatment of amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease). In pre-clinical models, PYM50018 has been observed to protect against neuronal damage, increase neurite outgrowth, reverse oxidative damage and reverse neuronal apoptosis in vitro. When administered orally to a transgenic pre-clinical model of ALS, PYM50018 delays the loss of muscle strength and extends survival time.",null,null,"Investigated for use/treatment in amyotrophic lateral sclerosis (ALS).",null,"Although the precise molecular pathways that cause the death of motor neurones in ALS remain unknown, possible mechanisms include abnormalities in neurofilament proteins, mitochondrial alterations and glutamate mediated excitotoxicity. In pre-clinical studies, the single chemical PYM50018 a novel neurotrophic factor inducer, protects against neuronal damage, reverses the decrease of neuronal growth factors and reverses neuronal degeneration observed in motor neurones. PYM50018 also increases neurite outgrowth, reverses oxidative damage and reverses neuronal apoptosisin vitro. When administered orally to a transgenic pre-clinical model of ALS, PYM50018 delays the loss of muscle strength and extends survival time.",null,"Therapeutic strategy associated"]
[711,"DB05130","investigational","small molecule","INCB3284",{"$nulls":3},"INCB3284 is a CCR2 antagonist for Inflammation-driven Diseases.",null,null,"Investigated for use/treatment in inflammatory disorders (unspecified).",null,null,"C-C chemokine receptor type 2","Target associated"]
[712,"DB05132","investigational","small molecule","ND1251",{"$nulls":3},"ND1251 is an orally active phosphodiesterase-4 (PDE4) inhibitor, a mechanism clinically proven to play a role in alleviating symptoms of depression. ND1251 is a very potent compound with a large safety margin. ND1251 may also have applications in other disorders, such as Alzheimer's disease, mild cognitive impairment, multiple sclerosis and certain respiratory diseases.",null,null,"Investigated for use/treatment in depression.",null,"ND1251 works by inhibiting the enzyme phophodiesterase. This increases the intracellular concentration of cAMP, a second messenger, which regulates enzymes involved in energy metabolism and cell division. This appears to play an important role in brain function.",null,"Indication associated"]
[713,"DB05133","investigational","small molecule","VP025",{"$nulls":3},"VP025, a novel drug formulation based on phospholipid microparticles incorporating phosphatidylglycerol, can inhibit neuroinflammation. VP025 may inhibit immune system activation and protect motoneurons from injury. It also shows the ability to reduce inflammation across the blood-brain barrier and improve correlates of memory and learning function. It is being developed to target the chronic inflammation within the central nervous system that is associated with a number of neurological diseases, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (Lou Gehrig’s disease). It is considered to be a systemic anti-inflammatory and neuroprotective agent.",null,null,"Investigated for use/treatment in alzheimer's disease and inflammatory disorders (unspecified).","VP025 may invoke the body's response ti cell surface phospholipid components, the result of which is an up-regulation of regulatory T cells promoting a suppression of inflammation.  VP025 cross the blood-brain barrier, demonstrating potent anti-inflammatory activity and preserving the function of neural pathways necessary for memory and learning.","VP025 is being developed to exert its anti-inflammatory effects using an cell clearance mechanism. VP025, a preparation of phospholipid microparticles containing\r\nphosphatidylglycerol, has been shown to exert anti-inflammatory effects in the brain, abrogating age-induced up-regulation of IL-1 beta and IL-1 beta -induced signalling, and reducing the activation of c-Jun N-terminal kinase (JNK), a kinase involved in the inflammatory process.","Interleukin-1 beta","Therapeutic strategy associated"]
[714,"DB05136","investigational","biotech","Bavituximab","Bavituximab",null,null,"Bavituximab is a chimeric Anti-PS monoclonal antibody analog which is used to potentially treat cancers and viral infections. It binds to phosphatidylserine and other exposed host cell lipids when induced by cellular stress. Additional analogs in the class include 3G4, 2aG4, 9d2 and Hu3g4.","648904-28-3",null,"Investigated for use/treatment in breast cancer, cancer/tumors (unspecified), HIV infection, hepatitis (viral, C), and solid tumors.",null,"Bavituximab Anti-Cancer is a monoclonal antibody that binds to a basic component of the cell structure called a phospholipid that is exposed only on the surface of tumor blood vessel cells or on cells infected with certain viruses. Bavituximab binding to the tumor blood vessel cells alerts the body’s immune system to attack the tumor and its blood supply. This has been shown to inhibit tumor growth and development. Because in healthy cells the phospholipids are concealed inside the cell, the bavituximab does not bind to them. This targets the bavituximab to the malignant cells and potentially minimizes unwanted side effects. \r\n\r\nBavituximab Anti-Viral represents a unique approach to treating viral diseases by recognizing features found only on infected cells and enveloped viruses. Bavituximab is a monoclonal antibody that binds to a basic component of the cell structure called an aminophospholipid that is exposed on the surface of cells only when they are infected with certain viruses or when they are malignant. After binding to these infected cells, the drug alerts the body’s immune system to attack the infected cells. This makes infected cells particularly susceptible to bavituximab treatment, while potentially sparing healthy cells. Also, bavituximab binds to phospholipids which are derived from the host (human) cell and not the virus, which indicates it may not be susceptible to viral drug resistance. In addition to treating an active illness, bavituximab may also confer long-term immunity. Bavituximab induces a pro-inflammatory cytokine profile, defined as an increase in the ratio of TNF alpha and TGF beta. Stimulating an immune response is a key proposed anti-viral mechanism of action of bavituximab.\r\n\r\n\r",null,"Therapeutic strategy associated"]
[715,"DB05140","investigational","biotech","RAV12",{"$nulls":3},"RAV12 is investigated for use/treatment in solid tumors. RAV12 is a solid. RAV12 is a chimeric antibody that recognizes RAAG12, an N-linked carbohydrate antigen found on gastric, colon, pancreatic, prostate, ovarian, breast, and kidney cancer cells.\r",null,null,"Investigated for use/treatment in solid tumors.",null,"RAV12 is a high affinity IgG1 chimeric antibody. RAAG12, the antigen target of RAV12 is a carbohydrate moiety whose expression is limited to primates. The structure of the RAV12 epitope is Galß 1-3GlcNacß 1-3Gal. Multiple RAV12 binding sites exist per sugar side-chain resulting in a very high apparent affinity and a nearly unmeasurable dissociation rate. Adenocarcinomas arising in breast, endometrial, ovarian, lung and prostate, display the RAA12 antigen to varying degrees. RAAG12 expression in normal tissues is generally limited to the apical membranes of certain epithelia of the GI track and the hepatobiliary system. Preclinical in vitro and in vivo experiments have suggested that RAV12 may have several anti-tumor activities, including direct cytotoxicity by a mechanism termed oncosis, antibody-dependent cellular cytotoxicity, complement mediated cytotoxicity, and alterations of cell survivability through down regulation of growth factor receptors. Oncosis is a form of cell death, distinct from apoptosis, that is characterized by loss of membrane integrity, followed by cell and organellar swelling, and death.",null,"Therapeutic strategy associated"]
[716,"DB05141","investigational","small molecule","LY2181308",{"$nulls":3},"LY2181308 is investigated in clinical trials for treating solid tumors. LY2181308 is a solid. LY2181308 is directed against a molecular target called survivin. LY2181308 is known to target baculoviral IAP repeat-containing protein 5. LY2181308 is an anti-sense oligonucleotide that potently downregulated survivin expression in human cancer cells derived from lung, colon, breast, prostate, ovary, cervix, skin and brain.",null,null,"Investigated for use/treatment in cancer/tumors (unspecified) and solid tumors.",null,"LY2181308 is directed against a molecular target called survivin. Survivin belongs to a family of proteins, called Inhibitor of Apoptosis Proteins, which play a key role in the regulation of apoptosis and cell division. The protein is expressed in a majority of human cancers but not in normal adult tissues, making it a potential target for cancer therapies. LY2181308 potently downregulates survivin expression in human cancer cells derived from lung, colon, breast, prostate, ovary, cervix, skin and brain.\r\n\r","Baculoviral IAP repeat-containing protein 5","Therapeutic strategy associated"]
[717,"DB05142","investigational","small molecule","ND7001",{"$nulls":3},"ND7001, a selective PDE2 inhibitor is in clinical trials for the treatment of depression. ND7001 is a solid. Known drug targets of ND7001 including phosphodiesterase 2A, cGMP-stimulated and cGMP-dependent 3',5'-cyclic phosphodiesterase. It is a new type of antidepressant drug with anxiolytic activity. It is the first representative of a new generation of psycho-active compounds potentially devoid of several problems seen with existing treatments.\r",null,null,"Investigated for use/treatment in anxiety disorders and depression.",null,null,"Phosphodiesterase 2A, cGMP-stimulated; cGMP-dependent 3',5'-cyclic phosphodiesterase","Indication associated"]
[718,"DB05145","investigational","biotech","TH0318","ThGLP-1",null,null,"TH0318 is a stabilized analogue of human GLP-1 (glucagon-like peptide-1) under investigation for the treatment of type 2 diabetes.",null,null,"Investigated for use/treatment in diabetes mellitus type 1 and 2.",{"$nulls":3},"Indication associated"]
[719,"DB05157","investigational","small molecule","KC706",{"$nulls":3},"KC706 is a novel anti-inflammatory drug that works by inhibiting the activity of p38 MAP kinase. KC706 holds potential to treat inflammatory conditions such as rheumatoid arthritis, psoriasis, inflammatory bowel disease and cardiovascular disease.",null,null,"Investigated for use/treatment in cardiovascular disorders, inflammatory bowel disease, inflammatory disorders (unspecified), psoriasis and psoriatic disorders, and rheumatoid arthritis.","KC706 has been demonstrated to be truly disease-modifying: it stops the destruction of joint tissue that is the underlying disease pathology in rheumatoid arthritis.","KC706 is a novel anti-inflammatory drug that works by inhibiting the activity of p38 MAP kinase. p38 MAP kinase is a key component of the signaling pathway that regulates the body's production of inflammatory mediators, including TNFα and IL-1 beta. It has been demonstrated to be truly disease-modifying: it stops the destruction of joint tissue that is the underlying disease pathology in rheumatoid arthritis.","Mitogen-activated protein kinase 14; Mitogen-activated protein kinase 11; Mitogen-activated protein kinase 12; Mitogen-activated protein kinase 13","Therapeutic strategy associated"]
[720,"DB05159","investigational","small molecule","CCX915",{"$nulls":3},"CCX915 is developed by ChemoCentryx which targets the chemokine receptor CCR2 and is in phase 1 of clinical trial for the treatment of Multiple Sclerosis and Neurologic Disorders. The CCR2 receptor is thought to be of central importance to inflammatory diseases, such as multiple sclerosis (MS), Type II diabetes and atherosclerosis.",null,null,"Investigated for use/treatment in multiple sclerosis and neurologic disorders.",null,"Mechanism of action indicates that CCX915 selectively inhibits CCR2-mediated migration of inflammatory white blood cells, but do not inhibit migration mediated by other chemokine receptors, even when administered at high concentrations. Based on the high degree of target specificity observed, CCX915 has the potential to avoid the undesirable side effects of traditional immunosuppressive therapies used in MS and other autoimmune disease indications.","C-C chemokine receptor type 2","Therapeutic strategy associated"]
[721,"DB05161","investigational","small molecule","Elafin",{"$nulls":3},"Elafin is a human protein that is produced naturally in the skin, lung and breast, protecting the respective tissue from destruction by the immune system. Elafin’s ability to block the activity of destructive enzymes that are involved in inflammatory reactions makes it a highly promising active compound for the treatment of inflammatory lung diseases or severe reperfusion injuries occurring after heart attacks, serious injuries and organ transplantation. The excellent tolerability of Elafin in human subjects was demonstrated in a Phase I clinical single dose escalating study.",null,null,"Investigated for use/treatment in inflammatory disorders (unspecified).",null,"Elafin is able to abrogate lipopolysaccharide-induced production of monocyte chemotactic protein 1 in monocytes by inhibiting AP-1 and NFkappaB activation. Due to its selective expression at mucosal surfaces as well as in alveolar macrophages, monocytes and neutrophils, the ability of Elafin to inhibit the lipopolysaccharide signaling pathway may be important in disease states such as cystic fibrosis, pneumonia, and acute respiratory distress syndrome. The inhibition of two key inflammatory pathways confirms the importance of Elafin as a mediator of the innate immune response.","Neutrophil elastase; Myeloblastin","Therapeutic strategy associated"]
[722,"DB05166","investigational","small molecule","APD668",{"$nulls":3},"APD668 is a novel, highly potent and orally active glucose-dependent insulinotropic receptor (GDIR) agonist intended to more efficiently stimulate insulin release by beta cells in response to elevated blood glucose levels, and to also avoid hypoglycemia.",null,null,"Investigated for use/treatment in diabetes mellitus type 2.",null,"The GDIR mechanism is glucose dependent: in preclinical studies, GDIR agonists only lowered blood glucose when it rose above normal levels, such as after a meal. Therefore, unlike the glucose-insensitive sulfonylureas, Arena's GDIR agonists are not expected to lower normal fasting blood glucose levels or cause hypoglycemia. In addition, GDIR stimulation has been found to increase the levels and activity of intracellular factors thought to be involved in the preservation of beta cells. \r","Glucose-dependent insulinotropic receptor","Indication associated"]
[723,"DB05170","investigational","small molecule","Benzimate",{"$nulls":3},"Benzimate is the lead compound selected from a series of compounds known as benzimidazoles. The anti-cancer and anti-viral activity of the benzimidazoles was originally investigated by the Proctor & Gamble Company beginning in the 1990's. It is currently under investigation by AmpliMed and is in phase I of clinical trial.",null,null,"Investigated for use/treatment in cancer/tumors (unspecified).",null,"Benzimate is a systemic fungicide with antitumor activity against a broad spectrum of tumors both in vitro and in vivo such as pancreas, prostate, colon, and breast. Studies indicate that benzimate may interfere with mitosis and thus may disrupt or inhibit microtubule function resulting in apoptosis. Benzimate is active in p53 positive and negative tumor cell lines and in tumor cells with multi-drug resistance to other agents. Further, it appears to induce cell cycle arrest at the G2/M phase portion of the cell cycle.",null,"Therapeutic strategy associated"]
[724,"DB05177","investigational","small molecule","DG051",{"$nulls":3},"DG051 is a novel small-molecule inhibitor of leukotriene A4 hydrolase (LTA4H), the protein made by one of the genes in the leukotriene pathway that has been shown to link to risk of heart attack. DG051 is designed to decrease risk of heart attack by decreasing the production of leukotriene B4 (LTB4), an end product of the leukotriene pathway and a potent promoter of inflammation.",null,null,"Investigated for use/treatment in myocardial infarction.",null,"DG051 is an inhibitor of leukotriene A4 hydrolase (LTA4H)which has been shown to link to risk of heart attack, and is directly involved in the synthesis of LTB4. By inhibiting LTA4H, DG051 decreases risk of heart attack by decreasing the production of leukotriene B4 (LTB4), an end product of the leukotriene pathway and a potent promoter of inflammation.","Leukotriene A-4 hydrolase","Indication associated"]
[725,"DB05183","investigational","small molecule","MLN0415",{"$nulls":3},"MLN0415 is a novel, small molecule IKK2 inhibitor, discovered by Millennium scientists. In preclinical studies, MLN0415 was shown to decrease NF-kB activation and down-regulate the expression of a number of inflammatory proteins. Because inflammatory proteins play a critical role in inflammation and drive the inflammatory response to disease, controlling these proteins may prevent or slow disease progression.",null,null,"Investigated for use/treatment in inflammatory disorders (unspecified).",null,"MLN0415 is an oral, highly selective, small molecule\r\ninhibitor of IKK2, which targets a major inflammatory pathway. MLN0415 was shown to decrease NF-kB activation and down-regulate the expression of a number of inflammatory proteins. Because inflammatory proteins play a critical role\r\nin inflammation and drive the inflammatory response to disease, controlling these proteins may prevent or slow disease progression.\r","Inhibitor of nuclear factor kappa-B kinase subunit beta","Therapeutic strategy associated"]
[726,"DB05186","investigational","small molecule","SQ-109",null,"C22H38N2","CC(C)=CCC\\C(C)=C\\CNCCNC1C2CC3CC(C2)CC1C3","SQ-109 is an orally active, small molecule antibiotic for treatment of pulmonary TB. Currently in Phase I clinical trials, SQ-109 could replace one or more drugs in the current first-line TB drug regimen, simplify therapy, and shorten the TB treatment regimen.","502487-67-4","330.5505","Investigated for use/treatment in bacterial infection, infectious and parasitic disease (unspecified), and tuberculosis.",null,"With a mechanism of action distinct from other antibiotics used in TB therapy, SQ109 inhibits cell wall synthesis and acts on multiple cellular pathways in a select group of microorganisms.",null,"Indication associated"]
[727,"DB05188","investigational","small molecule","KD3010",null,"C30H33F3N2O8S2","CC1=CC=C(C=C1)S(O)(=O)=O.[H]C1(CC2=C(C1)C(=CC=C2)S(=O)(=O)N1[C@@]([H])(C)CN(C[C@@]1([H])C)C1=CC=C(OC(F)(F)F)C=C1)C(O)=O","KD3010 is a small molecule peroxisome proliferator-activator receptor delta (PPAR Delta) agonist for the treatment of metabolic disorders, including obesity.","934760-90-4","670.72","Investigated for use/treatment in metabolic disease and obesity.","By activating PPAR Delta, which regulates lipid catabolism and energy utilization in peripheral tissues, KD3010 is designed to address the underlying metabolic derangement of these disorders. KD3010 results in significant reduction of central adiposity, atherogenic lipid profiles, and improved glucose utilization/insulin sensitivity.","KD3010 is a potent, orally administered, peroxisome proliferator-activated receptor-delta (PPARδ) agonist that exhibits ~1000-fold selectivity over PPARγ and PPARα. PPARδ regulates lipid catabolism and energy utilization in peripheral tissues. Activation of PPARδ reduces central adiposity, improves atherogenic lipid profiles, and increases glucose utilization/insulin sensitivity.\r\n\r","Peroxisome proliferator-activated receptor delta","Target associated"]
[728,"DB05189","investigational","small molecule","EPC2407",{"$nulls":3},"EPC2407 is a novel small molecule vascular disruption agent and apoptosis inducer for the treatment of patients with advanced solid tumors and lymphomas. It is intended for the treatment of advanced cancer patients with solid tumors that are well vascularized. These tumors\r\ninclude the frequently occurring cancers of the lung, gastrointestinal tract, ovaries, and breast.",null,null,"Investigated for use/treatment in cancer/tumors (unspecified).",null,"The molecule has been shown to induce tumor cell apoptosis and selectively inhibit growth of proliferating cell lines, including multi-drug resistant cell lines.",null,"Therapeutic strategy associated"]
[729,"DB05192","investigational","small molecule","MB07811",{"$nulls":3},"MB07811 is the first of a novel class of product candidates discovered by Metabasis designed to lower serum cholesterol and triglycerides. MB07811, a small molecule that is administered orally, has been extensively studied preclinically and is currently undergoing clinical testing. MB07811 combines a novel thyroid hormone receptor agonist with the Company's novel HepDirect liver targeting prodrug technology. The combination of selectivity for the beta form of the receptor, liver targeting and other structural characteristics that limit extra-hepatic activity is designed to provide significant efficacy while avoiding side effects associated with activation of thyroid hormone receptors outside the liver.",null,null,"Investigated for use/treatment in hyperlipidemia.","MB07811's TR beta receptor selectivity and liver targeting could harness the efficacy of the approach, while avoiding extra-hepatic activation of TR alpha and TR beta receptors that may lead to therapy limiting side effects. These benefits may include: reduction of LDL and total cholesterol, Reduced liver and serum triglycerides, reduced Lp(a) and enhanced clearance of liver fat.\r","Studies indicate that targeting TR agonists to the liver has the potential to lower both LDL-cholesterol (the \"bad\" cholesterol) and both hepatic and plasma triglyceride levels.","Thyroid hormone receptor beta","Target associated"]
[730,"DB05194","investigational","small molecule","KB002",{"$nulls":3},"KB002 is an engineered human IgG1k antibody engineered human. It is developed for the treatment of autoimmune diseases, initially rheumatoid arthritis.",null,null,"Investigated for use/treatment in rheumatoid arthritis.",null,"KB002 is an engineered human monoclonal antibody. The drug targets and neutralizes the activity of granulocyte macrophage colony-stimulating factor, (GM-CSF), a pro-inflammatory cytokine/growth factor that stimulates the survival, proliferation, differentiation and function of several types of white blood cells, including the monocytes/macrophages that play a key role in the tissue damage associated with many autoimmune diseases.","Granulocyte-macrophage colony-stimulating factor receptor subunit alpha; Granulocyte-macrophage colony-stimulating factor; GM-CSF receptor alpha subunit","Therapeutic strategy associated"]
[731,"DB05198","investigational","small molecule","CYC116",{"$nulls":3},"CYC116 is a novel anticancer compound with a unique target profile involving both cell cycle and angiogenesis inhibition mechanisms. In preclinical studies, CYC116 has demonstrated antitumor activity in both solid tumors and hematological cancers.\r\n\r\nCyclacel's small molecule investigational drug, CYC116, is the third orally-available Cyclacel drug to enter development, which demonstrated anticancer activity with a mechanism consistent with inhibition of Aurora kinase.",null,null,"Advanced solid tumors",null,"Aurora kinases are enzymes that help dividing cells share their materials between two daughter cells. In many people with cancer Aurora kinase malfunctions and normal control of cell division is lost resulting in abnormal growth.\r\nCYC116 inhibits Aurora kinase may slow down the growth of cancer cells and lead to their death by apoptosis.\r","Aurora kinase A; Vascular endothelial growth factor receptor 2","Therapeutic strategy associated"]
[732,"DB05199","investigational","small molecule","LX1031",{"$nulls":3},"LX1031 is an orally-dosed drug candidate for irritable bowel syndrome and other gastrointestinal disorders. LX1031 was generated by Lexicon medicinal chemists, and its target was internally identified as a key control point for the regulation of peripheral serotonin levels. LX1031 is designed to act locally in the gastrointestinal tract by reducing the serotonin available for receptor activation, without affecting serotonin levels in the brain or its central nervous system functions.",null,null,"Irritable bowel syndrome (IBS) and other gastrointestinal disorders",null,"LX1031 is designed to act locally in the gastrointestinal tract by reducing the serotonin available for receptor activation, without affecting serotonin levels in the brain or its central nervous system functions.","Tryptophan 5-hydroxylase 1","Indication associated"]
[733,"DB05201","investigational","small molecule","V24343",{"$nulls":3},"The anti-obesity drug, V24343, acts by targeting the CB1 receptor in the brain and suppressing a person's appetite.",null,null,"Obesity related disorders such as cardiovascular disease and type II diabetes",null,"About V24343 Scientists have long known that cannabis, which stimulates a receptor in the brain called the CB1 receptor, also stimulates appetite as evidenced by the hunger pangs or \"munchies\" often experienced by cannabis smokers. Blockade of these CB1 receptors by products like V24343 has been shown to cause weight loss and may reduce risk factors for obesity related disorders such as cardiovascular disease and type II diabetes.","Cannabinoid receptor 1","Therapeutic strategy associated"]
[734,"DB05202","investigational","biotech","Egaptivon pegol","Egaptivon pegol",null,null,"ARC1779 is a therapeutic aptamer antagonist of the A1 domain of von Willebrand Factor (vWF), the ligand for receptor glycoprotein 1b on platelets. ARC1779 is being developed as a novel antithrombotic agent for use in patients with acute coronary syndromes. ARC1779 is a therapeutic oligonucleotide (\"aptamer\") which blocks the binding of the A1 domain of vWF to the platelet GPIb receptor, and thereby modulates platelet adhesion, activation, and aggregation under the high shear conditions of coronary arterial stenosis and plaque rupture.","934868-74-3",null,"Platelet aggregation, thrombosis and acute coronary syndromes",null,"ARC1779 can inhibit vWF activation and platelet function, which are both widely recognized as playing critical roles in clot formation which can critically impede blood flow to the heart.","von Willebrand factor; Platelet glycoprotein Ib alpha chain","Target associated"]
[735,"DB05203","investigational","small molecule","SPP1148",{"$nulls":3},"SPP1148, the most promising compound from a new series of renin inhibitors for the treatment of hypertension and related end-organ disease.",null,null,"Investigated for use/treatment in hypertension.",null,null,"Angiotensin-converting enzyme 2; Renin","Indication associated"]
[736,"DB05204","investigational","small molecule","XL418",{"$nulls":3},"XL418 is  a novel anticancer compound.",null,null,"Cancer",null,"XL418 is a small molecule that inhibits the activity of protein kinase B (PKB or AKT) and S6 Kinase (S6K), which act downstream of phosphoinosotide-3 kinase (PI3K). Activation of these kinases is a frequent event in human tumors, promoting cell growth, survival, and resistance to chemotherapy and radiotherapy. Inactivation of the pathway through inhibition of AKT is expected to induce apoptosis (programmed cell death) in tumor cells. AKT inhibitors may also sensitize tumor cells to a wide range of chemotherapy.","Tyrosine-protein kinase BTK","Therapeutic strategy associated"]
[737,"DB05205","investigational","small molecule","CX157",{"$nulls":3},"CX157,3-fluoro-7-(2,2,2,-trifluoroethoxy)phenoxathiin-10,10-dioxide, is a reversible, selective inhibitor of MAO-A designed to have improved oral bioavailability and reduced clearance compared to previous MAO-A inhibitors of this class.",null,null,"Anxiety Disorders I,\r\nDepression I",null,"This drug increases the levels of three vital neurotransmitters that affect mood and anxiety: serotonin, norepinephrine and dopamine.","Amine oxidase [flavin-containing] A","Indication associated"]
[738,"DB05207","investigational","small molecule","SD118",{"$nulls":3},"SD118 was previously under investigation in Japan for a different indication and now, following re-profiling and evaluation in experimental animal models, has demonstrated its potential as a new oral therapy for neuropathic pain.",null,null,"Central Nervous System - Neuropathic pain",null,"Immune system modulator","Tumor necrosis factor; Interleukin-1 receptor type 1","Target associated"]
[739,"DB05212","investigational","small molecule","HE3286",null,"C21H30O3","[H][C@@]12CC[C@@](O)(C#C)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])[C@@H](O)C=C2C[C@@H](O)CC[C@]12C",null,"1001100-69-1","330.468","For the treatment of rheumatoid arthritis and type 2 diabetes.",null,"Potential mechanisms of action for HE3286 include regulation of NF-kB and increasing the production of regulatory T cells (Treg cells). NF-kB is a well-known transcription factor that controls the production of inflammatory cytokines such as TNF-a and interferon-g. Treg cells are referred to in the scientific literature as the peacekeepers of the body. Their role is to keep the immune system from attacking the body itself. Recent studies of Treg cells indicate that they may play a broader role than simply preventing autoimmune conditions. Manipulation of these cells may offer new treatments for conditions ranging from diabetes and organ rejection to cancer and infectious diseases. In type II diabetes, moderate inhibition of NF-kB improves glucose tolerance.","Nuclear factor NF-kappa-B p105 subunit; Nuclear factor NF-kappa-B p100 subunit","Therapeutic strategy associated"]
[740,"DB05218","investigational","biotech","PN0621",{"$nulls":3},"PN0621 is an anti-TNF, domain antibody (dAb) based therapeutic. It targets tumour necrosis factor (TNF) to treat auto-immune inflammatory diseases such as rheumatoid arthritis. It is being developed by Peptech.",null,null,"Intended for the treatment of auto-immune diseases such as rheumatoid arthritis, psoriasis and Crohn's disease.","PN0621 is an anti-TNF, a name given to a class of drugs being developed for the treatment of auto-immune diseases such as rheumatoid arthritis, psoriasis and Crohn's disease.","Auto-immune diseases are indicated where an individual's immune system mistakenly attacks the body's own tissues. PN0621 works by blocking the action of TNF (tumour necrosis factor) which is involved in this attack.","Tumor necrosis factor","Target associated"]
[741,"DB05219","approved; investigational","small molecule","Crisaborole","Crisaborole","C14H10BNO3","OB1OCC2=C1C=CC(OC1=CC=C(C=C1)C#N)=C2","Crisaborole is a novel oxaborole approved by FDA on December 14, 2016 as Eucrisa, a topical treatment of for mild to moderate atopic dermatitis. \r\nThis non-steroidal agent is efficacious in improving disease severity, reducing the risk of infection and reducing the signs and symptoms in patients 2 years old and older. It reduces the local inflammation in the skin and prevents further exacerbation of the disease with a good safety profile. Its structure contains a boron atom, which facilitates skin penetration and binding to the bimetal center of the phosphodiesterase 4 enzyme. It is currently under development as topical treatment of psoriasis.","906673-24-3","251.05","Intended for the topical treatment of mild to moderate atopic dermatitis in patients 2 years of age and older.","Crisaborole has broad-spectrum anti-inflammatory activity by mainly targeting phosphodiesterase 4 (PDE4) enzyme that is a key regulator of inflammatory cytokine production. As this enzyme is expressed in keratinocytes and immune cells, crisaborole mediates an anti-inflammatory effect on almost all inflammatory cells. Topical application of this drug is useful as it potentiates the localization of this drug in the skin and this anti-inflammatory activity is in the low micromolar range.","Inhibition of PDE4 by crisaborole leads to elevated levels of cyclic adenosine monophosphate (cAMP). Increased intracellular levels of cAMP inhibit the NF-kB pathway and suppress the release of pro-inflammatory mediators such as TNF-alfa and various interleukins that play a causative role in psoriasis and atopic dermatitis. Suppression of downstream effects in different cell types may explain the therapeutic role of crisaborole in immune-mediated skin diseases.","cAMP-specific 3',5'-cyclic phosphodiesterase 4A inhibitor; cAMP-specific 3',5'-cyclic phosphodiesterase 4B inhibitor; cAMP-specific 3',5'-cyclic phosphodiesterase 4C inhibitor; cAMP-specific 3',5'-cyclic phosphodiesterase 4D inhibitor","Therapeutic strategy associated"]
[742,"DB05222","investigational","biotech","KB001",{"$nulls":3},"KB001 is a Humaneered&trade; PEGylated monoclonal antibody fragment for the treatment of life-threatening Pseudomonas aeruginosa infections, a common problem of cystic fibrosis and mechanically ventilated patients.",null,null,"For the treatment of infections caused by multi-drug resistant <em>Pseudomonas aeruginosa</em>.","KaloBios is developing KB001, a PEGylated engineered human Fab' fragment for the prevention and treatment of <em>Pseudomonas aeruginosa</em> infections. The Fab' fragment is specific for the PcrV antigen, an essential component of the Type III secretion system, a key virulence factor with multiple roles in both infection and pathogenesis. KB001 shows potent activity in mouse models of pulmonary infection, reducing mortality and leading to effective clearance of bacteria from infected lungs. This molecule therefore represents an attractive candidate for clinical evaluation in the prevention or treatment of <em>Pseudomonas</em> infection in Cystic Fibrosis, pneumonia, and other indications.","KB001 targets and neutralizes the PcrV protein of the Type III secretion system of the Pseudomonas bacterium, which directly inhibits its toxic effects. This mechanism of action is different from that of other antibiotics and represents a new approach in the treatment of bacterial infections.","PcrV","Therapeutic strategy associated"]
[743,"DB05223","investigational","small molecule","Pracinostat",null,"C20H30N4O2","CCCCC1=NC2=C(C=CC(\\C=C\\C(=O)NO)=C2)N1CCN(CC)CC","Pracinostat is a novel HDAC inhibitor with improved in vivo properties compared to other HDAC inhibitors currently in clinical trials, allowing oral dosing. Data demonstrate that Pracinostat is a potent and effective anti-tumor drug with potential as an oral therapy for a variety of human hematological and solid tumors.","929016-96-6","358.486","For the treatment of various forms of cancer.","SB939 is a novel compound with superior pharmaceutical, metabolic and pharmacokinetic properties. SB939 has demonstrated excellent in vivo anti-tumour activity in various animal models with dose proportional pharmacodynamic effects. The pharmacokinetics and pharmacodynamic attributes of SB939 explain and differentiate it as the best in class HDAC inhibitor.\r","Inhibition of HDAC activity allows for the accumulation of acetyl groups on the histone lysine residues resulting in an open chromatin structure and transcriptional activation. In vitro, SB939 causes the accumulation of acetylated histones and induces cell cycle arrest and/or apoptosis of some transformed cells. The mechanism of the antineoplastic effect of SB939 has not been fully characterized.","Histone deacetylase 1; Histone deacetylase 2; Histone deacetylase 3; Histone deacetylase 6","Therapeutic strategy associated"]
[744,"DB05224","investigational","small molecule","REP8839",{"$nulls":3},"REP8839 is a novel methionyl-tRNA synthetase (MetS) inhibitor being developed by Replidyne (GlaxoSmithKline licensed REP8839 to Replidyne in June of 2003).",null,null,"For the treatment of bacterial infections caused by susceptible microorganisms (<i>Staphylococcus aureus</i>, including methicillin-resistant <i>S. aureus</i> (MRSA), and <i>Streptococcus pyogenes</i>).","REP8839 is a novel methionyl-tRNA synthetase (MetS) inhibitor with potent antibacterial activity against clinical isolates of Staphylococcus aureus, Streptococcus pyogenes, and other clinically important gram-positive bacteria but little activity against gram-negative bacteria.","REP8839 exerts its antibacterial activity through specific inhibition of MetS, a novel target.","Methionine--tRNA ligase","Indication associated"]
[745,"DB05227","investigational","small molecule","APD791",{"$nulls":3},"APD791 is an oral anti-thrombotic drug candidate being evaluated in a Phase 1 clinical trial by Arena. APD791 is intended to lower the risk of arterial thrombosis by reducing the amplification of platelet aggregation, arterial constriction and intimal hyperplasia mediated by serotonin.",null,null,"For the treatment and prophylaxis of arterial thrombosis.","APD791 is intended to lower the risk of arterial thrombosis by reducing the amplification of platelet aggregation, arterial constriction and intimal hyperplasia mediated by serotonin. Preclinical testing suggests that APD791 could have a unique risk-benefit profile because its anti-thrombotic activity may be less likely to cause the increased bleeding seen with anti-thrombotic agents that are members of other classes of drugs.","APD791 targets the 5-HT2A serotonin receptor, blocking the signal of serotonin, which facilitates thrombosis.","5-hydroxytryptamine receptor 2A","Therapeutic strategy associated"]
[746,"DB05229","investigational","small molecule","Beraprost","Beraprost","C24H30O5","[H][C@]12C[C@@H](O)[C@H](\\C=C\\[C@@H](O)C(C)CC#CC)[C@@]1([H])C1=C(O2)C(CCCC(O)=O)=CC=C1","Beraprost is a synthetic analogue of prostacyclin, under clinical trials for the treatment of pulmonary hypertension. It is also being studied for use in avoiding reperfusion injury.","88430-50-6","398.499","For the treatment of pulmonary hypertension.","Beraprost is a stable, orally active prostacyclin analogue with vasodilatory, antiplatelet and cytoprotective effects. Beraprost is generally well tolerated and appears to be an effective agent in the treatment of patients with Buerger's disease and arteriosclerosis obliterans. Comparative data from a large randomised trial indicated that the drug appears as effective as ticlopidine in patients with these conditions. In patients with intermittent claudication, significant benefits of beraprost compared with placebo were reported in a randomised clinical trial; however, the use of beraprost in these patients is not supported by recent preliminary unpublished data from a large, phase III, placebo-controlled study. Limited data suggest some efficacy with long-term beraprost treatment of patients with PAH, where options are few and where oral administration of the drug could be a considerable advantage over intravenous prostacyclin (PGI2) therapy.","Beraprost acts by binding to prostacyclin membrane receptors ultimately inhibiting the release of Ca<sup>2+</sup> from intracellular storage sites. This reduction in the influx of Ca<sup>2+</sup> has been postulated to cause relaxation of the smooth muscle cells and vasodilation.","Prostacyclin receptor","Indication associated"]
[747,"DB05230","investigational","small molecule","AC3056",{"$nulls":3},"AC3056 is a non-peptide antioxidant that acts as an inhibitor of vascular cell adhesion molecule expression originally developed by Aventis Pharmaceuticals. It as since been acquired by Amylin Pharmaceuticals and has completed phase I trials.",null,null,"For the treatment of atherosclerosis and other conditions related to the obstruction of blood vessels.","Oral administration of AC3056 results in dose-dependent antioxidant activity and was well tolerated. In 2002, positive results were reported from a phase I trial. In the double-blind, placebo-controlled, crossover trial, 14 healthy subjects received an oral formulation of AC3056 in a dose-escalating manner. Results demonstrated dose-dependent increases in blood levels of AC3056, as well as dose-dependent increases in serum antioxidant activity. The drug was well tolerated with no safety concerns.",null,null,"Indication associated"]
[748,"DB05234","investigational","small molecule","LGD2941",null,"C17H16F6N2O2","C[C@@H]1CC[C@H]([C@@H](O)C(F)(F)F)N1C1=CC2=C(NC(=O)C=C2C(F)(F)F)C=C1","LGD2941 is a non-steroidal, selective androgen receptor modulator (SARM) developed jointly by Ligand and TAP.",null,"394.3116","For the treatment and prevention of osteoporosis.","LGD2941 is a non-steroidal, selective androgen receptor modulator (SARM). SARMs are a novel class of non-steroidal, orally active molecules that selectively modulate the activity of the androgen receptor (AR) in different tissues, providing a wide range of opportunities for the treatment of many diseases and disorders with large patient populations in both men and women. Tissue-selective AR agonists or antagonists may provide utility in male hormone therapy and the treatment of patients with male hypogonadism, female and male osteoporosis, male and female sexual dysfunction, frailty, prostate cancer, hirsutism, acne, androgenetic alopecia and other diseases.","LGD2941 selectively modulates the activity of the androgen receptor (AR) in different tissues.","Androgen receptor","Indication associated"]
[749,"DB05235","investigational","small molecule","NRP409",{"$nulls":3},"NRP409 is a triiodothyronine (T3) hormone, being investigated by New River Pharmaceuticals as a treatment for patients with primary hypothyroidism.",null,null,"For use in treatment of hypothyroidism.","The company is hoping that NRP409 will mark a significant improvement in thyroid HRT by reducing the variability of the more active hormone's availability, while reducing the safety risk associated with other T3 based therapies.","NRP409 is presumed to work like the endogenous thyroid hormone thyroxine (T<sub>4</sub>, a tetra-iodinated tyrosine derivative). In the liver and kidney, T<sub>4</sub> is converted to T<sub>3</sub>, the active metabolite. In order to increase solubility, the thyroid hormones attach to thyroid hormone binding proteins, thyroxin-binding globulin, and thyroxin-binding prealbumin (transthyretin). Transport and binding to thyroid hormone receptors in the cytoplasm and nucleus then takes place. Thus by acting as a replacement for natural thyroxine, symptoms of thyroxine deficiency are relieved.","Ketimine reductase mu-crystallin; Thyroid hormone receptor alpha","Indication associated"]
[750,"DB05236","investigational","biotech","ReN001",{"$nulls":3},"ReN001 is a clonal human neural stem cell line developed for clinical use in the treatment of stable disability after stroke. ReN001 a strong candidate for one of the first cell-based IND applications to be submitted to the Food and Drug Administration in the United States for consideration for the treatment of stroke in humans.",null,null,"For the treatment of stroke.","ReN001 is a clonal human neural stem cell line which has been conditionally immortalized using the fusion transgene c-mycERTAM to allow controlled expansion when cultured in the presence of 4-hydroxytamoxifen. The cell line has been banked and fully characterized to assure there is genetic stability and no phenotypic drift with extended passages. In vivo studies determined the ability of the cell line to survive after implantation into damaged brain and its efficacy in the reduction of chronic behavioural dysfunction after implantation into a rodent model of stroke damage. A further study was conducted in this model and a dose-dependent effect was observed on behavioural recovery. No safety or toxicology issues were identified in in vivo studies with this cell line.",null,null,"Indication associated"]
[751,"DB05241","investigational","small molecule","XL765",{"$nulls":3},"XL765 is an orally available small molecule that has been shown in preclinical studies to selectively inhibit the activity of phosphoinositide-3 kinase (PI3K) and mammalian target of rapamycin (mTOR). It is being developed by Exelixis, Inc.",null,null,"For the treatment of various forms of cancer.","XL765 is an orally available small molecule that has been shown in preclinical studies to selectively inhibit the activity of phosphoinositide-3 kinase (PI3K) and mammalian target of rapamycin (mTOR). Activation of PI3K is a frequent event in human tumors, promoting tumor cell growth, survival, and resistance to chemotherapy and radiotherapy. mTOR is also frequently activated in human tumors and plays a central role in tumor cell growth. mTOR can be activated via upregulation of PI3K, or via PI3K-independent mechanisms. Inactivation of PI3K has been shown to inhibit growth and induce apoptosis (programmed cell death) in tumor cells, whereas inactivation of mTOR has been shown to inhibit the growth of tumor cells. In preclinical studies, XL765 slowed tumor growth or caused tumor shrinkage in multiple preclinical cancer models, including breast, lung, ovarian, and prostate cancers, and gliomas. XL765 has also been shown to enhance the anti-tumor effects of several chemotherapeutic agents in preclinical cancer models. XL765 has at least a 24-hour duration of action against both PI3K and mTOR readouts in tumors in vivo following a single oral (PO) dose of 30-100 mg/kg.\r\n\r","XL765 inhibits the activity of phosphoinositide-3 kinase (PI3K), which is frequently activated in tumors and promotes cell growth, survival and resistance to chemotherapy and radiotherapy. XL765 also inhibits mammalian target of rapamycin (mTOR), which also is activated frequently in human tumors and plays a central role in tumor cell growth. XL765 potently inhibits Class I PI3K isoforms and mTOR.\r","Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform; Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform; Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform; Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform; Serine/threonine-protein kinase mTOR","Therapeutic strategy associated"]
[752,"DB05244","investigational","small molecule","G4544",{"$nulls":3},"G4544 is an oral gallium compound that enables oral absorption of the active ingredient contained in Ganite&trade; (gallium nitrate injection). It targets bone tissue and is actively incorporated into bone mineral at sites where bone is metabolically active.",null,null,"For treatment of non-Hodgkin's lymphoma, bone metastases, Paget's disease, and osteoporosis","G4544 is one of a class of gallium containing compounds that were originally developed by the U.S. National Cancer Institute. In investigational studies, high doses of gallium nitrate demonstrated consistent antitumor activity in patients with non Hodgkin's lymphoma. However, experimental work by Genta personnel and others established that lower doses of gallium directly inhibited calcium release from bone, principally by decreasing bone resorption and possibly by also stimulating bone formation.","G4544 reduces bone loss by inhibiting calcium resorption from bone.  Preclinical evidence suggests that the mechanism of G4544 action is multifactorial and different from other current therapies used to treat bone loss, such as estrogen or selective estrogen receptor modulators (SERMs), calcitonin, or bisphosphonates (e.g., Zometa or Fosamax).  G4544 preferentially accumulates in metabolically active regions of bone, inhibits osteoclast-mediated bone resorption, and favorably alters bone mineral composition and properties.",null,"Indication associated"]
[753,"DB05255","investigational","small molecule","Ronacaleret","Ronacaleret","C25H31F2NO4","CC(C)(CC1CC2=C(C1)C=CC=C2)NC[C@@H](O)COC1=CC(CCC(O)=O)=CC(F)=C1F","Ronacaleret is a calcium-sensing receptor antagonist.","753449-67-1","447.523","Post-menopausal women with osteoporosis",null,"751689 is novel small molecules that work by antagonizing calcium-sensing receptors on the surface of the parathyroid gland, thereby triggering a transient release of the body's own stores of parathyroid hormone (PTH). This release of PTH may have the potential to rebuild the bone mass lost as a result of osteoporosis and improve overall bone microarchitecture in these patients.","Extracellular calcium-sensing receptor antagonist","Indication associated"]
[754,"DB05259","approved; investigational","biotech","Glatiramer","(T,G)-A-L; COP 1; COP-1; Copolymer I (synthetic peptide); Copolymer-1",null,null,"Glatiramer acetate consists of the acetate salts of synthetic polypeptides, containing four naturally occurring amino acids: L-glutamic acid, L-alanine, L-tyrosine, and L-lysine with an average molar fraction of 0.141, 0.427, 0.095, and 0.338, respectively. The average molecular weight of glatiramer acetate is 5,000-9,000 daltons.  It is an immunomodulator, licensed in much of the world for reduced frequency of relapses in relapsing-remitting multiple sclerosis.","28704-27-0",null,"For reduction of the frequency of relapses in patients with Relapsing-Remitting Multiple Sclerosis.","Glatiramer acetate was originally designed to mimic a protein in myelin, called myelin basic protein, with the intention of inducing EAE (an animal model of MS). Quite to the contrary, it was found to suppress the disease and as a result came to be trialed in human MS. There is some evidence that Glatiramer acetate converts the body's immune response from a Th1 type to a Th2 one, promotes suppressor T cells or acts as an altered peptide ligand. Studies in animals and in vitro systems suggest that upon its administration, glatiramer acetate-specific suppressor T-cells are induced and activated in the periphery. Some fraction of the injected material, either intact or partially hydrolyzed, is presumed to enter the lymphatic circulation, enabling it to reach regional lymph nodes, and some may enter the systemic circulation intact.","Glatiramer acetate (GA) exhibits strong and promiscuous binding to MHC molecules (HLA DRB1* variants) and consequent competition with various myelin antigens for their presentation to T cells. A further aspect of its action is potent induction of specific suppressor cells of the T helper 2 (Th2) type that migrate to the brain and lead to in situ bystander suppression. Furthermore, the GA-specific cells in the brain express the anti-inflammatory cytokines IL-10 and transforming growth factor beta, in addition to brain-derived neurotrophic factor, whereas they do not express the inflammatory cytokine IFN-gamma. Recent evidence also suggests that Glatiramer acetate directly inhibits dendritic cells and monocytes - both of which are circulating antigen presenting cells.","HLA class II histocompatibility antigen, DRB1-1 beta chain binder","Therapeutic strategy associated"]
[755,"DB05260","approved; investigational","small molecule","Gallium nitrate","Gallium nitrate (anhydrous); Nitric acid, gallium salt, anhydrate","GaN3O9","[Ga+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O","Gallium nitrate is a drug that is used to treat hyper-calcemia, or too much calcium in the blood. This condition may occur when individuals develop various types of cancer. Gallium nitrate is also known by the common brand name Ganite.","13494-90-1","255.738","For the treatment of hypercalcemia. Also intended for the treatment of non-hodgkin's lymphoma.","Gallium nitrate exerts hypocalcemic effect by inhibiting calcium resorption from bone, possibly by stabilizing bone matrix, thereby reducing increased bone turnover. Gallium nitrate inhibits the growth of various lymphoma cell lines in vitro and exhibits antitumor activity in patients with lymphoma. The mechanism(s) of cytotoxicity is (are) only partly understood but appears to involve a two-step process: (1) targeting of gallium to cells, and (2) acting on multiple, specific intracellular processes. Gallium shares certain chemical properties with iron; therefore, it binds avidly to the iron transport protein transferrin. Transferrin-gallium complexes preferentially target cells that express transferrin receptors on their surface. Expression of transferrin receptors is particularly high on lymphoma cells. Cellular uptake of the gallium-transferrin complex leads to inhibition of cellular proliferation primarily via disruption of iron transport and homeostasis and blockade of ribonucleotide reductase. Recent studies have shown that cellular uptake of gallium leads to activation of caspases and induction of apoptosis. In phase II trials in patients with relapsed or refractory lymphoma, the antitumor activity of gallium nitrate is similar to, or better than, that of other commonly used chemotherapeutic agents.","Gallium nitrate is believed to exert a hypocalcemic effect by inhibiting calcium resorption from bone. Gallium nitrate localizes preferentially where bone resorption and remodeling is occurring, and inhibits osteoclast activity. Inhibition of resorption may occur via a reduction in increased bone turnover. It seems to enhance hydroxyapatite function, inhibit osteocalcin, and inhibit the vacuolar ATPase on the osteoclast ruffled membrane. All these aid in the reduction of bone resorption.","Ribonucleoside-diphosphate reductase subunit M2 inhibitor; V-type proton ATPase subunit B, brain isoform inhibitor; Osteocalcin antagonist; Hydroxylapatite modulator; Protein-tyrosine-phosphatase inhibitor; Interleukin-1 beta antagonist","Therapeutic strategy associated"]
[756,"DB05262","investigational","small molecule","Oxypurinol","1H-Pyrazolo[3,4-d]pyrimidine-4,6(5H,7H)-dione; Alloxanthine; DHPP; Oxipurinol; Oxoallopurinol; Oxypurinol","C5H4N4O2","O=C1NC2=C(C=NN2)C(=O)N1","Oxypurinol, an inhibitor of xanthine oxidase, is a metabolite of allopurinol.","2465-59-0","152.1109","Intended for the treatment of congestive heart failure and hyperuricemia.",null,"Oxypurinol inhibits the enzyme xanthine oxidase, blocking the conversion of the oxypurines hypoxanthine and xanthine to uric acid. Elevated concentrations of oxypurine and oxypurine inhibition of xanthine oxidase through negative feedback results in a decrease in the concentrations of uric acid in the blood and urine. Oxypurinol also facilitates the incorporation of hypoxanthine and xanthine into DNA and RNA, resulting in further reductions of serum uric acid concentrations.","Xanthine dehydrogenase/oxidase","Indication associated"]
[757,"DB05266","investigational","small molecule","Ibudilast","Ibudilast","C14H18N2O","CC(C)C(=O)C1=C2C=CC=CN2N=C1C(C)C","Ibudilast is an anti-inflammatory and neuroprotective oral agent which shows an excellent safety profile at 60 mg/day and provides significantly prolonged time-to-first relapse and attenuated brain volume shrinkage in patients with relapsing-remitting (RR) and/or secondary progressive (SP) multiple sclerosis (MS). Ibudilast is currently in development in the U.S. (codes: AV-411 or MN-166), but is approved for use as an antiinflammatory in Japan.","50847-11-5","230.3055","For the treatment of multiple sclerosis, asthma, and cerebrovascular disease.",null,"Ibudilast has mechanisms that include anti-inflammatory effects, such as phosphodiesterase inhibition, and neuroprotective effects, such as inhibition of  synthesis and reduction in reactive oxygen species.","cAMP-specific 3',5'-cyclic phosphodiesterase 4A inhibitor; cAMP-specific 3',5'-cyclic phosphodiesterase 4B inhibitor; cAMP-specific 3',5'-cyclic phosphodiesterase 4C inhibitor; cAMP-specific 3',5'-cyclic phosphodiesterase 4D inhibitor; cGMP-inhibited 3',5'-cyclic phosphodiesterase A inhibitor","Therapeutic strategy associated"]
[758,"DB05273","approved; investigational","small molecule","Samarium (153Sm) lexidronam","153SM-EDTMP; Samarium (153 Sm) lexidronam; Samarium (153Sm) lexidronam; Samarium Sm-153 lexidronam; Samarium-153 lexidronam; Samarium-153-EDTMP","C6H17N2O12P4Sm","[153Sm+3].OP(O)(=O)CN(CCN(CP(O)([O-])=O)CP(O)([O-])=O)CP(O)([O-])=O","Samarium Sm 153 lexidronam is a radioactive medication used to treat pain caused by cancer that has spread to the bone. It is a radiopharmaceutical. Radiopharmaceuticals are radioactive agents that may be used to diagnose some diseases by studying the function of the body's organs or to treat certain diseases.Samarium Sm 153 lexidronam is used to help relieve the bone pain that may occur with certain kinds of cancer. The radioactive samarium is taken up in the bone cancer area and gives off radiation that helps provide relief of pain.","122575-21-7","586.021","Investigated for use/treatment in bone metastases, multiple myeloma, prostate cancer, and rheumatoid arthritis.",null,"Samarium Sm 153 lexidronam targets the sites of new bone formation, concentrating in regions of the bone that have been invaded with metastatic tumor. The drug goes to the source of cancer bone pain and irradiates the osteoblastic tumor sites resulting in relief of pain. The onset of pain relief was experienced as early as one week in the majority of patients.",null,"Indication associated"]
[759,"DB05282","investigational","small molecule","MCC",{"$nulls":3},"Mycobacterial Cell Wall-DNA Complex (MCC) is formulated from Mycobacterium phlei, a non-pathogenic strain of mycobacteria. MCC has been shown to have immune stimulatory and apoptosis (programmed cell death) activity against cancer cells. The product is a sterile biological composition in a sub-micron suspension. It is produced at the Bioniche manufacturing facility in Pointe-Claire, Quebec.",null,null,"Bladder cancer",null,"MCC has a therapeutic potential in high grade transitional cell carcinomas of the bladder, including refractory CIS. The combination of MCC with hyaluronic acid (HA) enhances both the apoptosis-inducing activity of MCC against prostate cancer cell lines, and the immune stimulatory activity of MCC (stimulation of anticancer cytokine synthesis by human immune effector cells). \r\n\r","Apoptosis-inducing factor 1, mitochondrial","Therapeutic strategy associated"]
[760,"DB05295","investigational","small molecule","Eldecalcitol","1α,25-dihydroxy-2β-(3-hydroxypropoxy)cholecalciferol; Eldecalcitol","C30H50O5","[H][C@@]1(CC[C@@]2([H])\\C(CCC[C@]12C)=C\\C=C1\\C[C@@H](O)[C@@H](OCCCO)[C@H](O)C1=C)[C@H](C)CCCC(C)(C)O","Eldecalcitol  (ED-71), a vitamin D analog, is a more potent inhibitor of bone resorption than alfacalcidol in an estrogen-deficient rat model of osteoporosis. Eldecalcitol, effectively and safely increased lumbar and hip bone mineral density (BMD) in osteoporotic patients who also received vitamin D3 supplementation.","104121-92-8","490.725","Investigated for use/treatment in osteoporosis.",null,"Eldecalcitol  is an analog of 1a,25-dihydroxyvitamin D3 , bearing a hydroxypropoxy residue at the 2b position. Eldecalcitol is also effective in increasing bone mass and was able to enhance bone strength in rodents. It binds to the vitamin D receptor (VDR) with less affinity but binds to vitamin D-binding protein with higher affinity than 1,25(OH)2D, showing a long half-life in plasma.","Vitamin D3 receptor","Indication associated"]
[761,"DB05297","investigational","small molecule","Paclitaxel docosahexaenoic acid","DHA Paclitaxel; DHA-paclitaxel; Paclitaxel 2'-(all-cis-4,7,10,13,16,19-docosahexaenoate); Paclitaxel docosahexaenoic acid ester","C69H81NO15","CC\\C=C/C\\C=C/C\\C=C/C\\C=C/C\\C=C/C\\C=C/CCC(=O)O[C@@H](C(=O)O[C@H]1C[C@@]2(O)[C@@H](OC(=O)C3=CC=CC=C3)[C@@]3([H])[C@@](C)([C@@H](O)C[C@@]4([H])OC[C@@]34OC(=O)C)C(=O)[C@H](OC(=O)C)C(=C1C)C2(C)C)[C@@H](NC(=O)C1=CC=CC=C1)C1=CC=CC=C1","A combination of DHA (a natural fatty acid) and paclitaxel (an anticancer drug) being studied in the treatment of cancer. It is a type of mitotic inhibitor.","199796-52-6","1164.3791","Investigated for use/treatment in breast cancer, colorectal cancer, gastric cancer, kidney cancer, lung cancer, pancreatic cancer, prostate cancer, and skin cancer.",null,"A prodrug comprised of the naturally occurring omega-3 fatty acid docosahexaenoic acid (DHA) covalently conjugated to the anti-microtubule agent paclitaxel. Because tumor cells take up DHA, DHA-paclitaxel is delivered directly to tumor tissue, where the paclitaxel moiety binds to tubulin and inhibits the disassembly of microtubules, thereby resulting in the inhibition of cell division. Paclitaxel also induces apoptosis by binding to and blocking the function of the apoptosis inhibitor protein Bcl-2 (B-cell Leukemia 2). DHA-paclitaxel exhibits improved pharmacokinetic and toxicity profiles when compared to conventional paclitaxel and has demonstrated antineoplastic activity in animal models of cancer.","Apoptosis regulator Bcl-2","Therapeutic strategy associated"]
[762,"DB05300","investigational","small molecule","PTI-801",{"$nulls":3},"PTI-801 represents a new class of drugs to treat pain. PTI-801 can minimize the opioid tolerance, dependence or addiction that is often associated with repeat use of oxycodone. It is a combination of oxycodone with ultralow-dose naltrexone, an opioid antagonist.","615580-67-1",null,"Investigated for use/treatment in addictions, osteoarthritis, and pain (acute or chronic).",null,"PTI-801 is a novel form of oxycodone that minimizes the abuse and drug dependence that is often associated with oxycodone and other narcotic painkillers. The goal of developing PTI-801 is to ensure the safety of patients who have a legitimate medical need to treat severe chronic pain with a narcotic painkiller, and to protect the public from the consequences of abuse.",null,"Indication associated"]
[763,"DB05301","investigational","small molecule","LAX-101",{"$nulls":3},"LAX-101 treats hungtington’s disease, not just the symptoms but the disease itself. The active molecule in LAX-101 is Eicosapentaenoic Acid (EPA). All molecules of EPA are identical. The molecules of EPA found in LAX-101 are identical to the molecules of EPA found in fish oil food supplements.","909712-41-0",null,"Investigated for use/treatment in depression and huntington's disease.","LAX-101, a novel and proprietary compound that inhibits certain harmful enzymes including phospholipases and caspases, represents a new class of drugs sometimes referred to as NPLs. This class may function as \"neuroprotectants\" and appears to inhibit degradation of brain tissue by a variety of proposed mechanisms, including stabilization of the phospholipid components of cell membranes and mitochondria, cell structures that are important in cell regulation and brain function.",null,"Phospholipase D1; Caspase-1","Target associated"]
[764,"DB05303","investigational","small molecule","OMS-103HP",{"$nulls":3},"OMS103HP is the first drug being developed to improve joint function following arthroscopic surgery, one of the most common procedures performed today by orthopedic surgeons.",null,null,"Investigated for use/treatment in inflammatory disorders (unspecified), knee replacement, orthopedic surgery, and pain (acute or chronic).",null,"OMS-103HP is used to inhibit inflammation and pain associated with arthroscopy, provided statistically significant improvement in postoperative pain reduction, joint motion and recovery of function. It is a unique product that is added to standard irrigation solutions and perfused through the joint during arthroscopic surgery.","Tumor necrosis factor; Interleukin-1 receptor type 1","Target associated"]
[765,"DB05305","investigational","biotech","Cintredekin besudotox","Cintredekin besudotox",null,null,"Cintredekin besudotox has been developed as a specific tumor-targeting agent, which is administered by positive-pressure convection-enhanced delivery (CED) directly to brain tissue at risk for residual infiltrating glioblastoma multiforme (GBM) after tumor resection. Cintredekin besudotox is made from a human protein, Interleukin 13 (IL13), linked to a bacterial toxin, _Pseudomonas exotoxin_ (PE). The IL13 portion binds to receptors on the tumor.","372075-36-0",null,"Investigated for use/treatment in brain cancer.",null,"A recombinant chimeric protein with potent antitumor activity. Cintredekin besudotox is composed of interleukin-13 (IL13), a pleiotropic immunoregulatory cytokine, linked to a mutated form of pseudomonas exotoxin A; this agent targets and kills tumor cells that express the IL13 receptor (IL13R). The IL13 moiety attaches to the IL13R on the tumor cell membrane, facilitating the entry of the exotoxin. The exotoxin moiety induces caspase-mediated apoptosis of tumor cells via a mechanism involving mitochondrial damage; it also catalyzes the transfer of ADP ribose from nicotinamide adenine dinucleotide (NAD) to elongation factor-2 in eukaryotic cells, thereby inactivating elongation factor 2 and inhibiting protein synthesis.","Interleukin-13","Therapeutic strategy associated"]
[766,"DB05309","investigational","small molecule","TP-508",{"$nulls":3},"TP508 is a non-proteolytic synthetic peptide representing the portion of human thrombin originally identified as the fibroblast high-affinity receptor binding domain.",null,null,"Investigated for use/treatment in bone fractures, diabetic foot ulcers, and wounds.",null,"TP508 is a 23-amino-acid peptide representing the receptor-binding domain of thrombin, and is thought to work by mimicking the ability of thrombin to activate platelets and a cascade of growth factors and enzymes that initiate and regulate the healing process. Although not tested with allografts, TP508/Chrysalin has been shown to improve fracture healing in experimental models and its application is associated with upregulation of angiogenic genes.","Fibroblast growth factor 4","Indication associated"]
[767,"DB05311","approved; investigational","biotech","Ecallantide","Ecallantide",null,null,"Ecallantide is a potent and selective human plasma kallikrein inhibitor that is indicated for the symptomatic treatment of hereditary angioedema. Ecallantide is a recombinant 60-amino-acid protein produced in _Pichia pastoris_ yeast cells that contains three intramolecular disulfide bonds . It was discovered by phage display technology . It shares sequence similarities with the naturally occurring human protein tissue-factor pathway inhibitor (TFPI), which is also known lipoprotein-associated coagulation inhibitor (LACI) . The amino acid sequence of two compounds differ by seven amino acids . \r\n\r\nEcallantide works by blocking kallikrein to participate in the kallikrein-kinin system, which is a complex proteolytic cascade that initiates inflammatory and coagulation pathways . The protease plasma kallikerin facilitates the conversion of kininogen to bradykinin, which is a pro-inflammatory vasodilator that  increases vascular permeability and induces pain . Hereditary angioedema is a rare autosomal dominant disorder with mutations to C1-esterase-inhibitor (C1-INH) located on Chromosome 11q, resulting in substantially lower levels of C4 and C1-INH activity . The disorder is associated with recurrent attacks of severe swelling and is thought to be caused by unregulated activity of kallikrein and excessive bradykinin production . By reversibly binding to plasma kallikrein, ecallantide displays a rapid on-rate and a slow off-rate that results in high affinity inhibition in the picomolar range . Ecallantide is marketed by FDA and EMA under the trade name Kalbitor for subcutaneous injection. Apart from its FDA and EMA indication, ecallantide has been used off label in the management of nonhistaminergic angioedema, not due to HAE .","460738-38-9",null,"Indicated for the symptomatic treatment of acute attacks of hereditary angioedema (HAE) in patients 12 years of age and older .","Intravenous administration of ecallantide doses ≥20 mg/m^2 resulted in prolongation of activated partial thromboplastin time (aPTT) without an indication of bleeding. Ecallantide administration has been associated with instances of arrhythmia. In a clinical trial of patients experiencing acute attacks of hereditary angioedema (HAE), intravenous administration of ecallantide demonstrated a significant improvement in symptoms affecting the oropharynx, abdomen, gastrointestinal tract, and limbs within 4 hours post-administration compared to placebo . A substantial decrease in the severity and duration of attacks was also observed in patients with moderate-to-severe HAE attacks . In clinical trials, ecallantide had no significant effect on the QTc interval, heart rate, or any other components of the ECG .","The kallikrein-kinin system is a complex proteolytic cascade that promotes inflammatory and coagulation pathways. Human plasma kallikrein acts as a protease to mediate the conversion of High Molecular Weight (HMW) kininogen to bradykinin, which is a vasoactive mediator that increases vascular permeability and induces localized swelling, inflammation, and pain . The actions of kallikrein is regulated by the major endogenous inhibitor, C1-esterase-inhibitor (C1-INH). C1-INH also functions to regulate the activation of the complement and intrinsic coagulation (contact system pathway) , which also initiates the production of bradykinin. Upon audoactivation via exposure to negatively charged surfaces, factor XII promotes the generation of factor XIIa and kallikrein . C1-INH inhibits both factor XIIa and kallikrein . Kallikrein may in turn reciprocally activate more FXII . Hereditary angioedema is associated with a deficiency of the C1 inhibitor is caused by a mutation in the C1 INH gene . Resulting effect is excessive production of the vasodilator, bradykinin. The actions of bradykinin produce typical edematous signs and symptoms of hereditary angioedema by enhancing vascular and endothelial permeability, leading to increased outflow of plasma into the interstitium to produce local edema . \r\n\r\nEcallantide is a potent, specific and reversible plasma kallikrein inhibitor with an Inhibitory Constant (Ki) of 25 pM . Upon binding to kallikrein and blocking its active site, ecallantide prevents the conversion of HMW kininogen to bradykinin and attenuates the production of bradykinin . By blocking the actions of kallikrein, ecallantide also reduces further activation of fXIIa, halting the positive feedback mechanism leading to more kallikrein production .","Plasma kallikrein inhibitor","Therapeutic strategy associated"]
[768,"DB05312","investigational","small molecule","NVS antibody",{"$nulls":3},"This drug has been developed using Medarex's UltiMAb Human Antibody Development System to treat autoimmune diseases.",null,null,"Investigated for use/treatment in autoimmune diseases and rheumatoid arthritis.",{"$nulls":3},"Indication associated"]
[769,"DB05317","investigational","small molecule","TAK-475",{"$nulls":3},"TAK-475 is a \"squalene synthase inhibitor\", a type of cholesterol-lowering drug that has not yet been brought to market.",null,null,"Investigated for use/treatment in hyperlipidemia.",null,"Squalene synthase inhibitors are believed to have potential advantages over statins, which inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. HMG-CoA catalyzes the conversion of HMG-CoA to mevalonate and thus serves as the primary rate-limiting enzyme in the hepatic biosynthesis of cholesterol. Squalene synthase acts downstream of mevalonate, catalyzing the dimerization of farnesyl-pyrophosphate to squalene. This is the first step in the cholesterol biosynthetic pathway that is solely committed to the production of cholesterol, and researchers believe that blockade at this site may avoid the effects associated with decreased formation of isoprenolated intermediates and metabolites in the pathway beyond HMG-CoA reductase.","Squalene synthase; 3-hydroxy-3-methylglutaryl-coenzyme A reductase","Target associated"]
[770,"DB05319","investigational","biotech","Oportuzumab monatox","Oportuzumab monatox",null,null,"VB4-845 is studied in the treatment of certain types of head and neck cancer. VB4-845 is made by linking a monoclonal antibody fragment to a toxic protein that may kill cancer cells. VB4-845 is a fusion protein containing humanized scFv specific for the epithelial cell adhesion molecule, Ep-CAM, a tumor cell-associated target highly expressed on carcinoma cells of epithelial origin and a truncated portion of Pseudomonas exotoxin A.","945228-48-8",null,"Investigated for use/treatment in bladder cancer and head and neck cancer.",null,"VB4-845 binds to EpCAM (a protein on the surface of epithelial cells and some types of cancer cells). Also called anti-EpCAM-Pseudomonas-exotoxin fusion protein and Proxinium. It targets and kills Ep-CAM-positive tumors by apoptosis.","Epithelial cell adhesion molecule","Therapeutic strategy associated"]
[771,"DB05321","investigational","biotech","PEG-uricase",{"$nulls":3},"PEG-uricase, a polyethylene glycol (\"PEG\") conjugate of recombinant porcine uricase (urate oxidase), which breaks down the uric acid deposits is being studied in Phase III clinical trials for the treatment of severe, treatment-refractory gout in the United States in 2006.",null,null,"Investigated for use/treatment in hyperuricemia.",null,"PEG-uricase is a recombinant, PEGylated formulation of a modified porcine urate oxidase intended to dramatically lower the blood level of uric acid safely and continuously in patients who have not benefited from conventional therapeutic approaches. Urate oxidase is a hepatic enzyme present in almost all mammals – but not in humans – that lowers uric acid levels in the blood by converting uric acid into allantoin, a benign substance which is then easily excreted in the urine.\r\n\r","Uric acid degradation bifunctional protein","Indication associated"]
[772,"DB05326","investigational","small molecule","INKP-102",{"$nulls":3},"INKP-102 is the next generation sodium phosphate tablet designed to aid bowl preparation before colonoscopy.",null,null,"Investigated for use/treatment in gastrointestinal diseases and disorders (miscellaneous).",null,"INKP-102 tablets are smaller in size and easier to swallow than the Company's currently marketed sodium phosphate tablet product, Visicol. The new INKP-102 tablets contain no microcrystalline cellulose (MCC), an inert, but highly insoluble, tablet binder.",null,"Indication associated"]
[773,"DB05336","approved","biotech","Obiltoxaximab","Obiltoxaximab",null,null,"Obiltoxaximab, an affinity-enhanced monoclonal antibody (Mab), is used for prevention and treatment of infection and death caused by anthrax toxin. Obiltoxaximab is a chimeric IgG1 kappa monoclonal antibody (mAb) that binds the PA component of B. anthracis toxin. It has an approximate molecular weight of 148 kDa.","1351337-07-9",null,"Investigated for use/treatment in anthrax exposure, bacterial infection, crohn's disease, and graft versus host disease.",null,"ETI-204 is an affinity-enhanced, de-immunized antibody, which means that its ability to bind to its target pathogen has been strengthened and that elements that might cause an immune response have been removed. ETI-204 targets and binds to Protective Antigen, which prevents the anthrax toxins from binding to and entering the cells in the body, thereby preventing death.",null,"Indication associated"]
[774,"DB05339","investigational","small molecule","MN-305",null,"C19H22ClNO5","Cl.C(CNC[C@H]1COC2=CC=CC=C2O1)COC1=CC2=C(OCO2)C=C1","MN-305 is a novel, potent and highly selective serotonin 5-HT1A receptor agonist under development by MediciNova for the treatment of anxiety disorders beginning with Generalized Anxiety Disorder (GAD).",null,"379.835","Investigated for use/treatment in anxiety disorders, depression, insomnia, and neurologic disorders.",null,"MN-305 is a potent and highly-selective full agonist at the serotonin 5-HT1A receptor under development by MediciNova both for the treatment of insomnia, as well as for anxiety disorders such as Generalized Anxiety Disorder (GAD). MN-305 has been evaluated in an extensive preclinical toxicology program which showed no evidence of inducing genetic mutations, immune response or cancer. MN-305 has also proved to be consistently well-tolerated in clinical safety, efficacy and pharmacokinetic studies in over 1,200 subjects.","5-hydroxytryptamine receptor 1A","Indication associated"]
[775,"DB05340","investigational","small molecule","ATL-2502",null,"C28H31NaO9S","[Na+].CC12CC(O)C3C(CCC4=CC(=O)C=CC34C)C1CCC2(O)C(=O)COC(=O)C1=CC(=CC=C1)S([O-])(=O)=O","ATL-2502(Colal-Pred) is an old drug (prednisolone metasulphobenzoate, a steroid) with a new delivery system that releases the medication only in the colon. Releasing the drug directly into the colon reduces the potential for significant side effects often experienced with steroid drugs. Colal-Pred is being studied for use in ulcerative colitis.",null,"566.595","Investigated for use/treatment in inflammatory bowel disease and ulcerative colitis.",null,"ATL-2502 is the combination of Alizyme's proprietary colonic drug delivery system, colal, and prednisolone metasulfobenzoate sodium (\"PMSBS\"), an approved steroid in Europe. colal-PRED has a starch coating that is only broken down in the gut by bacteria occurring in the colon. This leads to topical delivery of PMSBS to the colon rather than systemic delivery with the objective of providing efficacy, but without the side effects of steroids; however, the efficacy and safety of colal-PRED must be shown in well-controlled, prospective clinical trials and approved by the FDA.",null,"Therapeutic strategy associated"]
[776,"DB05346","investigational","small molecule","WL-1002",{"$nulls":3},"WL-1002 is developed by Winston Laboratories which is a topical cream formulation of 075% zucapaicin (also known as civamide), for the treatment of pain due to osteoarthritis.",null,null,"Investigated for use/treatment in osteoarthritis and pain (acute or chronic).",null,"An active ingredients in WL-1002 is civamide which has anticeptic property.The antinociception of civamide is probably mediated two mechanisms: (i) an acute receptor occupancy dependent effect; and (ii) a persistent and receptor independent effect which is initiated by the acute exposure to the drug.",null,"Indication associated"]
[777,"DB05367","investigational","small molecule","Actelion-1",{"$nulls":3},"Actelion-1 is a tissue-targeting Endothelin Receptor Antagonist that has been discovered by Actelion Pharmaceuticals.",null,null,"Investigated for use/treatment in cardiovascular disorders, hypertension, and pulmonary hypertension.",null,"Through complete blockade of tissular endothelin, Actelion-1 is expected to protect tissue from the damaging effect of elevated endothelin, specifically in the cardiovascular system. In pre-clinical studies, Actelion-1 also exhibited effects suggesting that it maintains the integrity of the vascular wall and improves long-term outcome. Accordingly, Actelion-1 may provide therapeutic benefit in a wide range of cardiovascular indications.","Endothelin-1 receptor","Indication associated"]
[778,"DB05383","investigational","small molecule","Pimagedine","Aminate base; Aminoguanidine; Guanyl hydrazine; Hydrazinecarboximidamide; Monoaminoguanidine; Pimagedine","CH6N4","NNC(N)=N","Pimagedine has been developed by Synvista Therapeutics, Inc for the treatment of diabetic kidney disease. It is an advanced glycation end product inhibitor which manages diabetic nephropathy, either alone or in combination with other therapies. It is beneficial in treating patients with diabetic nephropathy.","79-17-4","74.0851","Investigated for use/treatment in diabetic kidney disease.",null,"Pimagedine reportedly inhibits the formation of glycosylated proteins (advanced glycosylation end-products) and has other actions including inhibition of aldose reductase.","Nitric oxide synthase, inducible inhibitor; Aldose reductase; Metalloproteinase inhibitor 3","Indication associated"]
[779,"DB05387","investigational","small molecule","AE-941",{"$nulls":3},"AE-941 is a naturally occurring anti-angiogenic compound, extracted from cartilage, with multiple anti-angiogenic mechanisms of action that provide broad therapeutic potential for a number of diseases. It is currently in international Phase III trials for renal cell carcinoma and non-small-cell lung cancer.",null,null,"Investigated for use/treatment in kidney cancer, lung cancer, macular degeneration, multiple myeloma, prostate cancer, and psoriasis and psoriatic disorders.",null,"AE-941(Neovastat) contains a component that specifically prevents the binding of VEGF (Vascular Endothelial Growth Factor) to its receptors. It inhibits gelatinolytic and elastinolytic activities for MMP-2, MMP-9, and MMP-12. The MMP's are often over expressed in tumors and play an important role in the degradation of the matrix that surrounds the cell (extracellular matrix), which allows tumor growth and invasion (metastasis). It also induces apoptosis (programmed cell death) which is an additional Anti angiogenic activity found in Neovastat.","72 kDa type IV collagenase; Matrix metalloproteinase-9; Macrophage metalloelastase","Therapeutic strategy associated"]
[780,"DB05389","approved; investigational","small molecule","Tetrachlorodecaoxide","TCDO; Tetrachlorodecaoxygen","Cl4H2O11","O.O=O.[O-][Cl]=O.[O-][Cl]=O.[O-][Cl]=O.[O-][Cl]=O","WF10 is a chlorite-based, immunomodulating drug is developed by Nuvo Research Inc. Certain preclinical evidence and clinical pilot data suggest that WF10 may be effective in treating certain cancers. The Corporation believes the research to-date demonstrates that WF10 acts on macrophages (a type of white blood cell) by modulating the balance between inflammation and phagocytosis, a state in which the body digests foreign, potentially harmful substances. The Corporation has commenced a Phase II clinical trial in an effort to demonstrate the efficacy of WF10 in combination with Xeloda (capecitabine) in the treatment of pancreatic cancer. The trial is being conducted in Germany at the University of Heidelberg and the National Centre for Tumor Diseases.","92047-76-2","319.821","Investigated for use/treatment in acquired immune deficiency syndrome (AIDS) and aids-related infections, cancer/tumors (unspecified), HIV infection, and inflammatory disorders (unspecified).",null,"WF 10 is a 1: 10 dilution of tetrachlorodecaoxide (TCDO) formulated for intravenous injection. It was developed by Oxo Chemie in Switzerland as an adjunctive therapy to combination antiretroviral and opportunistic infection prophylaxis regimens in AIDS patients. WF 10 specifically targets macrophages. WF10 potentially modulates disease-related up-regulation of immune responses both in vitro and in vivo. Thus immune response is influenced in a way that inappropriate inflammatory reactions are downregulated.","Macrophage erythroblast attacher; Scavenger receptor cysteine-rich type 1 protein M130","Therapeutic strategy associated"]
[781,"DB05391","investigational","small molecule","liposomal prostaglandin E1",{"$nulls":3},"Liposome-encapsulated form of prostaglandin E1 (Liprostin) is known to be a potent vasodilator and platelet inhibitor as well as an anti-inflammatory and anti-thrombotic agent. The liposomal formulation of PGE-1 changes the drug’s dynamics and improve its therapeutic index in ways that PGE-1 alone could not achieve.",null,null,"Investigated for use/treatment in neuropathy (diabetic) and peripheral vascular disease.",null,"The encapsulated formulation (Liprostin) has been shown to improve the therapeutic index of PGE-1, positively impacting many areas of treatment, such as heart attacks, occlusive disease, ischemic ulcers, critical limb salvage, claudicants, and arthritis.","Platelet glycoprotein Ib alpha chain","Target associated"]
[782,"DB05395","investigational","small molecule","Amibegron","Amibegron","C22H26ClNO4","[H][C@](O)(CN[C@@]1([H])CCC2=C(C1)C=C(OCC(=O)OCC)C=C2)C1=CC(Cl)=CC=C1","Amibegron is an agonist for atypical beta3-adrenoceptors which inhibits intestinal motility.","121524-08-1","403.9","Investigated for use/treatment in depression, irritable bowel syndrome (IBS), and obesity.",null,"SR 58611 has positive chronotropic effect which is mainly of peripheral origin and can be attributed to a baroreceptor-mediated reflex due to the beta3-adrenoceptor mediated vasodilation with an increase in sympathetic tone and a reduction in vagal tone to the heart.","Beta-3 adrenergic receptor","Indication associated"]
[783,"DB05399","investigational","small molecule","Succinobucol","Succinobucol","C35H52O5S2","CC(C)(C)C1=CC(SC(C)(C)SC2=CC(=C(OC(=O)CCC(O)=O)C(=C2)C(C)(C)C)C(C)(C)C)=CC(=C1O)C(C)(C)C","AGI-1067, is a novel small molecule with anti-oxidant and anti-inflammatory properties that was discovered by AtheroGenics and designed to treat atherosclerosis of the blood vessels of the heart, or coronary artery disease.","216167-82-7","616.914","Investigated for use/treatment in atherosclerosis, coronary artery disease, diabetes mellitus type 2, and in-stent restenosis.",null,"AGI-1067 works by inhibiting key oxidant signals within cells of blood vessel walls that generate inflammatory processes that are key to the pathogenesis of atherosclerosis. This includes inhibition of inflammatory cytokines, chemokines and vascular adhesion molecules that participate in the initiation, growth and eventual destabilization of the plaque. Its anti-oxidant properties also play a role in its ability to inhibit the formation of oxidized LDL, a critical component in the formation of atherosclerotic plaque.","Vascular cell adhesion protein 1","Therapeutic strategy associated"]
[784,"DB05407","investigational","small molecule","TBC-3711",null,"C20H21N3O5S2","CC(=O)C1=C(NC(=O)C2=C(C=CS2)S(=O)(=O)NC2=C(C)C(C)=NO2)C(C)=CC(C)=C1","TBC3711 is a next-generation endothelin antagonist that is being studied through oral and intravenous formulations by Encysive Pharmaceuticals.","349453-49-2","447.52","Investigated for use/treatment in congestive heart failure, hypertension, and pulmonary hypertension.",null,"TBC3711 is a small molecule that blocks the action of endothelin, a potent mediator of blood vessel constriction and growth of smooth muscle in vascular walls. It is a next-generation endothelin A antagonist which possesses high oral bioavailability and is more selective and potent than THELIN(tm) (sitaxsentan sodium) Encysive's oral treatment for pulmonary arterial hypertension. TBC3711 is greater than 100,000-fold selective in the targeting of the endothelin A receptor versus the endothelin B receptor.","Endothelin-1","Indication associated"]
[785,"DB05409","investigational","small molecule","NCX 701",null,"C12H14N2O6","CC(=O)NC1=CC=C(OC(=O)CCCO[N+]([O-])=O)C=C1","Nitroparacetamol (NCX-701) is a newly synthesized nitric oxide-releasing derivative of paracetamol.",null,"282.2494","Investigated for use/treatment in pain (acute or chronic).",null,"NCX-701 (nitroparacetamol) is a NO-releasing derivative of paracetamol (acetaminophen) that has shown potent antinociceptive and anti-inflammatory properties. NCX-701 induces a potent antinociceptive effect by a mechanism different from and complementary to that of paracetamol, and its action is mainly located within the spinal cord in monoarthritic animals.\r\n\r",null,"Therapeutic strategy associated"]
[786,"DB05410","investigational","small molecule","NCX 1022",null,"C29H35NO9","CC12CC(O)C3C(CCC4=CC(=O)CCC34C)C1CCC2(O)C(=O)COC(=O)C1=CC=CC(CON(=O)=O)=C1","NCX is an NO-releasing derivative of hydrocortisone.","571186-50-0","541.597","Investigated for use/treatment in atopic dermatitis.",null,"NCX 1022 is designed to have potent anti- inflammatory activity combined with a significantly improved safety and tolerability profile, in particular the absence of skin blanching after repeated use.It is better than hydrocortisone in terms of inhibiting benzalkonium chloride-induced leukocyte adhesion to the endothelium, without affecting the flux of rolling leukocytes or venule diameter.",null,"Therapeutic strategy associated"]
[787,"DB05412","investigational","small molecule","Talmapimod","Talmapimod","C27H30ClFN4O3","[H][C@]1(C)CN(C(=O)C2=C(Cl)C=C3N(C)C=C(C(=O)C(=O)N(C)C)C3=C2)[C@]([H])(C)CN1CC1=CC=C(F)C=C1","Talmapimod is the first-generation oral p38 MAP kinase inhibitor developed by Scios. It has shown to be effective to cure inflammatory diseases such as Rheumatoid Arthritis.","309913-83-5","513.004","Investigated for use/treatment in pain (acute or chronic) and rheumatoid arthritis.",null,"SCIO-469 inhibits p38 kinase, a stimulatory modulator of pro-inflammatory factors including tumor necrosis factor-alpha (TNFa), interleukin-1 (IL-1), and cyclooxygenase-2 (COX-2), all of which are known to contribute to both symptoms and disease progression in patients with Rheumatoid Arthritis (RA). Existing protein-based products that antagonize TNFa have been shown to markedly relieve the symptoms and retard the progression of RA. It also has the potential for additional benefits associated with its inhibition of IL-1 and COX-2.","Mitogen-activated protein kinase 14; Tumor necrosis factor; Interleukin-1 beta; Cytochrome c oxidase subunit 2","Therapeutic strategy associated"]
[788,"DB05415","investigational","small molecule","OSI-461",{"$nulls":3},"OSI-461 is a second-generation molecule belonging to a new class of drugs termed selective apoptotic anti-neoplastic drugs (SAANDs).",null,null,"Investigated for use/treatment in crohn's disease, inflammatory bowel disease, kidney cancer, leukemia (lymphoid), and prostate cancer.",null,"OSI-461 is cGMP phosphodiesterase (cGMP-PDEs) inhibitors which is designed to lead to sustained activation of the intracellular signaling protein, Protein Kinase G (PKG), and subsequent stimulation of apoptosis through the c-Jun kinase pathway. Broad spectrum inhibition of cGMP-PDEs have been shown to lead to elevation in cGMP levels and the sustained activation of PKG. This in turn directly phosphorylates MEKK1 leading to activation of the N-terminal c-Jun kinase (JNK-1) pathway, a known pro-apoptotic signaling pathway.","cGMP-specific 3',5'-cyclic phosphodiesterase","Therapeutic strategy associated"]
[789,"DB05416","investigational","small molecule","Cardarine",null,"C21H18F3NO3S2","CC1=C(CSC2=CC(C)=C(OCC(O)=O)C=C2)SC(=N1)C1=CC=C(C=C1)C(F)(F)F","Cardarine (GW-501516) is a peroxisome proliferator-activator receptor-delta agonist for the potential treatment of dyslipidemia. Cardarine has been investigated for the treatment of Obesity, Lipid Disorders, and Cardiovascular Disease.","317318-70-0","453.498","Investigated for use/treatment in hyperlipidemia.",null,"This drug regulates  fatty acid oxidation in several tissues, such as skeletal muscle and adipose tissue. Overexpression of PPARdelta using a transgenic murine model promotes an increase of muscle oxidative capability. It also plays a major role in the metabolic adaptations to western diet characterized by an excessive amount of saturated fat.","Peroxisome proliferator-activated receptor delta agonist; Peroxisome proliferator-activated receptor alpha agonist","Target associated"]
[790,"DB05418","investigational","small molecule","GW 597599",{"$nulls":3},"GW 597599, a neurokinin-1 (NK1) receptor antagonist is currently in phase II trials for chemotherapy-induced vomiting; functional dyspepsia; depression and anxiety.",null,null,"Investigated for use/treatment in adverse effects (chemotherapy), anxiety disorders, depression, and gastrointestinal diseases and disorders (miscellaneous).",null,null,"Neurokinin 1 receptor","Indication associated"]
[791,"DB05421","investigational","small molecule","CP-122721",null,"C20H23F3N2O2","COC1=CC=C(OC(F)(F)F)C=C1CN[C@H]1CCCN[C@H]1C1=CC=CC=C1","CP-122721, neurokinin 1 (NK1) antagonist is developed by Pfizer to treat depression, emesis, and inflammatory diseases including asthma and irritable bowel syndrome.","145742-28-5","380.404","Investigated for use/treatment in asthma, depression, and irritable bowel syndrome (IBS).",null,"CP-122721 interacts with high affinity at the human NK1 receptor expressed in IM-9 cells.","Neurokinin 1 receptor","Indication associated"]
[792,"DB05422","investigational","small molecule","OPC-14523",null,"C23H28ClN3O2","COC1=CC=CC2=C1CCC(=O)N2CCCN1CCN(CC1)C1=CC=CC(Cl)=C1","OPC-14523 is an antidepressant drug developed by Otsuka America Pharmaceutical.","145969-30-8","413.95","Investigated for use/treatment in bulimia, depression, and obsessive-compulsive disorders.",null,"OPC-14523 is a serotonin reuptake inhibitor. It treats depression, especially refractory depression, in a mammal, including a human, by administering to the mammal a sigma receptor ligand in combination with an antidepressant agent. It also relates to pharmaceutical compositions containing a pharmaceutically acceptable carrier, a sigma receptor ligand and a serotonin reuptake inhibitor.","Sodium-dependent serotonin transporter","Indication associated"]
[793,"DB05423","investigational","small molecule","ORG-34517",null,"C28H30O4","[H][C@@]12CC[C@@](O)(C#CC)[C@@]1(C)C[C@H](C1=CC=C3OCOC3=C1)C1=C3CCC(=O)C=C3CC[C@@]21[H]","ORG-34517 is currently under  investigation by Organon for the treatment of depression. It has potential to treat a number of diseases such as Cushing’s disease, hypertension, diabetes, glaucoma etc, in which the activity of metabolites corticosterone and cortisol is high.","189035-07-2","430.544","Investigated for use/treatment in depression.",null,"Org-34517 is a glucocorticoid antagonist which may have a potential in a number of diseases where there is excess corticosterone/cortisol activity. The drug acts by normalizing hyperactivity in the hypothalamus-pituitary-adrenal (HPA) axis.","Glucocorticoid receptor","Indication associated"]
[794,"DB05426","investigational","biotech","Talactoferrin alfa","Talactoferrin alfa; Talactoferrin alpha",null,null,"Talactoferrin alfa is a novel immunomodulatory 80 kD protein with demonstrated oral anti-tumor properties. Lactoferrin, a protein found in breast milk is developed by Agennix. It increases body’s immune power and also works as a natural antioxidant, helping to control cell and tissue damage caused by oxidation.","308240-58-6",null,"Investigated for use/treatment in adverse effects (chemotherapy), cancer/tumors (unspecified), diabetic foot ulcers, lung cancer, solid tumors, and ulcers.",null,"Oral talactoferrin stimulated the production of the immunostimulatory cytokine IL-18 in mice, increasing IL-18 levels both in the gut and in systemic circulation. Oral talactoferrin was also shown to stimulate the activity of NK cells and to increase the production and activity of key circulating immune cells.\r\n\r",null,"Therapeutic strategy associated"]
[795,"DB05428","investigational","small molecule","Motexafin gadolinium","Gadolinium texaphyrin; Motexafin gadolinium","C52H72GdN5O14","[Gd+3].CC([O-])=O.CC([O-])=O.CCC1=C(CC)/C2=C/C3=N/C(=C\\N=C4/C=C(OCCOCCOCCOC)C(OCCOCCOCCOC)=C/C/4=N\\C=C4/N=C(/C=C\\1\\[N-]\\2)C(CCCO)=C4C)/C(C)=C3CCCO","Motexafin gadolinium is studied in the treatment of cancer by Pharmacyclics. It may make tumor cells more sensitive to radiation therapy, improve tumor images using magnetic resonance imaging (MRI), and kill cancer cells. It belongs to the family of drugs called metalloporphyrin complexes. Also called gadolinium texaphyrin.","246252-06-2","1148.4","Investigated for use/treatment in brain cancer, cancer/tumors (unspecified), lung cancer, and lymphoma (non-hodgkin's).",null,"Motexafin gadolinium (Xcytrin) is Pharmacyclics' most advanced anti-cancer product candidate, a small-molecule drug with a novel mechanism of action. Xcytrin accumulates selectively in cancer cells due to their increased rates of metabolism. Once inside the cell, Xcytrin induces apoptosis (programmed cell death) by disrupting redox-dependent pathways. Xcytrin inhibits the enzyme thioredoxin reductase, which is a tumor growth promoter. This mechanism provides the opportunity to use Xcytrin in a wide range of cancers. Xcytrin is paramagnetic, and therefore is detectable by magnetic resonance imaging (MRI), allowing the visualization of the drug in tumors.","Thioredoxin reductase 1, cytoplasmic; Thioredoxin reductase 2, mitochondrial; Ribonucleoside-diphosphate reductase subunit M2","Therapeutic strategy associated"]
[796,"DB05431","investigational","small molecule","MLN-977",null,"C16H19FN2O4","NC(=O)N(O)CCC#C[C@@H]1CC[C@@H](COC2=CC=C(F)C=C2)O1","MLN-977 is a small molecule compound that inhibits the production of leukotrienes, especially 5-lipoxygenase. It is developed by PharmaEngine to treat asthma and chronic obstructive pulmonary disease.","175212-04-1","322.336","Investigated for use/treatment in asthma and chronic obstructive pulmonary disease (COPD).",null,"MLN977 is a second generation compound in the class of asthma therapies known as 5-LO inhibitors, which block the production of leukotrienes. Leukotrienes are major mediators of the inflammatory response.\r","Arachidonate 5-lipoxygenase","Therapeutic strategy associated"]
[797,"DB05432","investigational","small molecule","DAS-431 IV",{"$nulls":3},"DAS-431 IV is a dopamine D1 receptor agonist developed by DrugAbuse Sciences for the treatment of Addictions, Schizophrenia, Schizoaffective Disorders, Dementia, Parkinson's Disease, Strokes etc.",null,null,"Investigated for use/treatment in addictions, dementia, parkinson's disease, schizophrenia and schizoaffective disorders, and strokes.",null,"DAS-431 IV is a dopamine D1 receptor agonist which is in Phase II evaluation for the treatment of cognitive impairment in the elderly and cocaine addiction and is in development for a broad range of CNS diseases, including schizophrenia. Dopamine D1 receptors are thought to play a role in mediating cognitive processes in the prefrontal cortex, particularly working memory. The number of D1 receptors appears to be decreased in the elderly, chronic addicts, patients with schizophrenia and, possibly, patients with Parkinson's disease and those who have experienced a stroke. DAS-431 directly activates D1 receptors in the prefrontal cortex and may be useful in treating these conditions.","Neuron-specific vesicular protein calcyon","Indication associated"]
[798,"DB05433","investigational","small molecule","rGLP-1",{"$nulls":3},"rGLP-1 is a continuous infusion of glucagon-like peptide 1, or GLP-1, targeted for the treatment of congestive heart failure (CHF) in patients ineligible for transplant. GLP-1 is a naturally occurring hormone produced in the intestines in response to food intake.",null,null,"Investigated for use/treatment in congestive heart failure and diabetes mellitus type 2.",null,"These rGLP-1 mimetics bind to rGLP-1 receptors with similar affinity and produce biological actions identical to those of native rGLP-1 which controls blood glucose via multiple actions including stimulation of insulin secretion and inhibition of both glucagon secretion and gastric emptying. Preclinical data suggest that rGLP-1 analogs engage signaling pathways in the islet beta-cell that lead to stimulation of beta-cell replication and inhibition of beta-cell apoptosis.",null,"Therapeutic strategy associated"]
[799,"DB05443","investigational","small molecule","ADL 10-0101",{"$nulls":3},"ADL 10-0101 is a peripheral kappa opioid agonist analgesic product candidate. Preclinical trials of ADL 10-0101 have suggested that the compound may be effective for the treatment of inflammatory pain, itch and visceral pain. Because ADL 10-0101 does not cross the blood-brain barrier and enter the brain when administered at therapeutic doses, it is expected to avoid central nervous system side effects.\r",null,null,"Investigated for use/treatment in pain (acute or chronic) and rheumatoid arthritis. Trials are also being conducted for relieving burn pain and dermal itch.","ADL 10-0101 is a peripheral kappa opioid agonist. It cannot cross the blood-brain barrier.","Agonist at peripheral kappa opioid receptors","Kappa-type opioid receptor","Indication associated"]
[800,"DB05444","investigational","small molecule","Iroxanadine","Iroxanadine","C14H20N4O","C(C1CONC(=N1)C1=CN=CC=C1)N1CCCCC1","BRX-235 (iroxanadine) is a a novel small molecule synthesized by Biorex, Hungary that acts as a cardioprotective agent. It induces phosphorylation of p38 SAPK, which plays an important role in EC homeostasis. endothelial cell (EC). EC function plays a central role in vascular diseases (e.g. atherosclerosis, restenosis, diabetic angiopathies, microvascular angina, peripheral arterial disease). BRX-235 also causes translocation of calcium-dependent protein kinase C isoform to membranes.","276690-58-5","260.3348","Investigated for use/treatment in atherosclerosis and vascular diseases as a cardioprotective agent. Its use has also been suggested for the prevention of early restenosis following vascular surgery or balloon angioplasty.","EC (endothelial cell) function plays a central role in vascular diseases (e.g. atherosclerosis, restenosis, diabetic angiopathies, microvascular angina, peripheral arterial disease). BRX-235 induces phosphorylation of p38 SAPK, which plays an important role in EC homeostasis.","BRX-235 induces phosphorylation of p38 SAPK, which plays an important role in EC (endothelial cell) homeostasis.",null,"Indication associated"]
[801,"DB05446","investigational","small molecule","LJP 1082",null,"C11H19N3O7S","NC(CCC(=O)NC(CSCO)C(=O)NCC(O)=O)C(O)=O","LJP 1082 is a Toleragen that is designed to shut down the B cells that produce antibodies to ß2 GP1. LJP 1082 is undergoing trial for for the treatment of stroke, deep-vein thrombosis and other conditions associated with antibody-mediated thrombosis. Antibody-mediated thrombosis, also called antiphospholipid syndrome (APS), is a blood clotting disorder. Patients with high levels of anticardiolipin antibodies (ACA) have an increased risk of stroke, heart attack, deep vein thrombosis, and recurrent fetal loss. The target of the LJP 1082's clot-promoting antibodies is a small region on a key blood protein called beta 2-glycoprotein I. To date, our scientists have shown that approximately 90% of patients studied with antibody-mediated thrombosis have antibodies that bind to this region.",null,"337.349","Investigated for use/treatment in autoimmune diseases, strokes, and thrombosis.","LJP 1082, a Toleragen that is designed to shut down the B cells that produce antibodies to ß2 GP1.","The target of the LJP 1082's clot-promoting antibodies is a small region on a key blood protein called beta 2-glycoprotein I.","Beta-2-glycoprotein 1","Indication associated"]
[802,"DB05448","investigational","small molecule","PX-12","1-Methylpropyl-2-imidazolyl disulfide","C7H12N2S2","CCC(C)SSC1=NC=CN1","PX-12 (1-methylpropyl 2-imidazolyl disulfide) is a small-molecule inhibitor of Trx-1 (thioredoxin-1), stimulates apoptosis, down-regulates HIF-1α and vascular endothelial growth factor (VEGF) and inhibits tumor growth in animal models. Since high levels of Trx-1 have been associated with colorectal, gastric and lung cancers, PX-12 is indicated as a potential cancer treatment in combination with chemotherapy for  patients with advanced metastatic cancer. Initial trials correlated doses of Px-12 with increased patient survival.","141400-58-0","188.314","Investigated for use/treatment in cancer/tumors (unspecified), gastric cancer, and pancreatic cancer.","PX-12 is a small molecule irreversible inhibitor of the redox protein thioredoxin. Thioredoxin is involved in the first unique step in DNA synthesis. Thioredoxin also provides control over a number of transcription factors affecting cell proliferation and death through the mechanism of redox regulation\r\nTrx regulates cell growth through the following steps:\r\n1) Trx is reduced into its active state, Trx (red) by the enzyme thioredoxin reductase.\r\n2) Trx enters the nucleus to regulate transcription factor activity (factors which affect DNA replication).\r\n3) Trx is excreted out of cell where it works with other growth factors (GF) to stimulate cell growth.\r\n\r\nIt has been shown that many cancer cells secrete thioredoxin; increased levels of thioredoxin protein have been reported in a wide range of human cancers including hepatoma, lung, squamous cervical carcinoma, primary gastric cancers, and colorectal carcinomas;thioredoxin stimulates the growth of a wide variety of human leukemia and solid tumor cell lines; thioredoxin, when it is over-produced, transforms normal cells into cancer cells; thioredoxin is a potent inhibitor of apoptosis and provides a survival as well as a growth advantage to tumors; elevated tumor thioredoxin levels have been associated with decreased patient survival in colon cancer and NSCLC; and elevated thioredoxin levels cause a decrease in sensitivity of cells to cancer drugs such as doxorubicin (14 fold), vincristine (8 fold), cisplatin (5 fold), and cytosine arabinoside (13 fold). Therefore PX-12, by limiting the over-expression of thioredoxin in human tumors, could reduce resistance to chemotherapy.\r","PX-12 irreversibly inhibits the redox protein thioredoxin, which has been associated with cancer and tumor growth.","Thioredoxin reductase 1, cytoplasmic","Therapeutic strategy associated"]
[803,"DB05449","investigational","small molecule","FM-VP4","Disodium ascorbyl phytostanol phosphates",null,null,"FM-VP4, is a novel hydrophilic phytostanol analogue representing a new class in cholesterol-lowering drugs called cholesterol absorption inhibitors. FM-VP4 has been shown to inhibit cholesterol absorption and to lower plasma LDL-cholesterol and total cholesterol in a broad range of animal species. Additional experiments suggest that FM-VP4 can reduce plasma LDL cholesterol levels and triglyceride levels, reduce weight gain and exert a anti-atherosclerosis effect.",null,null,"Investigated for use/treatment in hyperlipidemia and cancer/tumors (unspecified).\r\n\r\nMonotherapy is recommended for people with marginally high LDL-cholesterol or who cannot be prescribed statins due to drug interactions and safety concerns. Combination Therapy is recommended if statin therapy alone is either insufficient to achieve the guidelines set by the NCEP or there is concern over side effects as Statin doses can be lowered in combination treatment without losing efficacy.","FM VP4 is thought to bind competitively with cholesterol to MDR1 resulting in a synergistic decrease in cholesterol accumlation. Others have suggested that FM VP4 may act by inhibiting a transporter that mediates intestinal absorption of cholesterol.","FM VP4 is thought to bind competitively with cholesterol to MDR1 resulting in a synergistic decrease in cholesterol accumlation. Others have suggested that FM VP4 may act by inhibiting a transporter that mediates intestinal absorption of cholesterol.\r\nOne study indicates that FM-VP4 inhibits cholesterol accumulation within IEC-6 cells and is most effective at equimolar concentrations with cholesterol, further suggesting that the action of FM-VP4 is likely at the cell surface and not elicited intracellularly.","P-glycoprotein 1","Indication associated"]
[804,"DB05451","investigational","small molecule","P54",{"$nulls":3},"P54 reduces the inflammation associated with cancer/tumors, Crohn's disease, inflammatory bowel disease, osteoarthritis, and ulcerative colitis. It inhibits the induction of the enzyme NFkB, thereby inhibiting downstream inflammatory genes such as COX II and iNOS.",null,null,"Investigated for use/treatment in cancer/tumors (unspecified), crohn's disease, inflammatory bowel disease, osteoarthritis, and ulcerative colitis.","P54 inhibits the induction of the enzyme NFkB, thereby inhibiting downstream inflammatory genes such as COX II and iNOS.","P54 inhibits the induction of the enzyme NFkB, thereby inhibiting downstream inflammatory genes such as COX II and iNOS.","Nuclear factor NF-kappa-B p100 subunit; Nuclear factor NF-kappa-B p105 subunit","Therapeutic strategy associated"]
[805,"DB05456","investigational","small molecule","ETC-588",null,"C42H82NO8P","CCCCCCCCCCCCCCCC(=O)OC(COC(=O)CCCCCCC\\C=C/CCCCCCCC)COP([O-])(=O)OCC[N+](C)(C)C","ETC-588, or LUV (large unilamellar vesicles), is made of naturally occurring lipids that circulate through arteries to facilitate the role of high-density lipoprotein (HDL) in removing accumulated cholesterol and other lipids from cells including those in the arterial wall. LUV are capable of transporting excess cholesterol from the vasculature to the liver for eventual elimination as part of the reverse lipid transport (RLT) pathway. It is believed that the removal of cholesterol by ETC-588 through this pathway may result in the reversal of atherosclerosis. Esperion is currently developing ETC-588 as a treatment for patients with acute coronary syndromes.",null,"760.0761","Investigated for use/treatment in atherosclerosis, coronary artery disease, and vascular diseases.","ETC-588, or LUV (large unilamellar vesicles), is made of naturally occurring lipids that circulate through arteries to facilitate the role of high-density lipoprotein (HDL) in removing accumulated cholesterol and other lipids from cells including those in the arterial wall. LUV are capable of transporting excess cholesterol from the vasculature to the liver for eventual elimination as part of the reverse lipid transport (RLT) pathway.","ETC-588 is a phospholipid bilayer that can sequester cholesterol. Once the HDL particle, which is small enough to enter the arterial wall, pulls the cholesterol out of the plaque, it readily hands the cholesterol over to the LUV. The LUV then transports the cholesterol to the liver for processing.",null,"Indication associated"]
[806,"DB05459","investigational","biotech","Briakinumab","Briakinumab",null,null,"Briakinumab is a human anti-IL-12 monoclonal antibody being developed for the treatment of a number of T-cell driven autoimmune diseases. It targets and neutralize interleukin-12 and interleukin-23, two proteins associated with inflammation, such as pro-inflammatory interleukins or tumor necrosis factor- alpha. Briakinumab represents a novel approach to treating psoriasis, Multiple Sclerosis, Crohn’s Disease and other autoimmune and inflammatory disorders.  As of 2011 drug development for psoriasis has been discontinued in the U.S. and Europe.","339308-60-0",null,"Investigated for use/treatment in autoimmune diseases, crohn's disease, multiple sclerosis, psoriasis and psoriatic disorders, and rheumatoid arthritis.","Briakinumab is a human anti-IL-12 monoclonal antibody being developed for the treatment of a number of T-cell driven autoimmune diseases. It targets and neutralizes interleukin-12 and interleukin-23, two proteins associated with inflammation.","Briakinumab targets and neutralizes interleukin-12 and interleukin-23.","Interleukin-12 subunit beta; Interleukin-23 subunit alpha","Indication associated"]
[807,"DB05464","investigational","small molecule","NOX-700",{"$nulls":3},"NOX-700, an new orally active dithiocarbamate-based nitric oxide (NO) blocking agent that is in development for the treatment of diabetes mellitus (type 2 diabetes). In animal studies, NOX-700 lowered serum glucose, improved glucose tolerance, and reduced the percentage of total glycated hemoglobin. Immunohistochemical studies on\r\npancreatic tissue also showed that NOX-700 therapy effectively preserved islet structure and increased insulin immunoreactivity. It has since been found that oxidative signaling of the redox-sensitive transcription factor, NF-κB, and inhibiting protein glycation are responsible for the drug's therapeutic effects.\r",null,null,"Investigated for use/treatment in diabetes mellitus (type 2).","NOX-700 is an orally active nitric oxide (NO) blocking agent  in development for the treatment of diabetes mellitus (type 2). In animal studies, NOX-700 lowered serum glucose, improved glucose tolerance, and reduced the percentage of total glycated hemoglobin. Immunohistochemical studies on\r\npancreatic tissue also showed that NOX-700 therapy effectively preserved islet structure and increased insulin immunoreactivity. It has since been found that oxidative signaling of the redox-sensitive transcription factor, NF-κB, and inhibiting protein glycation are responsible for the drug's therapeutic effects.","It has been found that oxidative signaling of the redox-sensitive transcription factor, NF-κB, and inhibiting protein glycation are responsible for the drug's therapeutic effects.","Nuclear factor NF-kappa-B p100 subunit; Nuclear factor NF-kappa-B p105 subunit","Indication associated"]
[808,"DB05466","investigational","small molecule","R673",{"$nulls":3},"R673 is a novel NK1 antagonist that penetrates the blood-brain barrier, has excellent safety and tolerability and shows low P450-based drug interaction potential. The phase II program for treatment of depression and anxiety is ongoing in the US and EU.It is not clear how tachykinin antagonists exert their effect, but SP levels have been commonly linked to the functioning of limbic system with respect to anxiety and depression.",null,null,"Investigated for use/treatment in depression and anxiety.","R673 is a novel NK1 antagonist that penetrates the blood-brain barrier, has excellent safety and tolerability and shows low P450-based drug interaction potential. It is not clear how tachykinin antagonists exert their effect, but SP levels have been commonly linked to the functioning of limbic system with respect to anxiety and depression.","R673 is a novel NK1 antagonist that penetrates the blood-brain barrier, has excellent safety and tolerability and shows low P450-based drug interaction potential. It is not clear how tachykinin antagonists exert their effect, but SP levels have been commonly linked to the functioning of limbic system with respect to anxiety and depression.","Neurokinin 1 receptor","Indication associated"]
[809,"DB05470","investigational","small molecule","VX-702",null,"C19H12F4N4O2","NC(=O)N(C1=CC=C(C(N)=O)C(=N1)C1=CC=C(F)C=C1F)C1=C(F)C=CC=C1F","VX-702 is a small molecule investigational oral anti-cytokine therapy for treatment of inflammatory diseases, specifically rheumatoid arthritis (RA). It acts as a p38 MAP kinase inhibitor. In the future, VX-702 may be investigated for combination with methotrexate, a commonly used therapy for RA.","745833-23-2","404.325","Investigated for use/treatment in coronary artery disease, inflammatory disorders (unspecified), and rheumatoid arthritis.","VX-703 is an anti-cytokine therapy in which p38 MAP kinase inhibitor effectively inhibits LPS-stimulated TNF||, IL-6 and IL-1|| production.","This p38 MAP kinase inhibitor effectively inhibits LPS-stimulated TNF||, IL-6 and IL-1|| production.","Mitogen-activated protein kinase 14; Tumor necrosis factor; Interleukin-1 beta; Interleukin-6","Target associated"]
[810,"DB05474","investigational","small molecule","T487",{"$nulls":3},"T487 is a small molecule chemokine receptor antagonist to correct or modify immune system responses. It binds selectively and potently to CXCR3. The formulation is administered orally and has anti-inflammatory effects in conditions such as rheumatoid arthritis, inflammatory bowel disease and psoriasis.\r\n\r\n\r",null,null,"Investigated for use/treatment in inflammatory disorders \r\nsuch as rheumatoid arthritis, inflammatory bowel disease and psoriasis.","T487 is a small molecule chemokine receptor antagonist to correct or modify immune system responses. It binds selectively and potently to CXCR3.","T487 binds selectively and potently to CXCR3.",null,"Indication associated"]
[811,"DB05475","investigational","small molecule","Golotimod","Golotimod","C16H19N3O5","N[C@H](CCC(=O)N[C@@H](CC1=CNC2=CC=CC=C12)C(O)=O)C(O)=O","SCV-07 (g -D-glutamyl-L-tryptophan) is a novel synthetic dipeptide that acts broadly on the Toll-like receptor pathway. It has been shown to stimulate T-lymphocyte differentiation, macrocytic phagocytosis,  and specific immune responses, and enhance IL-2 and INF-g production. Due to this preferential activation of Th1 cytokine production, SCV-07 may show utility in treatment of tuberculosis. It can be administered orally or subcutaneously. In independent studies, treatment of tuberculosis with SCV-07 improved clearance of mycobacteria, improved cavity healing, improvements in immune parameters and reduced symptoms (fever, weakness, sweating, dry cough, productive cough, dyspnea, chest pain, tachycardia) without any adverse local or general effects. SCV-07 has shown efficacy in treating various viral and bacterial infections.","229305-39-9","333.3392","Investigated for use/treatment in hepatitis (viral, C), infectious and parasitic disease (unspecified), and tuberculosis.","SCV-07 (g -D-glutamyl-L-tryptophan) is a novel synthetic dipeptide that acts broadly on the Toll-like receptor pathway. It has been shown to stimulate T-lymphocyte differentiation, macrocytic phagocytosis,  and specific immune responses, and enhance IL-2 and INF-g production.","SCV-07 (g -D-glutamyl-L-tryptophan) has broad effects on the Toll-like receptor (TLR) pathway.","Toll-like receptor 2; Toll-like receptor 4; Toll-like receptor 7; Toll-like receptor 9","Target associated"]
[812,"DB05479","investigational","small molecule","CZEN 002",null,"C77H109N21O19S","CSCC[C@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(C)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)NC(CC1=CN=CN1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CNC2=CC=CC=C12)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(N)=O","CZEN-002 is a novel, non-azole anti-fungal synthetic octapeptide, derived from alpha-Melanocyte-Stimulating Hormone (a-MSH). CZEN-002 modulates inflammatory and immune responses. It has also been shown to kill Candida albicans (C. albicans), a single-celled fungal organism that causes a variety of infections, including vaginitis. This organism can invade tissues and produce fatal infections in individuals with compromised immune systems such as those suffering from HIV/AIDS or undergoing organ or bone transplants. The antimicrobial activity of CZEN-002 is unique in that it does not depend on direct damage to the microbial membrane. It appears that CZEN-002 works on a receptor in yeast that has yet to be identified. \r\n\r\nStudies attempting to understand the candidacidal activity of derivatives of alpha-MSH have focused on the alpha-MSH amino acid sequence (6-13), which contains the invariant core sequence His-Phe-Arg-Trp (6-9) that is important for binding to the known melanocortin receptors. A second focus was on the sequence Lys-Pro-Val (11-13) that is known to be important for antimicrobial activity. \r",null,"1664.884","Investigated for use/treatment in candidiasis and vaginitis.","CZEN-002 is a novel, non-azole anti-fungal synthetic octapeptide, derived from alpha-Melanocyte-Stimulating Hormone (a-MSH). CZEN-002 modulates inflammatory and immune responses. It has also been shown to kill Candida albicans (C. albicans). The antimicrobial activity of CZEN-002 is unique in that it does not depend on direct damage to the microbial membrane. It appears that CZEN-002 works on a receptor in yeast that has yet to be identified. \r\n\r","The antimicrobial activity of CZEN-002 is unique in that it does not depend on direct damage to the microbial membrane. It appears that CZEN-002 works on a receptor in yeast that has yet to be identified. \r\n\r\nStudies attempting to understand the candidacidal activity of derivatives of alpha-MSH have focused on the alpha-MSH amino acid sequence (6-13), which contains the invariant core sequence His-Phe-Arg-Trp (6-9) that is important for binding to the known melanocortin receptors. A second focus was on the sequence Lys-Pro-Val (11-13) that is known to be important for antimicrobial activity. \r","Melanocyte-stimulating hormone receptor","Therapeutic strategy associated"]
[813,"DB05484","investigational","small molecule","MDX-018",{"$nulls":3},"MDX-018, also known as HuMax-Inflam, is a fully human antibody that is directed to IL-8 (interleukin-8) and may have potential application in oncology and inflammation. Trials will initially focus on studies to treat glioblastoma, a cancer of the central nervous system. Other possible indications include chronic obstructive pulmonary disease (COPD) and pustular dermatoses. In pre-clinical studies, HuMax-Inflam has been shown to inhibit tumor growth in tumor models using primary human tumors in immunodeficient mice. HuMax-Inflam was also effective in reducing disease activity in palmoplantar pustulosis patients in a clinical study.",null,null,"Investigated for use/treatment in autoimmune diseases and inflammatory disorders (unspecified).","MDX-018 is a fully human anti-inflammatory antibody for the treatment of Autoimmune Disease. The drug inhibits tumour growth by targetting interleukin-8 (IL-8), a major inflammation mediator. It reduces disease activity in palmoplantar pustulosis patients and is also effective in the treatment of glioblastoma, which has a very low survival rate.","he drug inhibits tumour growth by targetting interleukin-8 (IL-8), a major inflammation mediator.","Interleukin-8","Therapeutic strategy associated"]
[814,"DB05485","investigational","biotech","ADH-1",{"$nulls":3},"Adherex's biotechnology compound, ADH-1, targets N-cadherin, a protein present on certain tumor cells and established tumor blood vessels. ADH-1 is currently in clinical development in a combination program with a range of chemotherapeutic agents to investigate the synergistic effects noted in our preclinical models. At the end of 2006, the Company also completed patient enrollment in our single-agent Phase Ib/II and Phase II trials of ADH-1.\r\n\r\n\r\nCadherins are cell adhesion and cell signaling molecules crucial to the development of tissues, organs and organisms. Agents that target and inhibit cadherin function have the potential to attack the progression of cancer at two distinct points:\r\n\r\n    * Direct targeting of cadherins expressed on cancer cells may disturb cadherin-mediated signaling, leading to apoptosis (death) of cancer cells.\r\n    * Cadherin inhibitors may exploit the inherent structural weaknesses of the tumor vasculature, causing angiolysis (disruption of blood vessels) and tumor damage.\r\n\r\nAs many tumors become more aggressive, invasive, and malignant, researchers have found that N-cadherin is expressed in greater amounts, making it an important target for developing anti-cancer treatments.\r\n\r\nPoorly differentiated, highly invasive carcinomas are characterized by over-expression of N-cadherin (as opposed to E-cadherin). This change in primary cadherin expression causes the epithelial cells to lose their tightly adherent, polarized and well-defined shape and become loosely adherent, flattened and migratory. Such cadherin switching promotes properties such as dedifferentiation, local invasion and metastasis, leading to poor prognosis.\r\n\r\nADH-1 may have utility in a wide variety of cancers as N-cadherin is overexpressed in a variety of tumors. As tumors progress to become higher grade, invasive and more metastatic, the frequency of N-cadherin expression generally rises.\r",null,null,"Investigated for use/treatment in breast cancer, cancer/tumors (unspecified), melanoma, ovarian cancer, and solid tumors.","ADH-1 is a biotech compounds that targets N-cadherin, a protein present on certain tumor cells and established tumor blood vessels. Cadherins are cell adhesion and cell signaling molecules crucial to the development of tissues, organs and organisms. Agents that target and inhibit cadherin function have the potential to attack the progression of cancer at two distinct points:\r\n\r\n    * Direct targeting of cadherins expressed on cancer cells may disturb cadherin-mediated signaling, leading to apoptosis (death) of cancer cells.\r\n    * Cadherin inhibitors may exploit the inherent structural weaknesses of the tumor vasculature, causing angiolysis (disruption of blood vessels) and tumor damage.\r\n\r\nThe compound is indicated for treatment of a variety of invasive carcinomas and ADH-1 has been shown to be synergistic with taxane-based chemotherapy in the systemic treatment of ovarian cancer xenografts.\r\n\r","While ADH-1 has a single molecular target, N-cadherin, we believe its anti-cancer effect results from two distinct mechanisms of action - apoptosis and tumor vessel angiolysis.\r\n\r\nN-cadherin appears to act as a tumor cell survival factor. In cell culture studies, inhibition of N-cadherin binding between tumor cells has been shown to cause apoptosis of tumor cells, we believe as a result of disrupting the cadherin-regulated cell survival signals.\r\n\r\nADH-1 also appears to disrupt the blood vessels needed for cancerous tumors to grow and flourish, with hemorrhaging having been noted in both our clinical and preclinical studies. We believe the mechanism for this disruption is either a competitive inhibition of the binding of cadherins between the endothelial cells of the tumor blood wall or apoptosis in tumor cells that form a part of the blood vessel wall, each leading to leakage and rupture of these vessels. The latter involves the phenomenon of tumor \"mosaicism,\" in which tumor cells form a portion of the vascular wall (along with the endothelial cells). Induction of cell death of these tumor cells would result in tumor vascular disruption.\r",null,"Therapeutic strategy associated"]
[815,"DB05487","investigational","small molecule","Custirsen","Custirsen","C231H312N78O119P20S20","COCCO[C@@H]1[C@H](O)[C@@H](COP(S)(=O)O[C@@H]2[C@@H](COP(S)(=O)O[C@@H]3[C@@H](COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@H]5C[C@@H](O[C@@H]5COP(S)(=O)O[C@H]5C[C@@H](O[C@@H]5COP(S)(=O)O[C@H]5C[C@@H](O[C@@H]5COP(S)(=O)O[C@H]5C[C@@H](O[C@@H]5COP(S)(=O)O[C@H]5C[C@@H](O[C@@H]5COP(S)(=O)O[C@H]5C[C@@H](O[C@@H]5COP(S)(=O)O[C@H]5C[C@@H](O[C@@H]5COP(S)(=O)O[C@H]5C[C@@H](O[C@@H]5COP(S)(=O)O[C@H]5C[C@@H](O[C@@H]5COP(S)(=O)O[C@H]5C[C@@H](O[C@@H]5COP(S)(=O)O[C@H]5C[C@@H](O[C@@H]5COP(S)(=O)O[C@H]5C[C@@H](O[C@@H]5COP(S)(=O)O[C@H]5C[C@@H](O[C@@H]5COP(S)(=O)O[C@@H]5[C@@H](COP(S)(=O)O[C@@H]6[C@@H](COP(S)(=O)O[C@@H]7[C@@H](COP(S)(=O)O[C@@H]8[C@@H](CO)O[C@H]([C@@H]8OCCOC)N8C=C(C)C(N)=NC8=O)O[C@H]([C@@H]7OCCOC)N7C=NC8=C7N=CN=C8N)O[C@H]([C@@H]6OCCOC)N6C=NC7=C6N=C(N)NC7=O)O[C@H]([C@@H]5OCCOC)N5C=C(C)C(N)=NC5=O)N5C=NC6=C5N=CN=C6N)N5C=NC6=C5N=C(N)NC6=O)N5C=CC(N)=NC5=O)N5C=NC6=C5N=CN=C6N)N5C=NC6=C5N=C(N)NC6=O)N5C=NC6=C5N=CN=C6N)N5C=NC6=C5N=C(N)NC6=O)N5C=C(C)C(=O)NC5=O)N5C=CC(N)=NC5=O)N5C=C(C)C(=O)NC5=O)N5C=C(C)C(=O)NC5=O)N5C=CC(N)=NC5=O)N5C=NC6=C5N=CN=C6N)O[C@H]([C@@H]4OCCOC)N4C=C(C)C(=O)NC4=O)O[C@H]([C@@H]3OCCOC)N3C=C(C)C(N)=NC3=O)O[C@H]([C@@H]2OCCOC)N2C=NC3=C2N=CN=C3N)O[C@H]1N1C=C(C)C(=O)NC1=O","Custirsen is a benzopyran with potential antineoplastic activity. Custirsen acts as a selective estrogen receptor modulator (SERM), inhibiting the proliferation of estrogen-sensitive breast cancer cells. This agent also inhibits growth and induces apoptosis of glioblastoma cells via a mechanism independent of estrogen receptor-related mechanisms. Custirsen is also being investigated in the treatment of primary brain tumors.","890056-27-6","7346.14","Investigated for use/treatment in brain cancer and breast cancer.","CC-8490, a new anti-cancer compound from Celgene's proprietary class of benzopyrans, being evaluated as a potential therapy for brain cancer. The National Cancer Institute also reports applications in breast cancer related to potential antineoplastic activity. CC-8490 acts as a selective estrogen receptor modulator (SERM), inhibiting the proliferation of estrogen-sensitive breast cancer cells. This agent also inhibits growth and induces apoptosis of glioblastoma cells via a mechanism independent of estrogen receptor-related mechanisms.","CC-8490 acts as a selective estrogen receptor modulator (SERM), inhibiting the proliferation of estrogen-sensitive breast cancer cells. This agent also inhibits growth and induces apoptosis of glioblastoma cells via a mechanism independent of estrogen receptor-related mechanisms.\r\n\r\nPreliminary results in studies regarding the mechanism of action in brain cancer suggest that C-8490 surpresses nuclear factor (NF)-KB with its target genes IEX-3, SOD2, IL6, and IL8.","Estrogen receptor alpha; Nuclear factor NF-kappa-B p100 subunit; Nuclear factor NF-kappa-B p105 subunit","Therapeutic strategy associated"]
[816,"DB05490","investigational","small molecule","AMG-131",null,"C21H12Cl4N2O3S","ClC1=CC=C(C(Cl)=C1)S(=O)(=O)NC1=CC(Cl)=C(OC2=CN=C3C=CC=CC3=C2)C(Cl)=C1","AMG-131 (T131), an orally-administered therapy, is expected to lower blood glucose in type II diabetic patients by improving the body’s ability to respond to insulin. T131 is a selective modulator of PPARg (peroxisome proliferator activated receptor gamma), a receptor involved in regulating the body’s ability to respond to insulin. T131 is not structurally related to the thiazolidinedione class of PPARg agonists, which includes Actos and Avandia.","315224-26-1","514.209","Investigated for use/treatment in diabetes mellitus type 2.","T131, an orally-administered therapy, is expected to lower blood glucose in type II diabetic patients by improving the body’s ability to respond to insulin. T131 is not structurally related to the thiazolidinedione class of PPARg agonists, which includes Actos and Avandia","T131 is a selective modulator of PPARg (peroxisome proliferator activated receptor gamma), a receptor involved in regulating the body’s ability to respond to insulin. T131 is not structurally related to the thiazolidinedione class of PPARg agonists, which includes Actos and Avandia","Peroxisome proliferator-activated receptor gamma partial agonist","Target associated"]
[817,"DB05495","investigational","small molecule","PG-530742",null,"C24H27N3O7S","COC1=CC=C(C=C1)C(=O)NC1=CC=C(C=C1)S(=O)(=O)NC(CC#CCN1CCOCC1)C(O)=O","PG-530742 selectively inhibits certain matrix metalloproteinases that have been implicated in the cartilage degradation that occurs in osteoarthritis. By inhibiting these MMPs, it potentially limits cartilage degradation and disease progression. Studies are currently assessing the efficacy and safety of PG-530742 in the treatment of mild to moderate knee osteoarthritis.","291533-11-4","501.55","Investigated for use/treatment in osteoarthritis.","PG-530742 selectively inhibits certain matrix metalloproteinases that have been implicated in the cartilage degradation that occurs in osteoarthritis. By inhibiting these MMPs, it potentially limits cartilage degradation and disease progression. Studies are currently assessing the efficacy and safety of PG-530742 in the treatment of mild to moderate knee osteoarthritis.","PG-530742 selectively inhibits certain matrix metalloproteinases: In an independent research study, the drug-treated group showed decreased levels of MMP-2, -3, -9, and -13.","Matrix metalloproteinase-9","Indication associated"]
[818,"DB05496","investigational","biotech","Otelixizumab","Otelixizumab",null,null,"Otelixizumab is a monoclonal antibody that binds to a receptor found on all T cells called CD3, which is involved in normal T cell signaling. Otelixizumab is believed to inhibit the function of autoreactive T cells, which are important in propagating autoimmune diseases, while inducing regulatory T cell pathways that promote immunological tolerance and inhibit autoreactive disease activity. Tolerx is developing otelixizumab to treat patients with type 1 diabetes, psoriasis and other autoimmune diseases such as rheumatoid arthritis.","881191-44-2",null,"Investigated for use/treatment in diabetes mellitus type 1, pediatric indications, and psoriasis and psoriatic disorders.","Otelixizumab is a monoclonal antibody that binds to a receptor found on all T cells called CD3, which is involved in normal T cell signaling. Tolerx is developing otelixizumab to treat patients with type 1 diabetes, psoriasis and other autoimmune diseases such as rheumatoid arthritis.","Otelixizumab is a monoclonal antibody that binds to a receptor found on all T cells called CD3, which is involved in normal T cell signaling. Otelixizumab is believed to inhibit the function of autoreactive T cells, which are important in propagating autoimmune diseases, while inducing regulatory T cell pathways that promote immunological tolerance and inhibit autoreactive disease activity.",null,"Indication associated"]
[819,"DB05500","investigational","biotech","AVN-944",{"$nulls":3},"AVN944 is a biotech drug that demonstrated a statistically meaningful impact on IMPDH and other proteins that are critical to activities in cancer cells, including nucleotide biosynthesis, energy and metabolism, DNA replication, apoptosis and cell cycle control. AVN944 has been associated with cancer cell death in clinical trials. It is being investigated for the treatment of patients with advanced hematologic malignancies.",null,null,"Investigated for use/treatment in cancer/tumors (unspecified), leukemia (unspecified), lymphoma (unspecified), multiple myeloma, and pancreatic cancer.","IMPDH is highly upregulated in most hematological cancers and in many solid tumors. AVN944 is a biotech drug that demonstrated a statistically meaningful impact in inhibiting IMPDH and other proteins that are critical to activities in cancer cells, including nucleotide biosynthesis, energy and metabolism, DNA replication, apoptosis and cell cycle control. AVN944 has been associated with cancer cell death in clinical trials. It is being investigated for the treatment of patients with advanced hematologic malignancies.","AVN944 inhibits IMPDH and appears to induce apoptosis. Specifically, it was found that the gene HspA1A, a marker of stress response found to correlate with depleted GTP pools in cancer cell lines, is induced within hours upon the first treatment of the drug in patients, even at the trial's lowest doses. Following continued dosing of AVN944, this marker of disease cell stress was elevated even in the absence of circulating levels of the drug between doses.",null,"Therapeutic strategy associated"]
[820,"DB05501","investigational","small molecule","AMD-070",null,"C21H27N5","NCCCCN(CC1=NC2=CC=CC=C2N1)[C@H]1CCCC2=C1N=CC=C2","AMD-070 is a small molecule drug candidate that belongs to a new investigational class of anti-HIV drugs known as entry (fusion) inhibitors. Currently there is only one FDA-approved entry inhibitor, enfuvirtide (Fuzeon), that is available for the treatment of HIV infection. Several experimental entry inhibitors are now in early stage testing, including AMD-070, which targets the CXCR4 receptor on HIV and prevents the virus from entering and infecting healthy cells. Other entry inhibitors target the CCR5 receptor of HIV.These new agents are widely viewed as next generation anti-HIV drugs with the potential to significantly advance HIV therapeutics.","558447-26-0","349.482","Investigated for use/treatment in HIV infection.","AMD-070 is a small molecule drug candidate that belongs to a new investigational class of anti-HIV drugs known as entry (fusion) inhibitors. Approximately 76% of HIV-patients with measurable viral load are infected with a strain of virus that is resistant to one or more classes of antiretroviral agents, thus reducing treatment options. Unlike many existing HIV drugs that target the virus after it has infected a healthy cell, AMD-070 blocks the virus from entering a healthy cell, thus preventing the replication process.  AMD-070 targets the CXCR4 receptor on HIV and prevents the virus from entering and infecting healthy cells. \r\n* AMD-070 is specific for the CXCR4 receptor and does not interact with any other chemokine receptors in vitro\r\n    * AMD-070 strongly inhibits viral infection by all CXCR4 using virus (including virus using CXCR4 alone and/or virus using CXCR4 and CCR5) in vitro\r\n    * AMD-070 is orally bioavailable in animals\r\n    * Suitable PK and toxicity profile for oral dosing\r\n    * AMD-070 shows additive or synergistic effects in vitro in combination with other known anti-HIV agents\r\n    * AMD-070 is active against CXCR4 using HIV strains that are resistant to existing antiretroviral therapies in vitro\r\n    * Potent anti-HIV activity against CXCR4-using laboratory strains and clinical isolates\r","Chemokine receptors expressed on the surface of immune cells are known to play a critical role in virus infection and transmission. CXCR4, and another chemokine receptor CCR5, are involved in HIV infection.\r\n\r\nThe process of HIV entry begins with binding of the viral envelope glycoprotein to both the CD4 receptor and one of only two chemokine receptors, and ends with fusion of viral and cell membranes. Viral entry provides novel therapeutic targets against HIV. To date, at least 3 sub classes of HIV viral entry/fusion inhibitors have emerged:\r\n\r\n   1. CD4 binding or attachment - targets initial recognition and binding of the viral glycoprotein gp120 to the cell-surface CD4 antigen.\r\n   2. Chemokine co-receptor binding - targets binding of virus to the CCR5 or CXCR4 co-receptor.\r\n   3. Fusion Inhibition - targets the viral glycoprotein gp41 inhibiting the fusion of virus with the cell.\r\n\r\n\r\nDifferent strains of HIV prefer one receptor or the other, or may use either receptor to infect cells.\r\n\r\n    * 35% of strains use both CXCR4 and CCR5\r\n    * 5% of strains are pure CXCR4 using\r\n    * 60% of strains are pure CCR5 using\r\n    * An infected individual may harbor different levels of both CXCR4 and CCR5 using virus\r\n    * CXCR4 using virus independently predicts CD4 decline and HIV clinical progression and is associated with earlier mortality\r\n\r","C-X-C chemokine receptor type 4; C-C chemokine receptor type 5","Target associated"]
[821,"DB05506","investigational","small molecule","ISIS 113715",{"$nulls":3},"ISIS 113715 is our second-generation antisense inhibitor of protein tyrosine phosphatase 1b, or PTP‑1b, for the treatment of type 2 diabetes. In early trials, ISIS 113715 induced statistically significant improvements in multiple measures of glucose control along with statistically significant\r\nreductions in LDL-cholesterol.",null,null,"Investigated for use/treatment in diabetes mellitus type 2.","Because ISIS 113715 is an insulin sensitizer that acts by increasing the activity of the insulin receptor in response to insulin, the most logical place for this drug in the diabetes treatment regimen is as an adjunct to insulin therapy. ISIS 113715 has a novel mechanism of PTP-1b inhibiting action, and acts as an insulin signal enhancer with anti-obesity and lipid lowering potential. PTP‑1b has long been recognized as an attractive target for treatment of diabetes, but due to structural similarities among closely related proteins, it has been difficult to identify small molecule drugs with sufficient specificity to be\r\nsafe. Antisense technology allowed for the design of very specific drugs that inhibit PTP‑1b and that do not inhibit other family members, making it possible to reduce PTP‑1b activity without having other effects on closely related proteins that would likely lead to unwanted side effects.\r\n\r","ISIS 113715 is our second-generation antisense inhibitor of protein tyrosine phosphatase 1b, or PTP‑1b, for the treatment of type 2 diabetes. PTP‑1b is responsible for turning off the activated insulin receptor, so by reducing levels of PTP‑1b, ISIS 113715 enhances the activity of insulin. Antisense technology allows us to design very specific drugs that inhibit PTP‑1b and that do not inhibit other family members, making it possible to reduce PTP‑1b activity without having other effects on closely related proteins that would likely lead to unwanted side effects.\r","Tyrosine-protein phosphatase non-receptor type 1","Therapeutic strategy associated"]
[822,"DB05507","investigational","small molecule","VX-765",{"$nulls":3},"VX-765 is the orally available prodrug of a potent and selective competitive inhibitor of ICE/caspase-1 (VRT-043198). VX-765 is currently under clinical development for the treatment of inflammatory and autoimmune conditions, as it blocks the hypersensitive response to an inflammatory stimulus.",null,null,"Investigated for use/treatment in inflammatory disorders (unspecified) and psoriasis and psoriatic disorders.","VX-765 is an orally-absorbed pro-drug of VRT-043198, a potent and selective inhibitor of ICE/caspase-1 sub-family caspases.   It has been shown to reduce disease severity and the expression of inflammatory mediators in models of rheumatoid arthritis and skin inflammation, suggesting that it may be useful for treatment of inflammatory diseases.","VX-765 is a potent and selective inhibitor of ICE/caspase-1 sub-family caspases. In preclinical trials, VX-765 was efficiently converted to VRT-043198 when administered orally to mice and inhibited LPS-induced cytokine secretion. The result was a blocking of IL-1beta and IL-18 secretion, with out much effect on the release of several other cytokines, including IL-1{alpha}, tumor necrosis factor-{alpha}, IL-6 and IL-8. There was also no demonstrable activity in cellular models of apoptosis and it did not affect the proliferation of activated primary T-cells or T-cell lines. \r","Caspase-1; Interleukin-1 beta","Therapeutic strategy associated"]
[823,"DB05511","investigational","small molecule","Piclidenoson","Piclidenoson","C18H19IN6O4","CNC(=O)[C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C=NC2=C(NCC3=CC(I)=CC=C3)N=CN=C12","CF 101 (known generically as IB-MECA) is an anti-inflammatory drug for rheumatoid arthritis patients. Its novel mechanism of action relies on antagonism of adenoside A3 receptors. \r\nCF101 is supplied as an oral drug and has an excellent safety profile. It is also being considered for the treatment of other autoimmune-inflammatory disorders, such as Crohn's disease, psorasis and dry eye syndrome.","152918-18-8","510.2857","Investigated for use/treatment in cancer/tumors (unspecified), eye disorders/infections, psoriasis and psoriatic disorders, and rheumatoid arthritis.\r\nCan-Fite BioPharma has reported that by targeting the adenosine A3-receptor, CF101 may also be used to treat Crohn's disease, a serious gastrointestinal disorder.","CF-101 is an adenoside A3 agonist for the treatment of a variety of autoimmune-inflammatory disorders, particularly rhematoid arthritis. In clinical trials, it was found to be safe, well tolerated and showed strong evidence of an anti-inflammatory effect in rheumatoid arthritis patients. In this trial, a statistically significant correlation was found between A(3)AR expression level and response to the drug, so A(3)AR expression may serve as a biopredictor of patient response.","CF 101 is an A(3)AR agonist. A(3)AR is highly expressed in inflammatory cells and overexpressed in peripheral blood mononuclear cells, reflecting its role in the remote inflammatory process. In normal tissues, there is low adenoside A3 receptor expression. A(3)AR activation with a specific agonist deregulates the NF-kappaB signaling pathway in inflammatory cells and initiates immunomodulatory effects.","Adenosine receptor A3","Therapeutic strategy associated"]
[824,"DB05512","investigational","biotech","MM-093",{"$nulls":3},"MM-093 is a recombinant version of human alpha-fetoprotein (hAFP), an immunomodulatory serum protein normally produced at very high levels by the fetus and present in low levels in the blood of adults and children. Research on AFP suggests that it may play a role in modulating the immune system of the mother in order to protect the developing fetus during pregnancy. The presence of hAFP in the pregnant mother’s blood has long been associated with remission of many autoimmune diseases, including rheumatoid arthritis, psoriasis and multiple sclerosis, during the third trimester of pregnancy. Current studies are assessing MM-093’s potential to improve the treatment of autoimmune disease.",null,null,"Investigated for use/treatment in autoimmune diseases, psoriasis and psoriatic disorders, and rheumatoid arthritis.","M-093 (Merrimack Pharmaceuticals, Cambridge, Massachusetts, USA) is a non-glycosylated version of human AFP produced by recombinant DNA technology in a transgenic goat expression system.. hAFP is an immunomodulatory serum protein normally produced at very high levels by the fetus and present in low levels in the blood of adults and children. Research on AFP suggests that it may play a role in modulating the immune system of the mother in order to protect the developing fetus during pregnancy. The presence of hAFP in the pregnant mother’s blood has long been associated with remission of many autoimmune diseases, including rheumatoid arthritis, psoriasis and multiple sclerosis, during the third trimester of pregnancy. Current studies are assessing MM-093’s potential to improve the treatment of autoimmune disease.","One study states that AFP suppresses autologous lymphocyte proliferation and that improvements in experimental arthritis and autoimmune thyroiditis were associated with significantly reduced numbers of CD4 and CD8 splenocytes, total thymocytes and CD4 thymocytes. This suggests that AFP modulates T cell development and immune responses.",null,"Indication associated"]
[825,"DB05513","investigational","small molecule","Atiprimod","Atiprimod; Azaspirane; N,N-Diethyl-8,8-dipropyl-2-azaspiro(4.5)decane-2-propanamine","C22H44N2","CCCC1(CCC)CCC2(CCN(CCCN(CC)CC)C2)CC1",null,"123018-47-3","336.608","Investigated for use/treatment in cancer/tumors (unspecified), multiple myeloma, and rheumatoid arthritis.",null,null,"Interleukin-6; Tumor necrosis factor","Target associated"]
[826,"DB05518","investigational","small molecule","Managlinat dialanetil","Managlinat dialanetil","C21H33N4O6PS","[H][C@@](C)(NP(=O)(N[C@@]([H])(C)C(=O)OCC)C1=CC=C(O1)C1=C(CC(C)C)SC(N)=N1)C(=O)OCC","CS-917 is a novel inhibitor of fructose 1,6-bisphphosphatase (FBPase) which is one of the rate-limiting enzymes of gluconeogenesis.","280782-97-0","500.55","Investigated for use/treatment in diabetes mellitus type 2.",null,"In type 2 diabetes, the liver produces excessive amounts of glucose through the gluconeogenesis (GNG) pathway and consequently is partly responsible for the elevated glucose levels characteristic of the disease. CS-917 targets the AMP binding site of fructose 1,6-bisphosphatase (FBPase), inhibiting the GNC pathway.","Fructose-1,6-bisphosphatase 1","Indication associated"]
[827,"DB05519","investigational","small molecule","Budiodarone","Budiodarone","C27H31I2NO5","CC[C@H](C)OC(=O)CC1=C(C(=O)C2=CC(I)=C(OCCN(CC)CC)C(I)=C2)C2=C(O1)C=CC=C2","Budiodarone (ATI-2042) is an antiarrhythmic related to amiodarone that is currently being studied in clinical trials.","335148-45-3","703.356","Investigated for use/treatment in arrhythmia and atrial fibrillation.",{"$nulls":3},"Indication associated"]
[828,"DB05528","approved; investigational","small molecule","Mipomersen","Mipomersen","C230H324N67O122P19S19","COCCO[C@H]1[C@@H](O)[C@H](COP(O)(=O)S[C@H]2[C@H](COP(O)(=O)S[C@H]3[C@H](COP(O)(=O)S[C@H]4[C@H](COP(O)(=O)S[C@@H]5[C@@H](COP(O)(=O)S[C@H]6C[C@@H](O[C@@H]6COP(O)(=O)S[C@H]6C[C@@H](O[C@@H]6COP(O)(=O)S[C@H]6C[C@@H](O[C@@H]6COP(O)(=O)S[C@H]6C[C@@H](O[C@@H]6COP(O)(=O)S[C@H]6C[C@@H](O[C@@H]6COP(O)(=O)S[C@H]6C[C@@H](O[C@@H]6COP(O)(=O)S[C@H]6C[C@@H](O[C@@H]6COP(O)(=O)S[C@H]6C[C@@H](O[C@@H]6COP(O)(=O)S[C@H]6C[C@@H](O[C@@H]6COP(O)(=O)S[C@H]6C[C@@H](O[C@@H]6COP(O)(=O)S[C@@H]6[C@@H](COP(O)(=O)S[C@@H]7[C@@H](COP(O)(=O)S[C@@H]8[C@@H](COP(O)(=O)S[C@@H]9[C@@H](COP(O)(=O)S[C@@H]%10[C@@H](CO)O[C@H]([C@@H]%10OCCOC)N%10C=NC%11=C%10N=C(N)NC%11=O)O[C@H]([C@@H]9OCCOC)N9C=C(C)C(N)=NC9=O)O[C@H]([C@@H]8OCCOC)N8C=C(C)C(N)=NC8=O)O[C@H]([C@@H]7OCCOC)N7C=C(C)C(=O)NC7=O)O[C@H]([C@@H]6OCCOC)N6C=C(C)C(N)=NC6=O)N6C=NC7=C6N=CN=C7N)N6C=NC7=C6N=C(N)NC7=O)N6C=C(C)C(=O)NC6=O)N6C=C(C)C(N)=NC6=O)N6C=C(C)C(=O)NC6=O)N6C=NC7=C6N=C(N)NC7=O)N6C=C(C)C(N)=NC6=O)N6C=C(C)C(=O)NC6=O)N6C=C(C)C(=O)NC6=O)N6C=C(C)C(N)=NC6=O)O[C@H]([C@@H]5OCCOC)N5C=NC6=C5N=C(N)NC6=O)O[C@@H]([C@H]4OCCOC)N4C=C(C)C(N)=NC4=O)O[C@@H]([C@H]3OCCOC)N3C=NC4=C3N=CN=C4N)O[C@@H]([C@H]2OCCOC)N2C=C(C)C(N)=NC2=O)O[C@@H]1N1C=C(C)C(N)=NC1=O","Mipomersen sodium, which was known as the investigational drug, isis-301012, is the salt form of a synthetic phosphorothioate oligonucleotide. Mipomersen sodium prevents the formation of apo B-100, resulting in a decrease in the levels of apolipoprotein B (apo B), low density lipoprotein (LDL), and total cholesterol. Mipomersen is indicated in patients with homozygous familial hypercholesterolemia as an adjunct to diet and other lipid-lowering medications. It is marketed under the brand name Kynamro in the United States, and the FDA label includes a black box warning of hepatoxicity. Specifically, elevations in the liver enzymes, i.e. transaminases, and in liver fat (hepatic steatosis) have been reported. Due to this serious risk of liver toxicity, mipomersen sodium is only available to patients under the restricted program called Kynamro Risk Evaluation and Mitigation Strategy program.","1000120-98-8","7177.11","Used in patients with homozygous familial hypercholesterolemia as an adjunct to diet and other lipid-lowering medications.","Mipomersen sodium decreases the levels of apolipoprotein B (apo B), low density lipoprotein (LDL) non-high density lipoprotein-cholesterol, and total cholesterol.","Mipomersen binds to the mRNA that codes for apoB-100. This binding leads to double-stranded RNA, which is degraded by RNase H and prevents translation of the mRNA to form the apo B-100 protein.","mRNA of ApoB-100 binder","Indication associated"]
[829,"DB05533","investigational","small molecule","QR-333",{"$nulls":3},"QR-333 has been investigated as a treatment for diabetic peripheral neuropathy. QR-333 is a concentrated and standardized nutrient based active compounds dosed in a topical cream designed to reduce oxidative stress and treat symptoms of Diabetic Peripheral Neuropathy, a nerve disorder that can lead to numbness, skin ulcers, constant pain or extreme sensitivity to a stimulus.",null,null,"Investigated for use/treatment in neuropathy (diabetic).",null,"QR-333, a topical compound that contains quercetin, a flavonoid with aldose reductase inhibitor effects, ascorbyl palmitate, and vitamin D(3), was formulated to decrease the oxidative stress that contributes to peripheral diabetic neuropathy and thus alleviate its symptoms.","Aldose reductase","Therapeutic strategy associated"]
[830,"DB05545","investigational","biotech","AMG 108",{"$nulls":3},"AMG 108 was investigated for use as an antirheumatic agent.","877879-38-4",null,"Investigated for use/treatment in osteoarthritis and rheumatoid arthritis.",{"$nulls":3},"Indication associated"]
[831,"DB05549","investigational","small molecule","INO-1001","(9-(N-(3-Morpholinopropyl)-sulfonyl)-5,6-dihydro-5-oxo-11-H-indeno (1,2-C) isoquinoline methanesulfonic acid","C24H29N3O7S2","CS(O)(=O)=O.O=C1NC2=C(CC3=C2C=CC(=C3)S(=O)(=O)NCCCN2CCOCC2)C2=CC=CC=C12",null,"501364-91-6","535.63","Investigated for use/treatment in brain cancer, cardiovascular disorders, and myocardial infarction.",{"$nulls":3},"Indication associated"]
[832,"DB05552","investigational","small molecule","TG100-115","3-(2,4-Diamino-6-(3-hydroxyphenyl)pteridin-7-yl)phenol; 6,7-Bis(3-hydroxyphenyl)pteridine-2,4-diamine","C18H14N6O2","NC1=NC(N)=C2N=C(C3=CC=CC(O)=C3)C(=NC2=N1)C1=CC(O)=CC=C1","An NSAID that inhibits PI-3K gamma and delta.","677297-51-7","346.35","Investigated for use/treatment in angioedema and myocardial infarction.",null,null,"Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform inhibitor; Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform inhibitor","Indication associated"]
[833,"DB05560","investigational","small molecule","Delcasertib","Delcasertib","C120H199N45O34S2","[H][C@](N)(CSSC[C@]([H])(N)C(O)=N[C@@]([H])(CC1=CC=C(O)C=C1)C(O)=NCC(O)=N[C@@]([H])(CCCNC(N)=N)C(O)=N[C@@]([H])(CCCCN)C(O)=N[C@@]([H])(CCCCN)C(O)=N[C@@]([H])(CCCNC(N)=N)C(O)=N[C@@]([H])(CCCNC(N)=N)C(O)=N[C@@]([H])(CCC(O)=N)C(O)=N[C@@]([H])(CCCNC(N)=N)C(O)=N[C@@]([H])(CCCNC(N)=N)C(O)=N[C@@]([H])(CCCNC(N)=N)C(O)=O)C(O)=N[C@@]([H])(CO)C(O)=N[C@@]([H])(CC1=CC=CC=C1)C(O)=N[C@@]([H])(CC(O)=N)C(O)=N[C@@]([H])(CO)C(O)=N[C@@]([H])(CC1=CC=C(O)C=C1)C(O)=N[C@@]([H])(CCC(O)=O)C(O)=N[C@@]([H])(CC(C)C)C(O)=NCC(O)=N[C@@]([H])(CO)C(O)=N[C@@]([H])(CC(C)C)C(O)=O",null,"949100-39-4","2880.31","Investigated for use/treatment in myocardial infarction.",{"$nulls":3},"Indication associated"]
[834,"DB05562","investigational","small molecule","Naluzotan","Naluzotan","C23H38N4O3S","CC(=O)NC1=CC=CC(=C1)N1CCN(CCCCNS(=O)(=O)CC2CCCCC2)CC1",null,"740873-06-7","450.64","Investigated for use/treatment in anxiety disorders and depression.",null,null,"5-hydroxytryptamine receptor 1A agonist","Indication associated"]
[835,"DB05580","investigational","small molecule","TRU-015",{"$nulls":4},"1169717-01-4",null,"Investigated for use/treatment in lymphoma (unspecified) and rheumatoid arthritis.",{"$nulls":3},"Indication associated"]
[836,"DB05607","investigational","small molecule","PRX-08066",null,"C23H21ClFN5O4S","OC(=O)\\C=C\\C(O)=O.FC1=C(C=C(CN2CCC(CC2)NC2=C3C=C(Cl)SC3=NC=N2)C=C1)C#N",null,null,"517.96","Investigated for use/treatment in chronic obstructive pulmonary disease (COPD) and pulmonary hypertension.",null,null,"5-hydroxytryptamine receptor 2B antagonist","Indication associated"]
[837,"DB05616","investigational","small molecule","4'-Methylene-5,8,10-trideazaaminopterin",null,"C23H23N5O5","NC1=NC2=CC=C(CCC3=CC=C(C=C3)C(=O)NC(CC(=C)C(O)=O)C(O)=O)C=C2C(N)=N1","CH-1504 is a an antirheumatic agent that has been shown in vitro to be a nonpolyglutamylatable and nonhydroxylatable antifolate that is more efficiently taken up into cells by the reduced folate carrier (RFC) system than is Methotrexate. It has been investigated for the treatment of Rheumatoid Arthritis (phase II).","238074-89-0","449.467","Investigated for use/treatment in inflammatory disorders (unspecified), psoriasis and psoriatic disorders, and rheumatoid arthritis.",{"$nulls":3},"Indication associated"]
[838,"DB05631","investigational","small molecule","ALT-2074",null,"C10H13NSe","CC1(C)CN[Se]C2=CC=CC=C12","An organoselenium drug previously studied by Oxis International in Phase-II clinical trials for ulcerative colitis patients. Some indications of efficacy were demonstrated. BXT-51072 has enthusiastic endorsement for treatment in cardiovascular indications, primarily because of its ability to mimic the function of glutathione peroxidase.","173026-17-0","226.18","Investigated for use/treatment in cardiovascular disorders and diabetes mellitus type 1 and 2.",{"$nulls":3},"Indication associated"]
[839,"DB05642","investigational","small molecule","DDP-225",null,"C17H20ClFN4OS","O.Cl.CC1=CC2=C(N=C(N=C2S1)N1CCNCC1)C1=CC=CC=C1F","DDP225 is both a noradrenaline reuptake inhibitor and a serotonin type 3 receptor (5-HT3) antagonist. Noradrenaline and serotonin are neurotransmitters that are known to be involved in the control of the gastrointestinal system.  The unique combination of noradrenaline reuptake inhibition and 5-HT3 antagonism in one orally delivered compound represents a novel approach to treating IBS-d and other functional GI diseases. Dynogen licensed preclinical and clinical data related to DDP225 from Mitsubishi Pharma in October 2003.","476148-82-0","382.88","Investigated for use/treatment in alzheimer's disease, depression, diarrhea, gastrointestinal diseases and disorders (miscellaneous), and irritable bowel syndrome (IBS).",null,"DDP225 is an orally-active compound that targets two key pathways that control the gastrointestinal (GI) system, thus giving it the potential to address multiple symptoms associated with IBS-d. DDP225 has a dual mechanism of action. It possesses both noradrenaline reuptake inhibition and 5-HT3 receptor antagonist properties.","5-hydroxytryptamine receptor 3A; Sodium-dependent noradrenaline transporter","Indication associated"]
[840,"DB05645","investigational","small molecule","Larazotide","Larazotide","C32H55N9O10","CC(C)C[C@H](NC(=O)[C@@H](NC(=O)CNC(=O)CN)C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O","An octapeptide inhibitor of paracellular permeability whose structure is derived from a protein (zonula occludens toxin) secreted by Vibrio cholerae for treatment of Coeliac disease.","258818-34-7","725.845","Investigated for use/treatment in autoimmune diseases, diabetes mellitus type 1, and gastrointestinal diseases and disorders (miscellaneous).",null,"AT-1001 is an orally administered octapeptide zonulin receptor antagonist that appears to exert its inhibitory effect on gliadin-induced tight junction disassembly by blocking putative zonulin receptors on the luminal surface of the small intestine.",null,"Indication associated"]
[841,"DB05649","investigational","biotech","NTx-265",{"$nulls":3},"NTx-265 is a combination of two currently marketed large molecules designed to stimulate the growth and differentiation of neural stem cells in adults who have suffered a stroke – the second leading cause of death worldwide. In May 2006, biotechnology company Stem Cell Therapeutics started a Phase IIa study of NTx-265. It is also investigating use of the compound for neurodegenerative disorders, such as Huntington’s disease and Alzheimer’s disease.\r",null,null,"Investigated for use/treatment in strokes.",{"$nulls":3},"Indication associated"]
[842,"DB05659","investigational","small molecule","Faropenem medoxomil","Faropenem daloxate; Faropenem medoxil; Faropenem medoxomil","C17H19NO8S","[H][C@]12SC(=C(N1C(=O)[C@]2([H])[C@@H](C)O)C(=O)OCC1=C(C)OC(=O)O1)[C@@]1([H])CCCO1","Faropenem medoxomil is an ester prodrug derivative of the beta-lactam antibiotic . The prodrug form of faropenem offers dramatically improved oral bioavailability and leads to higher systemic concentrations of the drug. Faropenem medoxomil is a broad-spectrum antibiotic that is highly resistant to beta-lactamase degradation. It is being developed jointly by Replidyne, Inc. and Forest Laboratories, Inc.","141702-36-5","397.4","Investigated for use/treatment in bacterial infection, bronchitis, otitis media, and pediatric indications.","Faropenem has demonstrated excellent in vitro activity against common respiratory pathogens, many aerobic gram-positive organisms, and anaerobes. Activity against gram-negative organisms is more reserved. In vivo data suggest that faropenem is efficacious in treating community-acquired infections including uncomplicated skin and skin structure infections; however, more data may help to characterize faropenem's place in antimicrobial therapy.","Like other beta-lactam antibiotics, faropenem acts by inhibiting the synthesis of bacterial cell walls. It inhibits cross-linkage between the linear peptidoglycan polymer chains that make up a major component of the cell wall of Gram-positive bacteria. It does this by binding to and competitively inhibiting the transpeptidase enzyme used by bacteria to cross-link the peptide (D-alanyl-alanine) used in peptidogylcan synthesis.","Penicillin-binding protein 1A; Penicillin-binding protein 2B; Peptidoglycan synthase FtsI","Indication associated"]
[843,"DB05660","investigational","small molecule","D-JNKI-1","D-JNKI 1 peptide","C164H285N65O41","CC(C)C[C@@H](NC(=O)[C@@H](CC1=CC=CC=C1)NC(=O)[C@H]1CCCN1C(=O)[C@@H](CCC(N)=O)NC(=O)[C@H](NC(=O)[C@H]1CCCN1C(=O)[C@@H](CCCNC(N)=N)NC(=O)[C@@H](CO)NC(=O)[C@@H](CCC(N)=O)NC(=O)[C@H](N)CC(O)=O)C(C)C)C(=O)N[C@H](CC(N)=O)C(=O)N[C@H](CC(C)C)C(=O)N[C@H]([C@H](C)O)C(=O)N[C@H]([C@H](C)O)C(=O)N1CCC[C@@H]1C(=O)N[C@H](CCCNC(N)=N)C(=O)N[C@H](CCCCN)C(=O)N1CCC[C@@H]1C(=O)N[C@H](CCCNC(N)=N)C(=O)N1CCC[C@@H]1C(=O)N1CCC[C@@H]1C(=O)N[C@H](CCCNC(N)=N)C(=O)N[C@H](CCCNC(N)=N)C(=O)N[C@H](CCCNC(N)=N)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H](CCCNC(N)=N)C(=O)N[C@H](CCCNC(N)=N)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCCNC(N)=N)C(=O)NCC(O)=O","A synthetic, cell permeable peptide that blocks the MAPK-JNK signal pathway; has potential therapeutic value for long-term protection of both the morphological integrity and physiological function of the organ of Corti during times of oxidative stress.","1198367-70-2","3823.498","Investigated for use/treatment in hearing loss.",null,"AM-111 is an inhibitor of c-Jun N-terminal kinase-mediated apoptosis and inflammation.",null,"Therapeutic strategy associated"]
[844,"DB05667","approved; investigational","small molecule","Levoketoconazole","Levoketoconazole","C26H28Cl2N4O4","CC(=O)N1CCN(CC1)C1=CC=C(OC[C@@H]2CO[C@](CN3C=CN=C3)(O2)C2=CC=C(Cl)C=C2Cl)C=C1","Levoketoconazole is a cortisol synthesis inhibitor that is being developed as a therapy for glucose and cholesterol control in patients with type 2 diabetes mellitus.","142128-57-2","531.431","Investigated for use/treatment in diabetes mellitus type 2.",null,"Preliminary data suggests that DIO-902 increases insulin sensitivity by lowering cortisol levels. The primary mechanism of action is via inhibition of the 11-β-hydroxylase enzyme, the terminal step in cortisol synthesis in the adrenal gland. DIO-902 has also been shown to lower total and LDL-cholesterol by inhibiting 14-α-demethylase, a key enzyme in cholesterol synthesis. In combination with a typical glucose-lowering agent, such as metformin, DIO-902 may enhance glucose control and improve total and LDL-cholesterol.","Cytochrome P450 11B1, mitochondrial; Lanosterol 14-alpha demethylase","Indication associated"]
[845,"DB05671","investigational","biotech","AC-100",{"$nulls":3},"AC-100 is a novel synthetic peptide derived from an endogenous human protein produced by bone and dental cells (a fragment from matrix extracellular phosphoglycoprotein). It is being developed by Acologix, Inc.",null,null,"Investigated for use/treatment in periodontal disease.","In animal models, AC-100 promoted cartilage regeneration. In the study, goats with an osteochondral femoral condylar (knee cartilage) defect were used to evaluate the effects of AC-100 on cartilage regeneration. Cylindrical defects were created in the knee cartilage and were filled with a collagen sponge containing AC-100 at two different doses or a collagen sponge soaked in saline (control group). Post-operative treatments included intra-articular injections of the test articles into the operated knee joint at weeks one, two and three post surgery. Cartilage regeneration was evaluated in one group after 84 days and 168 days in another group. The results demonstrated that the application of AC-100 dose dependently promoted cartilage defect repair. The groups treated with the higher dosage of AC-100 had greater healing outcome scores than the saline control groups. As there was no evidence of an inflammatory response, AC-100 demonstrated a favorable safety profile in the study.","In several preclinical models, AC-100 has demonstrated potent and selective dental tissue and bone formation activity, however the exact mechanism is not known. One study (PMID:15153459) showed that AC-100 enhances dental pulp stem cell (DPSC) proliferation by down-regulating P16, accompanied by up-regulation of ubiquitin protein ligase E3A and human ubiquitin-related protein SUMO-1. Enhanced cell proliferation required intact RGD and SGDG motifs in the peptide. This study shows that AC-100 can promote DPSC proliferation, with a potential role in pulp repair.",null,"Therapeutic strategy associated"]
[846,"DB05676","approved; investigational","small molecule","Apremilast","N-{2-[(1S)-1-(3-Ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}acetamide","C22H24N2O7S","CCOC1=CC(=CC=C1OC)[C@@H](CS(C)(=O)=O)N1C(=O)C2=CC=CC(NC(C)=O)=C2C1=O","Apremilast, also known as Otezla, is a phosphodiesterase 4 (PDE4) inhibitor used to treat various types of symptoms resulting from certain inflammatory autoimmune diseases. It belongs to the same drug class as  and . Initially approved in 2014, it is marketed by Celgene. In July 2019, apremilast was granted a new FDA approval for the treatment of oral ulcers associated with Behcet's disease, an autoimmune condition that causes recurrent skin, blood vessel, and central nervous system inflammation.","608141-41-9","460.5","Apremilast is indicated for the treatment of adults with active psoriatic arthritis and adults with oral ulcers associated with Behcet's Disease. In addition, apremilast is indicated for the treatment of plaque psoriasis, of any severity, in adult patients who are candidates for phototherapy or systemic therapy.","Apremilast reduces but does not completely inhibit various inflammatory cytokines such as IL-1α, IL-6, IL-8, IL-10 MCP-1, MIP-1β, MMP-3, and TNF-α, relieving the symptoms of psoriasis and Behcet's disease, which are caused by an increase in these inflammatory mediators. This drug has also been proven to be effective in relieving the pain associated with oral ulcers in Behcet's disease. \r\n\r\nApremilast may cause unwanted weight loss and worsen depression, leading to suicidal thoughts or actions. It is advisable to monitor for symptoms of depression and seek medical attention if they occur, especially in patients with pre-existing depression. The need for apremilast should be carefully assessed along with the risk of worsening depression and suicide. If weight loss occurs, the degree of weight loss should be evaluated, and consideration should be made for the possible discontinuation of apremilast.","The full mechanism of action of this drug is not fully established, however, it is known that apremilast is an inhibitor of phosphodiesterase 4 (PDE4), which mediates the activity of cyclic adenosine monophosphate (cAMP), a second messenger. The inhibition of PDE4 by apremilast leads to increased intracellular cAMP levels. An increase in cAMP results in the suppression of inflammation by decreasing the expression of TNF-α, IL-17, IL-23, and other inflammatory mediators. The above inflammatory mediators have been implicated in various psoriatic conditions as well as Behcet's disease, leading to their undesirable inflammatory symptoms such as mouth ulcers, skin lesions, and arthritis. Apremilast administration leads to a cascade which eventually decreases the levels of the above mediators, relieving inflammatory symptoms.","Phosphodiesterase isozyme 4 antagonist","Therapeutic strategy associated"]
[847,"DB05678","investigational","small molecule","SLx-4090",null,"C31H25F3N2O4","COC1=CC=CC(C(=O)NC2=CC3=C(CN(CC3)C(=O)OC3=CC=CC=C3)C=C2)=C1C1=CC=C(C=C1)C(F)(F)F","SLx-4090 is a microsomal triglyceride transfer protein (MTTP) inhibitor potentially for the treatment of type 2 diabetes.","913541-47-6","546.546","Investigated for use/treatment in hyperlipidemia.",null,"SLx-4090 inhibits Microsomal Triglyceride Transfer Protein (MTP). It acts selectively in the enterocytes lining the gastrointestinal tract, preventing the formation of chylomicrons which are used to transport triglyceride (TG) and cholesterol into the systemic circulation.","Microsomal triglyceride transfer protein large subunit inhibitor","Indication associated"]
[848,"DB05679","approved; investigational","biotech","Ustekinumab","Stelera; Ustekinumab",null,null,"Ustekinumab is a human immunoglobulin (Ig) G1 kappa monoclonal antibody directed against interleukin(IL)-12 and IL-23, which are cytokines that are involved in immune and inflammatory responses. It was generated via recombinant human IL-12 immunization of human Ig (hu-Ig) transgenic mice. It is a targeted biologic disease-modifying anti-rheumatic drug (bDMARDs) that is used in the management of various inflammatory conditions that involve the activation of IL-12 and IL-23 signalling pathways.\r\n\r\nThe therapeutic use of the drug started in Canada, the US, and Europe since 2009 when it was first approved for the treatment of adult patients with moderate to severe plaque psoriasis and active psoriatic arthritis, alone or in combination with . In September 2016, ustekinumab was additionally approved for the management of moderate to severe Crohn's disease in selected adult patients. In October 2019, it was also approved by the FDA for use to manage moderately to severely active ulcerative colitis in adults. Ustekinumab is currently the first and only approved biologic therapy for ulcerative colitis that targets the interleukin (IL)-12 and IL-23 cytokines. The dosing regimen for ustekinumab is based on the patient's weight and there are intravenous and subcutaneous formulations of the drug based on the dosing schedule and condition being treated. Ustekinumab is commonly marketed under the trade name STELARA.","815610-63-0",null,"Ustekinumab is indicated for the management of moderate to severe plaque psoriasis in children aged 6 and above, adolescents, and adults who are candidates for phototherapy or systemic therapy.\r\n\r\nIt is indicated for the management of active psoriatic arthritis in adults, alone or in combination with methotrexate.\r\n\r\nIt is indicated for the management of moderately to severely active Crohn’s disease in adults who were clinically unresponsive or intolerant to immunomodulator or corticosteroid therapy (but never failed a tutor necrosis factor (TNF) blocker) or treatment with one or more TNF blockers.\r\n\r\nIt is indicated for the management of moderately to severely active ulcerative colitis in adults.","Ustekinumab is a targeted antibody therapy that suppresses immune responses. It acts by reducing the signaling pathways of pro-inflammatory cytokines IL-12 and IL-23, which play a role in various inflammatory conditions. It downregulates the gene expression of inflammatory cytokines and chemokines such as MCP-1, TNF-alpha, IP-10, and IL-8. The formation of cytochrome P-450 enzymes may be altered by elevated levels of certain cytokines during chronic inflammation. Research shows that there is an inverse relationship between plasma levels of inflammatory cytokines and CYP450 enzyme formation and activity. While ustekinumab may potentially normalize the formation of CYP enzymes and enhance the CYP-mediated metabolism of drugs, there were no clinically significant effects on human CYP enzyme activities. The steady-state was achieved by 28 weeks after multiple subcutaneous dose administration in adult patients with psoriasis.","Interleukin (IL)-12 and IL-23 are heterodimeric cytokines that evoke immune and inflammatory responses, such as natural killer cell activation and CD4+ T-cell differentiation and activation. The role of IL-12 and IL-23 were implicated in a variety of chronic inflammatory conditions, such as psoriasis and inflammatory bowel diseases. They modulate lymphocyte function, including T-helper (Th) 1 and Th17 cell subsets, as CD4+ T cells can differentiate into T-helper (Th) effector lineages based on the environment. Th cells can further activate the downstream pro-inflammatory mediators and transcription factors such as TNFα and IFNγ that drive innate and adaptive immunity. \r\n\r\nIL-12 and IL-23 share a common p40 subunit, paired with p35 and p19 subunits of IL-12 and IL-23, respectively. \r\n The antigen-binding fragment (Fab) of ustekinumab binds the D1 domain of the p40 subunit of IL-12 and IL-23 in a 1:1 ratio. This prevents IL-12 and IL-23 from binding to the IL-12Rβ1 receptor chain of IL-12 (IL-12Rβ1/β2) and IL-23 (IL-12Rβ1/23R) receptor complexes on the surface of NK and T cells. Ustekinumab only binds to IL-12 and IL-23 that are unbound to IL-12Rβ1, so it is unlikely to initiate Fc effector functions, such as ADCC or CDC. Inhibition of the IL-12/23 signalling pathway leads to profound suppression of both the Th1 and Th17 cell lineage of cytokines and chemokines and their inflammatory pathways.","Interleukin-12 subunit beta inhibitor; Interleukin-23 inhibitor","Therapeutic strategy associated"]
[849,"DB05685","investigational","biotech","FX06",{"$nulls":3},"FX06 is a naturally occurring peptide derived from the neo-N-terminus of fibrin (Bbeta(15-42)). It prevents leukocyte migration through the gap junctions of endothelial cells. FX06 has proven safe in acute and subchronic toxicological studies and recently entered clinical development. It is being developed by Fibrex Medical Inc.",null,null,"Investigated for use/treatment in cardiac reperfusion injury and myocardial infarction.",null,"FX06 has a novel mechanism of action: it is a competitive inhibitor of the binding of fibrin E1 fragments to vascular endothelial (VE)-cadherin. Through this inhibition, it potently blocks the transmigration of inflammatory leukocytes through the endothelial barrier and prevents the downstream release of tissue-damaging mediators.","Cadherin-5","Therapeutic strategy associated"]
[850,"DB05688","investigational","small molecule","CRx-119",{"$nulls":3},"CRx-119 is a novel synergistic combination drug candidate discovered using the CombinatoRx combination High Throughput Screening (cHTS(TM)) technology with potential therapeutic use in a broad range of immuno-inflammatory conditions. CRx-119 is a combination of a low dose of the steroid prednisolone, 3mg, and amoxapine.",null,null,"Investigated for use/treatment in periodontal disease and rheumatoid arthritis.","CRx-119 is a novel orally available syncretic drug candidate in clinical development for immunoinflammatory diseases. A syncretic drug comprises two compounds that are designed to act together synergistically through multiple pathways to provide a novel therapeutic effect which neither component alone can achieve. CRx-119 contains a low dose of the steroid prednisolone and amoxapine. The target product profile for CRx-119 is to selectively amplify certain elements of prednisolone's anti-inflammatory and immunomodulatory effects, without replicating steroid toxicity.","Amoxapine acts by decreasing the reuptake of norepinephrine and serotonin (5-HT). Glucocorticoids such as prednisolone can inhibit leukocyte infiltration at the site of inflammation, interfere with mediators of inflammatory response, and suppress humoral immune responses. The antiinflammatory actions of glucocorticoids are thought to involve phospholipase A2 inhibitory proteins, lipocortins, which control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes. Prednisolone reduces inflammatory reaction by limiting the capillary dilatation and permeability of the vascular structures. These compounds restrict the accumulation of polymorphonuclear leukocytes and macrophages and reduce the release of vasoactive kinins. Recent research suggests that corticosteroids may inhibit the release of arachidonic acid from phospholipids, thereby reducing the formation of prostaglandins. Prednisolone is a glucocorticoid receptor agonist. On binding, the corticoreceptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing an increase or decrease in expression of specific target genes, including suppression of IL2 (interleukin 2) expression.","Sodium-dependent serotonin transporter; Sodium-dependent noradrenaline transporter","Therapeutic strategy associated"]
[851,"DB05695","investigational","small molecule","NPS-2143",null,"C24H25ClN2O2","CC(C)(CC1=CC=C2C=CC=CC2=C1)NC[C@@H](O)COC1=CC=CC(Cl)=C1C#N",null,"284035-33-2","408.93","Investigated for use/treatment in osteoporosis.",null,"NPS-2143 is the prototype calcilytic drug, designed to act on calcium receptors on the surface of parathyroid glands, stimulating the release of the body's own stores of native parathyroid hormone (PTH).","Extracellular calcium-sensing receptor","Indication associated"]
[852,"DB05719","investigational","small molecule","Elesclomol","1-N'-Benzenecarbothioyl-3-(2-benzenecarbothioyl-2-methylhydrazinyl)-N'-methyl-oxopropanehydrazidide","C19H20N4O2S2","CN(NC(=O)CC(=O)NN(C)C(=S)C1=CC=CC=C1)C(=S)C1=CC=CC=C1","Elesclomol is a novel, injectable, drug candidate that kills cancer cells by elevating oxidative stress levels beyond a breaking point, triggering programmed cell death. In preclinical models elesclomol showed potent killing of a broad range of cancer cell types at high doses, and an ability to strongly enhance the efficacy of certain chemotherapy agents, with minimal additional toxicity, at moderate doses. It is being developed by Synta Pharmaceuticals.","488832-69-5","400.518","Investigated for use/treatment in melanoma.","Elesclomol is a first-in-class heat shock protein 70 (Hsp70) inducer that activates natural killer (NK) cell-mediated tumor killing.","Elesclomol acts through a novel mechanism of action. Elesclomol has been shown to rapidly cause a dramatic increase in oxidative stress (ROS) inside cancer cells. The prolonged elevation of ROS inside cancer cells induced by elesclomol causes the cell to exceed a critical breaking point and undergo apoptosis. The triggering of the mitochondrial apoptosis pathway is observed within the first six hours of applying elesclomol. Cancer cells operate at a much higher intrinsic level of ROS than normal cells, and have a greatly reduced anti-oxidant capacity compared to normal cells. This leaves them more vulnerable to an agent such as elesclomol that elevates oxidative stress. In similar experiments at similar doses, elesclomol has been found to have little to no impact on normal cells.",null,"Therapeutic strategy associated"]
[853,"DB05730","investigational","small molecule","PMI-001",{"$nulls":3},"PMI-001 is a stand-alone, disease-modifying, anti-rheumatic drug (DMARD) being developed by Phytomedics Inc. It is an extract of the roots of an undisclosed perennial shrub which interferes with the production of IL-2 and COX-2 proteins, for the potential treatment of autoimmune diseases, such as rheumatoid arthritis, lupus erythematosus and psoriasis.",null,null,"Investigated for use/treatment in rheumatoid arthritis.","PMI-001 is a novel, orally bioavailable, small-molecule-based, plant-derived, multi-component disease modifying agent currently being developed for rheumatoid arthritis. Potential applications of this drug candidate beyond rheumatoid arthritis include a wide range of autoimmune disorders including psoriasis, lupus, inflammatory bowel disease (IBD), and multiple sclerosis (MS).","PMI-001 exerts its potent anti-inflammatory and immunosuppressant activities through unique and synergistic modes of action, which involves potent inhibition of several families of pro-inflammatory genes. PMI-001 most likely interferes with the production of IL-2 and COX-2 proteins.",null,"Therapeutic strategy associated"]
[854,"DB05732","investigational","small molecule","Strontium malonate",null,"C3H2O4Sr","[Sr++].[O-]C(=O)CC([O-])=O","Strontium malonate is being developed as a novel orally available pharmaceutical for the treatment and prevention of osteoporosis. It is being developed by Osteologix Inc.","183133-72-4","189.67","Investigated for use/treatment in osteoporosis.","Strontium is known to have a positive effect on bone by concomitantly increasing bone formation while decreasing bone resorption thereby providing a sustained skeletal benefit.",null,null,"Indication associated"]
[855,"DB05735","investigational","small molecule","Cefilavancin","Cefilavancin","C87H95Cl3N16O28S2","[H][C@]12SCC(C[N+]3=CC=CC=C3)=C(N1C(=O)[C@H]2NC(=O)C(=N/OCCCNC(=O)[C@H]1NC(=O)[C@H]2NC(=O)[C@H](NC(=O)[C@@H]3NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](NC(=O)[C@@H](CC(C)C)NC)[C@H](O)C4=CC=C(OC5=C(O[C@@H]6O[C@H](CO)[C@@H](O)[C@H](O)[C@@]6([H])O[C@H]6C[C@](C)(N)[C@H](O)[C@H](C)O6)C(OC6=C(Cl)C=C(C=C6)[C@H]2O)=CC3=C5)C(Cl)=C4)C2=CC(=C(O)C=C2)C2=C1C=C(O)C=C2O)\\C1=C(Cl)SC(N)=N1)C([O-])=O","Cefilavancin is a covalently-linked glycopeptide-cephalosporin (beta-lactam) heterodimer antibiotic that exhibits substantially greater activity than its component parts against Gram-positive bacteria.","722454-12-8","1983.27","Investigated for use/treatment in bacterial infection, skin infections/disorders, and staph bacterial infections.",{"$nulls":3},"Indication associated"]
[856,"DB05736","investigational","small molecule","MIV-701",{"$nulls":3},"MIV-701 is a selective, potent inhibitor of the protease Cathepsin K. It is developed for the treatment of osteoporosis.",null,null,"Investigated for use/treatment in osteoporosis.",null,"MIV-701 inhibits an enzyme, cathepsin K, which degrades bone, but most probably also contributes to cartilage damage in joint diseases. It greatly reduces degradation of bone.","Cathepsin K","Indication associated"]
[857,"DB05737","investigational","small molecule","Varespladib methyl","Varespladib methyl; Varespladib methyl ester","C22H22N2O5","CCC1=C(C(=O)C(N)=O)C2=C(OCC(=O)OC)C=CC=C2N1CC1=CC=CC=C1","Varespladib methyl has been investigated for the treatment of Acute Coronary Syndrome. Studies showed that Varespladib methyl treatment resulted in significant positive changes on lipoproteins and inflammation.","172733-08-3","394.427","Investigated for use/treatment in atherosclerosis and coronary artery disease.",null,"A–002 is an orally administered‚ potent inhibitor of secretory phospholipase spla2(spla2)‚ including groups IIA‚ V‚ and X. Atherosclerosis is a disease of the arteries that results from inflammation and the build-up of plaque under the lining of the blood vessel. This build-up can cause vascular swelling and eventual rupture. spla2 levels have been shown to be elevated in patients with both stable and unstable coronary artery disease. Higher levels of the enzyme have been shown to predict an increased risk for future cardiovascular events such as heart attacks and stroke.","Phospholipase A2, membrane associated; Group 10 secretory phospholipase A2","Indication associated"]
[858,"DB05739","investigational","biotech","CYT006-AngQb",{"$nulls":3},"CYT006-AngQb  is a therapeutic vaccine in development for treatment of hypertension. It is designed to instruct the patient’s immune system to produce an antibody response against angiotensin II, a small peptide that causes blood vessels to narrow and results in increased blood pressure. It is a unique treatment modality that aims to address the issue of patient compliance by offering convenient dosing schedules due to the long-lasting effect induced by vaccination.",null,null,"Investigated for use/treatment in hypertension.",null,"The so called renin-angiotensin system (RAS) is an important regulator of blood pressure and has already been successfully targeted by three major classes of\r\nantihypertensive drugs: by ACE inhibitors, by ARBs and by renin inhibitors. However, like other antihypertensives, they all have to be self-administered daily and don't\r\nprovide a good solution for improving patient compliance. CYT006-AngQb is a therapeutic vaccine designed to instruct\r\nthe patient’s immune system to produce a specific anti-angiotensin II antibody response. Angiotensin II is a small hormone in the body and part of the RAS. It causes blood vessels to narrow, resulting in an increase in blood pressure. Vaccination of humans with CYT006-AngQb has been shown to induce angiotensin II specific antibodies that should inhibit binding of angiotensin II to its receptors\r\nand thus reduce the narrowing of blood vessels. As first clinical data indicate, the achieved blood pressure reduction was particularly pronounced in the early morning when the vaccine effect suppressed the naturally occurring morning rise in blood pressure.","Type-1 angiotensin II receptor; Type-2 angiotensin II receptor","Therapeutic strategy associated"]
[859,"DB05744","investigational","small molecule","CRx-139",{"$nulls":3},"CRx-139 is an oral synergistic combination drug candidates with novel mechanisms of action targeting multiple biological pathways simultaneously. It is a dissociated steroid designed to enhance the immuno-modulatory activity of a low-dose glucocorticoid steroid without a comparable increase in steroid-related side effects. The synergistic combination containing low doses of the glucocorticoid steroid prednisolone and the antidepressant paroxetine. This novel synergistic combination is developed for the treatment of immuno-inflammatory diseases.\r\n\r",null,null,"Investigated for use/treatment in rheumatoid arthritis.",null,"CRx-139 inhibits certain pro-inflammatory biomarkers, such as TNF-alpha, IL-6 and CRP and increases the anti-inflammatory cytokine IL-10.","Tumor necrosis factor; Interleukin-6; C-reactive protein; Interleukin-10","Therapeutic strategy associated"]
[860,"DB05746","investigational","small molecule","PF-03187207",{"$nulls":3},"PF-03187207 is a nitric oxide-donating prostaglandin F2-alpha analogs for the potential treatment of glaucoma. Based on the very promising preclinical results and on the well-known activities of nitric oxide, PF-03187207 is expected to have an increased capacity to reduce high IOP. The development of abnormally high IOP, due to blockage or malfunction of systems controlling the amount of fluid in the eye, is believed to be one of the principal causes of glaucoma.",null,null,"Investigated for use/treatment in glaucoma and ocular hypertension.",{"$nulls":3},"Indication associated"]
[861,"DB05750","investigational","small molecule","AVE-1625",{"$nulls":3},"AVE-1625 is an oral selective and potent antagonist of cannabinoid 1 (CB1) receptors having the same mechanism of action as rimonabant. It is currently developed in obesity and its associated comorbidities. AVE-1625 is also being developed for the treatment of  Alzheimer disease.",null,null,"Investigated for use/treatment in alzheimer's disease, obesity, and schizophrenia and schizoaffective disorders.",null,"AVE-1625 is a selective and potent antagonist of cannabinoid 1 (CB1) receptors having the same mechanism of action as rimonabant.","Cannabinoid receptor 1","Indication associated"]
[862,"DB05754","investigational","small molecule","IPH 1101",{"$nulls":3},"IPH 1101 is a chemically-synthesized structural analog of non-conventional bacterial phosphoantigens which specifically activate the Vγ9Vδ2 T cell subset. IPH 1101 is the most advanced drug candidate of the γδ T cell platform",null,null,"Investigated for use/treatment in hepatitis (viral, C), leukemia (myeloid), and lymphoma (non-hodgkin's).","IPH 1101 potentiates the direct cytotoxic activity of Vγ9Vδ2 T cells against a large number of tumor cell lines and also triggers the synthesis of pro-inflammatory cytokines - thus inducing the recruitment of other cell effectors and facilitating implementation of an adaptive response.",null,null,"Therapeutic strategy associated"]
[863,"DB05757","investigational","small molecule","DNB-001",{"$nulls":3},"DNB-001 is a first-in-class oral therapy with dual mechanism of action, which is initially being developed for the treatment of glaucoma. In preclinical animal models, DNB-001 has demonstrated potent IOP- lowering effects as well as neuroprotective effects on the optic nerve.",null,null,"Investigated for use/treatment in ocular hypertension.",{"$nulls":3},"Indication associated"]
[864,"DB05758","investigational","biotech","CYT007-TNFQb",{"$nulls":3},"CYT007-TNFQb is an active immunization therapy that aims at\r\nproviding a novel treatment to people suffering from RA or psoriasis. The vaccine should allow for administration of low\r\namounts of drug to individual patients (in the microgram range) and for convenient dosing schedules.",null,null,"Investigated for use/treatment in psoriasis and psoriatic disorders.",null,"CYT007-TNFQb is designed to instruct the patient’s immune system to produce an anti-TNF-α antibody response. The induced antibodies aim to bind and neutrolize soluble TNF-α in order to inhibit its inflammatory activity. That way, the subsequent inflammatory process should be slowed down and the deterioration of skin or other tissues reduced.","Tumor necrosis factor","Therapeutic strategy associated"]
[865,"DB05767","investigational","small molecule","Andrographolide","3α,14,15,18-tetrahydroxy-5b,9bH,10a-labda-8(20),12-dien-16-oic acid γ-Lactone","C20H30O5","[H][C@]12CCC(=C)[C@@H](C\\C=C3/[C@H](O)COC3=O)[C@]1(C)CC[C@@H](O)[C@@]2(C)CO","Andrographolide (HMPL-004) is a botanical product extracted from a herb that occurs naturally in China. The herb has an extensive history of use in TCM for the treatment of upper respiratory tract infections and other inflammatory and infectious diseases.","5508-58-7","350.455","Investigated for use/treatment in ulcerative colitis.",null,"HMPL-004 acts on multiple cellular targets in the inflammatory signal transduction pathways resulting in suppressed inflammation cytokine expression including TNF-α, IL-1β and IL-6. HMPL-004 was demonstrated to inhibit TNF-α and IL-1β production in cell-based assays. HMPL-004 is also able to inhibit NF-kB activation. NF-kB is a family of transcriptional factors that regulate a wide spectrum of genes critically involved in host defence and inflammation. The mechanism of action of HMPL-004 was further supported in laboratory IBD animal models. Treatment of IBD rats with HMPL-004 caused a significant drop in plasma cytokine concentrations, including TNF-α and IL-1β.","Tumor necrosis factor; Interleukin-1 beta; Interleukin-6; Nuclear factor NF-kappa-B p100 subunit; Nuclear factor NF-kappa-B p105 subunit","Therapeutic strategy associated"]
[866,"DB05768","investigational","small molecule","Alkaline Phosphatase",{"$nulls":3},"Alkaline Phosphatase (AP) is an oral treatment and has a very\r\nfavorable side-effect profile. AP only acts locally in the colon to reduce the continuous inflammation of the colon by endotoxin from Gram-negative bacteria and extracellular ATP in UC patients.",null,null,"Investigated for use/treatment in ulcerative colitis.","Patients with UC have reduced AP levels and activity in the inflamed tissue in the intestines. A short treatment with AP helps to restore the intestinal mucosal barrier in UC patients, which can be classified as a disease modifying antiinflammatory effect.","Two substrates that can disturb the homeostasis in\r\nhuman organs are endotoxin from Gram-negative bacteria (LPS) and adenosine triphosphate (ATP). Dephosphorylation of LPS and extracellular ATP by AP has been shown to result in restoration of homeostasis in the target organs such as GI tract and kidney, through reduction of inflammationinduced\r\ndamage. In the gastrointestinal tract, the prime source of LPS is derived from the residing Gram-negative microorganisms. In UC patients the mucosal surface of the colon wall is characterized by intermittent lesions and hyperpermeability caused by chronic inflammation. A consequence of the damaged intestinal mucosa is a reduced AP level and an increased influx of LPS responsive cells that\r\nmaintain the inflammatory response. In the gastrointestinal tract, the prime source of LPS is derived from the residing Gram-negative microorganisms. AP reduces LPS-mediated\r\ninflammation, by preventing activation of the intestinal epithelium and preventing systemic inflammatory responses that result from transmigration of endotoxin though the\r\nleaky inflamed intestinal mucosa.",null,"Therapeutic strategy associated"]
[867,"DB05769","investigational","small molecule","LCP-AtorFen",{"$nulls":3},"LCP-AtorFen is a fixed-dose combination therapy for the treatment of high cholesterol levels combining atorvastatin (the active ingredient of Lipitor®) and the lowest dose of fenofibrate without food effect. LCP-AtorFen is designed to be a once daily tablet offering a powerful and safe treatment of high cholesterol levels, addressing three primary cardiovascular risk factors: low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglycerides (TG).",null,null,"Investigated for use/treatment in hyperlipidemia.",{"$nulls":3},"Indication associated"]
[868,"DB05772","investigational","small molecule","Rabeximod",null,"C22H24ClN5O","CN(C)CCNC(=O)CN1C2=CC=C(Cl)C=C2C2=C1N=C1C=C(C)C(C)=CC1=N2","Rabeximod is an orally administered compound for treatment of moderate or severe active rheumatoid arthritis that is currently undergoing phase II clinical testing in eight European countries.","872178-65-9","409.92","Investigated for use/treatment in rheumatoid arthritis.","Rob 803 is an immunomodulator.",null,null,"Indication associated"]
[869,"DB05773","approved; investigational","biotech","Trastuzumab emtansine","Ado-trastuzumab; Ado-trastuzumab emtansine; T-DM1; Trastuzumab emtansine; Trastuzumab-DM1; Trastuzumab-MCC-DM1",null,null,"Trastuzumab emtansine, formerly called Trastuzumab-DM1 (T-DM1) is a first-in-class HER2 antibody drug conjugate (ADC) comprised of Genentech's trastuzumab antibody linked to ImmunoGen's cell-killing agent, DM1. T-DM1 combines two strategies-- anti-HER2 activity and targeted intracellular delivery of the potent anti-microtubule agent, DM1 (a maytansine derivative)--to produce cell cycle arrest and apoptosis. Trastuzumab emtansine is marketed under the brand name Kadcyla and is indicated for use in HER2-positive, metastatic breast cancer patients who have already used taxane and/or trastuzumab for metastatic disease or had their cancer recur within 6 months of adjuvant treatment. The FDA label has two precautions. First that trastuzumab emtansine and trastuzumab cannot be interchanged. Second that there is a black box warning of serious side effects such as hepatotoxicity, embryo-fetal toxicity, and cardiac toxicity.","1018448-65-1",null,"Used in HER2-positive, metastatic breast cancer patients who have already used taxane and/or trastuzumab for metastatic disease or had their cancer recur within 6 months of adjuvant treatment.\r\n\r","Trastuzumab emtansine was evaluated in two Herceptin-responsive and one Herceptin-resistant breast tumor models. In the Herceptin-responsive models, Trastuzumab-DM1 caused complete tumor regression in all mice, whereas Herceptin alone slowed tumor growth. In the Herceptin- resistant model, Herceptin alone had no effect on tumor growth. In contrast, Trastuzumab-DM1 caused >90% tumor reduction in all mice. In this Herceptin- resistant model, tumor regrowth was observed after cessation of Trastuzumab- DM1 treatment, yet regression re-occurred when dosing was resumed. The effect was specific for HER2-positive tumors. Thus the physiological effects of trastuzumab emtansine are cell cycle arrest and cell death by apoptosis.","Trastuzumab emtansine is a HER2 antibody-drug conjugate. The antibody portion is trastuzumab, which is humanized anti-HER2 IgG1, and produced in the mammalian Chinese Hamster Ovary cells. The drug portion is DM1, which is a maytansine derivative that inhibits microtubules. These two portions are covalently connected by 4- cyclohexane-1-carboxylate (MCC), which is a stable thioether linker. Together MCC and DM1 are called emtansine and are produced by chemical synthesis.\r\n\r\nTrastuzumab emtansine binds to the HER2 receptor’s sub-domain IV and goes into the cell by receptor-mediated endocytosis. Lysosomes degrade trastuzumab emtansine and release DM1. DM1 binds to tubulin in microtubules and inhibits microtubule function producing cell arrest and apoptosis. As well, similar to trastuzumab, in vitro studies have shown that both HER2 receptor signalling inhibition and antibody-dependent cytotoxicity are mediated by trastuzumab emtansine.","Receptor tyrosine-protein kinase erbB-2 antibody","Therapeutic strategy associated"]
[870,"DB05775","investigational","small molecule","CRx-401",{"$nulls":3},"CRx-401 is a novel insulin sensitizer designed to provide anti-diabetic activity without promoting weight gain. It consists of a low dose of the analgesic diflunisal in conjunction with a modified-release therapeutic dose of bezafibrate, an anti-cholesterol agent. In third-party clinical studies, the dose of bezafibrate contained in CRx-401 has been observed to have a positive impact on cellular pathways that influence glycemic and lipid profiles, and this dose has proven to be well tolerated in clinical trials. Unlike other NSAIDs, or non-steroidal anti-inflammatory drugs, the dose of diflunisal in CRx-401 has demonstrated in preclinical studies the ability to synergistically enhance the anti-diabetic effects of bezafibrate through novel disease-targeted mechanisms.",null,null,"Investigated for use/treatment in diabetes mellitus type 2.",null,"CRx-401 has a novel mechanism of action that reduces hyperglycemia while improving HDL and triglyceride levels without promoting weight gain.",null,"Indication associated"]
[871,"DB05777","approved; investigational","biotech","Thrombomodulin Alfa","Thrombomodulin (human 498-amino acid fragment); Thrombomodulin Alfa",null,null,"Thrombomodulin Alfa is a novel, recombinant and soluble thrombomodulin (ART-123). It is a human protein with both thrombin inhibiting and protein C stimulating activities, for the potential treatment of thromboembolism and blood clotting disorders, such as disseminated intravascular thromboembolism.","120313-91-9",null,"Investigated for use/treatment in blood preservative, blood (blood forming organ disorders, unspecified), sepsis and septicemia, and thrombosis.","Thrombomodulin (TM) alfa, a recombinant human soluble TM, enhances activation of pro-carboxypeptidase B2 (pro-CPB2) by thrombin. Activated pro-CPB2 (CPB2) exerts anti-inflammatory and anti-fibrinolytic activities.","Thrombomodulin alfa is a soluble form of recombinant human thrombomodulin comprising all extracellular domains of thrombomodulin. Bound to thrombin,  Thrombomodulin alfa inhibits its procoagulant activity and promotes activation of protein C.  Thrombomodulin alfa  inhibits thrombin generation by the activation of protein C and the subsequent inactivation of factor Va in the presence of protein S.  Thrombomodulin alfa attenuates the extension of the clot by inhibiting further thrombin generation on clots, while other anticoagulants inhibit the initiation of clot formation. A higher concentration of Thrombomodulin alfa is needed to affect clotting time and platelet aggregation than thrombin generation.","Prothrombin inhibitor; Coagulation factor V","Therapeutic strategy associated"]
[872,"DB05787","investigational","biotech","LM-609",{"$nulls":3},"LM-609 (Vitaxin) is an artificial antibody that targets a protein on the surface of newly forming blood vessels, as well as on certain tumors. In addition to cancer, the protein has been implicated in bone destruction in rheumatoid arthritis and the inflammatory process in psoriasis.",null,null,"Investigated for use/treatment in colorectal cancer, melanoma, prostate cancer, psoriasis and psoriatic disorders, rheumatoid arthritis, and solid tumors.",null,"LM-609 targets the alpha-v beta-3 integrin, which is a protein complex expressed on the surface of newly forming blood vessels, certain tumor types, and on a number of other cell types, including macrophages and osteoclasts. As such, alpha-v beta-3 integrin is implicated in a number of disease processes, including the growth and metastasis of tumors, the bone destruction in RA and the inflammatory process in psoriasis.","Integrin beta-3","Therapeutic strategy associated"]
[873,"DB05792","investigational","small molecule","Arylacenamide",null,"C23H35Cl2N","Cl.CCN(C\\C=C/C1=CC(Cl)=C(C=C1)C1CCCCC1)C1CCCCC1","Arylacenamide (SR31747) is a peripheral  ligand that binds four proteins in human cells, i.e. SRBP-1, -2, HSI and its relative SRBP-2. It is a dual agent with both immunomodulatory and antiproliferative activities.","132173-07-0","396.437","Investigated for use/treatment in cancer/tumors (unspecified), immunosuppressive, and prostate cancer.",null,"SR31747 blocks proliferation of human lymphocytes, modulates the expression of pro- and anti-inflammatory cytokines, and was shown to protect animals in vivo against acute and chronic inflammatory conditions such as acute graft-versus-host reaction, lethality induced by staphylococcal enterotoxin B and lipopolysaccharide or rheumatoid arthritis. Besides these immunomodulatory activities, the molecule also inhibits the proliferation of various tumor cell lines in vitro in a time- and concentration-dependent manner.","HCG20471, isoform CRA_c","Therapeutic strategy associated"]
[874,"DB05796","investigational","small molecule","Daglutril","((3S)-3-{1-((2R)-2-Ethoxycarbonyl-4-phenylbutyl)cyclopentanecarboxamido}-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)acetic acid; Daglutril","C31H38N2O6","CCOC(=O)[C@H](CCC1=CC=CC=C1)CC1(CCCC1)C(=O)N[C@H]1CCC2=CC=CC=C2N(CC(O)=O)C1=O","Daglutril is an orally active, mixed neutral endopeptidase/endothelin converting enzyme inhibitor under development for the treatment of essential hypertension and congestive heart failure.","182821-27-8","534.6432","Investigated for use/treatment in congestive heart failure and hypertension.",null,"SLV306 increased plasma natriuretic peptides and big endothelin-1 levels in a dose-dependent manner, confirming neutral endopeptidase and endothelin-converting enzyme inhibition. The combined inhibition of neutral endopeptidase and endothelin-converting enzyme may be useful in heart failure by reducing right and left cardiac filling pressures","Neprilysin","Indication associated"]
[875,"DB05804","investigational","small molecule","Prasterone sulfate","(3-beta)-3-(Sulfooxy)androst-5-en-17-one; 17-Ketoandrost-5-en-3beta-yl sulfate; 17-oxoandrost-5-en-3β-yl hydrogen sulphate; 3-O-Sulfodehydroepiandrosterone; 3beta-Hydroxyandrost-5-en-17-one 3-sulfate; Androst-5-en-17-on-3beta-yl sulfuric acid; Dehydroepiandrosterone 3-sulfate; Dehydroepiandrosterone monosulfate; Dehydroepiandrosterone sulfate; Dehydroepiandrosterone sulphate; Dehydroisoandrosterone sulfate; Dehydroisoandrosterone-3-sulfate; DHEA sulfate; DHEA sulphate; DHEA-S; Prasterone sulphate","C19H28O5S","[H][C@@]12CCC(=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC=C2C[C@H](CC[C@]12C)OS(O)(=O)=O","DHEA sulfate is the major steroid of the fetal adrenal. DHEA-S is the principal adrenal androgen and is secreted together with cortisol under the control of ACTH and prolactin. DHEA-S is elevated with hyperprolactinemia.","651-48-9","368.488","Investigated for use/treatment in asthma and burns and burn infections.",null,"The low levels of dehydroepiandrosterone sulfate(DHEA-S)is associated with unfavorable levels of several strong cardiovascular disease risk factors, such as lipids and blood pleasure, which are components of the metabolic syndrome, and insulin levels. DHEA-S deficiency is risk factors of obesity and insulin resistance, but it is not clear, whether this possible influence is independent.",null,"Therapeutic strategy associated"]
[876,"DB05805","investigational","small molecule","NS-2359",null,"C16H21Cl2NO","COC[C@H]1[C@H]2CC[C@@H](C[C@@H]1C1=CC(Cl)=C(Cl)C=C1)N2C","NS2359 is a triple monoamine re-uptake inhibitor with a new, unique drug profile expected to yield important benefits compared to existing treatments of depression. Enhancing the function of the three neurotransmitters serotonin, noradrenalin and dopamine, NS2359 has a desired \"triple-mode-of-action\". This mode of action is expected to produce an optimal reduction in all disease symptoms and the possibility of an earlier onset of action compared to antidepressants already on the market.","195875-68-4","314.25","Investigated for use/treatment in addictions, attention deficit/hyperactivity disorder (ADHD), and depression.",null,"NS2359 has a triple mode of action, inhibiting neuronal reuptake of the three neurotransmitters serotonin, noradrenaline and dopamine, all of which play an important role in the development of depression. NS2359 also increases release of the neurotransmitter acetylcholine. This mode of action is expected to produce a better and faster reduction of the symptoms associated with depression. This rationale has been confirmed in independent studies in which existing anti-depressants affecting serotonin have been combined with drugs that affect noradrenaline/dopamine. Drugs with this triple mode of action are expected to become the future standard in the treatment of depression.",null,"Indication associated"]
[877,"DB05810","investigational","small molecule","99mTc-glucarate",{"$nulls":3},"99mTc-glucarate(GLA) is an agent for non-invasive detection of breast tumours.",null,null,"Investigated for use/treatment in myocardial infarction.",null,"99m Tc-Glucarate marks acute myocardial infarct very early after occlusion and appears to accurately assess infarct size when compared with triphenyltetrazolium chloride (TTC) staining.",null,"Indication associated"]
[878,"DB05819","investigational","biotech","NBI-6024",{"$nulls":3},"NBI-6024 is an altered peptide ligand that is designed to cause an immune response which result in preservation of beta-cell function and endogenous insulin production.",null,null,"Investigated for use/treatment in diabetes mellitus type 1 and pediatric indications.",null,"NBI-6024 is designed specifically to generate an immune response that could result in preservation of beta-islet cell function in patients with  Type I diabetes or juvenile-onset diabetes. Because there is progressive beta-islet destruction in Type I diabetes, an early intervention strategy with a product like NBI-6024 could delay or prevent insulin dependence.",null,"Indication associated"]
[879,"DB05820","investigational","small molecule","DP-b99",{"$nulls":3},"DP-b99 is a newly developed lipophilic, cell permeable derivative of BAPTA (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid), that is under development as a neuroprotectant for the potential treatment of stroke, head trauma and neurological damage associated with coronary artery bypass graft.",null,null,"Investigated for use/treatment in strokes and traumatic brain injuries.",null,"DP-b99 is a discovery product, rationally designed using D-Pharm’s proprietary technology, Membrane Active Chelators (MAC). Considerable evidence suggests that redistribution of metal ions and disturbances in metal ion homeostasis are key components in the cascade of events underlying cell damage in stroke. In the first hours post-stroke ion disturbances cause excitatory cell damage and in the days and weeks following they contribute to edema, inflammation and cell death. DP-b99 is a novel approach to neuroprotection based on selective modulation of calcium, zinc, copper and iron homeostasis in the vicinity of cell membranes.",null,"Indication associated"]
[880,"DB05825","investigational","small molecule","NCX 1015",{"$nulls":3},"NCX 1015 is nitric oxide-releasing derivative of prednisolone developed for the treatment of inflammatory bowel disease (IBD) by NicOx SA.",null,null,"Investigated for use/treatment in arthritis and arthritic pain and inflammatory bowel disease.",null,"NCX-1015 is the prototype of a new class of glucocorticoids, the nitro-steroids, capable of enchancing anti-inflammatory properties and reduced side effects. It also abrogates the plasma levels of a catabolite of cartilage and bone metabolism, indication of a disease modifying action.",null,"Therapeutic strategy associated"]
[881,"DB05829","approved; investigational","biotech","Parathyroid hormone","Parathormone; Parathormone (human recombinant); Parathyrin; Parathyroid hormone; Parathyroid hormone (1-84) human recombinant; Parathyroid hormone (rDNA); PTH; PTH(1-84); rhPTH; rhPTH(1-84); rPTH; rPTH(1-84)",null,null,"Parathyroid hormone (PTH)  is a single-chain polypeptide composed of 84 amino acids.  Available as Preotact, it is an identical form of human recombinant hormome which produced as a fusion protein undergoeing post-translational processing involving the cleavage of the OmpA leader sequence, leaving the mature protein as a single-chain 84 amino-acids polypeptide (9.4 kDa).\r\n\r\nPreotact is used in the treatment of osteoporosis in postmenopausal women at high risk of osteoporotic fractures and is marketed in Europe by Nycomed. Preos is a registered trade mark owned by NPS Pharmaceuticals, Inc. The name Preos and the New Drug Application is pending approval by the U.S. Food and Drug Administration (FDA).","9002-64-6",null,"For use/treatment in osteoporosis.","Parathyroid hormone is responsible for the fine regulation of serum calcium concentration on a minute-to-minute basis. This is achieved by the acute effects of the hormone on calcium resorption in bone and calcium reabsorption in the kidney. The phosphate mobilized from bone is excreted into the urine by means of the hormone's influence on renal phosphate handling. Parathyroid hormone also stimulates calcium absorption in the intestine, this being mediated indirectly by 1,25-dihydroxyvitamin D. Thus, a hypocalcemic stimulus of parathyroid hormone secretion results in an increased influx of calcium from three sources (bone, kidney, and intestine), resulting in a normalization of the serum calcium concentration without change in the serum phosphate concentration.","The biological actions of rhPTH are mediated through binding to at least two distinct high- affinity cell-surface receptors specific for the N-terminal and C-terminal regions of the molecule, both of which are required for normal bone metabolism. The N-terminal portion of the molecule is primarily responsible for the bone building effects of parathyroid hormone. The C-terminal portion of the molecule has antiresorptive activity and is necessary for normal regulation of N-terminal fragment activity.","Parathyroid hormone/parathyroid hormone-related peptide receptor activator; Parathyroid hormone 2 receptor activator","Indication associated"]
[882,"DB05839","investigational","small molecule","BG-777",{"$nulls":3},"BG-777 is an immunomodulator with proven efficacy against viral and bacterial infections in preclinical studies.",null,null,"Investigated for use/treatment in cytomegalovirus (CMV) retinitis, HIV infection, influenza, and pneumonia.",null,"BG-777 will activate the cells of the immune system and improve its ability to clear the virus, and resist infection.",null,"Indication associated"]
[883,"DB05840","investigational","small molecule","AGI-1096",{"$nulls":3},"AGI-1096 is a novel oral antioxidant and selective anti-inflammatory agent that is being developed to address the accelerated inflammation of grafted blood vessels, known as transplant arteritis, common in chronic organ transplant rejection.",null,null,"Investigated for use/treatment in transplant (rejection).",null,"AGI-1096 is a novel phenolic intracellular antioxidant with anti-inflammatory and antiproliferative properties.",null,"Therapeutic strategy associated"]
[884,"DB05843","investigational","small molecule","trans NV-04",{"$nulls":3},"trans NV-04 is a cardiovascular drug which  shows a significant reduction in blood pressure and arterial stiffness.",null,null,"Investigated for use/treatment in cardiovascular disorders and hypertension.",null,"trans-NV-04 promotes blood vessel relaxation, acts as an antioxidant and inhibits smooth muscle cell growth in blood vessels, factors contributing to build up of obstructive vascular plaques or atherosclerosis.            \r\n\r\n\r",null,"Indication associated"]
[885,"DB05849","investigational","small molecule","NCX 950",{"$nulls":3},"NCX 950, beta2-adrenoceptor agonists is widely used in the treatment of pulmonary diseases.",null,null,"Investigated for use/treatment in asthma and chronic obstructive pulmonary disease (COPD).",null,"NCX-950 elicits potent relaxant and anti-inflammatory activities compared with salbutamol, and these effects may be mainly due to the activation of the beta2-adrenoceptor rather than the cGMP pathway.","Beta-2 adrenergic receptor","Therapeutic strategy associated"]
[886,"DB05854","investigational","small molecule","CLX-0921",{"$nulls":3},"CLX-0921 is investigated for use/treatment in diabetes mellitus type 2. CLX-0921 is a solid. CLX-0921 has a spectrum of activity that differs from commercially available thiazolidinediones. This substance targets the protein peroxisome proliferator-activated receptor gamma. It is a pharmacologically active antihyperglycemic agent that acts by increasing peripheral tissue sensitivity to insulin.",null,null,"Investigated for use/treatment in diabetes mellitus type 2.",null,"CLX-0921 has a spectrum of activity that differs from commercially available TZDs. It also increases glycogen synthesis, an activity not typically associated with rosiglitazone or pioglitazone. Thus it appears to have a distinct spectrum of activity relative to other TZDs.","Peroxisome proliferator-activated receptor gamma","Target associated"]
[887,"DB05865","investigational","small molecule","VIT-100",{"$nulls":3},"VIT-100 was developed by ItherX Pharmaceuticals of San Diego. In preclinical studies, companyl has shown that VIT-100 inhibits the growth of cells taken from multiple keloid biopsies as compared to the same keloidal cells treated with a control. It is believed that similar effects would be seen in cells isolated from hypertrophic scars.",null,null,"Investigated for use/treatment in diabetic retinopathy, scar tissue, and vitreous hemorrhage.",null,"VIT-100 is used for  Proliferative Vitreoretinopathy (PVR), a serious eye disease characterized by uncontrolled cellular growth that can lead to retinal detachment and ensuing vision loss. It  is expected to reduce the incidence of repeat retinal detachment in patients who undergo surgical repair.",null,"Indication associated"]
[888,"DB05866","investigational","small molecule","ETC-1001",{"$nulls":3},"ETC-1001 is Pfizer’s lead oral small molecule product candidate which  is intended to be a chronic treatment for individuals with lipid disorders.",null,null,"Investigated for use/treatment in hyperlipidemia.",null,"ETC-1001 is a synthetic, orally-active lipid regulating agent designed to elevate levels of high-density lipoprotein cholesterol (HDL-C), the \"good\" cholesterol. In pre-clinical studies, it shows the ability to elevate HDL-cholesterol levels, while also reducing levels of low-density lipoprotein cholesterol (LDL-C), the \"bad\" cholesterol, and triglycerides. It  also inhibits the progression of atherosclerosis in pre- clinical models.",null,"Indication associated"]
[889,"DB05869","investigational","small molecule","Ethyl pyruvate","2-oxopropanoic acid ethyl ester; 2-oxopropionic acid ethyl ester; Ethyl 2-oxopropanoate; Ethyl 2-oxopropionate; Ethyl methylglyoxylate; Pyruvic acid ethyl ester; Pyruvic acid, ethyl ester","C5H8O3","CCOC(=O)C(C)=O","CTI-01 (ethyl pyruvate) is a novel anti-inflammatory agent for the treatment of critical inflammatory conditions. CTI-01 shows a  potent anti-inflammatory and tissue protection activity in multiple animal models of disease including pancreatitis, ischemia-reperfusion injury, sepsis, renal injury and endotoxemia.","617-35-6","116.1152","Investigated for use/treatment in burns and burn infections, cardiac surgery, inflammatory disorders (unspecified), ischemic reperfusion injury, and sepsis and septicemia.",null,"CTI-01 inhibits the systemic release of cytokines, such as TNF-alpha and HMGB1, which promote the body's inflammatory response. The over-expression of these cytokines has been linked to diseases that occur in critical care settings, such as severe organ damage following cardiopulmonary bypass (CPB) and post-operative ileus following abdominal surgery.","Tumor necrosis factor; High mobility group protein B1","Therapeutic strategy associated"]
[890,"DB05879","investigational","biotech","AME-527",{"$nulls":3},"AME-527 is a humanized monoclonal antibody that recognizes human TNF-alpha (hTNF-alpha) with high affinity and specificity. AME-527 was generated by protein engineering and identified from a library of antibody variants based on its improved binding properties.",null,null,"Investigated for use/treatment in rheumatoid arthritis.",null,"AME-527 is approximately ten-fold more potent than Remicade(R) in binding to and neutralizing the hTNF-alpha molecule, and 6 to 8-fold more potent than Humira(TM). Tumor necrosis factor-alpha (TNF-alpha) has a key role in rheumatoid synovitis, as an inflammatory cytokine at the top of the inflammatory cascade. Blocking TNF-alpha with AME-527 or fusion proteins is an important and established disease intervention, validating the role of the cytokine in disease activity and progression.","Tumor necrosis factor","Therapeutic strategy associated"]
[891,"DB05882","investigational","small molecule","CHF 4227",{"$nulls":3},"CHF 4227 is a new selective estrogen receptor modulator (SERM). The compound has a high receptor affinity and has shown promising efficacy in the prevention of bone loss in animal models of osteoporosis. Additionally, the compound has shown no uterotrophic activity suggesting a potential therapeutic advantage over drugs normally used in postmenopausal therapy.",null,null,"Investigated for use/treatment in osteoporosis.",null,"CHF 4227 binds with high affinity to the human estrogen receptor-alpha and beta. It compares favorably in efficacy and potency with raloxifene in preventing bone loss and in antagonizing EE2 stimulation of the uterus. This attribute along with the minimal uterine stimulation suggests a therapeutic advantage to CHF 4227 over EE2 or raloxifene for the treatment of postmenopausal women.","Estrogen receptor alpha; Estrogen receptor beta","Indication associated"]
[892,"DB05888","investigational","small molecule","MEM 1414",{"$nulls":3},"MEM 1414 is a PDE4 inhibitor that is being evaluated for the treatment of Alzheimer’s disease. This drug candidate has completed Phase 1 clinical trials. MEM 1414 works by blocking phosphodiesterase, an enzyme that breaks down an important brain chemical, cyclic AMP. It appears to work in the area of the brain where new memories are formed.",null,null,"Investigated for use/treatment in alzheimer's disease, depression, memory loss, and neurologic disorders.",null,"MEM 1414 is PDE4 inhibitor which is designed to selectively raise levels of cyclic adenosine monophosphate, or cAMP, by inhibiting the activity of PDE4, the enzyme which breaks down cAMP, and therefore they may be beneficial in restoring memory function. PDE4 inhibitors may also have potential therapeutic value in multiple other indications.","CAMP phosphodiesterase","Indication associated"]
[893,"DB05889","approved; investigational","biotech","Inotuzumab ozogamicin","Inotuzumab ozogamicin",null,null,"Inotuzumab ozogamicin is an antibody-drug conjugate using linker and cytotoxic drug technology similar to that developed for the ground-breaking treatment Mylotarg (), which was approved by the US FDA in 2000 for the treatment of acute myeloid leukaemia. Inotuzumab ozogamicin consists of a recombinant humanised IgG4 kappa CD22-targeting monoclonal antibody covalently attached to calicheamicin derivative, N-acetyl-gamma-calicheamicin dimethylhydrazide, which is a potent DNA-binding cytotoxic agent . Developed by Pfizer and UCB, inotuzumab ozogamicin was granted approval by EU in June 2017 followed by FDA on August 17th, 2017 for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). ALL is a rapidly progressing cancer of the bone marrow that is associated with high mortality rates and low therapeutic response from standard chemotherapies in relasping conditions. In a randomized trial, inotuzumab ozogamicin displayed higher percentages of patients undergoing longer periods of complete remission with no evidence of disease in comparison to patients receiving alternative chemotherapy .","635715-01-4",null,"Indicated as monotherapy for the treatment of adults with relapsed or refractory CD22-positive B cell precursor acute lymphoblastic leukaemia (ALL).","Inotuzumab ozogamicin is an antineoplastic agent that targets CD22 antigen expressed on immature B-cell lymphocytes and blocks further growth of tumor cells. The drug aims to restore normal blood counts and achieve complete remission from the disease. QT interval prolongation was observed in patients receiving inotuzumab ozogamicin.","Inotuzumab ozogamicin is comprised of cytotoxic antibiotic N-acetyl-gamma-calicheamicin dimethylhydrazide attached to a humanized monoclonal IgG4 antibody via 4-(4 acetylphenoxy) butanoic acid (acetyl butyrate) linker. The drug exerts a potent cytotoxic effect against CD22+ B-cell lymphoma when the antibody binds to the CD22 receptor on the surface of B cells . The drug-CD22 complex is rapidly internalized into the cell, forming an endosome which subsequently fuses with lysosomes. N-acetyl-gamma-calicheamicin dimethylhydrazide is then intracellularly released into the acidic environment. N-acetyl-gamma-calicheamicin dimethylhydrazide is a calicheamicin derivative, which is naturally produced by the bacterium Micromonospora echinospora, and is toxic to the body when not bound to the antibody. It mediates apoptosis of the cell by binding to the minor groove of DNA in a sequence-specific manner and undergoing a structural change to generate diradicals . These changes abstract hydrogen ions from the phosphodiester bonds of double-stranded DNA, resulting in breaks and cell apoptosis .","B-cell receptor CD22 antibody","Therapeutic strategy associated"]
[894,"DB05892","investigational","biotech","RI 624",{"$nulls":3},"RI 624 is a novel humanized monoclonal antibody that blocks nerve growth factor (NGF), a key mediator of acute and chronic pain. RI 624 is being developed by Rinat and is currently in Phase I clinical trials.",null,null,"Investigated for use/treatment in pain (acute or chronic).",null,"RI 624 works very differently from all currently approved drugs for the treatment of pain. Unlike the other pain relievers, RI 624 primarily works to inhibit the production of NGF, rather than COX-2 for instance. NGF is a member of a family of proteins known as neurotrophins that plays a role in the growth of certain sensory neurons, an activity that appears to end at birth or shortly afterward. Pain-causing injury or inflammation induces the synthesis and stimulates the release of NGF in later stages of life. Scientific observation has shown that the up-regulation of NGF is a common component of the inflammatory response that initiates and sustains the pain sensation. NGF therefore appears to have profound direct and indirect stimulatory effects on the primary sensory neurons that mediate pain. RI 624 essentially blocks NGF from binding to its target area and thus impedes an imflammatory response.","Beta-nerve growth factor","Therapeutic strategy associated"]
[895,"DB05894","investigational","small molecule","GT 389-255",{"$nulls":3},"Peptimmune’s lead product GT 389-255, is a novel lipase inhibitor and fat binding hydrogel polymer conjugate for the treatment of obesity which has completed single and multiple ascending dose (SAD and MAD) Phase I trials. It is expected to block fat absorption with fewer side effects than currently marketed lipase inhibitors.\r",null,null,"Investigated for use/treatment in obesity.",null,"GT 389-255 is a novel conjugate of a proprietary pancreatic lipase inhibitor and a fatbinding hydrogel polymer for the treatment of obesity. GT 389-255 is a novel conjugate of a proprietary pancreatic lipase inhibitor and a fat binding hydrogel polymer for the treatment of obesity. It acts within the gastro-intestinal tract to prevent fat digestion and is expected to inhibit > 30% of fat absorption. The novel conjugate is expected to have fewer side-effects than currently marketed therapies. The currently marketed pancreatic lipase inhibitor Orlistat, is associated with oily incontinence, caused by mal-absorbed triglycerides. GT 389-255 is expected to have minimal systemic exposure. Less than 1% of the lipase inhibitor is absorbed and the fat binding polymer is not absorbed.",null,"Therapeutic strategy associated"]
[896,"DB05895","investigational","biotech","HGS-TR2J",{"$nulls":3},"HGS-TR2J is a novel agonistic human monoclonal antibody to TRAIL Receptor 2, in patients with advanced solid malignancies. It is developed by Human Genome Sciences, Inc and is under Phase I of clinical trial.",null,null,"Investigated for use/treatment in solid tumors.",null,"HGS-TR2J binds TRAIL Receptor 2 with high affinity, induces apoptosis and has anti-tumor activity, both as a single agent and in combination with chemotherapy. HGS-TR2J mimics the activity of native TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) and, thus, is considered an agonistic antibody. Numerous nonclinical studies have shown that cell lines derived from a broad array of solid and hematological human tumors, including lung, colon, breast, multiple myeloma, prostate and pancreas, are sensitive to killing by apoptosis (programmed cell death) induced by native TRAIL or by agonistic antibodies to TRAIL Receptors 1 and 2.2-24.","Tumor necrosis factor receptor superfamily member 10B","Therapeutic strategy associated"]
[897,"DB05905","investigational","small molecule","TD-2749",null,"C26H38N6O2","CC(C)N1N=C(C(=O)N[C@@H]2C[C@@H]3CC[C@H](C2)N3CCN2CCN(CC2)C(C)=O)C2=CC=CC=C12","TD-2749 is selective 5-HT4 agonists discovered by Theravance through the application of multivalent drug design in a drug discovery program dedicated to finding new medicines for GI motility disorders such as chronic constipation, constipation-predominant irritable bowel syndrome (C-IBS), opioid-induced constipation, functional dyspepsia and diabetic gastroparesis.","863248-59-3","466.63","Investigated for use/treatment in constipation, gastrointestinal diseases and disorders (miscellaneous), gastroparesis, and irritable bowel syndrome (IBS).",null,null,"5-hydroxytryptamine receptor 4","Indication associated"]
[898,"DB05906","investigational","biotech","CCR5 mAb",{"$nulls":3},"CCR5 mAb is a fully human monoclonal antibody that specifically recognizes and binds the chemokine receptor CCR5, which is known to be a key facilitator of infection with human immunodeficiency virus (HIV-1). It was generated by HGS using the Abgenix XenoMouse technology.",null,null,"Investigated for use/treatment in HIV infection.",null,"The chemokine receptor CCR5 provides a portal of entry for HIV-1 and serves a target for potential new antiretroviral therapies. CCR5 monoclonal antibodies (mAb) and small-molecule CCR5 antagonists potently block HIV-1 entry in vitro, and controlled clinical trials have provided initial proof-of-concept for this mode of therapy.","C-C chemokine receptor type 5","Target associated"]
[899,"DB05911","investigational","small molecule","RUS 3108",{"$nulls":3},"RUS 3108 is being developed for the treatment of atherosclerosis, the major cause of cardiovascular disorders such as heart attacks and stroke by Dr. Reddy’s Laboratories. \r\nThe drug’s Phase I clinical trials have been initiated in Europe to assess safety of the drug compound in healthy volunteers. \r",null,null,"Investigated for use/treatment in atherosclerosis.",null,"RUS-3108 represents a new approach to the treatment of atherosclerosis. It is a first-in-class compound and works to directly modulate the disease through affecting multiple pathways involved in the disease process such as inflammation, proliferation and thrombosis by inducing a protein called perlecan. It has the potential to prevent the formation of atherosclerotic plaques and reverse atherosclerosis.",null,"Indication associated"]
[900,"DB05913","investigational","small molecule","OSI-930",null,"C22H16F3N3O2S","FC(F)(F)OC1=CC=C(NC(=O)C2=C(NCC3=CC=NC4=CC=CC=C34)C=CS2)C=C1","OSI-930 is an orally active inhibitor of two clinically validated targets: c-Kit and the vascular endothelial growth factor receptor-2 (VEGFR-2). OSI-930 is designed to target both cancer cell proliferation and blood vessel growth (angiogenesis) in selected tumors. In preclinical studies, OSI-930 shows broad efficacy in tumor models representative of small cell lung cancer, glioblastoma, colorectal, renal, head and neck, non-small cell lung cancer and gastric cancers.","728033-96-3","443.44","Investigated for use/treatment in solid tumors.",null,"OSI-930 is a multi-targeted tyrosine kinase inhibitor that is designed to act as a potent co-inhibitor of the receptor tyrosine kinases c-Kit and VEGFR-2. The inhibition of the tyrosine kinase activity of Kit is expected to result in reduced cancer cell proliferation and increased cellular apoptosis in tumor types driven by Kit, resulting in inhibition of tumor growth. OSI-930 is also capable of inhibiting VEGFR-2. This receptor is present on endothelial cells and is a key mediator of blood vessel growth in response to the angiogenic growth factor VEGF. This pathway is believed to be the single most important mechanism for recruitment of new blood vessels in nearly all solid tumors. Inhibition of this pathway should therefore impact the growth and metastases of a wide range of angiogenesis-dependent malignancies.","Mast/stem cell growth factor receptor Kit; Vascular endothelial growth factor receptor 1","Therapeutic strategy associated"]
[901,"DB05939","investigational","small molecule","MK-0354",null,"C7H8N6","C1CC2=C(C1)C(=NN2)C1=NNN=N1","MK-0354, is an orally administered drug candidate under development by Merck for the treatment of atherosclerosis and related disorders. It targets G protein-coupled receptor, or GPCR, that have the potential to regulate plasma lipid profiles, including HDL, or the good cholesterol, similar to the therapeutic action of niacin.","851776-28-8","176.183","Investigated for use/treatment in atherosclerosis.",null,null,"G-protein coupled estrogen receptor 1","Indication associated"]
[902,"DB05943","investigational","small molecule","Resatorvid","Resatorvid","C15H17ClFNO4S","[H][C@]1(CCCC=C1C(=O)OCC)S(=O)(=O)NC1=C(Cl)C=C(F)C=C1","Resatorvid is an investigational compound designed for the treatment of severe sepsis.","243984-11-4","361.81","Investigated for use/treatment in sepsis and septicemia.",null,"TAK-242 suppresses production of inflammatory mediators such as cytokine by inhibiting the signal transduction through Toll-like receptor 4 (TLR4) which is one of the receptors recognizing the bacterial components.","Cytokine receptor common subunit beta; Cytokine receptor common subunit gamma","Therapeutic strategy associated"]
[903,"DB05945","investigational","biotech","MDX-1303",{"$nulls":3},"MDX-1303 is a fully human antibody against the inhalation anthrax, the most lethal form of illness in humans caused by the Bacillus anthracis bacterium, and targets a protein component of these lethal toxins known as the anthrax protective antigen.","915947-57-8",null,"Investigated for use/treatment in anthrax exposure and bacterial infection.",null,"MDX-1303 targets a protein component of lethal toxins produced by the bacterium known as the anthrax protective antigen. The anthrax protective antigen initiates the onset of the illness by attaching to cells in the infected person, and then facilitates the entry of additional destructive toxins into the cells. MDX-1303 is designed to target anthrax protective antigen and protect the cells from damage by the anthrax toxins.","Anthrax toxin receptor 2; Anthrax toxin receptor 1","Indication associated"]
[904,"DB05959","investigational","small molecule","ENMD-1198",null,"C20H25NO2","COC1=C(C=C2CC[C@H]3[C@@H]4CC=C[C@@]4(C)CC[C@@H]3C2=C1)C(N)=O",null,"864668-87-1","311.425","Investigated for use/treatment in cancer/tumors (unspecified) and solid tumors.",null,"ENMD-1198, a new chemical entity (NCE) based on a modified chemical structure of 2-methoxyestradiol (2ME2), is designed to decrease metabolism while retaining 2ME2's multiple mechanisms of action, including inducing apoptosis, disrupting microtubules, and inhibiting HIF-1 alpha. In preclinical studies, ENMD-1198 has been shown to be an orally active, antimitotic agent that leads to arrest of cell division and apoptosis in tumor cells. It also exerts antiangiogenic activity that further contributes to its overall antitumor effects.","Tumor necrosis factor receptor superfamily member 11A; Hypoxia-inducible factor 1-alpha; Signal transducer and activator of transcription 3","Therapeutic strategy associated"]
[905,"DB05964","investigational","small molecule","Amitifadine",null,"C11H11Cl2N","[H][C@]12C[C@]1(CNC2)C1=CC(Cl)=C(Cl)C=C1",null,"410074-73-6","228.12","Investigated for use/treatment in depression.",null,"DOV 21947 exhibits antidepressant-like properties as well as potent analgesic activity. It inhibits reuptake of the three neurotransmitters most closely linked to depression - serotonin, norepinephrine and dopamine - can produce greater overall efficacy than currently marketed antidepressants.","Sodium-dependent serotonin transporter; Sodium-dependent noradrenaline transporter; Dopamine D2 receptor","Indication associated"]
[906,"DB05968","investigational","small molecule","PR-104",null,"C14H20BrN4O12PS","CS(=O)(=O)OCCN(CCBr)C1=C(C=C(C=C1[N+]([O-])=O)[N+]([O-])=O)C(=O)NCCOP(O)(O)=O",null,"851627-62-8","579.27","Investigated for use/treatment in cancer/tumors (unspecified) and solid tumors.",null,"PR-104 is a novel hypoxia-activated DNA cross-linking agent with marked activity against human tumor xenografts, both as monotherapy and combined with radiotherapy and chemotherapy. Upon intravenous administration, PR-104 is converted by systemic phosphatases to the alcohol intermediate PR-104A, which is reduced to form the active DNA-crosslinking mustard species hydroxylamine PR-104H intracellularly under hypoxic conditions. PR-104H specifically crosslinks hypoxic tumor cell DNA, resulting in the inhibition of DNA repair and synthesis, cell-cycle arrest, and apoptosis in susceptible hypoxic tumor cell populations while sparing normoxic tissues.","Tumor necrosis factor","Therapeutic strategy associated"]
[907,"DB05969","investigational","small molecule","SNS-032",null,"C17H24N4O2S2","CC(C)(C)C1=CN=C(CSC2=CN=C(NC(=O)C3CCNCC3)S2)O1",null,"345627-80-7","380.53","Investigated for use/treatment in cancer/tumors (unspecified), leukemia (unspecified), lymphoma (unspecified), multiple myeloma, and solid tumors.",null,"SNS-032 is a potent and selective inhibitor of CDKs 2, 7 and 9, which are critical in the communication and relay of signals to promote cellular growth and function. CDK2 is involved in cellular proliferation by regulating the initiation of and progression through the DNA-synthesis phase of the cell cycle. CDK7 and CDK9 are involved in transcriptional regulation of certain proteins involved in cell survival. Inappropriate activity by these CDKs can lead to unregulated proliferation, avoidance of apoptosis and increased cell survival, all of which are hallmarks of cancer. By selectively targeting these CDKs, SNS-032 may halt both aberrant cell proliferation and induce apoptosis.","Cyclin-dependent kinase 7; Vascular endothelial growth factor A","Therapeutic strategy associated"]
[908,"DB05971","investigational","small molecule","Archexin",{"$nulls":6},"Investigated for use/treatment in solid tumors.",null,"RX-0201 is a first-in-class signal inhibitor that directly represses the production of Akt, a protein kinase that plays a key role in cancer progression. A less toxic therapeutic approach to cancer treatment, RX-0201 blocks the growth of tumor cells and promotes cell death (apoptosis).","RAC-alpha serine/threonine-protein kinase","Therapeutic strategy associated"]
[909,"DB05973","investigational","small molecule","Inosine 5'-sulfate",null,"C10H12N4O8S","O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]1O)N1C=NC2=C1N=CNC2=O",null,"70023-32-4","348.29","Investigated for use/treatment in gastrointestinal diseases and disorders (miscellaneous), inflammatory bowel disease, and ulcerative colitis.",{"$nulls":3},"Indication associated"]
[910,"DB05974","investigational","small molecule","Transcrocetinate","8,8'-diapo-8,8'-carotenedioic acid; 8,8'-diapo-ψ,ψ-carotenedioic acid; 8,8'-diapocarotenedioic acid; Crocetin; trans-crocetin","C20H24O4","C\\C(\\C=C\\C=C(/C)C(O)=O)=C/C=C/C=C(\\C)/C=C/C=C(\\C)C(O)=O","Vitamin A-analog that increases diffusivity of oxygen in aqueous solutions, including plasma.","27876-94-4","328.408","Investigated for use/treatment in cancer/tumors (unspecified), hemorrhage, hypoxia, respiratory failure, and strokes.",null,"Trans sodium crocetinate is a novel drug, which has been shown to increase whole-body oxygen consumption during hemorrhagic shock. It works by increasing the diffusion rate of oxygen through plasma rather than on a specific symptom of hemorrhagic shock and has been suggested as a general treatment for hypoxemia. Thus it could also be beneficial for treating respiratory insufficiencies.",null,"Indication associated"]
[911,"DB05983","investigational","small molecule","Bardoxolone methyl","Bardoxolone methyl","C32H43NO4","COC(=O)[C@]12CCC(C)(C)C[C@H]1[C@H]1C(=O)C=C3[C@@]4(C)C=C(C#N)C(=O)C(C)(C)[C@@H]4CC[C@@]3(C)[C@]1(C)CC2",null,"218600-53-4","505.699","Investigated for use/treatment in lymphoma (unspecified), multiple myeloma, and solid tumors.",null,"RTA 402 inhibits the activity of nuclear factor kappa-B (NF-kB) activated by tumor necrosis factor (TNF) and other inflammatory agents in a variety of cancer cells. It is a novel targeted cancer therapy with a unique mechanism of action. It exploits fundamental physiological differences between cancerous and noncancerous cells by modulating oxidative stress response pathways. As a result, the drug is toxic to cancer cells but induces protective antioxidant and anti-inflammatory responses in normal cells.","NF-kappa-B inhibitor alpha","Therapeutic strategy associated"]
[912,"DB05992","investigational","small molecule","Plinabulin","Plinabulin","C19H20N4O2","CC(C)(C)C1=C(\\C=C2/NC(=O)\\C(NC2=O)=C\\C2=CC=CC=C2)N=CN1",null,"714272-27-2","336.395","Investigated for use/treatment in cancer/tumors (unspecified).",null,"NPI-2358 is a vascular disrupting agent currently in clinical development for the treatment of cancer by Nereus. NPI-2358 is one of over 200 synthetic analogues that were prepared following the discovery of the compound Halimide isolated from a marine fungus. In preclinical models of cancer, including lung, breast, sarcoma, colon and prostate, NPI-2358 demonstrated potent and selective anti-tumor effects in combination with docetaxel and other oncology therapies, as well as single-agent efficacy in a number of orthotopic models. NPI-2358 interacts with soluble beta-tubulin and prevents the polymerization of tubulin without altering dynamic microtubule function of formed microtubules. As demonstrated in preclinical testing, this target profile results in a highly specific nanomolar cytotoxicity while reducing the side effects seen in first-generation VDAs due to cardiotoxicity, hemodynamic changes and neuropathies.","Tumor necrosis factor","Target associated"]
[913,"DB05993","investigational","small molecule","PRX-07034",null,"C21H29Cl2N3O4S","Cl.COC1=C(OC)C(=CC(Cl)=C1)C(C)NC1=CC(=CC=C1S(C)(=O)=O)N1CCNCC1",null,"903580-39-2","490.44","Investigated for use/treatment in alzheimer's disease, obesity, and schizophrenia and schizoaffective disorders.",null,"PRX-07034 is a novel, highly selective, small-molecule antagonist of a specific G-protein coupled receptor (GPCR) known as 5-HT6 being developed for the treatment of obesity, Alzheimer's disease and cognitive impairment associated with schizophrenia.\r\n\r\nPRX-07034 has also been shown to enhance cognitive function in preclinical animal models of memory impairment through a dual mechanism of action.It has an effect on both the acetylcholine and glutamate neurotransmitter systems in the brain, which makes it a potentially complementary therapy to cholinesterase inhibitors, a class of drugs approved for the treatment of Alzheimer's disease.\r","5-hydroxytryptamine receptor 6","Therapeutic strategy associated"]
[914,"DB06011","investigational","small molecule","AMG-222",null,"C32H39N9O3","[H][C@](C)(CC1(C2=NNN=N2)C2=CC=C(C=C2CCC2=CC(=CC=C12)C(=O)N(C)C)C(=O)N(C)C)NCC(=O)N1CCC[C@@]1([H])C#N",null,"913978-37-7","597.724","Investigated for use/treatment in diabetes mellitus type 2.",null,"AMG-222 is an orally active, small molecule inhibitor of Dipeptidyl Peptidase IV (DPP-IV). DPP-IV inactivates glucagon-like peptide-1 (GLP-1), an important mediator of blood glucose levels following meals. DPP-IV inhibitors have been clinically shown to provide long term improvement of glucose control without the risk of hypoglycemia, and to improve the function of pancreatic beta cells, the cells responsible for the production of insulin. DPP-IV inhibitors represent a novel approach to the treatment of type II diabetes.","Dipeptidyl peptidase 4","Indication associated"]
[915,"DB06040","investigational","small molecule","Filanesib","Filanesib","C20H22F2N4O2S","CON(C)C(=O)N1N=C(S[C@@]1(CCCN)C1=CC=CC=C1)C1=CC(F)=CC=C1F","Filanesib is a potent Kinesin Spindle Protein (KSP) inhibitor that caused marked tumor regression in preclinical models of human solid tumors and human leukemias, often leading to durable responses.","885060-09-3","420.48","Investigated for use/treatment in cancer/tumors (unspecified).","This compound is a highly potent KSP inhibitor that demonstrates subnanomolar potency in both enzymatic and cellular assays and causes mitotic arrest, leading to cell death or apoptosis of the immensely proliferating cancer cells.","KSP has been identified as an attractive drug target against cancer. Cancer results when normal cellular processes go awry and lead to a massive, uncontrolled cell division, proliferation, and growth. Inhibitors of KSP cause mitotic arrest by preventing the formation of bipolar spindle. The monopolar spindle thus prevents the separation of centrosomes, organizes the microtubules from a single locus in the cell, and aligns the chromosomes around this locus. This compound is a highly potent KSP inhibitor that demonstrates subnanomolar potency in both enzymatic and cellular assays and causes mitotic arrest, leading to cell death or apoptosis of the immensely proliferating cancer cells.","Kinesin-like protein KIF11","Therapeutic strategy associated"]
[916,"DB06042","investigational","small molecule","ZEN-012",{"$nulls":3},"ZEN-012 is a novel small molecule and the first anti-cancer drug in development involving two mechanisms of action: tubulin and topoisomerase II inhibition. ZEN-012 also expresses additional modes of action such as pro-apoptotic and anti-angiogenic properties. It is developed for the treatment of solid tumors.",null,null,"Investigated for use/treatment in cancer/tumors (unspecified).","In vitro: ZEN-012 has shown potent in vitro anti-proliferative activity at nanomolar concentrations against human tumor cell lines of different origin. ZEN-012 is active in tumor cell lines which are resistant to cisplatin and doxorubicin as well as to tubulin inhibitors such as vincristine and paclitaxel. Furthermore, it was shown thatZEN-012 is a catalytic inhibitor of the enzyme topoisomerase II with the same potency as amsacrine.\r\n\r\nIn vivo: Given orally once or twice weekly, ZEN-012 proved to be a potent inhibitor of in vivo tumor growth in mammary, lung, renal, colon, melanoma xenograft models as well as in leukemia cancer models at well tolerated doses (16-40mg/kg). Furthermore,ZEN-012 showed good safety and toxicity profiles in a series of rodent and non-rodent studies.","Mode of action studies revealed that the compound ZEN-012 inhibits the polymerization of ß-tubulin in low micromolar concentrations. Competition studies suggest that ZEN-012 interacts with the same binding site on microtubules as colchicine. ZEN-012 destroys the mitotic spindles of the cancer cells, arrests the cancer cells in G2/M phase at low concentrations, mediates DNA fragmentation via inhibition of topoisomerase II and induces apoptosis via various mechanisms.","Tubulin beta chain; Tubulin beta-1 chain; Tubulin beta-3 chain; Tubulin beta-4A chain; DNA topoisomerase 2-alpha; DNA topoisomerase 2-beta","Therapeutic strategy associated"]
[917,"DB06045","investigational","small molecule","Trofinetide","Trofinetide","C13H21N3O6","C[C@]1(CCCN1C(=O)CN)C(=O)N[C@@H](CCC(O)=O)C(O)=O","Trofinetide (NNZ-2566), a neuroprotective analogue of , is a novel molecule that has a profile suitable for both intravenous infusion and chronic oral delivery. It is currently in development to treat traumatic brain injury.","853400-76-7","315.326","Investigated for use/treatment in traumatic brain injuries.","NNZ-2566 is shown to have multi-faceted action to significantly reduce both inflammation and apoptosis (cell death), protecting the neurons and their surrounding infrastructure.",null,null,"Therapeutic strategy associated"]
[918,"DB06050","investigational","biotech","TB-402",{"$nulls":3},"TB-402 is a human antibody binding to Factor VIII, which plays a crucial role in the coagulation of the blood. It is expected to be developed as a potential treatment to prevent blood clot formation in connection with certain types of heart arrhythmia, such as atrial fibrillation.",null,null,"Investigated for use/treatment in atrial fibrillation and thrombosis.",null,"TB-402 is a human antibody binding to Factor VIII, which plays a crucial role in the coagulation of the blood. The antibody has shown a beneficial partial inhibition of Factor VIII,\r\neven when applied in excess dosage. Extensive testing in several animal models has shown that TB-402 strongly reduces the risk of thrombosis without increasing the risk of bleeding.","Coagulation factor VIII","Indication associated"]
[919,"DB06075","investigational","small molecule","Linsitinib","Linsitinib","C26H23N5O","C[C@@]1(O)C[C@@H](C1)C1=NC(=C2N1C=CN=C2N)C1=CC=C2C=CC(=NC2=C1)C1=CC=CC=C1","An orally bioavailable small molecule inhibitor of the insulin-like growth factor 1 receptor (IGF-1R) with potential antineoplastic activity. IGF-1R inhibitor OSI-906 selectively inhibits IGF-1R, which may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis.","867160-71-2","421.504","Investigated for use/treatment in cancer/tumors (unspecified) and solid tumors.","In laboratory studies of 28 human tumor cell lines, OSI-906 reduced growth of 15 cell lines representative of colorectal, lung, breast, pancreatic, and pediatric tumors and in mouse models. OSI-906 was particularly effective against tumors that are highly IGF-dependent such as colorectal cancers. According to the researchers, OSI-906 not only slowed tumor growth in mice, but decreased the size of some pre-existing tumors.","IGF-1R stimulates proliferation, enables onogenic transformation, and suppresses apoptosis. Inhibitors of IGF-1R are expected to have broad utility in oncology since the over-expression of IGF-1R and/or its ligands or the down-regulation of ligand binding proteins occurs in numerous human malignancies including lung, colon, breast, prostate, brain and skin cancers. In addition, signaling through the IGF system has been implicated in protecting tumor cells from apoptosis induced by anti-cancer treatments such as cytotoxic agents and EGFR inhibitors.","Insulin-like growth factor 1 receptor inhibitor; Insulin receptor inhibitor","Therapeutic strategy associated"]
[920,"DB06080","investigational","small molecule","Linifanib","ABT-869; Linifanib","C21H18FN5O","CC1=CC(NC(=O)NC2=CC=C(C=C2)C2=C3C(N)=NNC3=CC=C2)=C(F)C=C1","Linifanib (ABT-869) is a small molecule vascular endothelial growth factor (VEGF) receptor-based kinase inhibitor that is designed to suppress tumor growth by preventing the formation of new blood vessels that supply the tumor with oxygen and nutrients and by inhibiting key angiogenic signaling pathways. Linifanib is intended for the treatment of hematologic malignancies and the solid tumors.","796967-16-3","375.407","Investigated for use/treatment in leukemia (myeloid), myelodysplastic syndrome, and solid tumors.","ABT-869 was effective in a broad range of cancers including small cell lung carcinoma, colon carcinoma, breast carcinoma and MV4-11 tumors in vitro and in vivo. ABT-869 induced significant apoptosis in cells with FLT3 mutation in vitro (IC50 value of 4 nM) and profound anti-leukemic effect in a mouse xenograft model. However, in vitro ABT-869 only shows minimal cytotoxic effect on AML cells with wild-type FLT3. Based on the preclinical studies suggesting the role of VEGF pathways in leukemogenesis, it is likely that the anti-leukemic effect of ABT-869 will be best evaluated in vivo.","ABT-869, a multi-targeted receptor tyrosine kinase inhibitor, has been shown to inhibit of all members of the VEGF and PDGF receptor families (e.g., KDR IC50 value of 4 nM), and have less activity (IC50 values >1 µM) against unrelated receptor tyrosine kinases, soluble tyrosine kinases and serine/threonine kinases. In addition, it exhibits potent anti-proliferative and apoptotic effects on tumor cells dependent on mutant, constitutively active, FLT3 and KIT kinases.","Receptor-type tyrosine-protein kinase FLT3; Vascular endothelial growth factor receptor 1; Vascular endothelial growth factor receptor 2; Vascular endothelial growth factor receptor 3; Mast/stem cell growth factor receptor Kit; Macrophage colony-stimulating factor 1 receptor","Therapeutic strategy associated"]
[921,"DB06081","approved; investigational","biotech","Caplacizumab","Caplacizumab; caplacizumab-yhdp",null,null,"Caplacizumab, firstly called ALX-0081, is a humanized single-variable-domain immunoglobulin consisting of two identical humanized building blocks genetically linked by a three-alanine linker. Caplacizumab was developed by Ablynx, a Sanofi company and FDA approved on February 6, 2019, and approved previously by the EU in October 2018 as a combination therapy with plasma exchange and immunosuppression.","915810-67-2",null,"Capacizumab is approved for the treatment of adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP) in conjunction with plasma exchange and immunosuppression in patients 18 years or older.\r\n\r\naTTP is a rare autoimmune condition presented by a disruption of blood clotting order which is translated into systemic microvascular thrombosis leading to profound thrombocytopenia, hemolytic anemia and organ ischemia. It is caused by the production of autoantibodies against ADAMTS-13 which is the protein in charge of cleaving the von-Wilebrand factor. The lack of this process produces the generation of ultra large von Wilebrand multimers that bind to platelets and form microthrombi and causing thromboembolic complications.\r\n\r\nPreviously, capacizumab was under review for the prevention of thrombosis in high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention but this indication was withdrawn.","_In vitro_ studies have shown a caplacizumab-driven complete inhibition of platelet aggregation and in phase II clinical trials, it was shown to reduce the activity of the von Willebrand factor by 20% from treatment day 1 until treatment day 30. The level of von Willebrand factor in the plasma was also significantly reduced due to the clearance of the von Willebrand-caplacizumab complex.\r\n\r\nIn phase III clinical trials, more than 50% of the tested individuals reached a platelet normal count. In these trials, it was observed as well a significant reduction in the incidence of aTTP as well as a significant reduction in the median time to response of about 39%. However, as caplacizumab does not target autoimmune response, relapses were observed after treatment discontinuation.\r\n\r\nThe last clinical trial prior approval showed production of a platelet count of more than 150,000 per mcl after the cessation of plasma exchange therapy for 5 days as well as a reduction of patient recurrent thrombotic thrombocytopenic purpura and of disease-related death during treatment.","Caplacizumab acts by targetting the A1 domain of the ultra-large von Willebrand factor which in order inhibits the interaction with the glycoprotein Ib-IX-V receptor in the platelets. Caplacizumab binds to von Willebrand factor with an affinity of 8.5 nM, thus it is very target specific. The blockage of the von Willebrand factor prevents the interaction between the von Willebrand factor and the platelets, hence, preventing platelet aggregation.","von Willebrand factor","Therapeutic strategy associated"]
[922,"DB06082","investigational","small molecule","PX-478",null,"C13H20Cl4N2O3","Cl.Cl.N[C@@H](CC1=CC=C(C=C1)[N+]([O-])(CCCl)CCCl)C(O)=O","PX-478 is a small molecule inhibitor of hypoxia inducible factor (HIF)-1 alpha currently in a clinical trial in patients with advanced metastatic cancer and lymphoma. PX-478 was effective in models of both non-small cell lung cancer\r\nand small cell lung cancer that express HIF-1 alpha.","685898-44-6","394.11","Investigated for use/treatment in cancer/tumors (unspecified).",null,"PX-478 is a novel small molecule compound that inhibits the activity of hypoxia inducible factor (HIF)-1 alpha, a transcription factor that controls the expression of a number of genes important for growth and survival of cancer cells. Genes regulated by HIF-1 alpha contribute to diverse functions including new blood vessel growth (angiogenesis), use of glucose for energy, and protection against apoptosis (programmed cell death). Preclinical data have demonstrated that PX-478 can induce apoptosis in experimental tumor models, as well as the down-regulation of factors which\r\ncontrol angiogenesis, such as vascular endothelial growth factor (VEGF).","Hypoxia-inducible factor 1-alpha","Therapeutic strategy associated"]
[923,"DB06087","investigational","small molecule","Friulimicin B","Friulimycin B","C59H94N14O19","CC(C)CCCCCCC\\C=C/CC(=O)N[C@@H](CC(N)=O)C(=O)N[C@H]1[C@H](C)NC(=O)[C@@H]2CCCN2C(=O)[C@@H](NC(=O)[C@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H]2CCCCN2C1=O)[C@H](C)C(O)=O)[C@@H](C)N)C(C)C","Friulimicin B is a naturally occurring antibiotic produced by a micro-organism, *Actinoplanes friuliensis*. It shows strong cidal activity against a number of Gram-positive pathogens which commonly cause serious infections in hospital patients and which are becoming more routinely acquired in the community.","239802-15-4","1303.48","Investigated for use/treatment in bacterial infection.",null,"Friulimicin B, in the presence of calcium, forms a complex with a lipid carrier that acts in cell wall biosynthesis and which is not targeted by other antibiotics currently in use. Friulimicin B appears to block two essential pathways in the cell envelope and the complexes formed prevent the formation of a functional cell wall.",null,"Indication associated"]
[924,"DB06094","investigational","small molecule","Apatorsen","Apatorsen","C224H304N79O116P19S19","COCCOC1C(O)C(COP(O)(=S)OC2C(COP(O)(=S)OC3C(COP(O)(=S)OC4C(COP(O)(=S)OC5CC(OC5COP(O)(=S)OC5CC(OC5COP(O)(=S)OC5CC(OC5COP(O)(=S)OC5CC(OC5COP(O)(=S)OC5CC(OC5COP(O)(=S)OC5CC(OC5COP(O)(=S)OC5CC(OC5COP(O)(=S)OC5CC(OC5COP(O)(=S)OC5CC(OC5COP(O)(=S)OC5CC(OC5COP(O)(=S)OC5CC(OC5COP(O)(=S)OC5CC(OC5COP(O)(=S)OC5C(COP(O)(=S)OC6C(COP(O)(=S)OC7C(COP(O)(=S)OC8C(CO)OC(C8OCCOC)N8C=NC9=C8NC(=N)N=C9O)OC(C7OCCOC)N7C=NC8=C7NC(=N)N=C8O)OC(C6OCCOC)N6C=NC7=C6NC(=N)N=C7O)OC(C5OCCOC)N5C=NC6=C(N)N=CN=C56)N5C=C(C)C(=N)N=C5O)N5C=NC6=C5NC(=N)N=C6O)N5C=C(C)C(=N)N=C5O)N5C=NC6=C5NC(=N)N=C6O)N5C=NC6=C5NC(=N)N=C6O)N5C=C(C)C(=N)N=C5O)N5C=NC6=C5NC(=N)N=C6O)N5C=C(C)C(=N)N=C5O)N5C=C(C)C(O)=NC5=O)N5C=C(C)C(=N)N=C5O)N5C=NC6=C5NC(=N)N=C6O)N5C=NC6=C5NC(=N)N=C6O)OC(C4OCCOC)N4C=C(C)C(O)=NC4=O)OC(C3OCCOC)N3C=C(C)C(=N)N=C3O)OC(C2OCCOC)N2C=NC3=C(N)N=CN=C23)OC1N1C=C(C)C(O)=NC1=O","Apatorsen is a second generation antisense drug which in preclinical experiments, inhibits production of Heat Shock Protein 27 (Hsp27) a cell survival protein found at elevated levels in many human cancers including prostate, lung, breast, ovarian, bladder, renal, pancreatic, multiple myeloma and liver cancer.","1002331-21-6","7156.97","Investigated for use/treatment in cancer/tumors (unspecified).","OGX-427 significantly decreases levels of Hsp27, induces apoptosis in several human cancer cell lines, has single agent anti-tumor activity, and acts as a chemosensitizer in combination with several cytotoxic drugs including docetaxel.",null,"Heat shock protein beta-1","Therapeutic strategy associated"]
[925,"DB06097","investigational","small molecule","GSK-923295",{"$nulls":3},"GSK-923295 is a small-molecule inhibitor of the mitotic kinesin centromere-associated protein E (CENP-E), and the third novel drug candidate to arise from Cytokinetics' broad strategic alliance with GlaxoSmithKline (GSK). GSK-923295 demonstrated a broad spectrum of activity against a range of human tumor xenografts grown in nude mice, including models of colon, breast, ovarian, lung and other tumors. GSK-923295 is the first drug candidate to enter human clinical trials that specifically targets CENP-E and is currently in Phase I human clinical trials being conducted by GSK.",null,null,"Investigated for use/treatment in cancer/tumors (unspecified) and solid tumors.",null,"GSK-923295 is an inhibitor of the mitotic kinesin centromere-associated protein E (CENP-E). CENP-E plays an essential role in chromosome movement during early cell division or mitosis and integrates mitotic spindle mechanics with regulators of the mitotic checkpoint regulating cell-cycle transition from metaphase to anaphase. Inhibition of CENP-E induces cell cycle arrest during cell duplication leading to subsequent apoptosis or cell death.","Centromere-associated protein E","Therapeutic strategy associated"]
[926,"DB06101","investigational","biotech","IMC-1C11",{"$nulls":3},"IMC-1C11 is an anti-angiogenesis agent. It is a chimeric anti-kinase insert domain-containing receptor (KDR) antibody that blocks VEGFR-KDR interaction and inhibits VEGFR-induced endothelial cell proliferation. IMC-1C11 is used for treatment of patients with liver metastases from colorectal carcinoma.",null,null,"Investigated for use/treatment in cancer/tumors (unspecified).",null,"IMC-1C11 is a chimerized antibody that targets the KDR receptor (also referred to as VEGFr) on vascular endothelial cells by inhibiting binding of the essential ligand, vascular endothelial growth factor (VEGF), to its receptor. KDR is a key receptor associated with tumor angiogenesis. As solid tumors cannot grow efficiently without new blood supply, use of IMC-1C11 results in the inhibition of tumor growth and death of tumor cells by apoptosis.","Vascular endothelial growth factor receptor 1; Vascular endothelial growth factor receptor 2; Vascular endothelial growth factor receptor 3","Therapeutic strategy associated"]
[927,"DB06111","experimental","small molecule","AB192",{"$nulls":3},"AB192 is a DPP IV enzymatic activity inhibitor.",null,null,"Investigated for use/treatment in diabetes mellitus type 2.",{"$nulls":3},"Indication associated"]
[928,"DB06127","investigational","small molecule","Bisegliptin","Bisegliptin","C18H26FN3O3","[H][C@@]1(F)CN(C(=O)CNC23CCC(CC2)(CC3)C(=O)OCC)[C@@]([H])(C1)C#N","Bisegliptin is a compound for the treatment of type 2 diabetes. It is an orally active, dipeptidyl peptidase-IV (DPPIV) inhibitor which lowers blood glucose levels by blocking the degradation of the hormone GLP-1 thereby stimulating glucose-dependent insulin secretion and lowering blood glucose levels without hypoglycemic effects.","862501-61-9","351.422","Investigated for use/treatment in diabetes mellitus type 2.",null,"Bisegliptin is an orally active, dipeptidyl peptidase-IV (DPPIV) inhibitor which lowers blood glucose levels by blocking the degradation of the hormone GLP-1 thereby stimulating glucose-dependent insulin secretion and lowering blood glucose levels without hypoglycemic effects.","Dipeptidyl peptidase 4","Indication associated"]
[929,"DB06137","approved; investigational","small molecule","Tirbanibulin","Tirbanibulin","C26H29N3O3","O=C(CC1=CC=C(C=N1)C1=CC=C(OCCN2CCOCC2)C=C1)NCC1=CC=CC=C1","Tirbanibulin (KX-O1 or KX2–391) is a dual inhibitor of Src Kinase and tubulin. On December 14, 2020, tirbanibulin was approved by the FDA for the topical treatment of actinic keratosis on the face or scalp. It is marketed under the brand name Klisyri. Actinic keratosis is a chronic condition characterized by lesions, which can potentially transform into invasive squamous cell carcinoma with a risk of 1% over 10 years. Tirbanibulin blocks the molecular pathways that promote the proliferation, survival, and metastasis of malignant cells. Tirbanibulin exhibits antitumour effects in vitro and in vivo  and has been investigated for its antitumor efficacy in the management of various cancers, such as prostate cancer and breast cancer.","897016-82-9","431.536","Tirbanibulin is indicated for the topical treatment of actinic keratosis on the face or scalp.","In clinical trials composed comprising patients with actinic keratosis of the face or scalp, tirbanibulin promoted complete clearance of actinic keratosis lesions at day 57 in treated areas in 44-54% of patients compared to 5-13% of patients who received the placebo. Actinic keratosis is a chronic, pre-malignant condition characterized by lesions and proliferation of neoplastic keratinocytes. Tirbanibulin mediates an anti-proliferative effect by inhibiting tubulin polymerization and Src kinase signalling. \r\n\r\nTirbanibulin inhibited primary tumour growth and metastasis in many preclinical animal models of cancer. In human triple-negative breast cancer, or estrogen receptor (ER)/progesterone receptor (PR)/human epidermal growth factor receptor 2 (HER2)-negative tumour, xenografts, tirbanibulin suppressed tumour growth and metastasis. Tirbanibulin was also shown to restore functional ERα expression in ERα-negative breast tumours. Tirbanibulin promoted synergistic tumour growth inhibition of breast cancer cell lines when used in combination with tamoxifen  and paclitaxel.\r\n\r\nIn a clinical trial comprising patients with advanced solid tumours, dose-limiting toxicities of tirbanibulin included elevated liver transaminases, neutropenia and fatigue.","Src tyrosine kinases regulate normal cell growth: the expression of Src kinase is upregulated during the normal hair cycle during the proliferative anagen phase. Additionally, Src tyrosine kinases act as key modulators of cancer cell proliferation, survival, angiogenesis, migration, invasion and metastasis. Src is frequently upregulated in various epithelial tumours including colon, breast and pancreas compared with the adjacent normal tissues. The expression and activity of Src are also enhanced in human actinic keratosis, which is characterized by hyperproliferative premalignant skin lesions. The pathogenesis of actinic keratosis commonly involves skin inflammation, oxidative stress, immunosuppression, impaired apoptosis, mutagenesis, dysregulation of keratinocyte growth and proliferation, and tissue remodelling. _In vitro_ studies suggest that Src plays a predominant role in the early stages of human skin tumour development, rather than at later stages of tumour progression. \r\n\r\nThe exact mechanism of tirbanibulin as a topical treatment of actinic keratosis has not been fully elucidated; however, it mainly works by inhibiting fast proliferating cells. Tirbanibulin is a non-ATP competitive Src kinase inhibitor and tubulin polymerization inhibitor. It binds to the peptide substrate binding site of Src, a primary target of tirbanibulin, and blocking its downstream signalling pathways that promote cancer cell migration, proliferation, and survival. Tublin is responsible for cell migration, protein transport, and mitosis: tibranibulin directly binds to the colchicine-binding site of beta-tubulin and causes induces tubulin depolymerization. It is also hypothesized that inhibition of Src can also contribute to the inhibitory effects on microtubule polymerization. At low nanomolar concentrations, tirbanibulin induces G2/M phase cell cycle arrest in a reversible  and dose-dependent manner. By inhibiting microtubule polymerization, tirbanibulin also induces mitotic catastrophe.","Proto-oncogene tyrosine-protein kinase Src inhibitor; Tubulin beta chain inhibitor","Therapeutic strategy associated"]
[930,"DB06148","approved; investigational","small molecule","Mianserin","1,2,3,4,10,14b-Hexahydro-2-methyldibenzo(c,f)pyrazino(1,2-a)azepine; Mianserin","C18H20N2","CN1CCN2C(C1)C1=CC=CC=C1CC1=CC=CC=C21","A tetracyclic compound with antidepressant effects. Mianserin was previously available internationally, however in most markets it has been phased out in favour of .","24219-97-4","264.3648","For the treatment of depression.","Mianserin is a tetracyclic antidepressant that has antihistaminic and hypnosedative, but almost no anticholinergic, effect. It is a weak inhibitor of norepinephrine reuptake and strongly stimulates the release of norepinephrine. Interactions with serotonin receptors in the central nervous system have also been found. Its effect is usually noticeable after one to three weeks. Mianserin may cause drowsiness and hematological problems.","Mianserin's mechanism of therapeutic action is not well understood, although it apparently blocks alpha-adrenergic, histamine H1, and some types of serotonin receptors.","Alpha-2A adrenergic receptor antagonist; 5-hydroxytryptamine receptor 2A antagonist; 5-hydroxytryptamine receptor 2C antagonist; Histamine H1 receptor antagonist; Sodium-dependent noradrenaline transporter inhibitor; Sodium-dependent serotonin transporter inhibitor; Histamine H4 receptor binder; 5-hydroxytryptamine receptor 1A blocker; Alpha-2C adrenergic receptor antagonist; 5-hydroxytryptamine receptor 2B binder; 5-hydroxytryptamine receptor 1F binder; Alpha-2B adrenergic receptor antagonist; Dopamine D3 receptor binder; Kappa-type opioid receptor agonist; Sodium-dependent dopamine transporter binder; 5-hydroxytryptamine receptor 7 antagonist; Dopamine D2 receptor antagonist; 5-hydroxytryptamine receptor 6 binder; Alpha-1 adrenergic receptors antagonist; D(1) dopamine receptor binder","Indication associated"]
[931,"DB06149","approved; investigational","small molecule","Teicoplanin","Teichomycin A2; Teicoplanin",null,null,"Teicoplanin is a glycopeptide antibiotic consisting of a mixture of several compounds, five major (named teicoplanin A2-1 through A2-5) and four minor (named teicoplanin RS-1 through RS-4). All teicoplanins share a same glycopeptide core, teicoplanin A3-1, but differ in the length and conformation of side chains attached to their β-D-glucosamine moiety.","61036-62-2",null,"For the treatment of bacterial infections caused by susceptible microorganisms.","It is a glycopeptide antiobiotic extracted from <i>Actinoplanes teichomyceticus</i>, with a similar spectrum of activity to vancomycin. Its mechanism of action is to inhibit bacterial cell wall synthesis. Oral teicoplanin has been demonstrated to be effective in the treatment of pseudomembranous colitis and Clostridium difficile-associated diarrhoea, with comparable efficacy to vancomycin.","Teicoplanin inhibits peptidoglycan polymerization, resulting in inhibition of bacterial cell wall synthesis and cell death.","D-Ala-D-Ala moiety of NAM/NAG peptide subunits of peptidoglycan inhibitor","Indication associated"]
[932,"DB06152","approved","small molecule","Nylidrin","Buphenin; Buphenine","C19H25NO2","CC(CCC1=CC=CC=C1)NC(C)C(O)C1=CC=C(O)C=C1","Nylidrin, also known as _buphenine_ belongs to the category of drugs called _vasodilators_, which relax blood vessels and increase blood flow. Nylidrin is a peripheral vasodilator. Some studies show the evidence of improving cognitive impairment in selected individuals, such as geriatric patients with mild to moderate symptoms of cognitive, emotional and physical impairment .\r\n\r\nNylidrin is utilized to treat several disorders that may benefit from increased blood flow (for example, certain mental disorders, blood vessel disease due to diabetes, frostbite, night leg cramps, and certain types of ulcers). This medication works by dilating (widening) blood vessels to help increase blood flow (improving circulation) throughout the body, including the extremities and central nervous system. This effect may help to improve memory/judgment, improve walking ability, and support the healing of frostbite/ulcers .\r\n\r\nFDA has considered nylidrin as \"lacking substantial evidence of effectiveness\" in cerebral ischemia, cerebral arteriosclerosis, and other cerebral circulatory insufficiencies. Therefore, the FDA has withdrawn nylidrin from the U.S. market .","447-41-6","299.414","Nylidrin is mainly indicated in conditions like arteriosclerosis, cerebrovascular disease, peripheral vascular disease, Raynaud's disease, thrombo-angitis obliterans, and thrombophlebitis . It may sometimes be used in the treatment of peripheral vascular disorders in addition premature labor (however, the drug is not approved for premature labor).","\r\nNylidrin hydrochloride acts mainly by beta-receptor stimulation , . Beta stimulation with nylidrin has been studied and confirmed in a variety of isolated tissues from rabbits, guinea pigs, as well as dogs. This drug has been shown to dilate arterioles in skeletal muscle and to increase cardiac output in the anesthetized dog and cat as well as the unanesthetized man. An increase in cerebral blood flow and a decrease in vascular resistance has also been reported. The result of this combination of mechanisms is an improved blood supply to ischemic tissues, with minimal change in blood pressure (generally) .  \r\n\r\n Nylidrin causes peripheral vasodilation, a positive inotropic effect, and an increased volume of gastric acid.  , .  According to one study, there are two primary effects of this agent following the intra‐arterial route of administration: one, to decrease total peripheral resistance; and two, a direct effect on the heart tissue to increase cardiac output .  It also acts directly on the arteries and arterioles of the skeletal muscles. Additionally, it suppresses uterine contractility thereby preventing or halting premature labor .\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r","This drug is classified as a beta receptor agonist .The β2-adrenergic receptor belongs to the widely expressed _7-transmembrane receptors superfamily_, which signals through heterotrimeric _G-proteins_. They are frequently referred to as G-protein-coupled receptors because they accomplish signal transduction to the interior of the cell by interactions with _guanine nucleotide regulatory binding proteins_. The receptor-coupled G-proteins work as “molecular switches” which alternate from an inactive guanosine-diphosphate to an active guanosine-triphosphate (GTP) state, which then act to modulate all downstream cell processes. Signaling by various hormones and neurotransmitters, as well as photons and odors, follows the same general pathway, (i.e., by binding of an extracellular ligand to the receptor, which then interacts with the membrane-bound G-protein). This complex, often referred to as the ternary complex, then acts through the activated G-protein to regulate an effector, such as _adenylyl cyclase_, _phospholipase C_, or ion channels .  \r\n\r\n\r\nThe main effects of Nylidrin may be divided into 3 categories:\r\n\r\n**Blood vessels**\r\n\r\nVascular smooth muscle has β2-adrenoceptors that have a high binding affinity for circulating epinephrine and a lower affinity to norepinephrine released by sympathetic adrenergic nerves .  When nylidrin binds to the beta-adrenergic receptors, it prevents the binding of epinephrine, leading to decreased blood vessel contractility as epinephrine is unable to bind .\r\n\r\n**Heart:**\r\n\r\nIncreased intracellular cAMP by beta-2-agonists inhibits _myosin light chain kinase_, leading to relaxation\r\nThese receptors, like the receptors in the heart, are coupled to a Gs-protein, which acts stimulate the formation of cAMP. Although increased cAMP increases cardiac myocyte contraction, in vascular smooth muscle, an increase in cAMP causes smooth muscle relaxation. The reason for this is the fact that cAMP inhibits myosin light chain kinase that is responsible for phosphorylating smooth muscle myosin. Increases in intracellular cAMP caused by β2-agonists inhibit myosin light chain kinase thereby producing less contractile force (i.e., promoting relaxation) .\r\n\r\n\r\n**Other tissues**\r\n\r\n\r\nActivation of _β2-adrenoceptors_ in the lungs causes bronchodilation. β2-adrenoceptor activation leads to hepatic glycogenolysis and the pancreatic secretion of glucagon, increasing plasma glucose concentrations. β1-adrenoceptor stimulation in the kidneys promotes the release of renin, stimulating the production of angiotensin II and the subsequent release of aldosterone by the adrenal cortex .","Voltage-dependent T-type calcium channel subunit alpha-1I antagonist&agonist; Interferon alpha/beta receptor 2 agonist","Indication associated"]
[933,"DB06154","approved","small molecule","Pentaerythritol tetranitrate","Corpent; PENT; PENTA; Pentaerithrityl tetranitrate; Pentaerythritol tetranitrate; Penthrite; TEN","C5H8N4O12","[O-][N+](=O)OCC(CO[N+]([O-])=O)(CO[N+]([O-])=O)CO[N+]([O-])=O","Pentaerythritol tetranitrate is the nitrate ester of pentaerythritol that possesses explosive properties. When mixed with a plasticizer, this chemical forms a plastic explosive. It is recognized by the FDA to be a coronary vasodilator in the treatment of heart conditions such as angina .\r\n\r\nIt is a pentaerythritol nitrate in which all four hydroxy groups of pentaerythritol have been converted to the corresponding nitrate ester. It is a vasodilator with properties that are quite similar to those of glyceryl trinitrate, however, with a more prolonged duration of action. It is also one of the most powerful high explosives known and is a component of the plastic explosive known as Semtex .\r\n\r\nPETN has the chemical formula C5H8N4O12. It is formed by reacting pentaerythritol (C5H12O4), an alcohol commonly used in paints and varnishes, with nitric acid (HNO2). The reacting solution is chilled to precipitate the PETN.  It is then filtered out, washed, dried, and recrystallized to produce a colorless crystalline material that is stored and shipped as a mixture with water and alcohol .\r\n\r\nInterestingly, this drug was studied for potential benefits in chronic ischemic heart failure patients.  PETN targeting reactive oxygen species generation halted the changes of mitochondrial antioxidant enzymes and progressive fibrotic remodeling, leading to amelioration of cardiac functional performance in rats with ischemic heart failure .","78-11-5","316.1366","Used for the treatment of angina pectoris .","Organic nitrate which causes systemic vasodilation, decreasing cardiovascular preload .\r\n\r\nNitrate enters vascular smooth muscle and converted to nitric oxide (NO) which acts as a cellular messenger, leading to activation of cyclic GMP and, therefore, vasodilation .\r\n\r\nThe nitrovasodilator group of drugs relaxes most smooth muscles in the body, including those in the walls of arteries and veins, and selectively dilate large coronary vessels . Lower doses of nitrates increase coronary blood flow without significantly affecting systemic arterial pressure. Higher doses, especially if repeated frequently, decrease systolic and diastolic blood pressure as well as cardiac output, which can result in a headache, weakness, dizziness, and the activation of compensatory sympathetic reflexes, including tachycardia and peripheral arteriolar vasoconstriction .\r\n\r\nSmooth muscles in the bronchi, biliary tract, gastrointestinal tract, ureters, and uterus also can be relaxed by nitrovasodilators. PETN seems to be unique among the long-acting nitrovasodilators in that patients do not demonstrate  tolerance to treatment, which results in sustained vasodilation in humans with continuous PETN treatment .\r\n\r\nImportant to note is that this drug is devoid of induction of oxidative stress and related side-effects such as endothelial dysfunction or tolerance to nitrates. Some of these effects are related to special pharmacokinetics of PETN, but upon chronic administration, PETN also induces antioxidative pathways at the genomic level, resulting in increased expression of heme _oxygenase-1 (HO-1)_ _and ferritin_, both possessing highly protective properties. There is good experimental evidence that at least part of the beneficial profile of long-term treatment with this drug is based on the activation of the _heme oxygenase-1/ferritin_ system .\r","Pentaerythritol tetranitrate is the lipid soluble polyol ester of nitric acid belonging to the family of _nitro-vasodilators_. Pentaerythritol tetranitrate releases free nitric oxide (NO) after the denitration reaction, which triggers NO-dependent signaling transduction involving soluble _guanylate cyclase (sGC_). Nitric oxide binds reversibly to the ferrous-heme center of sGC, causing conformational change and activating the enzyme. This enzyme activation results in increased cellular concentrations of _cyclic guanosine monophosphate _(cGMP) within the vascular smooth muscle, resulting in vasodilation mediated by cGMP-dependent protein kinases. Additionally, this agent causes dose-dependent arterial and venous bed .","Hemoglobin subunit alpha agonist; Hemoglobin subunit beta agonist; Free radicals antagonist","Therapeutic strategy associated"]
[934,"DB06156","investigational","small molecule","Tesofensine","Tesofensine","C17H23Cl2NO","CCOC[C@H]1[C@H]2CC[C@@H](C[C@@H]1C1=CC(Cl)=C(Cl)C=C1)N2C",null,"195875-84-4","328.28","Investigated for use/treatment in alzheimer's disease, parkinson's disease, and obesity.",null,"Tesofensine is a Serotonin-norepinephrine-dopamine-reuptake-inhibitor (SNDRI). SNDRIs are a class of psychoactive antidepressants. They act upon neurotransmitters in the brain, namely, serotonin, norepinephrine and dopamine. These three biogenic monoamines are associated with depression and increasing the availability in the brain is one method used to treat the condition.","Sodium-dependent serotonin transporter; Sodium-dependent noradrenaline transporter; Sodium-dependent dopamine transporter","Indication associated"]
[935,"DB06160","investigational","small molecule","Garenoxacin","Garenoxacin","C23H20F2N2O4","C[C@H]1NCC2=CC(=CC=C12)C1=CC=C2C(=O)C(=CN(C3CC3)C2=C1OC(F)F)C(O)=O","Garenoxacin, a quinolone antibiotic, is being investigated for the treatment of gram-positive and gram-negative bacterial infections.","194804-75-6","426.42","Investigated for use/treatment in bacterial infection.",{"$nulls":3},"Indication associated"]
[936,"DB06168","approved; investigational","biotech","Canakinumab","Canakinumab",null,null,"Canakinumab is a recombinant, human anti-human-IL-1β monoclonal antibody that belongs to the IgG1/κ isotype subclass. It is expressed in a murine Sp2/0-Ag14 cell line and comprised of two 447- (or 448-) residue heavy chains and two 214-residue light chains, with a molecular mass of 145157 Daltons when deglycosylated. Both heavy chains of canakinumab contain oligosaccharide chains linked to the protein backbone at asparagine 298 (Asn 298). Canakinumab binds to human IL-1β and neutralizes its inflammatory activity by blocking its interaction with IL-1 receptors, but it does not bind IL-1alpha or IL-1 receptor antagonist (IL-1ra). Canakinumab is marketed under the brand name Ilaris and indicated for patients 4 years of age and older to treat Familial Cold Autoinflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS), which are both part of the Cryopyrin-Associated Periodic Syndromes (CAPS) as well as for patients 2 years of age and older to treat systemic juvenile idiopathic arthritis (SJIA). Clinical trials have established the administration of canakinumab every 2 weeks to be safe and effective, offering a considerable advantage over the existing treatment with the human IL-1 receptor antagonist, anakinra, which must be injected daily and which is often poorly tolerated by patients.","914613-48-2",null,"Used in patients 4 years of age and older to treat Familial Cold Autoinflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS), which are both part of the Cryopyrin-Associated Periodic Syndromes (CAPS) as well as for patients 2 years of age and older to treat systemic juvenile idiopathic arthritis (SJIA).","Novartis AG has developed canakinumab as a subcutaneous injection and fully human mAb that neutralizes the bioactivity of human IL-1beta, which is involved in several inflammatory disorders. Canakinumab has promising clinical safety and pharmacokinetic properties, and demonstrated potential for the treatment of cryopyrin-associated periodic syndromes (CAPS), systemic juvenile idiopathic arthritis (SJIA), and possibly for other complex inflammatory diseases, such as rheumatoid arthritis, COPD disease and ocular diseases.","In inflammatory diseases involving Cryopyrin-Associated Periodic Syndromes (CAPS), interleukin-1 beta (IL-1β) is excessively activated and drives inflammation. The protein cryopyrin controls the activation of IL-1β, and mutations in cryopyrin's gene, NLRP-3, up-regulate IL-1β activation. Canakinumab is a human monoclonal anti-human IL-1β antibody of the IgG1/κ isotype. Canakinumab binds to human IL-1β and neutralizes its inflammatory activity by blocking its interaction with IL-1 receptors, but it does not bind IL-1α or IL-1 receptor antagonist (IL-1ra).\r\n\r","Interleukin-1 beta binder","Therapeutic strategy associated"]
[937,"DB06176","approved; investigational","small molecule","Romidepsin","Romidepsin","C24H36N4O6S2","C\\C=C1/NC(=O)[C@H]2CSSCC\\C=C\\[C@H](CC(=O)N[C@H](C(C)C)C(=O)N2)OC(=O)[C@@H](NC1=O)C(C)C","Romidepsin is a selective inhibitor of histone deacetylase, approved in the US in 2009 for the treatment of cutaneous T-cell lymphoma (CTCL) or/and peripheral T-cell lymphoma (PTCL) in patients who have received at least one prior systemic therapy. These indications are based on response rate. Clinical benefit such as improvement in overall survival has not been demonstrated.","128517-07-7","540.69","For the treatment of cutaneous T-cell lymphoma (CTCL) or/and peripheral T-cell lymphoma (PTCL) in patients who have received at least one prior systemic therapy. These indications are based on response rate. Clinical benefit such as improvement in overall survival has not been demonstrated.",null,"Romidepsin is a prodrug, where it becomes active once taken up into the cell. The active metabolite has a free thiol group, which interacts with zinc ions in the active site of class 1 and 2 HDAC enzymes, resulting in inhibition of its enzymatic activity. Certain tumors have over expressed HDACs and downregulated/mutated histone acetyltransferases. This imbalance of HDAC relative to histone acetyltransferase can lead to a decrease in regulatory genes, ensuing tumorigenesis. Inhibition of HDAC may restore normal gene expression in cancer cells and result in cell cycle arrest and apoptosis.","Histone deacetylase 1 antagonist&inhibitor; Histone deacetylase 2 antagonist&inhibitor; Histone deacetylase 4 inhibitor; Histone deacetylase 6 inhibitor; Multidrug resistance-associated protein 1","Therapeutic strategy associated"]
[938,"DB06190","investigational","small molecule","Solabegron","Solabegron","C23H23ClN2O3","[H][C@](O)(CNCCNC1=CC(=CC=C1)C1=CC(=CC=C1)C(O)=O)C1=CC=CC(Cl)=C1","Solabegron (GW-427,353) is a selective β3 adrenoceptor agonist being developed for the treatment of overactive bladder and irritable bowel syndrome.","252920-94-8","410.9","Investigated for use/treatment in diabetes mellitus type 2, irritable bowel syndrome (IBS), and urinary incontinence.",null,null,"Beta-3 adrenergic receptor agonist","Indication associated"]
[939,"DB06193","approved; investigational","small molecule","Pixantrone","6,9-bis((2-aminoethyl)amino)benzo(g)isoquinoline-5,10-dione; Pixantrone","C17H19N5O2","NCCNC1=CC=C(NCCN)C2=C1C(=O)C1=C(C=NC=C1)C2=O","Pixantrone is an aza-anthracenedione and DNA intercalator which inhibits topoisomerase II. It is similar in structure to anthracyclines such as mitoxantrone, but exerts fewer toxic effects on cardiac tissue.  The lower cardio-toxic effects of pixantrone may be explained, in part, by its redox inactivity . Pixantrone does not bind iron and promotes the formation of reactive oxygen species to a lesser degree than other anthracyclines. It also inhibits doxorubicinol formation in human myocardium.  As a result, it is believed to be less cardiotoxic while still exerting efficacy.  \r\n\r\nPixantrone was designed to treat relapsed or refractory aggressive non-Hodgkin's lymphoma(NHL) in patients who have failed two prior lines of therapy.  For patients suffering from NHL, first line therapies consist of anthracycline containing multi-drug treatments which unfortunately are known to cause irreversible myocardial tissue damage. Patients refractory to treatment, or those who relapse, are discouraged from further anthracycline use due to cumulative cardiotoxicity. Pixantrone dimaleate, administered intravenously, was designed by Cell Therapeutics Incorporated as an alternative second line therapy in refractory or relapsed NHL. It is currently being tested in Phase III trials. \r\n\r\nAlthough pixantrone has not yet received FDA approval in the United States, it has been granted conditional marketing approval by the European Union. Conditional approval was granted by the European Medicines Agency after a phase III EXTEND trial of patients with NHL showed that pixantrone was tolerable and that it resulted in significantly higher complete response rate and progression free survival in comparison to other single chemotherapy agents. However, it is notable that the EXTEND trial was stopped early, leaving the statistical significance of the results in question. Based on this uncertainty, in 2009, the FDA ultimately rejected Cell Therapeutic's initial application for accelerated approval for pixantrone use in relapsed or refractory NHL. Another phase III trial, PIX-R, is now ongoing to clarify pixantrones place in therapy. It will compare pixantrone efficacy to that of gemcitabine.","144510-96-3","325.372","Currently in Phase III investigation for treatment of relapsed or refractory aggressive non-Hodgkin's lymphoma in patients who have failed two prior lines of therapy. Presently, no standard therapy exists for patients with relapsed or refractory NHL.  After first line therapy has been initiated, most patients have received their lifetime limit of doxorubicin and further use of anthracyclines may potentially lead to anthracycline-induced congestive heart failure (CHF). Pixantrone is an attractive alternative as a second line agent, due to its lack of cardiac toxicity.  \r\n\r\nThe phase III trial, PIX-R, is ongoing and will compare pixantrone multidrug therapy with an equivalent regimen in patients with diffuse large B-cell lymphoma (the most common type of NHL).\r\n\r\nPrevious study results have also suggested the possibility that pixantrone may be safe and effective in doxorubicin naive patients. In myocardial strips which are doxorubicin naive, pixantrone is taken up to a higher degree than in myocardial strips which are doxorubicin exposed, and once absorbed exhibits redox inactivity.  \r\n\r\nPixantrone dimaleate has also been investigated as a treatment for acute myelogenous leukemia, diffuse large B-cell lymphoma, follicular lymphoma, metastatic breast cancer, low grade small lymphocytic lymphomas and general metastatic cancers.","Pixantrone has a wide range of antitumor activity, especially in terms of treating leukemias and lymphomas . \r\n\r\nPixantrone lacks cardio-toxic effects. It has postulated that his is because of its redox inactivity and lack and inhibition of doxorubicinol formation in human myocardium.","Pixantrone is an aza-anthracenedione which acts as a DNA intercalator. By intercalating between DNA, with modest affinity, it stimulates DNA cleavage by topoisomerase II. (Pixantrone acts as a poison to topoisomerase II by stabilizing protein-DNA complexes which are usually transient, giving rise to double stranded DNA breaks.)\r\nHowever, pixantrone is believed to have additional mechanisms of action as its potency does not correlate to the degree of double stranded DNA breaks observed. It has been postulated that this second mechanism may be pixantrone-DNA adduct formation.   \r\n\r\nIt is important to note that the formation of a pixtantrone-DNA adduct requires pixantrone activation by formaldehyde. Formadehyde may be generated in vitro by hydrogen peroxide, and is derived by various sources in biological systems. It is present in low levels as a result of normal metabolism, and may be present in elevated levels in some haematolgical malignancies.  The formation of pixantrone-DNA adducts is thus feasible, and it is believed that a long pixantrone-DNA adduct half life has the potential to maximize DNA damage. It may do so by enhancing the disruption of DNA replication and transcription, and potentially by encourage apoptosis. \r\n\r\nIn explanation of pixantrones lack of cardiotoxicity, it has been elucidated that pixantrone is structurally similar to mitoxantrone; however, instead of a 5,8-dihydroxyphenyl ring (thought to be responsible for cardiotoxicity) it has a nitrogen heteroatom. This nitrogen heteroatom helps to create additional hydrogen bonding sites amd increases pixantrone interaction with DNA and topoisomerase II.  \r\n\r\nPixantrone's lack of a hydroquinone is believed to render it resistant to one electron reduction. In contrast, doxorubicin - which contains a hydroquinone - experiences one electron redox cycling and ROS formation via NADH dehydrogenase.  Pixantrone also does not bind iron, and thus does not produce ROS by redox cycling between oxidative states of iron, as other anthracyclines do. \r\n\r\nThe first line agent doxorubicin is cardiotoxic, in part, due to its ability to redox activate the superoxide anion and hydrogen peroxide, and form a long-lived secondary alcohol metabolite: doxorubicinol.  Clearance of doxorubicin from myocardial tissue is incomplete, and it can be found months or years after the last administration.  In doxorubicin treated ex vivo cardiac strips, pixantrone formed an N-dealkylated product that inhibited metabolism of residual doxorubicin into doxorubicinol. Additionally, in ex vivo human myocardial strips (doxorubicin naive, and doxorubicin pretreated) pixantrone showed high cardiac uptake without formation of superoxide anion or hydrogen peroxide. Pixantrones lack of cardiotoxicity is thus attributed to its redox inactivity and inhibition of doxorubicinol formation.",null,"Therapeutic strategy associated"]
[940,"DB06200","investigational","small molecule","Tedisamil","Tedisamil","C19H32N2","C(C1CC1)N1CC2CN(CC3CC3)CC(C1)C21CCCC1","Tedisamil (planned trade name Pulzium) is an investigational drug for atrial fibrillation and atrial flutter. It is currently being developed by Solvay and is currently under regulatory review by the United States Food and Drug Administration.","90961-53-8","288.4708","Investigated for use/treatment in arrhythmia, atrial fibrillation, and angina.",null,"It is hypothesized tedisamil prevents Ca2+ overload by the cAMP dependent SR Ca2+ uptake .",null,"Indication associated"]
[941,"DB06202","approved; investigational","small molecule","Lasofoxifene","(-)-cis-5,6,7,8-Tetrahydro-6-phenyl-5-(p-(2-(1-pyrrolidinyl)ethoxy)phenyl)-2-naphthol; Lasofoxifene","C28H31NO2","[H][C@@]1(CCC2=CC(O)=CC=C2[C@@]1([H])C1=CC=C(OCCN2CCCC2)C=C1)C1=CC=CC=C1","Lasofoxifene is a non-steroidal 3rd generation selective estrogen receptor modulator (SERM) that selectively binds to both ERα and ERβ with high affinity. It is a naphthalene derivative marketed for prevention and treatment of osteoporosis and for the treatment of vaginal atrophy. It was initially developed as Oporia by Pfizer as a treatment for postmenopausal osteoporosis and vaginal atrophy, in which were both rejected for approval by FDA. Later Fablyn was developed as a result of a research collaboration between Pfizer and Ligand Pharmaceuticals with a newly submitted New Drug Application in 2008. It gained approval by European Commission in March 2009. Ligand Pharmaceuticals signed a license agreement with Sermonix Pharmaceuticals for the development and commercialization of oral lasofoxifene in the USA.","180916-16-9","413.5512","Investigated for use/treatment in postmenopausal osteoporosis to reduce the risk of both vertebral and novertebral fractures, as well as address other postmenopausal conditions, including reduction in risk of breast cancer and treatment of vulvar and vaginal atrophy (VVA)","Lasofoxifene exhibits both significant estrogenic and antiestrogenic activity both in vitro and in vivo, targeting any tissues that possess ERs, such as bone, uterus, breast, blood vessels, and liver. Binding assays demonstrated high affinity of the compound for both ERα and ERβ in a tissue-dependent manner. It mimics the effects of estradiol with varying agonist and antagonist effects.","Lasofoxifene mediates an agonist effect on estrogen receptors expressed on bone to mimic the positive effects of estrogen to reduce the production and lifespan of osteoclasts via altering the NF-kappaB ligand (RANKL)/RANK/osteoprotegerin system, stimulation of osteoblast (the bone forming cells) activity and additional effects on calcium homeostasis . It acts as an antagonist at uterus and mammary glands  by suppressing the estrogen signaling in oncogenic pathways and inhibits the downstream gene transcription .\r\nA study also suggests that lasofoxifene may also act as an inverse agonist at CB2 cannabinoid receptor which is expressed in bone to inhibit osteoclast formation and resorptive activity.","Estrogen receptor alpha antagonist&agonist&negative modulator; Estrogen receptor beta agonist; Cannabinoid receptor 2 inverse agonist","Indication associated"]
[942,"DB06203","approved","small molecule","Alogliptin","Alogliptin","C18H21N5O2","CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O","Alogliptin is a selective, orally-bioavailable inhibitor of enzymatic activity of dipeptidyl peptidase-4 (DPP-4). Chemically, alogliptin is prepared as a benzoate salt and exists predominantly as the R-enantiomer (>99%). It undergoes little or no chiral conversion in vivo to the (S)-enantiomer. FDA approved January 25, 2013.","850649-61-5","339.3916","Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.","Peak inhibition of DPP-4 occurs within 2-3 hours after a single-dose administration to healthy subjects. The peak inhibition of DPP-4 exceeded 93% across doses of 12.5 mg to 800 mg. Inhibition of DPP-4 remained above 80% at 24 hours for doses greater than or equal to 25 mg.  Alogliptin also demonstrated decreases in postprandial glucagon while increasing postprandial active GLP-1 levels compared to placebo over an 8-hour period following a standardized meal. Alogliptin does not affect the QTc interval.","Alogliptin inhibits dipeptidyl peptidase 4 (DPP-4), which normally degrades the incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon like peptide 1 ( GLP-1). The inhibition of DPP-4 increases the amount of active plasma incretins which helps with glycemic control. GIP and GLP-1 stimulate glucose dependent secretion of insulin in pancreatic beta cells. GLP-1 has the additional effects of suppressing glucose dependent glucagon secretion, inducing satiety, reducing food intake, and reducing gastric emptying.","Dipeptidyl peptidase 4 inhibitor","Indication associated"]
[943,"DB06204","approved","small molecule","Tapentadol","Tapentadol","C14H23NO","CC[C@H]([C@@H](C)CN(C)C)C1=CC(O)=CC=C1","Opioid analgesic for treatment of moderate to severe pain. FDA approved on Nov 20, 2008.","175591-23-8","221.3385","The immediate-release formulation of tapentadol is indicated for the relief of moderate to severe acute pain. The long-acting formulation serves as a continuous, around-the-clock analgesic that is indicated for the relief of moderate to severe chronic pain or neuropathic pain associated with diabetic peripheral neuropathy.","Tapentadol is a centrally-acting synthetic analgesic that is 18 times less potent than morphine in binding mu-opioid receptors. It also increases norepinephrine concentrations in the brains of rats via inhibition of norepinephrine reuptake. Selective mu-opioid antagonists like naloxone can block analgesia from tapentadol. It also has not effect on the QT interval.","Tapendadol causes large increases in levels of extracellular norepinephrine (NE) due to a dual mechanism of action involving mu opioid receptor (MOR) agonism as well as noradrenaline reuptake inhibition.\r\n\r","Mu-type opioid receptor agonist; Sodium-dependent noradrenaline transporter inhibitor; Kappa-type opioid receptor; Delta-type opioid receptor; 5-hydroxytryptamine receptor 3A; Sodium-dependent serotonin transporter inhibitor","Indication associated"]
[944,"DB06207","approved","small molecule","Silodosin","Silodosin","C25H32F3N3O4","C[C@H](CC1=CC2=C(N(CCCO)CC2)C(=C1)C(N)=O)NCCOC1=CC=CC=C1OCC(F)(F)F","Silodosin is a selective antagonist of alpha(α)-1 adrenergic receptors that binds to the α<sub>1A</sub> subtype with the highest affinity. α1-adrenergic receptors regulate smooth muscle tone in the bladder neck, prostate, and prostatic urethra: the α<sub>1A</sub> subtype accounts for approximately 75% of α1-adrenoceptors in the prostate. \r\n\r\nSilodosin was first approved by the FDA in October 2008  and it is also approved in Europe and Canada. Silodosin is available as oral capsules with common trade names Rapaflo and Urorec. It is indicated for the symptomatic treatment of benign prostatic hyperplasia in adults. Most commonly affecting males over the age of 40 years, benign prostatic hyperplasia is the non-malignant enlargement of the prostate gland, associated with lower urinary tract symptoms that have a negative impact on the quality of life of patients. Silodosin works by binding to α<sub>1A</sub>-adrenoceptors with high affinity and relaxing the lower urinary tract, thereby improving urinary symptoms and alleviating bladder outlet obstruction.","160970-54-7","495.5345","Silodosin is indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH). It is not indicated for the treatment of hypertension.","Silodosin is an antagonist of α<sub>1</sub>-adrenoceptors. It has the highest selectivity for the α<sub>1A</sub>-adrenoceptor subtype, with a 162-fold greater affinity than α<sub>1B</sub>-adrenoceptor and about a 50-fold greater affinity than for α<sub>1D</sub>-adrenoceptor. In clinical trials, silodosin improved maximum urinary flow rate, voiding symptoms, and storage symptoms of benign prostatic hyperplasia. Following oral administration, silodosin had a rapid onset of effect in men, with early effects of relieving lower urinary tract symptoms occurring within two to six hours post-dose.\r\n\r\nSilodosin inhibited the human ether-a-go-go-related gene (HERG) tail current; however, it has weak cardiovascular effects. As with all α<sub>1</sub>-adrenoceptor antagonists blocking α<sub>1</sub>-adrenoceptors in the iris dilator muscle, silodosin may cause intraoperative floppy iris syndrome (IFIS), which is characterized by small pupils and iris billowing during cataract surgery in patients taking α1-AR antagonists.","The pathogenesis of benign prostatic hyperplasia is not fully understood: it is believed to involve several pathways, including inflammation, apoptosis, and cellular proliferation. Most drug therapies aim to alleviate symptoms of benign prostatic hyperplasia, silodosin included. Lower urinary tract symptoms of benign prostatic hyperplasia are categorized into three main groups: voiding or obstructive (hesitancy, slow stream, intermittency, incomplete emptying), storage or irritative (frequency, urgency, nocturia, urge urinary incontinence), and postmicturition (postvoid dribbling). Prostate contraction is the main contributor to lower urinary tract symptoms of benign prostatic hyperplasia. The smooth muscle tone of the prostate is regulated by α<sub>1A</sub>-adrenoceptors, which are the most highly expressed subtype of α<sub>1</sub>adrenoceptors in the human prostate tissue. It has been reported that blockade of α<sub>1A</sub>-adrenoceptors relieves bladder outlet obstruction. Blockade of α<sub>1D</sub>-adrenoceptors, another subtype found in prostate tissue, is believed to alleviate storage symptoms due to detrusor overactivity.\r\n\r\nα<sub>1</sub>-adrenoceptors are G protein-coupled receptors: upon binding of its natural ligand, norepinephrine and epinephrine, leads to the activation of phospholipase C and downstream signalling molecules, including inositol triphosphate and diacylglycerol. Ultimately, there is an increase in intracellular calcium levels and, consequently, smooth muscle contraction. Silodosin is an antagonist of α<sub>1</sub>-adrenoceptors, with the highest selectivity for the α<sub>1A</sub>-adrenoceptor subtype. By blocking the α<sub>1A</sub>-adrenoceptor signalling pathway, silodosin promotes prostatic and urethral smooth muscle relaxation, thereby improving lower urinary tract symptoms such as voiding. Silodosin also targets afferent nerves in the bladder, relieving bladder overactivity and storage symptoms.","Alpha-1A adrenergic receptor antagonist; Alpha-1D adrenergic receptor antagonist; Alpha-1B adrenergic receptor antagonist; HERG human cardiac K+ channel blocker","Therapeutic strategy associated"]
[945,"DB06209","approved","small molecule","Prasugrel","Prasugrel","C20H20FNO3S","CC(=O)OC1=CC2=C(CCN(C2)C(C(=O)C2CC2)C2=CC=CC=C2F)S1","Prasugrel, a thienopyridine derivative, is a platelet activation and aggregation inhibitor structurally and pharmacologically related to clopidogrel and ticlopidine. Similar to clopidogrel, prasugrel is a prodrug that requires enzymatic transformation in the liver to its active metabolite, R-138727. R-138727 irreversibly binds to P2Y12 type ADP receptors on platelets thus preventing activation of the GPIIb/IIIa receptor complex. As a result, inhibition of ADP-mediated platelet activation and aggregation occurs. Prasugrel was developed by Daiichi Sankyo Co. and is currently marketed in the United States and Canada in cooperation with Eli Lilly and Company for acute coronary syndromes planned for percutaneous coronary intervention (PCI). FDA approved in 2009.","150322-43-3","373.441","Indicated in combination with acetylsalicylic acid (ASA) to prevent atherothrombotic events in patients with acute coronary syndrome (ACS) who are to be managed with percutaneous coronary intervention (PCI). May be used in patients with unstable angina (UA), non-ST elevation myocardial infarction (NSTEMI), ST-elevation myocardial infarction (STEMI) who are to be managed with PCI. Prasugrel is not recommended in patients 75 years of age or greater, those that weigh<60kg, and patients with a history of stroke or transient ischemic attack due to increased risk of fatal and intracranial bleeding.","Prasugrel is a thienopyridine ADP receptor inhibitors which inhibits platelet aggregation by irreversibly binding to P2Y12 receptors.","Prasugrel is an thienopyridine and a prodrug which inhibits ADP receptors by irreversibly acting on the P2Y12 receptor on platelets. The active metabolite of prasugrel prevents binding of adenosine diphosphate (ADP) to its platelet receptor, impairing the ADP-mediated activation of the glycoprotein GPIIb/IIIa complex. Prasugrel is proposed to have a similar mechanism of action to clopidogrel.","P2Y purinoceptor 12 antagonist","Therapeutic strategy associated"]
[946,"DB06217","approved; investigational","small molecule","Vernakalant","(3R)-1-((1R,2R)-2-(2-(3,4-dimethoxyphenyl)ethoxy)cyclohexyl)pyrrolidin-3-ol; Vernakalant","C20H31NO4","COC1=C(OC)C=C(CCO[C@@H]2CCCC[C@H]2N2CC[C@@H](O)C2)C=C1","Vernakalant was developed by Cardiome Pharma as as an antiarrhythmic drug intended for rapid conversion of atrial fibrillation to sinus rhythm. It acts as an atypical class III antiarrhythmic drug that potentiates its effect in higher heart rates. Intravenous formulation was approved in Europe in September 2010 as Brinavess and in Canada in April 2017. It is an investigational drug under regulatory review by FDA.","794466-70-9","349.471","Indicated for the rapid conversion of recent onset of atrial fibrillation to sinus rhythm in adults for non-surgery patients that lasts for less than 7 days of duration and post-cardiac surgery patients with atrial fibrillation lasting less than 3 days of duration.","Vernakalant blocks currents in all phases of atrial action potential including atria-specific potassium currents (the ultra-rapid delayed rectifier and the acetylcholine dependent potassium currents)  and prolongs the refractory period. It dose-dependently prolongs atrial refractoriness, prolongs AV nodal conduction and refractoriness, and slightly prolongs QRS duration without significantly affecting ventricular refractory period. Vernakalant has a high affinity to ion channels specifically involved in repolarization of atrial tissue and is thought to have a low proarrhythmic potential.","Vernakalant blocks atrial voltage-gated sodium channels in a dose and frequency-dependent manner and inhibits late sodium current (INa)which confers its effect on intra-atrial conduction. This current blockade enhance and onset of drug action accelerates in higher heart rate as the affinity of vernakalant for INa also increases. Its binding offset is quick once the heart rate slows . It also blocks Kv 1.5 channel and its early activating potassium channels (IKur) and inhibits acetylcholine-activated potassium channels (IKAch), which are specific to the atrium and cause prolongation of atrial refractoriness. Vernakalant also blocks Kv4.3 channel and its cardiac transient outward potassium current (Ito), which is involved more with atrial than ventricular refractoriness . \r\nVernakalant minimally blocks hERG channels and its rapidly activating/delayed rectifying potassium current (IKr) which accounts for mild QT prolongation. QRS widening due to INa blockade also contributes to QT prolongation .","Sodium channel protein type 5 subunit alpha blocker; Potassium voltage-gated channel subfamily A member 5 blocker; Potassium voltage-gated channel subfamily D member 3 blocker; Potassium voltage-gated channel subfamily H member 2 blocker","Indication associated"]
[947,"DB06224","investigational","small molecule","Alicaforsen","Alicaforsen",{"$nulls":3},"185229-68-9",null,"Investigated for use/treatment in crohn's disease and ulcerative colitis.",null,"Alicaforsen selectively inhibits ICAM‑1 gene expression. Over-expression of ICAM‑1 occurs in a wide variety of inflammatory disorders, including ulcerative colitis (UC), pouchitis and tissues in the eye, gastrointestinal teact, lungs and skin. UC is an inflammatory bowel disease of the colon, a part of the large intestine, and pouchitis is an inflammation of the surgically constructed internal pouch created in UC patients when their diseased colons are removed.  \r\nAlicaforsen is a RNase H dependent phosphorothioate-modified antisense oligodeoxynucleotide inhibitor which shuts down specific sequences of intracellular adhesion molecule 1 (ICAM1) mRNA and thus production of ICAM1, which prevents the inflammatory response. ICAM is a cell surface glycoprotein (immunoglobulin superfamily) which facilitates leukocyte adhesion and antigen presentation in the intestinal mucosa. Alicaforsen hybridizes the oligonucleotide strand with the target mRNA to suppress expression of ICAM1.",null,"Therapeutic strategy associated"]
[948,"DB06225","investigational","small molecule","HMR4011",{"$nulls":3},"HMR4011 (IPL 576,092) is a novel steroidal anti-inflammatory compound with a mechanism of action distinct from that of glucocorticoid. IPL 576,092 has previously been investigated as a treatment for asthma.",null,null,"Investigated for use/treatment in asthma.",null,"HMR4011 is a leukocyte suppressing/selective anti-inflammatory drug (LSAID) that was investigated for asthma treatment, a chronic inflammatory disease of the airways.",null,"Therapeutic strategy associated"]
[949,"DB06228","approved","small molecule","Rivaroxaban","Rivaroxaban","C19H18ClN3O5S","ClC1=CC=C(S1)C(=O)NC[C@H]1CN(C(=O)O1)C1=CC=C(C=C1)N1CCOCC1=O","Rivaroxaban is an anticoagulant and the first orally active direct factor Xa inhibitor. Unlike warfarin, routine lab monitoring of INR is not necessary. However there is no antidote available in the event of a major bleed. Only the 10 mg tablet can be taken without regard to food. The 15 mg and 20 mg tablet should be taken with food. FDA approved on July 1, 2011.","366789-02-8","435.881","Rivaroxaban is indicated for the prevention of venous thromboembolic events (VTE) in patients who have undergone total hips replacements and total knee replacement surgery; prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation; treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE); to reduce risk of recurrent DVT and/or PE. Rivaroxaban is also indicated, in combination with aspirin, for reducing the risk of major cardiovascular events in patients with chronic coronary artery disease or peripheral artery disease. Its use is also not recommended in those with severe renal impairment (<30mL/min).\r\n\r\nRivaroxaban is also indicated for the treatment and prevention of VTE in pediatric patients (from birth to 18 years of age) and for thromboprophylaxis in pediatric patients ≥2 years old with congenital heart disease following the Fontan procedure.\r","Rivaroxaban is an anticoagulant which binds directly to factor Xa. Thereafter, it effectively blocks the amplification of the coagulation cascade, preventing the formation of thrombus. Rivaroxaban is a unqiue anticoagulant for two reasons. First of all, it is does not involve antithrombin III (ATIII) to exert its anticoagulant effects. Secondly, it is an oral agent whereas the widely used unfractionated heparin and low molecular weight heparins are for parenteral use only. Although the activated partial thromboplastin time (aPTT) and HepTest (a test developed to assay low molecular weight heparins) are prolonged in a dose-dependant manner, neither test is recommended for the assessment of the pharmacodynamic effects of rivaroxaban. Anti-Xa activity and inhibition of anti-Xa activity monitoring is also not recommended despite being influenced by rivaroxaban.","Rivaroxaban competitively inhibits free and clot bound factor Xa. Factor Xa is needed to activate prothrombin (factor II) to thrombin (factor IIa). Thrombin is a serine protease that is required to activate fibrinogen to fibrin, which is the loose meshwork that completes the clotting process. Since one molecule of factor Xa can generate more than 1000 molecules of thrombin, selective inhibitors of factor Xa are profoundly useful in terminating the amplification of thrombin generation. The action of rivaroxaban is irreversible.\r\n \r","Coagulation factor X antagonist","Indication associated"]
[950,"DB06231","investigational","small molecule","Caldaret","Caldaret","C11H16N2O3S","CC1=CC=C(N2CCNCC2)C(=C1)S(O)(=O)=O",null,"133804-44-1","256.32","Investigated for use/treatment in heart disease and myocardial infarction.",null,"Cardiac damage due to the buildup of sodium (Na+) ischemia and early reperfusion leads to increased calcium (Ca2+) through the reverse mode Na+/Ca2+(NCX) ion exchanger. Caldaret is an intracardiac calcium (Ca2+) handling modulator whose cardioprotective actions are presumed to be due to inhibition of the NCX exhanger and increasing the uptake of Ca2+ via the sarcoplasmic reticulum (SR).\r\n\r","Sodium/calcium exchanger 1","Indication associated"]
[951,"DB06237","approved","small molecule","Avanafil","(S)-4-(3-Chloro-4-methoxybenzylamino)-2-(2-hydroxymethylpyrrolidin-1-yl)-N-pyrimidin-2-ylmethyl-5-pyrimidinecarboxamide; Avanafil","C23H26ClN7O3","COC1=C(Cl)C=C(CNC2=C(C=NC(=N2)N2CCC[C@H]2CO)C(=O)NCC2=NC=CC=N2)C=C1","Avanafil is a phosphodiesterase-5 (PDE5) inhibitor used in the treatment of erectile dysfunction. In comparison with other drugs of the same class, it shows greater selectivity for PDE5 over PDE6 than both  and  but less selectivity than , suggesting a relatively lower risk of visual disturbances associated with off-target PDE6 inhibition.\r\n\r\nIt first received FDA approval on April 27, 2012, with subsequent EMA approval in June 2013.","330784-47-9","483.951","Avanafil is indicated for the treatment of erectile dysfunction.","Avanafil is a strong competitive inhibitor of phosphodiesterase 5 (PDE5) with a demonstrated _in vitro_ IC<sub>50</sub> of 5.2 nM. Its inhibitory effects on PDE5 are 100-fold more potent than on PDE6 and >1000-fold more potent than on other PDE enzymes, meaning it is less likely to cause visual disturbances and cardiovascular adverse effects when compared with less selective PDE5 inhibitors such as  and . It has a relatively quick onset of action allowing for administration as early as 15 minutes prior to sexual activity.\r\n\r\nPDE5 inhibitors like avanafil can cause significant drug interactions when administered alongside certain antihypertensive agents (e.g. alpha blockers, substantial amounts of alcohol). PDE5 inhibitors have also been associated with the development of non-arteritic anterior ischemic optic neuropathy (NAION), a rare condition that typically presents as sudden loss of vision in one or both eyes and appears to be more common in patients with a \"crowded\" optic disc. Patients presenting with any degree of vision loss should immediately discontinue use of all PDE5 inhibitors and seek medical attention. In some jurisdictions, a history of NAION or other degenerative retinal disorders is considered a contraindication to avanafil therapy.","Avanafil inhibits the cGMP-specific phosphodiesterase type 5 (PDE5) which is responsible for the degradation of cGMP in the corpus cavernosum located around the penis. Sexual arousal results in the local release of nitric oxide, which in turn stimulates the enzyme guanylate cyclase to produce cGMP. Elevated levels of cGMP result in local smooth muscle relaxation and increased blood flow to the penis (i.e. an erection).\r\n\r\nAs PDE5 inhibitors like avanafil require the endogenous release of nitric oxide in order to exert their pharmacologic effect, they have no effect on the user in the absence of sexual stimulation/arousal.","cGMP-specific 3',5'-cyclic phosphodiesterase inhibitor","Therapeutic strategy associated"]
[952,"DB06241","investigational","biotech","Clenoliximab","Clenoliximab",null,null,"Clenoliximab is a chimeric monoclonal antibody from _Macaca irus_ against CD4 which acts as an immunomodulator. It has investigated for the treatment of rheumatoid arthritis.",null,null,"Investigated for use/treatment in rheumatoid arthritis.",null,"Clenoliximab is a macaque-human chimeric monoclonal antibody (immunoglobulin G4)that binds specifically to the CD4 receptor present on T-lympocytes (Helper T lymphocytes). CD-4 lymphocytes are implicated in the pathogenesis of rheumatoid arthritis (RA). Clenoliximab coats the CD4 T-lymphocytes and thus down-modulates the CD4 T-lympocytes in a dose and concentration-dependent manner without decreasing the amount of CD4 T-lympocytes in circulation.\r","T-cell surface glycoprotein CD4","Indication associated"]
[953,"DB06244","investigational","biotech","Trafermin","Recombinant human basic fibroblast growth factor; rhbFGF; Trafermin",{"$nulls":3},"131094-16-1",null,"Investigated for use/treatment in coronary artery disease, peripheral vascular disease, periodontal disease, bone fractures, entero-related fistulae, and diabetic foot ulcers.",null,"Trafermin, or basic fibroblast growth factor 2 (bFGF) is a recombinant human growth factor used to stimulate angiogenesis and keratinization in wound healing. It stimulates migration of monocytes, neutrophils, macrophages, fibroblasts and also assists in creation of granulation tissue (the tissue that replaces fibrin clots in healing wounds).\r\n\r",null,"Indication associated"]
[954,"DB06245","investigational","biotech","Lanoteplase","Lanoteplase",{"$nulls":3},"171870-23-8",null,"Investigated for use/treatment in myocardial infarction.",null,"Lanoteplase is a second generation derivative of alteplase, and a third generation recombinant plasminogen activator made from a deletion and point mutant of tissue type-plasminogen activator (t-PA). Lanoteplase has a longer half life than alteplase. Lanoteplase is a serine protease that binds to fibrin in a thrombus (blood clot)and cleaves the Arg-Val bond in plasminogen, producing active plasmin. Plasmin is an enzyme that degrades plasma proteins such as fibrin clots to clear blocked blood vessels that cause myocardial infarction (heart attack) or stroke. \r\n \r","Urokinase plasminogen activator surface receptor; Fibrinogen alpha chain; Kallikrein-1; Laminin subunit alpha-5; Coagulation factor X; Fibronectin; Plasminogen activator inhibitor 2; Tetranectin; Keratin, type II cytoskeletal 8; Annexin A2; Laminin subunit beta-1; Laminin subunit gamma-1; Laminin subunit alpha-1; Calreticulin; Calnexin; Prolow-density lipoprotein receptor-related protein 1; Laminin subunit alpha-3","Indication associated"]
[955,"DB06246","investigational","small molecule","Exisulind","5-Fluoro-2-methyl-1-((Z)-p-(methylsulfonyl)benzylidene)indene-3-acetic acid; cis-5-Fluoro-2-methyl-1-(p-methylsulfonylbenzylidenyl)indene-3-acetic acid; Exisulind; Sulindac sulfone","C20H17FO4S","CC1=C(CC(O)=O)C2=CC(F)=CC=C2\\C1=C/C1=CC=C(C=C1)S(C)(=O)=O",null,"59973-80-7","372.41","Investigated for use/treatment in adenomatous polyposis coli, lung cancer, prostate cancer, colon polyps, Barrett's esophagus disease, and pediatric indications.",null,"Exisulind is a sulindac derivative of a class of compounds called selective apoptotic anti-neoplastic drugs (SAANDs), which inhibit the enzyme cyclic guanosine monophosphodiesterase (cGMP - PDE). Exisulind is specific for apoptotic effects in precancerous and cancerous colorectal cells due to their overexpression of cGMP. Sustained elevation of cGMP and protein kinase G (PKG) activation may be also implicated in the induction of apoptosis by Exisulind.","cAMP-specific 3',5'-cyclic phosphodiesterase 4D; cAMP-specific 3',5'-cyclic phosphodiesterase 4C; cGMP-specific 3',5'-cyclic phosphodiesterase; cGMP-dependent 3',5'-cyclic phosphodiesterase; Glutathione S-transferase P inhibitor; Aldose reductase inhibitor; Aldo-keto reductase family 1 member B10 inhibitor","Therapeutic strategy associated"]
[956,"DB06248","investigational","small molecule","Amelubant","Amelubant","C33H34N2O5","CCOC(=O)NC(=N)C1=CC=C(OCC2=CC=CC(COC3=CC=C(C=C3)C(C)(C)C3=CC=C(O)C=C3)=C2)C=C1",null,"346735-24-8","538.644","Investigated for use/treatment in asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, and rheumatoid arthritis.",null,"Amelubant is a long-acting oral Leukotriene B4 (LTB4) receptor antagonist. Amelubant is a prodrug which is metabolized by ubiquitous esterases to BIIL 260 and its glucuronidated metabolite BIIL 315.14. BIIL 260 and BIIL 315.14 interact directly with the LTB4 receptors. LTB4 is a chemotactic factor for immune cells and potentiates the immune response. The G-protein coupled receptors BLT1, (high affinity for LTB4, expressed in most leukocytes) and BLT2 (low affinity for LTB4) are responsible for mediating LTB4's effects.\r","Leukotriene B4 receptor 2; Leukotriene B4 receptor 1","Indication associated"]
[957,"DB06249","approved; investigational","small molecule","Arzoxifene","Arzoxifene","C28H29NO4S","COC1=CC=C(C=C1)C1=C(OC2=CC=C(OCCN3CCCCC3)C=C2)C2=C(S1)C=C(O)C=C2",null,"182133-25-1","475.6","Investigated for use/treatment in breast cancer, osteoporosis, and endometrial cancer.",null,"Arzoxifene is a selective estrogen receptor modulator (SERM) \r\nwhich antagonizes estrogen in mammary and uterine tissue, but acts as an estrogen receptor agonist in bone tissue. Arzoxifene reduces bone loss and risk of osteoperosis and decreases serum cholesterol.\r","Estrogen receptor alpha; Estrogen receptor beta","Indication associated"]
[958,"DB06250","investigational","small molecule","Fluasterone",null,"C19H27FO","C[C@]12CC[C@H]3[C@@H](CC=C4CCCC[C@]34C)[C@@H]1C[C@@H](F)C2=O","Has antiproliferative effects on HIV-1 and reduces HIV-1 replication.","112859-71-9","290.422","Investigated for use/treatment in psoriasis and psoriatic disorders, hyperlipidemia, metabolic disease, cancer/tumors (unspecified), and obesity.",null,"Fluasterone is a synthetically stable adrenocortical steroid fluorinated analogue of dehydroepiandrosterone (DHEA), a powerful anti-inflammatory molecule with androgenic or estrogenic side effects. It is proposed that fluasterone inhibits NF-kB activation and reduces oxidative stress, but other mechanisms may play a role. Fluasterone suppresses\r\ninflammation and is effective in preclinical models of chronic inflammatory disease including psoriasis, asthma, rheumatoid arthritis, multiple sclerosis and lupus erythematosus. Fluasterone has anti-inflammatory effects inpreclinical models of chronic\r\ninflammatory disease including psoriasis, asthma, rheumatoid\r\narthritis, multiple sclerosis and lupus erythematosus.\r\n\r\n\r",null,"Therapeutic strategy associated"]
[959,"DB06253","investigational","small molecule","Thioctic acid tromethamine","(R)-5-(1,2-dithiolaln-3-yl)-pentanoic acid tromethamine; Thioctic acid tromethamine","C12H25NO5S2","NC(CO)(CO)CO.OC(=O)CCCC[C@@H]1CCSS1","A salt of alpha-lipoic acid and tromethamine; may be useful in treating vascular stress in patients with diabetes.","137314-40-0","327.45","Investigated for use/treatment in diabetes mellitus type 2, neuropathy (diabetic), and vascular diseases.",{"$nulls":3},"Indication associated"]
[960,"DB06255","experimental","small molecule","Incadronic acid","Cimadronate; Incadronate; Incadronic acid","C8H19NO6P2","OP(O)(=O)C(NC1CCCCCC1)P(O)(O)=O","Incadronate, or YM-175, is a nitrogen containing bisphosphonate. Along with being investigated to treat hypercalcemia of malignancy, it has also been investigated in the treatment of myeloma, leukemia, and other cancers.\r\n\r\nIncadronic acid was first described in the literature in 1991.","124351-85-5","287.189","Incadronate has been investigated in the treatment of myeloma, leukemia, and other cancers. It has also been investigated in patients with hypercalcemia of malignancy.",null,"Bisphosphonates are taken into the bone where they bind to hydroxyapatite. Bone resorption by osteoclasts causes local acidification, releasing the bisphosphonate, which is taken into the osteoclast by fluid-phase endocytosis. Endocytic vesicles become acidified, releasing bisphosphonates into the cytosol of osteoclasts where they act.\r\n\r\nOsteoclasts mediate resorption of bone. When osteoclasts bind to bone they form podosomes, ring structures of F-actin. Disruption of the podosomes causes osteoclasts to detach from bones, preventing bone resorption.\r\n\r\nNitrogen containing bisphosphonates such as incandronate are known to induce apoptosis of hematopoietic tumor cells by inhibiting the components of the mevalonate pathway farnesyl diphosphate synthase, farnesyl diphosphate, and geranylgeranyl diphosphate. These components are essential for post-translational prenylation of GTP-binding proteins like Rap1. The lack of prenylation of these proteins interferes with their function, and in the case of Rap1, leads to apoptosis. incadronate also activated caspases 3, 4, and 7; further contributing to apoptosis.","Farnesyl pyrophosphate synthase inhibitor; Caspase-3 activator; Caspase-4 activator; Caspase-7 activator","Therapeutic strategy associated"]
[961,"DB06256","investigational","biotech","rPSGL-Ig","rPSGL-Ig; YSPSL",null,null,"Recombinant P-selectin glycoprotein ligand IgG fusion protein (rPSGL-Ig) is a fusion protein of human P-selectin ligand and IgG1-Fc.",null,null,"Investigated for use/treatment in myocardial infarction, red blood cell disorders, anemia, kidney transplant surgery, transplant (rejection), liver transplant surgery, and ischemic reperfusion injury.",{"$nulls":3},"Indication associated"]
[962,"DB06257","investigational","small molecule","HE-2200","beta-Aet","C19H30O3","[H][C@@]12CC[C@H](O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])[C@@H](O)C=C2C[C@@H](O)CC[C@]12C",null,"2697-85-0","306.446","Investigated for use/treatment in adverse effects (chemotherapy), hyperlipidemia, autoimmune diseases, and hepatitis (viral, B).",{"$nulls":3},"Indication associated"]
[963,"DB06263","investigational","small molecule","Amrubicin","Amrubicin","C25H25NO9","[H][C@@]1(C[C@@](N)(CC2=C1C(O)=C1C(=O)C3=CC=CC=C3C(=O)C1=C2O)C(C)=O)O[C@H]1C[C@H](O)[C@H](O)CO1","Amrubicin is a third-generation synthetic anthracycline currently in development for the treatment of small cell lung cancer. Pharmion licensed the rights to Amrubicin in November 2006. In 2002, Amrubicin was approved and launched for sale in Japan based on Phase 2 efficacy data in both SCLC and NSCLC. Since January 2005, Amrubicin has been marketed by Nippon Kayaku, a Japanese pharmaceutical firm focused on oncology, which licensed Japanese marketing rights from Dainippon Sumitomo, the original developer of Amrubicin .","110267-81-7","483.473","Investigated for use/treatment in lung cancer .","The _anthracycline glycoside_ group of antibiotics, which includes amrubicin, represent a group of potent anticancer agents with potent activity against both solid tumors and hematological malignancies. They are the principal subjects of a large number of studies for the treatment of adult and childhood neoplastic diseases .\r\n\r\nAmrubicin is a 9-aminoanthracycline derivative and promotes cell growth inhibition by stabilizing protein – DNA complexes followed by double-stranded DNA breaks, which are mediated by topoisomerase-II enzyme .\r\n\r\nAnthracyclines have been observed to have a variety molecular effects (for example, DNA intercalation, inhibition of topoisomerase II, and stabilization of topoisomerase IIα cleavable complexes). Amrubicin shows decreased DNA intercalation when compared with doxorubicin. The decreased DNA interaction likely influences the intracellular distribution because amrubicin and its metabolite, _amrubicinol_. Amrubicin showed 20% distribution into the nucleus of P388 cells compared with the 80% nuclear distribution shown by doxorubicin (another anthracycline drug). The cell growth inhibitory effects of amrubicin appear to be mainly due to the inhibition of topoisomerase II .\r\n\r","As an anthracycline, amrubicin has antimitotic and cytotoxic activity through a variety of mechanisms of action. Amrubicin is found to form complexes with DNA via intercalation between base pairs, and it inhibits topoisomerase II enzyme activity by stabilizing the DNA-topoisomerase II complex, which prevents the re-ligation portion of the ligation-religation reaction that topoisomerase II normally catalyzes .\r\n\r\nTopoisomerase II is an enzyme located in the nucleus that regulates DNA structure through double-strand breakage and re-ligation, therefore modulating DNA replication and transcription. Inhibition of the enzyme leads to inhibition of DNA replication and halt cell growth with an arrest of the cell cycle occurring at the G2/M phase. The mechanism by which amrubicin inhibits DNA topoisomerase II is believed to be through stabilization of the cleavable DNA–topo II complex, ending in re-ligation failure and DNA strand breakage . \r\n\r\nDNA damage triggers activation of caspase-3 and -7 and cleavage of the enzyme PARP (Poly ADP ribose polymerase), leading to apoptosis and a loss of mitochondrial membrane potential. Amrubicin, like all anthracyclines, intercalates into DNA and produces reactive oxygen free radicals via interaction with NADPH, which causes cell damage .\r\n \r\nCompared with doxorubicin, another member of the anthracycline drug class, amrubicin binds DNA with a 7-fold lower affinity and therefore, higher concentrations of amrubicin are necessary to promote DNA unwinding .","DNA topoisomerase 2-alpha; DNA","Therapeutic strategy associated"]
[964,"DB06266","investigational","small molecule","Lonidamine","1-(2,4-dichlorbenzyl)-indazole-3-carboxylic acid; DICA; diclondazolic acid; Doridamina; Lonidamine","C15H10Cl2N2O2","OC(=O)C1=NN(CC2=C(Cl)C=C(Cl)C=C2)C2=C1C=CC=C2","Lonidamine (LND) is a drug that interferes with energy metabolism of cancer cells, principally inhibiting aerobic glycolytic activity, by its effect on mitochondrially-bound hexokinase (HK). In such way LND could impair energy-requiring processes, as recovery from potentially lethal damage, induced by radiation treatment and by some cytotoxic drugs.","50264-69-2","321.158","Investigated for use/treatment in benign prostatic hyperplasia, prostate disorders, and cancer/tumors (unspecified).",null,"Lonidamine is an orally administered small molecule that inhibits glycolysis by the inactivation of hexokinase. Hexokinase is an enzyme that catalyzes glucose, the first step in glycolysis. The inhibition of hexokinase by lonidamine is well established. In addition, there is evidence that lonidamine may increase programmed cell death. This stems from the observation that mitochondria and mitochondria-bound hexokinase are crucial for induction of apoptosis; agents that directly effect mitochondria may, therefore, trigger apoptosis. Indeed, in vitro models with lonidamine exhibit the hallmarks of apoptosis, including mitochondrial membrane depolarization, release of cytochrome C, phosphatidylserine externalization, and DNA fragmentation.","Cystic fibrosis transmembrane conductance regulator; Hexokinase-1","Therapeutic strategy associated"]
[965,"DB06267","approved; investigational","small molecule","Udenafil","Udenafil","C25H36N6O4S","CCCOC1=C(C=C(C=C1)S(=O)(=O)NCCC1CCCN1C)C1=NC(=O)C2=C(N1)C(CCC)=NN2C","Udenafil is a new phosphodiesterase type 5 (PDE5) inhibitor used to treat erectile dysfunction (ED). It has been approved in South Korea and will be marketed under the brand name Zydena. It is not yet approved for use in the U.S., E.U., or Canada.","268203-93-6","516.656","Investigated for use/treatment in erectile dysfunction and hypertension.","Udenafil is a potent selective phosphodiesterase type 5 (PDE5) inhibitor.","Udenafil inhibits the cGMP specific phosphodiesterase type 5 (PDE5) which is responsible for degradation of cGMP in the corpus cavernosum located around the penis. Penile erection during sexual stimulation is caused by increased penile blood flow resulting from the relaxation of penile arteries and corpus cavernosal smooth muscle. This response is mediated by the release of nitric oxide (NO) from nerve terminals and endothelial cells, which stimulates the synthesis of cGMP in smooth muscle cells. Cyclic GMP causes smooth muscle relaxation and increased blood flow into the corpus cavernosum. The inhibition of phosphodiesterase type 5 (PDE5) by udenafil enhances erectile function by increasing the amount of cGMP.","cGMP-specific 3',5'-cyclic phosphodiesterase inhibitor","Indication associated"]
[966,"DB06268","approved; investigational; withdrawn","small molecule","Sitaxentan","Sitaxentan; Sitaxsentan","C18H15ClN2O6S2","CC1=NOC(NS(=O)(=O)C2=C(SC=C2)C(=O)CC2=CC3=C(OCO3)C=C2C)=C1Cl","Sitaxentan was marketed under the trade name Thelin for the treatment of pulmonary arterial hypertension (PAH) by Encysive Pharmaceuticals until Pfizer purchased Encysive in February 2008. In 2010, Pfizer voluntarily removed sitaxentan from the market over concerns of hepatotoxicity.","184036-34-8","454.905","Investigated for use/treatment in pulmonary hypertension, connective tissue diseases, hypertension, and congestive heart failure.","Sitaxentan belongs to a class of drugs known as endothelin receptor antagonists (ERAs). Patients with PAH have elevated levels of endothelin, a potent blood vessel constrictor, in their plasma and lung tissue. Sitaxentan blocks the binding of endothelin to its receptors, thereby negating endothelin's deleterious effects.","Sitaxentan is a competitive antagonist of endothelin-1 at the endothelin-A (ET-A) and endothelin-B (ET-B) receptors. Under normal conditions, endothelin-1 binding of ET-A or ET-B receptors causes pulmonary vasoconstriction. By blocking this interaction, Sitaxentan decreases pulmonary vascular resistance. Sitaxentan has a higher affinity for ET-A than ET-B.","Endothelin-1 receptor antagonist; Endothelin B receptor antagonist","Indication associated"]
[967,"DB06270","investigational","small molecule","MAHDL01",{"$nulls":3},"MAHDL01 is a pharmaceutical combination of whole plants, which is used to increase the HDL/LDL ratio that improves overall cardiovascular health.",null,null,"Investigated for use/treatment in hyperlipidemia.",{"$nulls":3},"Indication associated"]
[968,"DB06271","approved; investigational","biotech","Sulodexide","Sulodexide",null,null,"Sulodexide is a mixture of glycosaminoglycans (GAGs) composed of dermatan sulfate (DS) and fast moving heparin (FMH).","57821-29-1",null,"Sulodexide has been used clinically for the prophylaxis and treatment of vascular diseases with increased risk of thrombosis, including intermittent claudication, peripheral arterial occlusive disease and post-myocardial infarc-tion. Also investigated in the treatment of diabetic kidney disease and diabetic neuropathy. New anti-inflammatory properties have also extended its use in venous disease.","Sulodexide is extensively absorbed owing to its low molecular weight compared to unfractionated heparin. It offers the potential advantages of a longer half-life and reduced global anticoagulation effects, properties which differ from other glycosaminoglycans. Sulodexide potentiates antithrombin III and heparin cofactor II due to the presence of both glycoaminoglycan fractions. It is capable of inhibiting both anti-IIa and anti-Xa. It promotes fibrinolytic activity by releasing tissue plasminogen activator and reduces plasminogen activator inhibitor. The drug also blocks platelet adhesion and platelet function induced by cathepsin G and thrombin. Research has also shown that Sulodexide had endothelial protective properties by inducing the overexpression of growth factors important for the protection of organs. It has anti-inflammatory properties via its effect on the release of inflammatory mediators from macrophages. This results in anti-proliferative effects such as the regulation of growth factors like VEGF and FGF. \r\nThe intravenous administration has also been shown capable of releasing tissue factor pathway inhibitor from the endothelium, which also contributes to the anti-thrombotic effects of Sulodexide. Lastly, this drug is known for its ability to inhibit the secretion of MMPs, particularly MMP-9, from leukocytes in a dose dependent manner, resulting in the restoration of the balance with their tissue inhibitors.","Thrombin inhibition produced by sulodexide is due to the additive effect of its components, namely, heparin cofactor II (HCII) catalysis by dermatan sulfate  and antithrombin-III catalysis by fast moving heparin (FMH).","Heparin cofactor 2 agonist; Antithrombin-III potentiator","Therapeutic strategy associated"]
[969,"DB06273","approved","biotech","Tocilizumab","Atlizumab; Tocilizumab",null,null,"Tocilizumab is a recombinant humanized monoclonal antibody IL-6 receptor inhibitor used to treat inflammatory and autoimmune conditions. It was first described in the literature in 2003 when Chugai, a subsidiary of Roche began developing IL-6 inhibiting monoclonal antibodies. It is currently being investigated to treat severely ill patients with COVID-19.\r\n\r\nTocilizumab was granted FDA approval on 8 January 2010.","375823-41-9",null,"Tocilizumab is indicated to treat moderate to severe rheumatoid arthritis, giant cell arteritis, polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis, and cytokine release syndrome.","Tocilizumab is an IL-6 inhibiting monoclonal antibody used to treat autoimmune and inflammatory conditions. Tocilizumab has a long duration of action as it is generally given every 4 weeks and has a wide therapeutic index. Patients should be counselled regarding the risk of infections, GI perforation, and hepatotoxicity.","Interleukin 6 (IL-6) is a pro-inflammatory cytokine produced by cells including T-cells, B-cells, lymphocytes, monocytes, fibroblasts. IL-6 rapidly induces C-reactive protein, serum amyloid A, fibrinogen, haptoglobin, and α-1-antichymotrypsin while inhibiting production of fibronectin, albumin, and transferrin. IL-6 also induces antibody production, induces cytotoxic T-cell differentiation, and inhibits regulatory T-cell differentiation. Tocilizumab binds soluble and membrane bound IL-6 receptors, preventing IL-6 mediated inflammation.","Interleukin-6 receptor subunit alpha inhibitor&antibody","Therapeutic strategy associated"]
[970,"DB06276","investigational","small molecule","Tanomastat","Tanomastat","C23H19ClO3S","OC(=O)[C@@H](CSC1=CC=CC=C1)CC(=O)C1=CC=C(C=C1)C1=CC=C(Cl)C=C1",null,"179545-77-8","410.91","Investigated for use/treatment in pancreatic cancer, lung cancer, ovarian cancer, and osteoarthritis.",{"$nulls":3},"Indication associated"]
[971,"DB06281","investigational","small molecule","Torcetrapib","Torcetrapib","C26H25F9N2O4","CCOC(=O)N1[C@H](CC)C[C@H](N(CC2=CC(=CC(=C2)C(F)(F)F)C(F)(F)F)C(=O)OC)C2=C1C=CC(=C2)C(F)(F)F","Torcetrapib (CP-529414, Pfizer) was developed to treat hypercholesterolemia but its development was halted in 2006 when phase III studies showed excessive mortality in the treatment group receiving a combination of atorvastatin and the study drug.","262352-17-0","600.4733","Investigated for use/treatment in peripheral vascular disease and hyperlipidemia.",null,"Torcetrapib is an inhibitor of cholesteryl ester-transfer protein (CETP) that increases high-density lipoprotein (HDL) cholesterol levels. The drug increases HDL-cholesterol and apolipoprotein A-I levels and decreases LDL-cholesterol and apolipoprotein B levels. The effect is showed in monotherapy and when administered in combination with statins.","Cholesteryl ester transfer protein antagonist","Indication associated"]
[972,"DB06283","approved","small molecule","Ziconotide","Ziconotide","C102H172N36O32S7","[H][C@]12CSSC[C@]3([H])NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CSSC[C@]([H])(NC(=O)[C@]([H])(CSSC[C@H](NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC1=O)C(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC3=O)C(=O)N[C@@]([H])([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N2","Ziconotide (also known as SNX-111) is a neurotoxic peptide derived from the cone snail _Conus magus_ comprising 25 amino acids with three disulphide bonds. Other such peptides, collectively termed conotoxins, exist, and some have shown efficacy in binding specific subsets of calcium channels; ziconotide is used in part because it can be synthesized without loss of proper bond formation or structural elements. Ziconotide is used to manage severe chronic pain refractory to other methods, through its ability to inhibit N-type calcium channels involved in nociceptive signalling.\r\n\r\nZiconotide was granted FDA approval on December 28, 2004 for marketing by TerSera therapeutics LLC. under the name Prialt. To date, ziconotide is the only calcium channel blocking peptide approved for use by the FDA.","107452-89-1","2639.14","Ziconotide is indicated for the management of severe chronic pain in patients refractory to other treatments, and for whom intrathecal therapy is warranted.","Ziconotide inhibits N-type calcium channels involved in nociceptive signalling, primarily in the dorsal horn of the spinal cord. Although binding is reversible, careful dosing is required to ensure therapeutic effects while minimizing adverse effects, and ziconotide has been described as possessing a narrow therapeutic window. Patients taking ziconontide may experience cognitive and neuropsychiatric symptoms, reduced levels of consciousness, and elevated serum creatine kinase levels. In addition, ziconotide may increase the risk of infection, including serious cases of meningitis. Patients who withdraw from opiates for ziconotide initiation are advised to taper off the dose.","Nociceptive pain signalling is a complex processing pathway involving peripheral nociceptors, primary afferent nerve fibres, and downstream CNS neurons located in the spinal cord. Voltage-gated calcium channels (VGCCs) are important regulatory components of neural signalling and include the N-type (Cav2.2) heteromultimeric high-voltage type calcium channels. Chronic pain conditions, including inflammatory and neuropathic pain, often involve the aberrant upregulation of VGCC activity through various cellular mechanisms, which can lead to allodynia and hyperalgesia.\r\n\r\nSpecifically, N-type channel activation in lightly myelinated Aδ- and C-fibres is known to mediate the release of neurotransmitters substance P (SP), calcitonin gene-related peptide (CGRP), and glutamate, which influence downstream neural activation and pain perception. In addition, SP and CGRP induce inflammation, potentially exacerbating pre-existing inflammatory chronic pain.\r\n\r\nZiconotide belongs to the ω-conotoxin class of neurotoxic peptides derived from the cone snail _Conus magus_ which are capable of inhibiting N-type VGCCs. Although the exact mechanism is yet to be elucidated, it is thought that ω-conotoxins function through direct occlusion of the ion pore to prevent calcium translocation across the membrane. Additional studies involving expression of chimeric subunits and molecular modelling suggest that insertion of the ziconotide Met<sup>12</sup> residue into a hydrophobic pocket formed by Ile<sup>300</sup>, Phe<sup>302</sup>, and Leu<sup>305</sup> of Cav2.2 increases binding and may be associated with toxic adverse effects.","Voltage-dependent N-type calcium channel subunit alpha-1B inhibitor; Voltage-dependent P/Q-type calcium channel subunit alpha-1A inhibitor","Therapeutic strategy associated"]
[973,"DB06285","approved; investigational","biotech","Teriparatide","PTH (1-34); PTH 1-34; Teriparatide; Teriparatide recombinant human",null,null,"Teriparatide (recombinant human parathyroid hormone) is a potent anabolic agent used in the treatment of osteoporosis. It is manufactured and marketed by Eli Lilly and Company.","52232-67-4",null,"For the treatment of osteoporosis in men and postmenopausal women who are at high risk for having a fracture. Also used to increase bone mass in men with primary or hypogonadal osteoporosis who are at high risk for fracture.","Clinical trials indicate that teriparatide increases predominantly trabecular bone in the lumbar spine and femoral neck; it has less significant effects at cortical sites. The combination of teriparatide with antiresorptive agents is not more effective than teriparatide monotherapy. The most common adverse effects associated with teriparatide include injection-site pain, nausea, headaches, leg cramps, and dizziness. After a maximum of two years of teriparatide therapy, the drug should be discontinued and antiresorptive therapy begun to maintain bone mineral density.","Teriparatide is the portion of human parathyroid hormone (PTH), amino acid sequence 1 through 34 of the complete molecule which contains amino acid sequence 1 to 84. Endogenous PTH is the primary regulator of calcium and phosphate metabolism in bone and kidney. Daily injections of teriparatide stimulates new bone formation leading to increased bone mineral density.","Parathyroid hormone/parathyroid hormone-related peptide receptor binder","Indication associated"]
[974,"DB06287","approved","small molecule","Temsirolimus","Temsirolimus","C56H87NO16","OCC(C)(CO)C(=O)O[C@@H]1CC[C@@H](C[C@@H](C)[C@]2([H])CC(=O)[C@H](C)\\C=C(C)\\[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)\\C=C\\C=C\\C=C(C)\\[C@@H](OC)C[C@]3([H])CC[C@@H](C)[C@@](O)(O3)C(=O)C(=O)N3CCCC[C@H]3C(=O)O2)C[C@H]1OC","Temsirolimus is a derivative of sirolimus used in the treatment of renal cell carcinoma (RCC). It was developed by Wyeth Pharmaceuticals under the trade name Torisel. Temsirolimus was approved by the FDA in late May 2007 as well as the European Medicines Agency (EMEA) on November 2007.","162635-04-3","1030.2871","For the treatment of renal cell carcinoma (RCC). Also investigated for use/treatment in breast cancer, lymphoma (unspecified), rheumatoid arthritis, and multiple myeloma.",null,"Temsirolimus is an inhibitor of mTOR (mammalian target of rapamycin). Temsirolimus binds to an intracellular protein (FKBP-12), and the protein-drug complex inhibits the activity of mTOR that controls cell division. Inhibition of mTOR activity resulted in a G1 growth arrest in treated tumor cells. When mTOR was inhibited, its ability to phosphorylate p70S6k and S6 ribosomal protein, which are downstream of mTOR in the PI3 kinase/AKT pathway was blocked. In in vitro studies using renal cell carcinoma cell lines, temsirolimus inhibited the activity of mTOR and resulted in reduced levels of the hypoxia-inducible factors HIF-1 and HIF-2 alpha, and the vascular endothelial growth factor.","Serine/threonine-protein kinase mTOR inhibitor","Indication associated"]
[975,"DB06297","investigational","small molecule","LX-2931",null,"C9H15N3O5","C\\C(=N/O)C1=NC=C(N1)[C@@H](O)[C@H](O)[C@H](O)CO",null,"948840-25-3","245.235","Investigated for use/treatment in rheumatoid arthritis, inflammatory disorders (unspecified), and autoimmune diseases.",{"$nulls":3},"Indication associated"]
[976,"DB06307","investigational","small molecule","Apoptone",null,"C21H32O2","C[C@]12CC[C@H]3[C@@H](CC[C@H]4C[C@H](O)CC[C@]34C)[C@@H]1CC[C@@]2(O)C#C",null,"183387-50-0","316.485","Investigated for use/treatment in cancer/tumors (unspecified).",null,"HE3235 is a second generation antitumor agent that causes apoptosis (cell death). HE3235 inhibits the BCL2 gene which translates proteins that prevent apoptosis and stimulates the expression proteins that induce apoptosis.  HE3235 also downregulates the gene that codes for the multi-drug resistant protein ABCG2 (BCRP1 – Breast Cancer Resistance Protein1).\r\n\r","Apoptosis regulator Bcl-2","Therapeutic strategy associated"]
[977,"DB06309","investigational","small molecule","Refametinib","Refametinib","C19H20F3IN2O5S","[H][C@@](O)(CO)CC1(CC1)S(=O)(=O)NC1=C(OC)C=C(F)C(F)=C1NC1=C(F)C=C(I)C=C1",null,"923032-37-5","572.337","Investigated for use/treatment in cancer/tumors (unspecified).",null,"RDEA119 is a potent, non-ATP competitive, highly selective inhibitor of MEK. RDEA119 is a highly potent and selective inhibitor of mitogen-activated ERK kinase (MEK), a key component of the RAS/RAF/MEK/ERK pathway that is commonly defective in human tumors. The MEK1/2 pathway is important in cell cycle regulation in inflammatory bowel disease, including ulcerative colitis and Crohn's disease. RDEA119 was shown to reduce damage to colonic tissue in two different mouse models of colitis, murine trinitrobenzene sulfonic acid (TNBS) colitis model and murine dextran sulfate sodium (DSS) colitis model.",null,"Therapeutic strategy associated"]
[978,"DB06311","investigational","small molecule","Darapladib","Darapladib","C36H38F4N4O2S","CCN(CC)CCN(CC1=CC=C(C=C1)C1=CC=C(C=C1)C(F)(F)F)C(=O)CN1C2=C(CCC2)C(=O)N=C1SCC1=CC=C(F)C=C1",null,"356057-34-6","666.78","Investigated for use/treatment in atherosclerosis.",null,"Darapladib is a selective lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor.  Lp-PLA2 is an enzymatic upstream mediator of inflammatory processes.\r\nEvidence from experimental settings show that the breakdown products from oxidized low density lipoprotein C (LDL-C)such as lysophosphatidylcholine species and oxidized nonesterified fatty acids are pro-inflammatory and pro-apoptotic. These products are suspected to cause athlerosclerosis progression and plaque vulnerability, which leads to increased risk of cardiovascular problems.\r","Cytosolic phospholipase A2","Therapeutic strategy associated"]
[979,"DB06314","investigational","small molecule","SGX-523","6-{[6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-b]pyridazin-3-yl]sulfanyl}quinoline","C18H13N7S","CN1C=C(C=N1)C1=NN2C(SC3=CC=C4N=CC=CC4=C3)=NN=C2C=C1","A MET receptor tyrosine kinase inhibitor.","1022150-57-7","359.408","Investigated for use/treatment in solid tumors and cancer/tumors (unspecified).",null,"SGX523 is selective inhibitor of the receptor tyrosine kinase MET. MET is implicated in development and progression of cancer. SGX523 ihibits MET autophosphorylation and signalling, as well as activates cysteine-aspartic acid protease 3 (caspase 3), an enzyme which is part of the apoptosis signalling cascade.","Hepatocyte growth factor receptor","Therapeutic strategy associated"]
[980,"DB06323","investigational","biotech","AZX-100",{"$nulls":4},"1217194-46-1",null,"Investigated for use/treatment in scar tissue.",null,"AZX100 is a synthetic 24 amino acid peptide in the field of smooth muscle relaxation and fibrosis. Signaling pathways for actin-mediated smooth muscle relaxation converge by activating a protein called heat shock related protein 20 (HSP20). AZX-100 is a cell permeant peptide that mimics HSP20, bypassing the signaling pathways leading to smooth muscle relaxation. This mechanism of action is particularly important in certain patients, such as asthmatics with mutations in the β-receptor (β16 Arg/Arg genotype) or in some forms of vasospasm (such as subarachnoid hemorrhage induced vasospasm which leads to strokes).",null,"Therapeutic strategy associated"]
[981,"DB06324","investigational","biotech","XmAb 2513",{"$nulls":3},"XmAb 2513 is a humanized monoclonal antibody that targets the antigen CD30, a molecule expressed on the surface of a number of tumor cell types. It has been investigated for the treatment of hodgkin’s lymphoma.",null,null,"Investigated for use/treatment in lymphoma (unspecified) and lymphoma (non-hodgkin's).",null,"XmAb™2513 is a humanized monoclonal antibody that targets the antigen CD30, a molecule expressed on the surface of a number of tumor cell types. XmAb™2513 has an XmAb™ Fc domain which increases its cytotoxic potency. XmAb™2513 recruits primary human immune cells to kill tumor cells in vitro models and is active in blocking tumor growth in rodent models.","Tumor necrosis factor receptor superfamily member 8","Target associated"]
[982,"DB06326","investigational","biotech","Latiglutenase","Latiglutenase",{"$nulls":3},"1360452-96-5",null,"Investigated for use/treatment in gastrointestinal diseases and disorders (miscellaneous) and autoimmune diseases such as celiac disease.",null,"ALV003 is an orally administered combination of two proteases engineered to digest gluten. It targets the glutamine and proline residues that are common in gluten. ALV003 consists of a glutamine-specific cysteine protease (EP-B2) and a proline specific prolyl endopeptidase (PEP).  The proposed mechanism of action of ALV003 is to digest gluten into non-immunotoxic fragments.",null,"Indication associated"]
[983,"DB06329","investigational","small molecule","RG-7795",null,"C12H14N4O5S","CC(=O)O[C@@H]1C[C@@H](CO)O[C@H]1N1C(=O)SC2=CN=C(N)N=C12",null,"892498-64-5","326.33","Investigated for use/treatment in solid tumors.",null,"ANA773 is an oral Toll like-receptor 7 (TLR7) prodrug agonist  whose active metabolite promotes natural killer (NK) cell-mediated anti-tumor response by inducing cytokine secretion, enhanced cytolysis of tumor cells by natural killer (NK cells) and enhanced antibody-dependent cellular cytotoxicity (ADCC).  ANA773 induced the secretion of interferon-alpha (IFN-alpha) and various other cytokines from human peripheral blood mononuclear cells (PBMC) cultured in vitro.  Innate immunity provides the first line of defense against tumor cells by inducing a broad immune response that includes the secretion of cytokines and the stimulation of NK cells. NK cells mediate anti-tumor activity by multiple mechanisms. NK cells directly lyse tumor cells through the secretion of cytotoxic granules; they promote apoptosis through the production of interferon-gamma (IFN-gamma), and they enhance the anti-tumor response of other immune cells. NK cells are activated by diverse signals, including type I interferons. Large amounts of type I IFN are produced by plasmacytoid dendritic cells (pDCs) upon engagement of the pattern recognition receptor TLR7. The natural ligand for TLR7 is single stranded RNA, although a variety of small molecule agonists have also been discovered.","Toll-like receptor 7","Therapeutic strategy associated"]
[984,"DB06333","investigational","small molecule","Trodusquemine","Trodusquemine","C37H72N4O5S","[H][C@@]1(CC[C@@]2([H])[C@]3([H])[C@H](O)C[C@@]4([H])C[C@H](CC[C@]4(C)[C@@]3([H])CC[C@]12C)NCCCNCCCCNCCCN)[C@H](C)CC[C@@H](OS(O)(=O)=O)C(C)C","Trodusquemine, a spermine metabolite of cholesterol, is a naturally occurring aminosterol that inhibits protein tyrosine phosphatase 1B. It has demonstrated the ability to stimulate regeneration of heart and multiple other tissues in animal models .","186139-09-3","685.07","Investigated for use/treatment in obesity and diabetes mellitus type 2.",null,"Trodusquemine is a spermine metabolite of cholesterol which possibly acts on the paraventricular nucleus in the hypothalamus. Trodusquemine suppresses feeding, prevents reduction in energy expenditure, causes hormonal changes, and induces patterns of neuropeptide expression normally associated with weight loss. Trosdusquemine enhances insulin sensitivity through inhibition of protein tyrosine phostphatase 1B centrally and peripherally (PTP-1B), dopamine and norepinephrine reuptake, an ion transport modulator and a downregulator of Agouti-related peptide (AgRP) and neuropeptide Y (NPY) expression.","Tyrosine-protein phosphatase non-receptor type 1; Sodium-dependent dopamine transporter; Sodium-dependent noradrenaline transporter","Therapeutic strategy associated"]
[985,"DB06335","approved","small molecule","Saxagliptin","(1S,3S,5S)-2-((2S)-Amino(3-hydroxytricyclo(3.3.1.13,7)dec-1-yl)acetyl)-2-azabicyclo(3.1.0)hexane-3-carbonitrile; Saxagliptin; Saxagliptin anhydrous","C18H25N3O2","[H][C@@]12C[C@]1([H])N([C@@H](C2)C#N)C(=O)[C@@H](N)C12CC3CC(CC(O)(C3)C1)C2","Saxagliptin (rINN) is an orally active hypoglycemic (anti-diabetic drug) of the new dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. FDA approved on July 31, 2009.","361442-04-8","315.41","Treatment of type 2 diabetes mellitus to improve glycemic control in combination with other agents or as monotherapy.","Post-administration of saxagliptin, GLP-1 and GIP levels rise up to 2- to 3- fold. Because it is very selective of DPP-4 inhibition, there are fewer systemic side effects. Saxagliptin inhibits DPP-4 enzyme activity for a 24-hour period. It also decreased glucagon concentrations and increased glucose-dependent insulin secretion from pancreatic beta cells. The half maximal inhibitory concentration (IC50) is 0.5 nmol/L.  Saxagliptin did not prolong the QTc interval to a clinically significant degree.","Saxagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor antidiabetic for the treatment of type 2 diabetes. DPP-4 inhibitors are a class of compounds that work by affecting the action of natural hormones in the body called incretins. Incretins decrease blood sugar by increasing consumption of sugar by the body, mainly through increasing insulin production in the pancreas, and by reducing production of sugar by the liver. \r\nDPP-4 is a membrane associated peptidase which is found in many tissues, lymphocytes and plasma. DPP-4 has two main mechanisms of action, an enzymatic function and another mechanism where DPP-4 binds adenosine deaminase, which conveys intracellular signals via dimerization when activated. Saxagliptin forms a reversible, histidine-assisted covalent bond between its nitrile group and the S630 hydroxyl oxygen on DPP-4. The inhibition of DPP-4 increases levels active of glucagon like peptide 1 (GLP-1), which inhibits glucagon production from pancreatic alpha cells and increases production of insulin from pancreatic beta cells.\r","Dipeptidyl peptidase 4 inhibitor","Indication associated"]
[986,"DB06343","approved; investigational","biotech","Teprotumumab","Immunoglobulin G1, anti-(human insulin-like growth factor I receptor) (human monoclonal heavy chain), disulfide with human monoclonal light chain, dimer; Teprotumumab; teprotumumab-trbw",null,null,"Teprotumumab is a fully human IgG1 monoclonal antibody directed against the human insulin-like growth factor-1 receptor. Following a clinical trial in which its efficacy in the treatment of thyroid eye disease (TED) was assessed, it received \"breakthrough therapy\" designation from the FDA in 2016 and was approved by the FDA in January 2020 for the treatment of TED. Thyroid eye disease is a potentially debilitating complication of Graves' Disease involving inflammation and tissue remodeling behind the eye, and previous treatment options typically involved multiple invasive surgeries - teprotumumab is the first drug ever approved for the treatment of TED and therefore represents a significant step forward in the treatment this disease.","1036734-93-6",null,"Teprotumumab is indicated for the treatment of thyroid eye disease.","Teprotumumab inhibits the downstream effects of IGF-1R signaling, namely tissue inflammation and remodeling, which are responsible for the various symptoms of thyroid eye disease. Teprotumumab may cause disease flares in patients with pre-existing inflammatory bowel disease (IBD) - patients experiencing an exacerbation should discontinue therapy with teprotumumab. Significant hyperglycemia has been observed in patients receiving treatment with teprotumumab which may require antihyperglycemic medications. Based on its mechanism of action, it is likely that teprotumumab will cause fetal harm in pregnant woman - for this reason, females of child-bearing age should use effective contraception prior to initiation, during therapy, and for 6 months following the last dose of teprotumumab.","Graves’ Disease is an autoimmune syndrome involving the thyroid, orbital connective tissues, and some regions of the skin. One manifestation of Graves’ Disease is thyroid-associated ophthalmopathy, or thyroid eye disease, which is characterized by orbital inflammation, tissue remodeling, and fibrosis. As the disease progresses, patients may develop proptosis, strabismus, corneal ulceration, and optic neuropathy. It has been demonstrated that insulin-like growth factor-1 receptors (IGF-1R) are overexpressed by orbital fibroblasts in patients with thyroid eye disease, in addition to being overexpressed on T-cells and B-cells in these patients. It was found that Graves’ Disease IgG molecules could mimic the principal ligand of IGF-1R, insulin-like growth factor-1 (IGF-1), and their binding of IGF-1R induces the expression of chemokines that play roles in tissue remodeling and inflammation. For these reasons, IGF-1R was sought after as a potential therapeutic target for the treatment of thyroid eye disease.\r\n\r\nTeprotumumab is a fully human IgG1 monoclonal antibody directed against IGF-1R. It binds to and induces internalization and degradation of these receptors, thus preventing their downstream effects and alleviating symptoms of thyroid eye disease.","Insulin-like growth factor 1 receptor binder&antibody","Therapeutic strategy associated"]
[987,"DB06345","investigational","small molecule","AR-9281","APAU","C18H29N3O2","CC(=O)N1CCC(CC1)NC(=O)NC12CC3CC(CC(C3)C1)C2","AR-9281 inhibits soluble epoxide hydrolase.","913548-29-5","319.449","Investigated for use/treatment in hypertension.",null,"AR9281 inhibits soluble epoxide hydrolase (s-EH), an enzyme that plays a key role in the cytochrome P450 pathway of arachidonic acid metabolism. Nuclear factor alpha B (NF-alphaB) is a transcription factor implicated in cardiac hypertrophy, and can be anti or pro apoptotic under different conditions. Epoxyeicosatrienoic acids (EETs), a product of cytochrome P450 epoxygenase enzyme action, have a variety of anti-hypertensive and anti-inflammatory effects. EETs have a vasodilatory action similar to endothelium derived hyperpolarizing factor and may inhibit NF-alphaB through a currently unknown mechanism. The enzyme s-EH catalyzes the breakdown of EETs to dihydroxyeicosatrienoic acids. AR9281's inhibition of s-EH enhances EETs anti-hypertensive and anti-inflammatory activities by preventing their breakdown by s-EH, as well as inhibiting NF-alphaB.","Bifunctional epoxide hydrolase 2","Therapeutic strategy associated"]
[988,"DB06346","investigational","small molecule","Fiboflapon","Fiboflapon","C38H43N3O4S","CCOC1=CC=C(C=N1)C1=CC=C(CN2C(CC(C)(C)C(O)=O)=C(SC(C)(C)C)C3=CC(OCC4=CC=C(C)C=N4)=CC=C23)C=C1",null,"936350-00-4","637.84","Investigated for use/treatment in inflammatory disorders (unspecified).",null,"FLAP (5-Lipoxygenase Activating Protein) is a key component early in the leukotriene pathway, a complex signaling process that exerts control over biological processes, such as inflammation and immunity. Excessive production of leukotrienes exacerbates inflammatory diseases, such as asthma; the FLAP gene has also been linked to a significant increase in the risk of myocardial infarction and stroke. AM803 binds to FLAP, inhibiting the synthesis of leukotrienes that cause inflammation.","Arachidonate 5-lipoxygenase-activating protein","Therapeutic strategy associated"]
[989,"DB06347","investigational","small molecule","Cenisertib","Cenisertib","C24H30FN7O","[H][C@@]12C[C@@]([H])(C=C1)[C@@H]([C@@H]2NC1=C(F)C=NC(NC2=CC=C(N3CCN(C)CC3)C(C)=C2)=N1)C(N)=O","Cenisertib is an aurora kinase inhibitor.","871357-89-0","451.55","Investigated for use/treatment in solid tumors, leukemia (myeloid), myelodysplastic syndrome, and cancer/tumors (unspecified).",null,"R763 is a highly potent and specific inhibitor of Aurora kinase, which has been shown to block proliferation and trigger apoptosis (cell death) in several tumor cell lines including cervical, colon, lung, pancreas and prostate. The over-expression of Aurora kinase can cause cells to rapidly develop an abnormal number of chromosomes. Elevated levels of Aurora kinase are frequently associated with various human cancers and inhibition of this enzyme disrupts cell division and promotes apoptosis.  A probable target for R763 is Aurora kinase A (serine/threonine protein kinase 6).","Aurora kinase A","Therapeutic strategy associated"]
[990,"DB06350","investigational","small molecule","Elinogrel","Elinogrel","C20H15ClFN5O5S2","CNC1=C(F)C=C2C(NC(=O)N(C2=O)C2=CC=C(NC(=O)NS(=O)(=O)C3=CC=C(Cl)S3)C=C2)=C1","A P2Y12 inhibitor and platelet aggregation inhibitor.","936500-94-6","523.94","Investigated for use/treatment in cardiovascular disorders and myocardial infarction.",null,"PRT060128 is a specific, reversible ADP receptor antagonist that binds to the P2Y12 receptor on platelets. PRT06128 prevents binding of adenosine diphosphate (ADP) to its platelet receptor, impairing the ADP-mediated activation of the glycoprotein GPIIb/IIIa complex, a key step in the coagulation cascade. PRT060128 likely has a similar mechanism of action to clopidogrel.\r","P2Y purinoceptor 12","Indication associated"]
[991,"DB06358","investigational","small molecule","Iclaprim","Iclaprim","C19H22N4O3","COC1=CC(CC2=CN=C(N)N=C2N)=C2C=CC(OC2=C1OC)C1CC1",null,"192314-93-5","354.41","Investigated for use/treatment in bacterial infection, skin infections/disorders, obesity, liver disease, kidney disease, and pneumonia.",null,"Iclaprim is a novel diaminopyrimidine, and an inhibitor of dihydrofolate reductase, which has shown potent, extended-spectrum in vitro activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, vancomycin-intermediate and vancomycin-resistant S. aureus and macrolide-, quinolone- and trimethoprim-resistant strains. In addition, iclaprim has demonstrated activity against Streptococcus pneumoniae including penicillin-, erythromycin-, levofloxacin- and trimethoprim/sulfamethoxazole-resistant strains.","Dihydrofolate reductase","Indication associated"]
[992,"DB06360","investigational","biotech","Lucatumumab","Lucatumumab",{"$nulls":3},"903512-50-5",null,"Investigated for use/treatment in leukemia (lymphoid), multiple myeloma, and lymphoma (unspecified).",null,"HCD122 is a fully human, antagonist antibody that targets the CD40 antigen. HCD122 binds to tumor cells that express CD40 and antagonizes (prevents) CD40 ligand-mediated growth and survival of malignant B cells. Based on preclinical data, HCD122 also induces antibody-dependent cellular cytotoxicity (ADCC), killing CD40 expressing tumor cells by immune effector cells. This dual mechanism of action makes HCD122 a drug candidate with potential for the treatment of B-cell malignancies.","Tumor necrosis factor receptor superfamily member 5","Target associated"]
[993,"DB06362","investigational","small molecule","Becatecarin","Becatecarin","C33H34Cl2N4O7","CCN(CC)CCN1C(=O)C2=C(C1=O)C1=C(N([C@@H]3O[C@H](CO)[C@@H](OC)[C@H](O)[C@H]3O)C3=C(Cl)C=CC=C13)C1=C2C2=C(N1)C(Cl)=CC=C2","Becatecarin is a derivative of .","119673-08-4","669.56","Investigated for use/treatment in cancer/tumors (unspecified), liver cancer, gastric cancer, and leukemia (unspecified).",null,"Becatecarin is a small molecule, anticancer compound for the treatment of hepatobiliary duct tumors, a rare and aggressive form of cancer with a high medical need and very limited survival. Becatecarin intercalates into DNA and stabilizes the DNA-topoisomerase I complex, thereby interfering with the topoisomerase I-catalyzed DNA breakage-reunion reaction and initiating DNA cleavage and apoptosis.","DNA topoisomerase 2-alpha; DNA topoisomerase 2-beta","Therapeutic strategy associated"]
[994,"DB06366","approved","biotech","Pertuzumab","2C4 Antibody; MOAB 2C4; Monoclonal Antibody 2C4; Pertuzumab; rhuMAb-2C4",null,null,"Pertuzumab is a recombinant humanized monoclonal antibody that targets the extracellular dimerization domain (subdomain II) of the human epidermal growth factor receptor 2 protein (HER2). It consists of two heavy chains and two lights chains that have 448 and 214 residues respectively. It was first approved by the FDA in 2012 for use with  and another HER2-targeted monoclonal antibody, , in the treatment of metastatic HER2-positive breast cancer. Its indicated conditions have since expanded to include use as both a neoadjuvant therapy and an adjuvant therapy in the treatment of HER2-positive breast cancers at high risk of recurrence.","380610-27-5",null,"Pertuzumab is indicated for intravenous administration in combination with  and  for the treatment of patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. It is also indicated in combination with trastuzumab and other chemotherapies for the neoadjuvant treatment of HER2-positive locally advanced, inflammatory, or early-stage breast cancer as part of a complete treatment regimen and as adjuvant treatment in patients with HER2-positive early-stage breast cancer at high risk of recurrence.\r\n\r\nPertuzumab is also indicated for subcutaneous injection - in combination with trastuzumab and  - in the treatment of HER2-positive breast cancers in adults.","Pertuzumab exerts its antineoplastic effects by binding to and inhibiting the activity of HER2, an oncogene that has been implicated in the formation of numerous cancers. As with other therapeutic monoclonal antibodies, pertuzumab has a relatively long duration of action necessitating dosing every 3 weeks. Drugs that block HER2 activity, including pertuzumab, have been implicated in the development of cardiotoxicity (specifically left ventricular dysfunction) - a baseline assessment of left ventricular ejection fraction (LVEF) should be conducted prior to beginning therapy with pertuzumab and at regular intervals throughout therapy to ensure LVEF remains within normal limits. Consider indefinite suspension of therapy if LVEF declines and does not improve.","Human epidermal growth factor receptor-2 (HER2) is a tyrosine kinase receptor that plays an integral role in cell proliferation, differentiation, and survival. HER2 becomes active following dimerization with another HER2 receptor, another member of the HER protein family (e.g. HER3), or with a ligand - this dimer then phosphorylates and activates numerous intracellular signaling proteins, initiating signal transduction via pathways that include the Ras/mitogen-activated protein kinase pathway, the phosphatidylinositol 3' kinase (PI3K)/Akt pathway, and then Janus kinases/signal transducer and activator transcription pathway. HER2 is also a known oncogene - it is overexpressed or gene-amplified (i.e. HER2-positive) in approximately 20% of breast cancers and these cancers carry a generally poorer prognosis than HER2-negative breast cancers.\r\n\r\nPertuzumab targets the extracellular dimerization domain (subdomain II) of HER2, thereby inhibiting ligand-initiated intracellular signaling via the MAP kinase and PI3K pathways. Inhibition of these pathways results in inhibition of cell growth and the initiation of apoptosis, respectively. Pertuzumab also appears to mediate antibody-dependent cell-mediated cytotoxicity.","Receptor tyrosine-protein kinase erbB-2 binder&antibody","Therapeutic strategy associated"]
[995,"DB06367","investigational","small molecule","Relacatib","Relacatib","C27H32N4O6S","CC(C)C[C@H](NC(=O)C1=CC2=CC=CC=C2O1)C(=O)N[C@H]1CC[C@@H](C)N(CC1=O)S(=O)(=O)C1=CC=CC=N1",null,"362505-84-8","540.64","Investigated for use/treatment in osteoporosis and bone metastases.",null,"Relacatib is a small-molecule drug that inhibits the activity of cathepsin K, an enzyme that appears to be implicated in osteoporosis, osteoarthritis and certain other disorders causing bone degradation.","Cathepsin K","Indication associated"]
[996,"DB06372","approved; investigational","biotech","Rilonacept","interleukin-1 (IL-1) trap; Rilonacept",null,null,"Rilonacept is a dimeric fusion protein consisting of portions of IL-1R and the IL-1R accessory protein linked to the Fc portion of immunoglobulin G1. Rilonacept functions as an interleukin 1 inhibitor and is used in the treatment of CAPS, also known as cryopyrin-associated periodic syndromes, including familial cold auto-inflammatory syndrome (FCAS) and Muckle-Wells Syndrome (MWS), in adults and children greater than 12 years old.","501081-76-1",null,"Rilonacept is currently used in the treatment of cryopyrin-associated periodic syndrome. In May 2012, an advisory panel for the FDA voted 11-0 against the use of Rilonacept for the treatment of gout.","Treatment with Rilonacept resulted in decreased levels of mean C-Reactive Protein (CRP) and Serum Amyloid A (SAA). Higher levels of CRP and SAA are associated with inflammatory disease activity found in patients with Cryopyrin-Associated Periodic Syndromes.","CAPS refer to rare genetic syndromes generally caused by mutations in the NLRP-3  gene (also known as Cold-Induced Auto-inflammatory Syndtrome-1 ). CAPS disorders are inherited in an autosomal dominant pattern with male and female offspring equally affected. Fever, urticaria-like rash, arthralgia, myalgia, fatigue, and conjunctivitis are features common to all disorders. In most cases, inflammation in CAPS is associated with mutations in the NLRP-3 gene which encodes the protein cryopyrin, an important component of the inflammasome. Cryopyrin regulates the protease caspase-1 and controls the activation of interleukin-1 beta (IL-1β). Mutations in NLRP-3 result in an overactive inflammasome resulting in excessive release of activated IL-1β that drives inflammation. Rilonacept blocks IL-1β signaling by acting as a soluble decoy receptor that binds IL-1β and prevents its interaction with cell surface receptors. Rilonacept also binds IL-1α and IL-1 receptor antagonist (IL-1ra) with reduced affinity. By binding IL-1, rilonacept prevents the activation of IL-1 receptors, thus reducing inflammatory responses and other effects related to an excess of IL-1.","Interleukin-1 beta binder; Interleukin-1 alpha binder; Interleukin-1 receptor antagonist protein binder","Therapeutic strategy associated"]
[997,"DB06376","investigational","small molecule","CHGN111",{"$nulls":3},"CHGN111 is an inhibitor of the mitochondrial enzyme CLK-1 which is a demethoxyubiquinone hydroxylase. Numerous parameters of mitochondrial function are altered when the activity of CLK-1 is reduced, which results in a decrease of ROS at critical cellular sites, as well as in a decrease of systemic oxidative stress. It was under investigation until approximately 2007.",null,null,"Investigated for use/treatment in skin infections/disorders.",null,"CHGN111 is an inhibitor of the mitochondrial enzyme CLK-1 which is a demethoxyubiquinone hydroxylase. Numerous parameters of mitochondrial function are altered when the activity of CLK-1 is reduced, which results in a decrease of ROS at critical cellular sites, as well as in a decrease of systemic oxidative stress. Compared to free radical scavengers or other detoxifying agents they directly modulate reactive oxygen species production and detoxification at an early stage to prevent damage and stop disease initiation as well as progression. Such drugs with a new mechanism of action allows Chronogen to target different pathological situations from acute and severe conditions like reperfusion-injury to more chronic situations in cardiovascular and central nervous system diseases.","Dual specificity protein kinase CLK1","Therapeutic strategy associated"]
[998,"DB06379","investigational","biotech","Calcitonin gene-related peptide","Calcitonin gene related peptide; Calcitonin-gene-related peptide; CGRP; LAB CGRP",null,null,"A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA from the calcitonin gene. The neuropeptide is widely distributed in the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator.\r\n\r\nAs a potential drug, it has demonstrated in preclinical studies a profile that could make it an ideal anti-asthmatic drug candidate with bronchodilatory, bronchoprotecting and anti-inflammatory properties.","83652-28-2",null,"Investigated for use/treatment in myocardial infarction, heart disease, and asthma.",null,"While current drugs for treating HF and MI have a single mechanism of action, CGRP appears to work on several levels: for example, it (1) increases local blood flow enhancing hemodynamic proficiency; (2) protects heart muscle cells from the damage due to lack of oxygen (ischemia); and, (3) modulates the immune system by boosting anti-inflammatory cytokine expression while suppressing pro-inflammatory cytokines, which reduces the inflammatory response to provide a cardioprotective effect. All these actions are meant to minimize heart muscle damage and subsequent scar tissue formation, while promoting the healing process.",null,"Therapeutic strategy associated"]
[999,"DB06395","investigational","small molecule","Abafungin","Abafungin","C21H22N4OS","CC1=CC(C)=C(OC2=CC=CC=C2C2=CSC(N=C3NCCCN3)=N2)C=C1",null,"129639-79-8","378.49","Investigated for use/treatment in fungal infections, bacterial infection, skin infections/disorders, and onychomycosis.",null,"Abafungin has been shown to have fungicidal and fungistatic effects on a wide variety of pathogens, including dermatophytes, yeasts (Candida) and moulds. The drug acts on the infecting organisms in two ways: by interfering with the formation of a vital sterol in the fungal cell membrane, thereby preventing cell growth, and also by direct interaction with another membrane component resulting in membrane disruption, leakage of cellular contents and death of the cell and independent of whether it is in a non-metabolising (`resting') phase of development or actively growing. These features of abafungin, combined with the attainment of microbicidal concentrations in the skin from a 1% preparation, its long residence at the site of dermal application and the lack of significant systemic absorption, mean that Abasol(tm) is particularly attractive for the topical treatment of dermatomycoses, which is the first indication under review for marketing approval.",null,"Indication associated"]
[1000,"DB06397","investigational","small molecule","Nicaraven",null,"C15H16N4O2","CC(CNC(=O)C1=CC=CN=C1)NC(=O)C1=CC=CN=C1",null,"79455-30-4","284.319","Investigated for use/treatment in cerebrovascular disease (unspecified).",null,"Nicaraven is presently being developed for the treatment of cerebral stroke including subarachnoid hemorrhage. This drug is promising because some data suggest it to have an ability to scavenge the hydroxyl radical under physiological conditions in vivo, while it also has a high permeability through the blood brain barrier.",null,"Indication associated"]
[1001,"DB06399","investigational","biotech","Atacicept","Atacicept; Human Transmembrane Activator and CAML Interactor (TACI) Immunoglobulin G1 Fc Domain Fusion Protein (Fc5); TACI-Fc5; TACI-IG",null,null,"Atacicept is a recombinant fusion protein combined with the extracellular ligand binding portion of TACI.","845264-92-8",null,"Investigated for use/treatment in autoimmune diseases, systemic lupus erythematosus, rheumatoid arthritis, multiple myeloma, lymphoma (non-hodgkin's), and leukemia (lymphoid).",null,"Atacicept contains the soluble TACI receptor that binds to the cytokines BLyS and APRIL. These cytokines are members of the tumor necrosis factor family that promote B-cell survival and autoantibody production associated with certain autoimmune diseases such as systemic lupus erythematosus. Current data indicates that levels of BLyS and APRIL are elevated in patients with rheumatoid arthritis, lupus erythematosus, B-cell malignancies and multiple sclerosis. Atacicept has been shown to affect several stages of B-cell development and may inhibit the survival of cells responsible for making antibodies.",null,"Indication associated"]
[1002,"DB06401","approved; investigational","small molecule","Bazedoxifene","Bazedoxifene","C30H34N2O3","CC1=C(N(CC2=CC=C(OCCN3CCCCCC3)C=C2)C2=C1C=C(O)C=C2)C1=CC=C(O)C=C1","Bazedoxifene is a third generation selective estrogen receptor modulator (SERM), developed by Pfizer following the completion of their takeover of Wyeth Pharmaceuticals. In late 2013, Pfizer received approval for bazedoxifene as part of the combination drug DUAVEE in the prevention (not treatment) of postmenopausal osteoporosis. It is approved in the European Union (marketed in Italy and Spain) and Japan as monotherapy. In 2013, the combination product containing conjugated estrogens and bazedoxifene was approved by the FDA for the treatment of moderate to severe vasomotor symptoms associated with menopause, as well as the prevention of postmenopausal osteoporosis in women.","198481-32-2","470.613","Indicated for following conditions alone or in combination with conjugated estrogens in women with a uterus:\r\n\r\n- Treatment of moderate to severe vasomotor symptoms associated with menopause\r\n\r\n- Prevention of postmenopausal osteoporosis",null,"Bazedoxifene belongs to a class of compounds known as selective estrogen receptor modulators (SERMs). Bazedoxifene acts as both an oestrogen-receptor agonist and/or antagonist, depending upon the cell and tissue type and target genes. Bazedoxifene decreases bone resorption and reduces biochemical markers of bone turnover to the premenopausal range. These effects on bone remodelling lead to an increase in bone mineral density (BMD), which in turn contributes to a reduction in the risk of fractures. Bazedoxifene functions primarily as an oestrogen-receptor antagonist in uterine and breast tissues.","Estrogen receptor alpha antagonist&agonist; Estrogen receptor beta","Indication associated"]
[1003,"DB06402","approved","small molecule","Telavancin","Telavancin","C80H106Cl2N11O27P","CCCCCCCCCCNCCN[C@@]1(C)C[C@H](O[C@@H]2[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]2OC2=C3OC4=CC=C(C=C4Cl)[C@@H](O)[C@@H](NC(=O)[C@@H](CC(C)C)NC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]4C(C=C2OC2=C(Cl)C=C(C=C2)[C@@H](O)[C@@H]2NC(=O)[C@H](NC4=O)C4=CC(=C(O)C=C4)C4=C(O)C(CNCP(O)(O)=O)=C(O)C=C4[C@H](NC2=O)C(O)=O)=C3)O[C@@H](C)[C@H]1O","Telavancin is a semi-synthetic derivative of vanocymycin that has bactericidal activity against Methicillin-resistant Staphylococcus aureus (MRSA) and other gram-positive bacteria.  MRSA is an important pathogen capable of causing hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and skin and subcutaneous tissue infections among others.","372151-71-8","1755.65","For the treatment of complicated skin and skin structure infections (cSSSI) caused by gram-positive bacteria like methicillin-susceptible or -resistant Staphylococcus aureus, vancomycin-susceptible Enterococcus faecalis, and Streptococcus pyogenes, Streptococcus agalactiae, or Streptococcus anginosus group. Also for the treatment of adult patients with hospital-acquired bacterial pneumonia (HAP) and ventilator-associated bacterial pneumonia (VAP), known or suspected to be caused by susceptible isolates of Staphylococcus aureus (including methicillin-susceptible and methicillin-resistant S. aureus).","Telavancin is a semi-synthetic derivative of vancomycin, therefore the mode of bactericidal action is similar to vancomycin in which both antibiotics inhibit cell wall synthesis. Not only that, it displays concentration-dependent bactericidal action. Furthermore, telavancin is a more potent inhibitor (10-fold) of peptidoglycan synthesis and, unlike vancomycin, disrupts cell membrane integrity via its interaction with lipid II. AUC/MIC ratio best predicts the extent of in-vivo response in which the higher the ratio, the greater the bactericidal activity. The smallest ratio in which one would be able to observe no bacterial growth at 24 hours is 50. Maximal bactericidal activity is observed at a AUC/MIC ratio of 404.","Telavancin is a bactericidal lipoglycopeptide that is active against a broad range of gram-positive bacteria. Telavancin prevents polymerization of N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG) and cross-linking of peptidoglycan by binding to D-Ala-D-Ala. As a result, inhibition of bacterial cell wall synthesis occurs. Furthermore, telavancin disrupts membrane potential and cell permeability as a result of the lipophillic side chain moiety. This additional bactericidal mechanism is what sets telavancin apart from vancomycin.",null,"Indication associated"]
[1004,"DB06403","approved; investigational","small molecule","Ambrisentan","(2S)-2-[(4,6-dimethylpyrimidin-2-yl)oxy]-3-methoxy- 3,3-diphenylpropanoic acid; Ambrisentan","C22H22N2O4","COC([C@H](OC1=NC(C)=CC(C)=N1)C(O)=O)(C1=CC=CC=C1)C1=CC=CC=C1","Ambrisentan is an orally active selective type A endothelin receptor antagonist indicated for the treatment of pulmonary arterial hypertension. It is approved in Europe, Canada and the United States for use as a single agent to improve exercise ability and delay clinical worsening. In addition, it is approved in the United States for use in combination with tadalafil to reduce the risks of disease progression, hospitalization and to improve exercise ability. Studies establishing the efficacy of Ambrisentan included patients with both idiopathic or heritable pulmonary arterial hypertension and those with pulmonary arterial hypertension associated with connective tissue diseases. Patients studied displayed symptoms and etiologies predominantly of WHO Functional Class II-III. As an endothelin receptor antagonist, Ambrisentan prevents endogenous endothelin peptide from constricting the muscles in blood vessels, allowing them to relax and permit a reduction in blood pressure.","177036-94-1","378.428","Ambrisentan is indicated for treatment of idiopathic (‘primary’) pulmonary arterial hypertension (IPAH) and pulmonary arterial hypertension (PAH) associated with connective tissue disease in patients with WHO functional class II or III symptoms. In the United States of America, ambrisentan is also indicated in combination with tadalafil to reduce the risks of disease progression and hospitalization for worsening PAH, and to improve exercise ability.","Ambrisentan 10 mg daily had no significant effect on the QTc interval, whereas a 40 mg daily dose of ambrisentan increased mean QTc at tmax by 5 ms with an upper 95% confidence limit of 9 ms. Significant QTc prolongation is not expected in patients taking ambrisentan without concomitant metabolic inhibitors. \r\nPlasma concentrations of B-type natriuretic peptide (BNP) in patients who received ambrisentan for 12 weeks were significantly decreased. Two Phase III placebo-controlled studies demonstrated a decrease in BNP plasma concentrations by 29% in the 2.5 mg group, 30% in the 5 mg group, and 45% in the 10 mg group (p < 0.001 for each dose group) and an increase by 11% in the placebo group.","Endothelin-1 (ET-1) is an endogenous peptide that acts on the endothelin type A (ETA) and endothelin type B (ETB) receptors in vascular smooth muscle and endothelium. ETA-mediated actions include vasoconstriction and cell proliferation, whereas ETB predominantly mediates vasodilation, anti-proliferation, and ET-1 clearance. In patients with pulmonary arterial hypertension, ET-1 levels are increased and correlate with increased right arterial pressure and severity of disease.\r\nAmbrisentan is one of several newly developed vasodilator drugs that selectively target the endothelin type A (ETA) receptor, inhibiting its action and preventing vasoconstriction. Selective inhibition of the ETA receptor prevents phospholipase C-mediated vasoconstriction and protein kinase C-mediated cell proliferation. Endothelin type B (ETB) receptor function is not significantly inhibited, and nitric oxide and prostacyclin production, cyclic GMP- and cyclic AMP-mediated vasodilation, and endothelin-1 (ET-1) clearance is preserved.","Endothelin-1 receptor antagonist; Endothelin B receptor antagonist","Indication associated"]
[1005,"DB06405","investigational","small molecule","Eprodisate","1,3-propanedisulfonic acid; Eprodisate; Propane-1,3-disulfonate; Propane-1,3-disulfonic acid; Propane-1,3-disulphonate","C3H8O6S2","OS(=O)(=O)CCCS(O)(=O)=O","Eprodisate slows the decline of renal function in AA amyloidosis.","21668-77-9","204.21","Investigated for use/treatment in amyloidosis.",null,"Decline in renal function associated with Amyloid A (AA) amyloidosis can be slowed by eprodisate (Kiacta), a drug that inhibits the deposit of the complex protein in tissues. AA amyloidosis is a serious, frequently fatal disorder involving deposits of amyloid fibrils in various organs and tissues. It is a complication of many chronic inflammatory disorders, but little is known about its etiology or natural history. Eprodisate delays the progression of AA amyloidosis-associated renal disease.",null,"Therapeutic strategy associated"]
[1006,"DB06406","investigational","small molecule","Idraparinux",null,"C38H64O49S7","[H][C@]1(O[C@H]2[C@H](OC)[C@@H](OC)[C@]([H])(O[C@@H]3[C@@H](COS(O)(=O)=O)O[C@]([H])(O[C@H]4[C@H](OC)[C@@H](OC)[C@]([H])(O[C@@H]5[C@@H](COS(O)(=O)=O)O[C@H](OC)[C@H](OS(O)(=O)=O)[C@H]5OS(O)(=O)=O)O[C@H]4C(O)=O)[C@H](OS(O)(=O)=O)[C@H]3OS(O)(=O)=O)O[C@@H]2C(O)=O)O[C@H](COS(O)(=O)=O)[C@@H](OC)[C@H](OC)[C@H]1OC","Idraparinux, a synthetic pentasaccharide is an antithrombin-dependent inhibitor of activated factor X. It was developed for the treatment and prevention of thromboembolic events. However, clinical trials have revealed that idraparinux had lead to bleeding. As a result, Sanofi stopped the development of the drug.","162610-17-5","1529.3","Investigated for use/treatment in thrombosis, venous thromboembolism, strokes, heart disease, and atrial fibrillation.",null,"Idraparinux sodium is a novel long-acting synthetic highly potent synthetic and specific indirect inhibitor of coagulation factor Xa, injectable subcutaneously.","Coagulation factor X","Indication associated"]
[1007,"DB06413","approved; investigational","small molecule","Armodafinil","(–)-2-[(R)-(diphenylmethyl)sulfinyl]acetamide; (−)-(R)-modafinil; (−)-modafinil; (R)-(−)-modafinil; (R)-modafinil","C15H15NO2S","NC(=O)C[S@@](=O)C(C1=CC=CC=C1)C1=CC=CC=C1","Armodafinil is the enantiopure of the wakefulness-promoting agent modafinil (Provigil), and is indicated to improve wakefulness in adult patients with excessive sleepiness associated with obstructive sleep apnea (OSA), narcolepsy, or shift work disorder (SWD). Research has shown that armodafinil significantly improves driving simulator performance in patients with SWD. Armodafinil consists of the (−)-R-enantiomer of the racemic modafinil. Armodafinil is produced by the pharmaceutical company Cephalon Inc. (a wholly owned subsidiary of Teva Pharmaceutical Industries Ltd.) and was approved by the U.S. Food and Drug Administration (FDA) in June 2007.","112111-43-0","273.35","Investigated for use/treatment in sleep disorders, obstructive sleep apnea, schizophrenia and schizoaffective disorders, depression, and bipolar disorders.",null,"Nuvigil (armodafinil) is a single-isomer of modafini. The exact mechanism of action is unknown. Armodafinil belongs to a class of drugs known as eugeroics, which are stimulants that provide long-lasting mental arousal. Pharmacologically, armodafinil does not bind to or inhibit several receptors and enzymes potentially relevant for sleep/wake regulation. Armodafinil is not a direct- or indirect-acting dopamine receptor agonist. However, in vitro, both armodafinil and modafinil bind to the dopamine transporter and inhibit dopamine reuptake.","Sodium-dependent dopamine transporter antagonist&inhibitor","Indication associated"]
[1008,"DB06421","investigational","small molecule","Declopramide","Declopramide","C13H20ClN3O","CCN(CC)CCNC(=O)C1=CC=C(N)C(Cl)=C1",null,"891-60-1","269.77","Investigated for use/treatment in colorectal cancer and inflammatory bowel disease.",null,"Declopramide is a member of the N-substituted benzamide class of DNA repair inhibitors. There are two possible mechanisms of action of declopramide, with one involving (nuclear localizing factor kappaB) NFkB and the other involving the activation of the caspase cascade via the mitochondrial pathway, both of which lead to cell death (apoptosis). Declopramide may also increase the susceptibility of cancer cells to traditional radiation and/or chemotherapy treatment. It is proposed that G2/M cell cycle block is induced by pathways other than the protein 53 (p53) pathway.","DNA; DNA topoisomerase 2-alpha; DNA topoisomerase 2-beta","Therapeutic strategy associated"]
[1009,"DB06423","investigational","biotech","Endostatin","Endostatins; Recombinant human endostatin",{"$nulls":3},"187888-07-9",null,"Investigated for use/treatment in cancer/tumors (unspecified), macular degeneration, and diabetic retinopathy.",null,"Endostatin is an endogenous antitumor protein. Endostatin is a 20-kDa C-terminal fragment derived from type XVIII collagen which inhibits cell proliferation and migration, and induces endothelial cell apoptosis and cell cycle arrest. It is proposed that endostatin's effects are due to inhibition of  vascular endothelial growth factor (VEGF) tyrosine phosphorylation of KDR/F1k-1 (VEGF receptor 2),  the cell surface receptor for VEGF. VEGF is an important mediator of angiogensis. Endostatin additionally blocks activation of extracellular signal related kinases, or ERK, protein 38 mitogen activated protein kinase, or p38 MAPK (signal transduction pathways involving kinases that couple growth factors to cell surface receptors), as well as focal adhesion kinase (p125FAK). Studies are being done to determine if endostatin has possible impact on other pathways, and may also target E-selectin and block activity of metalloproteinases 2, 9 and 13. There is further research into a possible mechanistic link involving endostatin's angiogenic and zinc binding ability.","72 kDa type IV collagenase; Matrix metalloproteinase-9; Collagenase 3; Focal adhesion kinase 1; E-selectin","Therapeutic strategy associated"]
[1010,"DB06429","investigational","small molecule","Talnetant","Talnetant","C25H22N2O2","CCC(NC(=O)C1=C(O)C(=NC2=CC=CC=C12)C1=CC=CC=C1)C1=CC=CC=C1","Talnetant (SB-223,412) is a neurokinin 3 receptor antagonist developed by GlaxoSmithKline, which is being researched for several different functions, primarily for irritable bowel syndrome and as a potential antipsychotic drug for the treatment of schizophrenia.","174636-32-9","382.4544","Investigated for use/treatment in schizophrenia and schizoaffective disorders, irritable bowel syndrome (IBS), and chronic obstructive pulmonary disease (COPD).",null,null,"Neuromedin-K receptor antagonist","Indication associated"]
[1011,"DB06431","investigational","small molecule","Evernimicin","Evernimicin","C70H97Cl2NO38","[H][C@]12CO[C@@H](O[C@]3([H])O[C@H](COC)[C@@H](O[C@]4([H])O[C@H](C)[C@H](OC)[C@H](O[C@]5([H])O[C@H](C)[C@@]6([H])O[C@]7(C[C@@H](O)[C@H](O[C@@]8([H])C[C@@H](O[C@@]9([H])C[C@@](C)([C@@H](OC)[C@H](C)O9)[N+]([O-])=O)[C@H](OC(=O)C9=C(OC)C(Cl)=C(O)C(Cl)=C9C)[C@@H](C)O8)[C@@H](C)O7)O[C@]6(C)[C@@H]5O)[C@H]4O)[C@H](O)[C@@H]3OC)[C@H](O)[C@]1([H])O[C@@]1(O2)OC[C@@H](OC(=O)C2=C(O)C=C(O)C=C2C)[C@]2([H])OCO[C@@]12[H]",null,"109545-84-8","1631.42","Investigated for use/treatment in bacterial infection.",{"$nulls":3},"Indication associated"]
[1012,"DB06433","investigational","small molecule","Tezacitabine","2'-Deoxy-2'-(fluoromethylene)cytidine; Tezacitabine","C10H12FN3O4","NC1=NC(=O)N(C=C1)[C@@H]1O[C@H](CO)[C@@H](O)\\C1=C/F","A synthetic purine nucleoside analogue with potential antineoplastic activity.","171176-43-5","257.2184","Investigated for use/treatment in colorectal cancer, lung cancer, leukemia (unspecified), and gastric cancer.",null,"Phosphorylated by cellular kinases, tezacitabine is converted into its active diphosphate and triphosphate metabolites. Tezacitabine diphosphate binds to and irreversibly inhibits the activity of the enzyme ribonucleotide reductase (RNR), which may result in the inhibition of DNA synthesis in tumor cells and tumor cell apoptosis. Tezacitabine triphosphate acts as a substrate for DNA polymerase, further compromising DNA replication. This agent is relatively resistant to metabolic deactivation by cytidine deaminase. RNR catalyzes the conversion of ribonucleoside 5'-diphosphates to deoxyribonucleoside 5'-diphosphates necessary for DNA synthesis and is overexpressed in many tumor types.","Ribonucleoside-diphosphate reductase large subunit","Therapeutic strategy associated"]
[1013,"DB06435","investigational","small molecule","Tarazepide","Tarazepide","C28H24N4O2","CN1C2=CC=CC=C2C(=N[C@H](NC(=O)C2=CC3=CC=CC4=C3N2CCC4)C1=O)C1=CC=CC=C1",null,"141374-81-4","448.526","Investigated for use/treatment in gastrointestinal diseases and disorders (miscellaneous).",{"$nulls":3},"Indication associated"]
[1014,"DB06437","investigational","small molecule","Tifacogin","Tifacogin",{"$nulls":3},"148883-56-1",null,"Investigated for use/treatment in sepsis and septicemia and pneumonia.",{"$nulls":3},"Indication associated"]
[1015,"DB06441","approved","small molecule","Cangrelor","[dichloro-[[[(2R,3S,4R,5R)-3,4-dihydroxy-5-[6-(2-methylsulfanylethylamino)-2-(3,3,3-trifluoropropylsulfanyl)purin-9-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]methyl]phosphonic acid; Cangrelor","C17H25Cl2F3N5O12P3S2","CSCCNC1=C2N=CN([C@@H]3O[C@H](COP(O)(=O)OP(O)(=O)C(Cl)(Cl)P(O)(O)=O)[C@@H](O)[C@H]3O)C2=NC(SCCC(F)(F)F)=N1","Cangrelor is an intravenous, direct-acting, reversible P2Y12 inhibitor for patients undergoing percutaneous coronary intervention (PCI) who have not been yet treated by oral P2Y12 inhibitors. An advantage Cangrelor provides over oral P2Y12 inhibitors (such as prasugrel, ticagrelor, and clopidogrel) is that it is an active drug not requiring metabolic conversion therefore providing a rapid onset and offset of action. Cangrelor was approved by the FDA in June 2015 for intravenous application.","163706-06-7","776.35","For use as an adjunct to percutaneous coronary intervention (PCI) for reducing the risk of periprocedural myocardial infarction (MI), repeat coronary revascularization, and stent thrombosis (ST) in patients in who have not been treated with a P2Y12 platelet inhibitor and are not being given a glycoprotein IIb/IIIa inhibitor.",null,"Cangrelor is a selective, reversible, P2Y12 platelet receptor antagonist which inhibits ADP platelet aggregation. ADP is typically released by damaged blood vessels, red blood cells, and/or platelets due to agonists stimulating platelet activity. ADP binds to P2Y12 to stimulate and complete platelet aggregation by inhibiting adenylyl cyclase by a Gi protein, thus potentiating dense granule secretion and increasing coagulation activity. Cangrelor acts on the same target as oral irreversible inhibitors clopidogrel and ticlopidine and has a similar mechanism of action, but is reversible and provides a fast onset and offset of action.","P2Y purinoceptor 12 inhibitor","Therapeutic strategy associated"]
[1016,"DB06444","investigational","small molecule","Dexanabinol","Sinnabidol","C25H38O3","CCCCCCC(C)(C)C1=CC(O)=C2[C@H]3CC(CO)=CC[C@@H]3C(C)(C)OC2=C1",null,"112924-45-5","386.576","Investigated for use/treatment in traumatic brain injuries and neurologic disorders.",null,null,"Tumor necrosis factor","Target associated"]
[1017,"DB06447","investigational","small molecule","E5531",null,"C73H136N2O22P2","[H]N([C@H]1[C@@H](OP(O)(O)=O)O[C@H](CO[C@@H]2O[C@H](COC)[C@@H](OP(O)(O)=O)[C@H](OCC[C@@H](CCCCCCC)OC(=O)CCC\\C=C/CCCCCC)[C@H]2N([H])C(=O)CC(=O)CCCCCCCCCCC)[C@@H](O)[C@@H]1OCC[C@H](O)CCCCCCC)C(=O)CC(=O)CCCCCCCCCCC","E5531 is an endotoxin antagonist.","162679-36-9","1455.831","Investigated for use/treatment in sepsis and septicemia.",null,null,"Toll-like receptor 4","Target associated"]
[1018,"DB06448","approved; investigational","small molecule","Lonafarnib",null,"C27H31Br2ClN4O2","NC(=O)N1CCC(CC(=O)N2CCC(CC2)[C@H]2C3=C(CCC4=C2C(Br)=CC(Cl)=C4)C=C(Br)C=N3)CC1","Hutchinson-Gilford progeria syndrome (HGPS) is a rare autosomal dominant disorder estimated to affect approximately one in 20 million individuals resulting in adverse symptoms associated with premature ageing: skeletal dysplasia, joint contractures, atherosclerosis, myocardial fibrosis/dysfunction, scleroderma-like cutaneous effects, lipoatrophy, alopecia, and a severe failure to thrive; HGPS is uniformly fatal. Mechanistically, HGPS is underpinned by a single heterozygous C-to-T mutation at position 1824 of the _LMNA_ gene, which results in the accumulation of an aberrant farnesylated form of lamin A called progerin in the inner nuclear membrane. Lonafarnib is a farnesyl transferase (FTase) inhibitor (FTI), which reduces the farnesylation of numerous cellular proteins, including progerin; as progerin farnesylation is important for localization to the nuclear membrane, lonafarnib inhibits progerin accumulation and improves symptoms in HGPS patients.\r\n\r\nMerck originally developed Lonafarnib and subsequently licensed it to Eiger Biopharmaceuticals Inc., which currently markets it under the trademark ZOKINVY™. Lonafarnib was granted FDA approval on November 20, 2020, and is the first FDA-approved treatment for HGPS and other related progeroid laminopathies.","193275-84-2","638.822","Lonafarnib is a farnesyltransferase inhibitor indicated in patients aged 12 months and older with a body surface area of at least 0.39 m<sup>2</sup> to reduce the risk of mortality associated with Hutchinson-Gilford progeria syndrome (HGPS). It is also indicated in this same population for the treatment of processing-deficient progeroid laminopathies that either involve a heterozygous _LMNA_ mutation resulting in the accumulation of a progerin-like protein or homozygous/compound heterozygous mutations in _ZMPSTE24_.","Lonafarnib is a direct farnesyl transferase inhibitor that reduces the farnesylation of numerous cellular proteins, including progerin, the aberrantly truncated form of lamin A that accumulates in progeroid laminopathies such as Hutchinson-Gilford progeria syndrome. Treatment with lonafarnib has been associated with electrolyte abnormalities, myelosuppression, and increased liver enzyme levels (AST/ALT), although causation remains unclear. Also, lonafarnib is known to cause nephrotoxicity in rats and rod-dependent low-light vision decline in monkeys at plasma levels similar to those achieved under recommended dosing guidelines in humans; patients taking lonafarnib should undergo regular monitoring for both renal and ophthalmological function. In addition, based on observations from animal studies with rats, monkeys, and rabbits with plasma drug concentrations approximately equal to those attained in humans, lonafarnib may cause both male and female fertility impairment and embryo-fetal toxicity.","Hutchinson-Gilford progeria syndrome (HGPS) is a rare autosomal dominant disorder estimated to affect approximately one in 20 million individuals resulting in premature ageing, associated cardiovascular, cerebrovascular, and musculoskeletal effects and early death around 14 years of age. The _LMNA_ gene encodes lamin A and lamin C, two proteins involved in nuclear integrity and function at the inner nuclear membrane. Under normal conditions, the 12-exon _LMNA_ gene produces full-length prelamin A, which undergoes farnesylation of the C-terminal _CaaX_ motif, followed by proteolytic cleavage of the terminal three amino acids (_aaX_) by the metalloproteinase ZMPSTE24, subsequent carboxymethylation, and finally removal of the last 15 amino acids to yield mature, unfarnesylated, lamin A protein. In HGPS, a single heterozygous C-to-T mutation at position 1824 results in a cryptic splice site that removes the last 150 nucleotides of exon 11 and a concomitant 50-amino acid deletion in the C-terminus of the prelamin A protein. This aberrant prelamin A protein, often called progerin, is permanently farnesylated but unable to complete maturation due to the removal of the second endoproteolytic cleavage site.\r\n\r\nAlthough the exact mechanism is unclear, progerin accumulation results in a host of adverse symptoms associated with ageing such as skeletal dysplasia, joint contractures, atherosclerosis, myocardial fibrosis/dysfunction, scleroderma-like cutaneous effects, lipoatrophy, alopecia, and a severe failure to thrive. An additional notable effect of HGPS is increased vascular and peripheral calcification. Children affected by HGPS typically die due to myocardial infarction or stroke. Mechanistic understanding of HGPS remains unclear, although a recent study correlated progerin accumulation, telomere dysfunction, DNA damage-mediated inflammatory cytokine release, and HGPS symptoms, suggesting that the nuclear effects of progerin accumulation may result in pleiotropic downstream effects.\r\n\r\nLonafarnib is a farnesyl transferase (FTase) inhibitor (FTI), with a reported IC<sub>50</sub> value of 1.9 nM; lonafarnib is specific for FTase, as it does not appreciably inhibit the related GGPT-1 enzyme at concentrations up to 50 μM. Inhibition of progerin farnesylation reduces progerin accumulation in the inner nuclear membrane, which subsequently slows the progression of HGPS and other progeroid laminopathies.","Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha inhibitor; Protein farnesyltransferase subunit beta inhibitor","Therapeutic strategy associated"]
[1019,"DB06449","investigational","small molecule","Ilodecakin","Ilodecakin",{"$nulls":3},"149824-15-7",null,"Investigated for use/treatment in inflammatory disorders (unspecified), crohn's disease, and rheumatoid arthritis.",{"$nulls":3},"Indication associated"]
[1020,"DB06455","investigational","small molecule","Meclinertant","Meclinertant; Reminertant","C32H31ClN4O5","COC1=CC=CC(OC)=C1C1=CC(=NN1C1=C2C=CC(Cl)=CC2=NC=C1)C(=O)NC1(C2CC3CC(C2)CC1C3)C(O)=O",null,"146362-70-1","587.07","Investigated for use/treatment in colorectal cancer, prostate cancer, schizophrenia and schizoaffective disorders, psychosis, depression, and lung cancer.",{"$nulls":3},"Indication associated"]
[1021,"DB06464","investigational","biotech","IR501",{"$nulls":3},"IR501 (Ravax) is a potential first-in-class vaccine for the treatment of Rheumatoid Arthritis. It specifically targets autoreactive T-cells, reducing their activity. It was last known to be in phase III clinical trials.",null,null,"Investigated for use/treatment in rheumatoid arthritis.",{"$nulls":3},"Indication associated"]
[1022,"DB06467","investigational","biotech","Apolizumab","Apolizumab",null,null,"Apolizumab is a humanized monoclonal antibody that is being studied as a treatment for hematologic cancers.","267227-08-7",null,"Investigated for use/treatment in lymphoma (non-hodgkin's), leukemia (lymphoid), and solid tumors.",null,"Apolizumab is a humanized monoclonal antibody directed against 1D10, a polymorphic determinant on the HLA-DR beta chain that is expressed on normal and neoplastic B cells. Apolizumab induces complement-mediated cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and apoptosis of 1D10 antigen-positive B cells in vitro.",null,"Therapeutic strategy associated"]
[1023,"DB06469","investigational","small molecule","Lestaurtinib","Lestaurtinib","C26H21N3O4","C[C@]12O[C@H](C[C@]1(O)CO)N1C3=C(C=CC=C3)C3=C1C1=C(C4=C3C(=O)NC4)C3=CC=CC=C3N21",null,"111358-88-4","439.471","Investigated for use/treatment in pancreatic cancer, prostate cancer, and leukemia (myeloid).",null,"Lestaurtinib inhibits autophosphorylation of FMS-like tyrosine kinase 3 (FLT3), resulting in inhibition of FLT3 activity and induction of apoptosis in tumor cells that overexpress FLT3.","Receptor-type tyrosine-protein kinase FLT3","Therapeutic strategy associated"]
[1024,"DB06470","investigational","small molecule","Clomethiazole","Clomethiazole","C6H8ClNS","CC1=C(CCCl)SC=N1","Clomethiazole is a well-established γ-aminobutyric acid (GABAA)-mimetic drug. It is a sedative and hypnotic that is widely used in treating and preventing symptoms of acute alcohol withdrawal. It is a drug which is structurally related to thiamine (vitamin B1) but acts like a sedative, hypnotic, muscle relaxant and anticonvulsant. It is also used for the management of agitation, restlessness, short-term insomnia and Parkinson's disease in the elderly.","533-45-9","161.65","Investigated for use/treatment in strokes.",null,"clomethiazole interacts with the GABAA receptor complex. It inhibits the binding of butyl-bicyclophosphorothionate (TBPS), an effect indicative of GABAA receptor-channel activation, by increasing the rate of TBPS dissociation and decreasing the binding affinity. Gamma-aminobutyric acid (GABA), acting at GABAA receptors, is the main fast inhibitory neurotransmitter in mammalian central nervous system","Gamma-aminobutyric acid receptor subunit alpha-1","Indication associated"]
[1025,"DB06472","investigational","small molecule","Fradafiban","Fradafiban","C20H21N3O4","NC(=N)C1=CC=C(C=C1)C1=CC=C(OC[C@@H]2C[C@@H](CC(O)=O)C(=O)N2)C=C1",null,"148396-36-5","367.405","Investigated for use/treatment in angina.",null,"Fradafiban is a glycoprotein IIb/IIIa receptor antagonist. Activation of the platelet glycoprotein (GP IIb/IIIa) receptor on the platelet surface is the final pathway of platelet aggregation that may lead to embolism, which is one on the cause of angina.","Integrin alpha-IIb; Integrin beta-3","Therapeutic strategy associated"]
[1026,"DB06479","investigational","small molecule","Propentofylline","Propentofylline","C15H22N4O3","CCCN1C=NC2=C1C(=O)N(CCCCC(C)=O)C(=O)N2C",null,"55242-55-2","306.3602","Investigated for use/treatment in alzheimer's disease.",null,"Propentofylline is a xanthine derivative and phosphodiesterase inhibitor with purported neuroprotective effects. It inhibits both phosphodiesterase and adenosine uptake. Phosphodiesterase has shown to associated with age-related memory impairment and Alzheimer's disease. β-Amyloid protein 1–42 (β42) can induce apoptosis in the cultured hippocampal neurons, suggesting that it plays an important role in causing neurodegeneration in Alzheimer's disease. Propentofylline is also capable of activating a cAMP–PKA system, depressing the caspase cascade and modifying Bcl-2 family proteins. Propentofylline blocked both the apoptotic features induced by β42 and further induced an anti-apoptotic protein, Bcl-2. It suggests that the protection of propentofylline on the β42-induced neurotoxicity is caused by enhancing anti-apoptotic action through cAMP–PKA system.","cAMP-specific 3',5'-cyclic phosphodiesterase 4A","Therapeutic strategy associated"]
[1027,"DB06480","approved","small molecule","Prucalopride","Prucalopride","C18H26ClN3O3","COCCCN1CCC(CC1)NC(=O)C1=C2OCCC2=C(N)C(Cl)=C1","Prucalopride is a dihydrobenzofurancarboxamide derivative from the benzofurane family that selectively stimulates 5-HT4 receptors and thus, it presents enterokinetic properties. The high selectivity of prucalopride allowed further development as it prevented the cardiac adverse reactions observed due to non-target effects of precedent therapies. Prucalopride was developed by Shire Development LLC and approved for use in Europe in 2009, in Canada on December 7, 2011 and by the FDA on December 17, 2018.","179474-81-8","367.87","Prucalopride is indicated for the treatment of chronic idiopathic constipation (CIC) in adults.\r\n\r\nCIC is one of the most common chronic functional gastrointestinal disorders worldwide. The diagnosis of this agent is very hard and it can be confirmed if the patient experience at least two of the following:\r\n\r\n-Straining during more than 25% of the bowel movements.\r\n\r\n-Lumpy or hard stools in 25% of the bowel movements.\r\n\r\n-Sensation of incomplete evacuation in more than 25% of all bowel movements.\r\n\r\n-Sensation of anorectal blockage or obstruction in more than 25% of the bowel movements.\r\n\r\n-Manual maneuvers required in more than 25% of the bowel movements.\r\n\r\n-Fewer than 3 bowel movements per week.","In animal studies, prucalopride induced a dose-dependent stimulation of contractile activity in the proximal colon and inhibition of the contractility in the distal colon. As well it has been shown that prucalopride stimulates and amplifies giant migratory contraction which is the high-amplitude type of contraction that initiates the urge to defecate. Thus, prucalopride not only accelerates the colonic transit but also accelerates gastric emptying and small bowel transit. \r\n\r\nIn supratherapeutic concentrations, prucalopride can be observed to interact with hERG potassium channels and L-type calcium channels.\r\n\r\nIn clinical trials, prucalopride showed to significantly increase the spontaneous bowel movements with a standardized mean difference of about 0.5 after the use of 1 mg when compared with the placebo group. In this studies as well, it was observed a numerical improvement in mean colonic transit time and a significant increase in spontaneous complete bowel movement without marked changes in the anorectal function. \r\n\r\nIn phase III clinical trials, 86% of the tested individuals opted to continue with the open-label study and based on Patients Assessments, 67% of the patients increase more than one point improvement in their satisfaction.\r\n\r\nIn the final set of clinical trials for approval, there was a significant increase in the number of patients that reached over 3 complete spontaneous bowel movements per week when compared with the placebo.","Prucalopride acts as a selective stimulator of the 5-HT4 receptors while having no interaction with hERG channel or 5-HT1 receptors which reduces significantly the cardiovascular risk found in other similar drugs.\r\n\r\n5-HT4 receptors can be found throughout the gastrointestinal tract primarily in smooth muscle cells, enterochromaffin cells, and myenteric plexus. Its activation produces the release of acetylcholine which is the major excitatory neurotransmitter in the GI tract.\r\n\r\nHence, prucalopride stimulates motility by interacting specifically with 5-HT4 receptors in the GI tract which causes a release of acetylcholine and further contraction of the muscle layer of the colon and relaxation of the circular muscle layer leading to the propulsion of luminal content.","5-hydroxytryptamine receptor 4 agonist","Indication associated"]
[1028,"DB06486","investigational","small molecule","Enzastaurin","Enzastaurin","C32H29N5O2","CN1C=C(C2=CC=CC=C12)C1=C(C(=O)NC1=O)C1=CN(C2CCN(CC3=CC=CC=N3)CC2)C2=CC=CC=C12","Enzastaurin, an investigational, targeted, oral agent, will be evaluated at more than 100 sites worldwide for the treatment of relapsed glioblastoma multiforme (GBM), an aggressive and malignant form of brain cancer.","170364-57-5","515.617","Investigated for use/treatment in brain cancer, lymphoma (non-hodgkin's), and lung cancer.",null,"Enzastaurin is an oral serine-threonine kinase inhibitor that is designed to suppress tumor growth through multiple mechanisms. Preclinical data indicate it may reduce the cell's ability to reproduce (cell proliferation), increase the natural death of the tumor cells (apoptosis), and inhibit tumor- induced blood supply (angiogenesis). Enzastaurin has been shown to inhibit signaling through the PKC-B and PI3K/AKT pathways. These pathways have been shown to be activated in a wide variety of cancers. In addition to glioblastoma, enzastaurin is also being studied in multiple other tumor types, including non-Hodgkin's lymphoma, colorectal cancer, non-small cell lung cancer, pancreatic cancer, and mantle cell lymphoma.","Protein kinase C beta type; Aurora kinase B; Aurora kinase A; Cyclin-dependent kinase 15; Serine/threonine-protein kinase Chk1; Serine/threonine-protein kinase Chk2; RAC-alpha serine/threonine-protein kinase; Phosphatidylinositol 3-kinase regulatory subunit alpha","Therapeutic strategy associated"]
[1029,"DB06492","investigational","biotech","Mirococept","Mirococept",null,null,"Mirococept (APT070) is a complement inhibitor currently under development for treatment of rheumatoid arthritis and I/RI. It is a truncated form of the human Complement Receptor 1 (CR1) linked to a unique Prodaptin™ construct that regulates the over-production of complement at the cell surface, which occurs in inflammation. It consists of the first three short consensus domains of human complement receptor 1 (CR1), manufactured in recombinant bacteria and modified with a membrane-targeting amphiphilic peptide based on the naturally occurring membrane-bound myristoyl-electrostatic switch peptide.","507453-82-9",null,"Investigated for use/treatment in transplant (rejection), kidney disease, and rheumatoid arthritis.",null,"Mirococept comprises the C3/C5 convertase-inhibiting region of CR1. This complement inhibitory domains of CR1 (in APT070) contain C3b-binding sites that lead to dissociation and inactivation of C3b from the classical and alternative pathway convertases.  Mirococept effectively blocks and reduces the generation of the activated form of C3, and thwarts the release of both C3a and C5a.","Complement C3","Indication associated"]
[1030,"DB06495","investigational","biotech","Onercept","Onercept; R-HTBP-1",{"$nulls":3},"199685-57-9",null,"Investigated for use/treatment in psoriasis and psoriatic disorders and crohn's disease.",null,"Tumor necrosis factor (TNF) is a proinflammatory cytokine that plays a pivotal part in the pathogenesis of Crohn’s disease (CD).1 A number of anti-TNF therapies have been developed for the treatment of CD. Onercept is a recombinant form of the soluble human p55 TNF-greek small letter alpha receptor (also known as TNF-binding protein 1) produced by recombinant DNA technology. Its putative mechanism of action involves neutralizing the effects of TNF by the formation of high-affinity complexes.","Tumor necrosis factor","Therapeutic strategy associated"]
[1031,"DB06497","investigational","small molecule","Aplaviroc","Aplaviroc","C33H43N3O6","[H][C@@]1(NC(=O)C2(CCN(CC3=CC=C(OC4=CC=C(C=C4)C(O)=O)C=C3)CC2)N(CCCC)C1=O)[C@H](O)C1CCCCC1","A spiro-diketo-piperazine; a potent noncompetitive allosteric antagonist of the CCR5 receptor with concomitantly potent antiviral effects for HIV-1.","461443-59-4","577.722","Investigated for use/treatment in HIV infection.",null,"GW873140 is a novel CCR5 receptor antagonist that binds specifically to human CCR5. It binds to human CCR5 with a unique profile as evidenced by the selective inhibition of monoclonal antibody binding. One of the many ways in which CCR5 inhibitors differ from the currently available classes of HIV drugs is that they bind to the host (CCR5 receptor), the cell, target rather than to the viral enzymes in cells like the CD4 cell.","C-C chemokine receptor type 5","Target associated"]
[1032,"DB06503","investigational","biotech","MLN2222",{"$nulls":3},"MLN2222 is a novel, proprietary recombinant protein that blocks both the C3 and C5 convertases, which are essential components of the complement activation pathway.",null,null,"Investigated for use/treatment in coronary artery disease.",null,"MLN2222 is a proprietary recombinant protein that blocks both the C3 and C5 convertases, which are essential components of the complement activation pathway. Complement activation is believed to contribute to harmful inflammatory responses to heart bypass surgery that can result in significant complications; MLN2222 is being developed to reduce the incidence of death and heart attacks in patients undergoing procedures involving the use of cardiopulmonary bypass (CPB), a heart-lung bypass machine.","Complement factor B","Therapeutic strategy associated"]
[1033,"DB06506","investigational","small molecule","Repinotan","Repinotan","C21H24N2O4S","O=C1N(CCCCNC[C@H]2CCC3=CC=CC=C3O2)S(=O)(=O)C2=CC=CC=C12","Repinotan is a high-affinity, selective, full agonist of the 5HT1A-receptor subtype with neuroprotective properties.","144980-29-0","400.49","Investigated for use/treatment in strokes, cerebral ischemia, and depression.",null,"Repinotan is a 5-HT1A receptor agonist which inhibits glutamate induced depolarization. The effect of repinotan in neuronal cells has been reported to be mediated by a variety of mechanisms/signaling pathways, including activation of the anti-apoptotic phosphatidylinositol 3-kinase (PI-3K) pathway, inhibition of glutamate release (probably via opening of K+ channels leading to membrane hyperpolarization), extracellular-regulated kinase (Erk)-stimulated Bcl-2 expression or inhibition of caspase-3 activity, and increased release of the neurite extension factor S-100 beta.","5-hydroxytryptamine receptor 1A","Indication associated"]
[1034,"DB06510","investigational","small molecule","Muraglitazar","Muraglitazar","C29H28N2O7","COC1=CC=C(OC(=O)N(CC(O)=O)CC2=CC=C(OCCC3=C(C)OC(=N3)C3=CC=CC=C3)C=C2)C=C1","Muraglitazar (Bristol-Myers Squibb/Merck) is a new agent under investigation for the treatment of patients with type 2 diabetes. It belongs to a novel class of drugs that target the peroxisome proliferator-activated receptors, both alpha and gamma subtypes. In addition to improvements in blood glucose and hemoglobin A1c (HbA1c), muraglitazar treatment is associated with a substantial reduction in triglycerides (TGs), an increase in HDL-C, and a modest decrease in LDL-C levels.","331741-94-7","516.55","Investigated for use/treatment in diabetes mellitus type 2.",null,"Muraglitazar is one of the dual peroxisome proliferator-activated receptor (PPAR) agonists. It interacts with both PPAR alpha and gamma receptors. Working through the PPAR gamma receptor, muraglitazar has very potent insulin-sensitizing effects on liver and muscle to lower the blood sugar levels. working through the PPAR alpha receptor, muraglitazar is very potent in terms of lowering the triglycerides and raising the HDL  cholesterol and converting small dense LDL  particles to larger, more buoyant particles, so it promotes a very good lipid profile from the standpoint of prevention of atherosclerosis.","Peroxisome proliferator-activated receptor alpha; Peroxisome proliferator-activated receptor gamma","Target associated"]
[1035,"DB06511","investigational","biotech","AMGN-0007","Osteoclastogenesis inhibitory factor; Osteoprotegerin recombinant; rOPG",null,null,"Recombinant osteoprotegerin (AMGN-0007) is a recombinant OPG construct developed as a potential therapeutic agent in the treatment of bone disease.",null,null,"Investigated for use/treatment in osteoporosis and bone metastases.",null,null,"Tumor necrosis factor ligand superfamily member 11","Target associated"]
[1036,"DB06518","investigational","small molecule","R-1487",null,"C19H18F2N4O3","CN1C(=O)C(OC2=CC=C(F)C=C2F)=CC2=C1N=C(NC1CCOCC1)N=C2",null,"449811-92-1","388.368","Investigated for use/treatment in rheumatoid arthritis.",null,null,"Mitogen-activated protein kinase 14","Indication associated"]
[1037,"DB06519","investigational","small molecule","Edaglitazone","Edaglitazone","C24H20N2O4S2","CC1=C(CCOC2=C3C=CSC3=C(CC3SC(=O)NC3=O)C=C2)N=C(O1)C1=CC=CC=C1",null,"213411-83-7","464.55","Investigated for use/treatment in diabetes mellitus type 2.",{"$nulls":3},"Indication associated"]
[1038,"DB06521","investigational","small molecule","Ertiprotafib","Ertiprotafib","C31H27BrO3S","CC1=C(C)C2=C(C3=CC(C)=C(O[C@H](CC4=CC=CC=C4)C(O)=O)C(C)=C3)C3=CC=CC=C3C(Br)=C2S1","Ertiprotafib belongs to a novel class of insulin sensitizers developed for treatment of type 2 diabetes. In insulin-resistant rodent models, ertiprotafib and a close analog lowered both fasting blood glucose and insulin levels and improved glycemic excursion during an oral glucose tolerance test.","251303-04-5","559.52","Investigated for use/treatment in diabetes mellitus type 2.",null,"The complete mechanism of action for ertiprotafib and related compounds in vivo may involve multiple independent mechanisms, including (but not necessarily limited to) PTP1b inhibition and dual PPARalpha/PPARgamma agonism.","Tyrosine-protein phosphatase non-receptor type 1; Inhibitor of nuclear factor kappa-B kinase subunit beta; Peroxisome proliferator-activated receptor alpha; Peroxisome proliferator-activated receptor gamma","Target associated"]
[1039,"DB06527","investigational","small molecule","Tramiprosate","Tramiprosate","C3H9NO3S","NCCCS(O)(=O)=O",null,"3687-18-1","139.173","Investigated for use/treatment in strokes and alzheimer's disease.",{"$nulls":3},"Indication associated"]
[1040,"DB06532","investigational","small molecule","Pafuramidine","Pafuramidine","C20H20N4O3","CONC(=N)C1=CC=C(C=C1)C1=CC=C(O1)C1=CC=C(C=C1)C(=N)NOC","Pafuramidine, a prodrug of furamidine, currently has orphan status for _Pneumocystis jiroveci_ pneumonia.","186953-56-0","364.405","Investigated for use/treatment in pneumonia, trypanosomiasis, malaria, HIV infection, and infectious and parasitic disease (unspecified).",{"$nulls":3},"Indication associated"]
[1041,"DB06533","investigational","small molecule","Ragaglitazar","Ragaglitazar","C25H25NO5","CCO[C@H](CC1=CC=C(OCCN2C3=CC=CC=C3OC3=C2C=CC=C3)C=C1)C(O)=O",null,"222834-30-2","419.477","Investigated for use/treatment in diabetes mellitus type 2.",null,null,"Peroxisome proliferator-activated receptor alpha; Peroxisome proliferator-activated receptor gamma","Target associated"]
[1042,"DB06536","investigational","small molecule","Tesaglitazar","Tesaglitazar","C20H24O7S","CCO[C@@H](CC1=CC=C(OCCC2=CC=C(OS(C)(=O)=O)C=C2)C=C1)C(O)=O","Tesaglitazar is a dual peroxisome proliferator-activated receptor alpha/gamma agonist which improves apolipoprotein levels in non-diabetic subjects with insulin resistance. Tesaglitazar is a proposed treatment for type 2 diabetes and has completed several phase III clinical trials, however in May 2006 AstraZeneca announced that they had discontinued further development.","251565-85-2","408.465","Investigated for use/treatment in diabetes mellitus type 2.","Treatment with tesaglitazar lowered fasting plasma glucose, improved glucose tolerance, substantially reduced fasting and postload insulin levels, and markedly lowered fasting TG and improved lipid tolerance.",null,"Peroxisome proliferator-activated receptor alpha; Peroxisome proliferator-activated receptor gamma","Target associated"]
[1043,"DB06538","investigational","small molecule","Robalzotan","(R)-3-(Dicyclobutylamino)-8-fluoro-5-chromancarboxamide; Robalzotan","C18H23FN2O2","NC(=O)C1=C2C[C@H](COC2=C(F)C=C1)N(C1CCC1)C1CCC1",null,"169758-66-1","318.392","Investigated for use/treatment in anxiety disorders and depression.",null,null,"5-hydroxytryptamine receptor 1A","Indication associated"]
[1044,"DB06546","investigational","biotech","Atibuclimab","Atibuclimab",null,null,"Atibuclimab (IC14) is a chimeric CD14 antibody investigated for the treatment of patients with severe sepsis.","2417175-94-9",null,"Investigated for use/treatment in sepsis and septicemia and pneumonia.",null,"Atibuclimab (IC14) is a chimeric CD14 antibody investigated for the treatment of patients with severe sepsis. It acts as a pattern recognition receptor for bacterial cell wall components in gram-positive and negative bacteria. CD14 antibody action stimulates a pro-inflammatory cytokine cascade often associated with inflammation in sepsis. Atibuclimab neutralization of this antibody results in the inhibition of TNF-a, IL-6 and IL-10, dampening systemic inflammatory responses. Atibuclimab also delays the release of sTNFR(1) and IL-1ra.","Monocyte differentiation antigen CD14","Therapeutic strategy associated"]
[1045,"DB06548","investigational","small molecule","Minodronic acid","Minodronate; Minodronic acid","C9H12N2O7P2","OC(CC1=CN=C2C=CC=CN12)(P(O)(O)=O)P(O)(O)=O",null,"180064-38-4","322.1483","Investigated for use/treatment in multiple myeloma, breast cancer, osteoporosis, and lung cancer.",null,null,"Farnesyl pyrophosphate synthase inhibitor; Geranylgeranyl pyrophosphate synthase inhibitor","Indication associated"]
[1046,"DB06569","investigational","small molecule","P-57AS3",null,"C47H74O15","[H][C@@]12CC=C3C[C@H](CC[C@]3(C)[C@@]1([H])C[C@@H](OC(=O)C(\\C)=C\\C)[C@]1(C)[C@H](CC[C@]21O)C(C)=O)O[C@H]1C[C@H](OC)[C@H](O[C@H]2C[C@H](OC)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@H](OC)[C@H]3O)[C@@H](C)O2)[C@@H](C)O1",null,"384329-61-7","879.094","Investigated for use/treatment in obesity.",{"$nulls":3},"Indication associated"]
[1047,"DB06576","investigational","biotech","Baminercept","Baminercept; Baminercept alfa",{"$nulls":3},"909110-25-4",null,"Investigated for use/treatment in rheumatoid arthritis.",{"$nulls":3},"Indication associated"]
[1048,"DB06582","investigational","small molecule","Dextofisopam","Dextofisopam; R-tofisopam","C22H26N2O4","CC[C@@H]1C2=CC(OC)=C(OC)C=C2C(=NN=C1C)C1=CC=C(OC)C(OC)=C1",null,"82059-50-5","382.46","Investigated for use/treatment in irritable bowel syndrome (IBS).",{"$nulls":3},"Indication associated"]
[1049,"DB06586","investigational","small molecule","Cetilistat","Cetilistat","C25H39NO3","CCCCCCCCCCCCCCCCOC1=NC2=C(C=C(C)C=C2)C(=O)O1","Cetilistat is a novel inhibitor of pancreatic lipase being developed by Alizyme for the treatment of obesity and associated co-morbidities, including type 2 diabetes.","282526-98-1","401.5821","Investigated for use/treatment in obesity.",null,"Cetilistat is a gastrointestinal lipase inhibitor that blocks fat digestion and absorption, leading to reduced energy intake, and thus weight loss. It is distinct from most other anti-obesity agents as it does not act on the brain to reduce appetite, but acts peripherally. The compound remains in the gastrointestinal tract with no significant absorption into the body.","Pancreatic triacylglycerol lipase","Therapeutic strategy associated"]
[1050,"DB06587","investigational","small molecule","Mitemcinal","Mitemcinal","C40H69NO12","CC[C@H]1OC(=O)[C@H](C)[C@@H](O[C@H]2C[C@@](C)(OC)[C@@H](O)[C@H](C)O2)[C@H](C)[C@@H](O[C@@H]2O[C@H](C)C[C@@H]([C@H]2O)N(C)C(C)C)[C@@]2(C)CC(C)=C(O2)[C@H](C)C(=O)[C@]1(C)OC","Mitemcinal (GM-611) is a novel erythromycin-derived prokinetic agent that acts as an agonist at the motilin receptor.","154738-42-8","755.987","Investigated for use/treatment in gastroparesis and irritable bowel syndrome (IBS).",null,"Mitemcinal, an oral motilin agonist, accelerates gastric emptying.","Motilin receptor","Indication associated"]
[1051,"DB06589","approved","small molecule","Pazopanib",null,"C21H23N7O2S","CN(C1=CC2=NN(C)C(C)=C2C=C1)C1=CC=NC(NC2=CC=C(C)C(=C2)S(N)(=O)=O)=N1","Pazopanib is a small molecule inhibitor of multiple protein tyrosine kinases with potential antineoplastic activity. It is developed by GlaxoSmithKline and was FDA approved on October 19, 2009.","444731-52-6","437.518","Treatment of advanced renal cell cancer and advanced soft tissue sarcoma (in patients previously treated with chemotherapy)","Pazopanib is a synthetic indazolylpyrimidine and reaches steady state concentrations of >15 μg/ml. This concentration is high enough to observe maximal inhibition of VEGFR2 phosphorylation and some anti-tumour activity (concentration required to inhibit receptors is 0.01 - 0.084 μmol/L). A reduction in tumour blood flow, increased tumour apoptosis, inhibition of tumour growth, reduction in tumour interstitial fluid pressure, and hypoxia in cancer cells can be observed in patients receiving treatment.","Pazopanib is a second-generation multitargeted tyrosine kinase inhibitor against vascular endothelial growth factor receptor-1, -2, and -3, platelet-derived growth factor receptor-alpha, platelet-derived growth factor receptor-beta, and c-kit. These receptor targets are part of the angiogenesis pathway that facilitates the formation of tumour blood vessel for tumour survival and growth.","Vascular endothelial growth factor receptor 1 inhibitor; Vascular endothelial growth factor receptor 2 inhibitor; Vascular endothelial growth factor receptor 3; Platelet-derived growth factor receptor alpha inhibitor; Platelet-derived growth factor receptor beta inhibitor; Mast/stem cell growth factor receptor Kit inhibitor; Fibroblast growth factor receptor 3 inhibitor; Tyrosine-protein kinase ITK/TSK inhibitor; Fibroblast growth factor 1 inhibitor; SH2B adapter protein 3 inhibitor","Therapeutic strategy associated"]
[1052,"DB06595","approved; investigational","small molecule","Midostaurin","4'-N-benzoylstaurosporine; Midostaurin","C35H30N4O4","CO[C@@H]1[C@@H](C[C@H]2O[C@]1(C)N1C3=C(C=CC=C3)C3=C1C1=C(C4=C(C=CC=C4)N21)C1=C3CNC1=O)N(C)C(=O)C1=CC=CC=C1","Midostaurin (as Rydapt) is a multitarget kinase inhibitor for the treatment for adult patients with newly diagnosed acute myeloid leukemia (AML) who have a specific genetic mutation called FLT3. It was initially characterized as a potential broad-spectrum antineoplastic agent, with activity toward diverse solid and hematopoietic tumors . It was approved on April 28, 2017 and has shown to increase the overall survival rate in patients with AML as an adjunct therapy along with chemotherapeutic agents.","120685-11-2","570.649","Investigated for use/treatment in adult patients with high-risk acute myeloid leukemia (AML) who are FLT3 mutation-positive, agressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL).","It targets multiple WT and mutated kinases that, when activated, constitutively stimulate aberrant signalling cascades that lead to malignancies such as AML and ASM.  Alternative pharmacodynamic effect of midostaurin in prolonging QTc intervals was not clinically significant in patients with advanced SM or AML when compared to placebo. Midostaurin is therapeutically beneficial as a combination therapy for patients undergoing chemotherapy.","It potently inhibits multiple receptor tyrosine kinases. Midostaurin and its major active metabolites CGP62221 and CGP52421 inhibit the activity of protein kinase C alpha (PKCalpha), VEGFR2, KIT, PDGFR and WT and/or mutant FLT3 tyrosine kinases. Inhibition of FLT3 receptor signalling cascades induces apoptosis of target leukemia cells expressing target receptors and mast cells, in addition to its antiproliferative activity toward multiple cancer cell lines . \r\nMidostaurin also interacts with organic anion transporter (OATP) 1A1 and multidrug resistance protein (MRP)-2 according to preliminary in vitro studies.","Protein kinase C alpha type antagonist&inhibitor; Vascular endothelial growth factor receptor 2 antagonist&inhibitor; Mast/stem cell growth factor receptor Kit antagonist&inhibitor; Platelet-derived growth factor receptor alpha antagonist&inhibitor; Platelet-derived growth factor receptor beta antagonist&inhibitor; Receptor-type tyrosine-protein kinase FLT3 antagonist&inhibitor","Therapeutic strategy associated"]
[1053,"DB06599","investigational","biotech","Lexatumumab","Lexatumumab",null,null,"Lexatumumab is a fully humanized, high-affinity immunoglobulin G(1 lambda) monoclonal antibody (mAb).","845816-02-6",null,"Investigated for use/treatment in cancer/tumors (unspecified).",null,"Lexatumumab agonizes the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor 2 (TRAIL-R2), triggering the extrinsic apoptotic pathway.","Tumor necrosis factor receptor superfamily member 10B","Therapeutic strategy associated"]
[1054,"DB06600","investigational","small molecule","Nemonoxacin","Nemonoxacin","C20H25N3O4","COC1=C2N(C=C(C(O)=O)C(=O)C2=CC=C1N1C[C@@H](C)C[C@H](N)C1)C1CC1",null,"378746-64-6","371.437","Investigated for use/treatment in bacterial infection and pneumonia.",{"$nulls":3},"Indication associated"]
[1055,"DB06602","approved; investigational","biotech","Reslizumab","Reslizumab",null,null,"Reslizumab is a humanized interleukin-5 (IL-5) antagonist monoclonal antibody (IgG4 kappa) that is produced by recombinant DNA technology in murine myeloma non-secreting 0 (NS0) cells. IL-5 is a pro-inflammatory cytokine that is responsible for the growth and differentiation, recruitment, activation, and survival of eosinophils . Elevated levels of eosinophils increase the risk for asthma exacerbations, including both allergic forms and nonallergic forms of asthma where eosinophilia is prominent. By targeting the IL-5 and disrupting its signalling pathways, reslizumab aims to inhibit eosinophil maturation and promote programmed cell death .\r\n\r\nAsthma is a chronic respiratory disease that causes inflammation in the lungs with asthma attacks that lead to severe breathing difficulties. Patients often experience persistent or exacerbating symptoms overtime despite conventional first-line therapies available. Inflammation-predominant asthma, which is chatacterized by eosinophilic infiltration of airway mucosa and elevated levels of eosinophils in the blood, sputum and BAL fluid, is associated with an increased risk for recurrent exacerbation and asthma-related hospitalizations . In four double-blind, randomized, placebo‑controlled trials in patients with severe asthma on currently available therapies, patients receiving reslizumab had fewer asthma attacks, and a longer time to the first attack compared to patients receiving placebo . In addition, a significant improvement in lung function was seen, as measured by the volume of air exhaled by patients in one second . Studies demonstrated that reslizumab was not effective in various asthma outcomes in patients without eosinophilia .\r\n\r\nReslizumab was developed by Teva Pharmaceuticals. Approved by the FDA in March 2016, reslizumab is marketed under the brand name Cinqair for intravenous injection. It is injected once every four weeks via intravenous infusion. Cinqair is indicated as an add-on maintenance therapy for adults with severe asthma with an eosinophilic phenotype. It is approved for patients who have a history of severe asthma attacks (exacerbations) despite receiving their current asthma medicines. Reslizumab is marketed as Cinqaero in Europe.","241473-69-8",null,"Indicated for the add-on maintenance treatment of patients with severe asthma aged 18 years and older with an eosinophilic phenotype.","A reduction in blood eosinophil counts was observed in clinical studies following an initial infusion of 3 mg/kg reslizumab and was maintained through 52 weeks of treatment with no signs of tachyphylaxis. Greater reductions of blood eosinophils were observed in subjects with higher reslizumab serum concentrations. This effect was independent of the presence of treatment-emergent anti-reslizumab antibodies .","Reslizumab an interleukin-5 (IL-5) antagonist (IgG4, kappa) that binds to IL-5 with a dissociation constant of 81 pM. IL-5 is a proinflammatory cytokine responsible for the terminal maturation of eosinophils and increases chemotaxis, endothelial adhesion, activation and survival of eosinophils. Eosinophils are known to play a central role in the pathophysiology of many patients with asthma; upon activation, eosinophils release leukotrienes, platelet activation factor, major basic protein, eosinophil cationic protein, eosinophil peroxidase, eosinophil-derived neurotoxin, and other cytokines that are cytotoxic to the bronchial epithelium and lead to airway inflammation and bronchospasm . IL-5 production is increased by upon activation of TH2 lymphocytes after antigen exposure and IL-5 stimulates the production and maturation of eosinophil precursors in the bone marrow . IL-5 promotes the growth and differentiation, recruitment, activation, and survival of eosinophils via interacting with the IL-5 receptor expressed on the eosinophil surface . Increased production and activation of eosinophils is especially prominent in nonallergic forms of asthma .\r\n\r\nReslizumab is a humanized monoclonal antibody that occupies the region ERRR (glutamic acid, arginine, arginine, arginine) corresponding to amino acids 89–92 on IL-5, which is a region critical for its interaction with the IL-5 receptor on the eosinophil surface . By binding to IL-5 and disrupting its binding to the alpha chain of the IL-5 receptor complex, reslizumab inhibits the bioactivity of IL-5 and attenuates IL-5 signaling. Blocking of IL-5 signalling thereby reduces the production and survival of eosinophils and inhibits eosinophilic-driven inflammation.","Interleukin-5 antagonist","Therapeutic strategy associated"]
[1056,"DB06604","investigational","small molecule","Ilepatril","Ilepatril","C22H28N2O5S","[H][C@]12CCC[C@H](N1C(=O)[C@H](CC1=C2C=CC=C1)NC(=O)[C@@H](SC(C)=O)C(C)C)C(O)=O",null,"473289-62-2","432.533","Investigated for use/treatment in hypertension.",{"$nulls":3},"Indication associated"]
[1057,"DB06605","approved","small molecule","Apixaban","Apixaban","C25H25N5O4","COC1=CC=C(C=C1)N1N=C(C(N)=O)C2=C1C(=O)N(CC2)C1=CC=C(C=C1)N1CCCCC1=O","Apixaban is an oral, direct, and highly selective factor Xa (FXa) inhibitor of both free and bound FXa, as well as prothrombinase, independent of antithrombin III for the prevention and treatment of thromboembolic diseases. It is marketed under the name Eliquis. Apixaban was approved by the FDA on December 28, 2012.","503612-47-3","459.4971","Apixaban is indicated for reducing the risk of stroke and systemic embolism in patients who have nonvalvular atrial fibrillation, prophylaxis of deep vein thrombosis(DVT) leading to pulmonary embolism(PE) in patients after a hip or knee replacement surgery, and treatment of DVT and PE to reduce the risk of recurrence.","Apixaban selectively inhibits factor Xa in its free and bound forms, independant of antithrombin III. Apixaban also inhibits prothrominase. These effects prevent the formation of a thrombus.","Apixaban selectively inhibits factor Xa in its free and bound forms, independant of antithrombin III. Apixaban also inhibits prothrominase. These effects prevent the formation of a thrombus.","Coagulation factor X inhibitor","Indication associated"]
[1058,"DB06606","investigational","biotech","Teplizumab","Teplizumab",null,null,"Type 1 diabetes (T1D) is an autoimmune condition in which T cell-mediated destruction of pancreatic β cells leads to loss of insulin production, impaired glycemic control, and reliance on exogenous insulin. Targeting T cells can be achieved through antibodies against the T cell receptor (TCR) component CD3 ε. However, if Fc binding is left intact, severe adverse effects related to cytokine release syndrome (CRS) are observed, and therefore Fc-nonbinding antibodies are the preferred method of choice. Anti-CD3 therapy has traditionally been used to prevent graft-versus-host-disease in organ transplantation but more recently has been explored to prolong the onset of (T1D) in high-risk patients.\r\n\r\nTeplizumab is a humanized IgG1κ Fc-nonbinding anti-CD3 monoclonal antibody currently under development for use in T1D.","876387-05-2",null,"Investigated for use/treatment in diabetes mellitus type 1.",null,"Type 1 diabetes (T1D) is an autoimmune condition in which T cell-mediated destruction of pancreatic β cells leads to loss of insulin production, impaired glycemic control, and reliance on exogenous insulin. T1D is a progressive disease with three recognizable stages and in which only Stage 3 is associated with clinically apparent symptoms. The earliest indication of T1D risk is the presence of at least two autoantibodies against relevant antigens, confirming an important role for B cells in what has traditionally been considered a T cell-dominated condition. Combined with other observations from animal and human studies, it is clear that the T-B axis plays a role in T1D; treatment has focussed on targeting B and T cells independently, as well as their interactions.\r\n\r\nThe T cell receptor (TCR) comprises TCR α and β chains together with six CD3 molecules, including two CD3 ε chains. It is responsible for recognizing antigens displayed on the MHC complex of other cells to elicit a response. Teplizumab, a humanized IgG1κ Fc-nonbinding version of an existing mouse OKT3 antibody (also designated huOKT3γala-ala), is specific for CD3 ε and inhibits T cell activation through steric inhibition of antigen recognition. Recently, teplizumab has shown efficacy in delaying the time to diagnosis in patients at high risk of developing T1D. However, the exact mechanism underlying this effect remains clear.\r\n\r\nOne hypothesis is that teplizumab acts as a partial agonist at the TCR, increasing the number of exhausted T cells positive for KLRG1, TIGIT, and CD8. These exhausted T cells persist but cannot perform effector functions and, therefore, would be unlikely to contribute to further β cell destruction. Other studies have noted changes in the T cell populations of clinical responders, including an increase in circulating CD8<sup>+</sup> central memory (CD8CM) T cells. It is clear, however, that treatment is most effective in patients who have very recently or not yet progressed to Stage 3 and who have an active immune response.","T-cell surface glycoprotein CD3 epsilon chain antagonist","Indication associated"]
[1059,"DB06607","approved; investigational; withdrawn","biotech","Catumaxomab","Catumaxomab",null,null,"Catumaxumab is a trifunctional monoclonal antibody developed for use in cancer treatment. It has affinity for T-cells, accessory immune cells, and cancer cells. Catumaxumab was initially authorized for market by the European Medicines Agency in April 2009 for the treatment of malignant ascites . Its market authorization was withdrawn in the EU in June 2017 at the manufacturer's request due to the company's insolvency. Catumaxumab was approved for market in Canada in May 2012 for the same condition . It is currently available under the brand name Removab.","509077-98-9",null,"For use in the management of malignant ascites tumours via intraperitoneal infusion where standard therapy is not available or feasible .","Catumaxomab brings cancer cells, T cells, and accessory immune cells into close proximity and stimulates activation and of immune cells . This facilitates immune system-mediated destruction of the cancer cells.","Catumaxomab contains epitopes for human CD3 and human epithelial cell adehesion molecule. It also has an intact immunoglobulin gamma constant region allowing it to bind to Fcγ I, IIa, and III receptors . By binding to CD3 on killer T cells, EpCAM on cancer cells, and Fcγ receptors on accessory immune cells like macrophages and NK cells, Catumaxomab brings immune cells into close proximity to EpCAM positive cancer cells. As a functional antibody, Catumaxomab also stimulates bound NK cells to release cytotoxic mediators like granzyme or bound macrophages to phagocytose the cancer cell. Phagocytosed cancer cells can be processed and have their antigens presented on major histocompatibililty complex II to activate helper T cells and contribute to humoural immunity and activation of killer T cells against EpCAM postive cancer cells. These macrophages also release inflammatory cytokines to attract additional immune cells to EpCAM positive tissues. When antibodies reach higher concentrations, they can stimulate complement-mediated cytotoxicity against EpCAM positive cancer cells. Bound killer T cells are activated resulting in proliferation and release of cytotoxic mediators resulting in antibody-dependent cell-mediated cytotoxicity against the cancer cell.","Epithelial cell adhesion molecule ligand; Low affinity immunoglobulin gamma Fc region receptor II-a agonist; Low affinity immunoglobulin gamma Fc region receptor III-A agonist; Low affinity immunoglobulin gamma Fc region receptor III-B agonist; T-cell surface glycoprotein CD3 epsilon chain agonist; High affinity immunoglobulin gamma Fc receptor I agonist","Therapeutic strategy associated"]
[1060,"DB06609","investigational","small molecule","Odiparcil","Odiparcil","C15H16O6S","[H][C@@]1(O)CS[C@@]([H])(OC2=CC3=C(C=C2)C(C)=CC(=O)O3)[C@]([H])(O)[C@@]1([H])O",null,"137215-12-4","324.35","Investigated for use/treatment in atrial fibrillation, cardiovascular disorders, thrombosis, and venous thromboembolism.",{"$nulls":3},"Indication associated"]
[1061,"DB06610","investigational","small molecule","Omiganan","Omiganan","C90H127N27O12","[H]N=C(N([H])[H])N([H])CCC[C@H](N([H])C(=O)[C@H](CCCN([H])C(=N[H])N([H])[H])N([H])C(=O)[C@H](CC1=CN([H])C2=CC=CC=C12)N([H])C(=O)[C@@H]1CCCN1C(=O)[C@H](CC1=CN([H])C2=CC=CC=C12)N([H])C(=O)[C@H](CC1=CN([H])C2=CC=CC=C12)N([H])C(=O)[C@@H]1CCCN1C(=O)[C@H](CC1=CN([H])C2=CC=CC=C12)N([H])C(=O)[C@H](CCCN([H])C(=N[H])N([H])[H])N([H])C(=O)[C@H](CC(C)C)N([H])C(=O)[C@@H](N([H])[H])[C@@H](C)CC)C(=O)N([H])[C@@H](CCCCN([H])[H])C(=O)N([H])[H]","Omiganan has been investigated for the treatment of Mupirocin-resistant MRSA skin infections.","204248-78-2","1779.183","Investigated for use/treatment in bacterial infection and rosacea.",{"$nulls":3},"Indication associated"]
[1062,"DB06611","investigational","biotech","Pegsunercept","Pegsunercept; sTNF-R1",null,null,"Pegsunercept is used for treating rheumatoid arthritis. Phase II clinical trials were completed in January 2010.","330988-75-5",null,"Investigated for use/treatment in rheumatoid arthritis.",{"$nulls":3},"Indication associated"]
[1063,"DB06612","approved; investigational","biotech","Mepolizumab","Mepolizumab",null,null,"Eosinophils are involved in inflammatory immune responses, and prolonged hypereosinophilia (typically defined as absolute eosinophil levels of 1500/mm<sup>3</sup> or more) is associated with a spectrum of diseases, including severe asthma, eosinophilic granulomatosis with polyangiitis (EGPA), and hypereosinophilic syndrome (HES). The pathogenesis of eosinophilia is complex, but IL-5 is recognized as a key cytokine involved in the differentiation, recruitment, activation, and prolonged survival of eosinophils in peripheral tissue. Activated eosinophils further stimulate an inflammatory response and also induce tissue lesions and promote fibrosis, all of which contribute to the multifactorial symptomatology of hypereosinophilic diseases.\r\n\r\nMepolizumab is a fully-humanized recombinant IgG1 kappa monoclonal antibody directed against IL-5 produced in Chinese hamster ovary cells. Mepolizumab was first approved by the FDA on November 4, 2015, as an add-on therapy for severe asthma and marketed under the brand name Nucala by GlaxoSmithKline. This indication was subsequently expanded to cover EGPA on December 12, 2017, and HES on September 25, 2020.","196078-29-2",null,"Mepolizumab is an anti-IL-5 IgG1 kappa monoclonal antibody indicated as an add-on maintenance treatment in patients aged six years and older with severe eosinophilic asthma and as a treatment in adult patients for eosinophilic granulomatosis with polyangiitis (EGPA). Mepolizumab is also indicated for the treatment of hypereosinophilic syndrome (HES) in patients aged 12 and older in whom eosinophilia is present for at least six months without an identifiable non-hematologic secondary cause.","Mepolizumab is a monoclonal antibody that acts through interleukin-5 (IL-5) antagonism to reduce blood eosinophil levels, generally in the range of 60-90% of baseline depending on dose, which in turn offers therapeutic benefit in the specific conditions for which mepolizumab is indicated. Mepolizumab has a relatively long half-life of between 16 and 22 days, which allows for long-lasting therapeutic benefit and a four-week dosing schedule. Despite a good demonstrated safety profile, mepolizumab use does act to depress part of the immune system and may be associated with increased infections, such as with herpes zoster virus; pre-existing helminth infections should be treated before starting mepolizumab therapy. Inhaled and oral corticosteroids should not be discontinued after starting mepolizumab but may be tapered as appropriate. Mepolizumab should not be used to treat acute bronchospasms or status asthmatics. Finally, hypersensitivity reactions, including anaphylaxis, have been reported in patients; mepolizumab should be discontinued in patients with suspected or confirmed hypersensitivity.","Hypereosinophilia is typically considered as an absolute eosinophil count of 1500/mm<sup>3</sup> or higher and is associated with aberrant immune responses in several conditions, including severe asthma, eosinophilic granulomatosis with polyangiitis, and the variable spectrum of hypereosinophilic syndrome (HES). Eosinophils are involved in the inflammatory response by secretion of molecules such as MBP, leukotrienes, matrix metalloproteinases, transforming growth factor-β, nitric oxide, and other reactive oxygen species. Interleukin-5 (IL-5) is the primary cytokine associated with the differentiation of bone marrow progenitor cells into mature inflammatory neutrophils and the subsequent migration, activation, and prolonged survival of activated neutrophils. In concert with other cells, including lymphocytes, neutrophils, mast cells, and macrophages, which themselves can secrete additional pro-inflammatory molecules, high concentrations of neutrophils are associated with tissue damage and fibrosis, leading to the symptoms of eosinophilic diseases.\r\n\r\nTypically, eosinophils arise from both CD34<sup>+</sup> and dual CD34<sup>+</sup>, IL-5 receptor-positive (IL-5R<sup>+</sup>) progenitor cells, which is in part mediated by the cytokines IL-5, IL-3, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Although there exists a population of eosinophils that are insensitive to IL-5 levels, the main population of inflammatory eosinophils proliferates and migrates into the tissue in response to IL-5. Mepolizumab is a fully-humanized monoclonal IgG1 kappa antibody that binds IL-5 with a dissociation constant of 100 pM, preventing IL-5 from binding to and subsequently activating IL-5R<sup>+</sup> cells. This reduction lowers circulating blood eosinophil levels and therefore exerts a beneficial effect in eosinophilic disease; the exact mechanistic nature of mepolizumab action has not been definitively determined. Not all patients will benefit from mepolizumab treatment, such as those with milder asthma or those with a sub-type of HES that is independent of IL-5 signalling.","Interleukin-5 antagonist","Therapeutic strategy associated"]
[1064,"DB06618","investigational","small molecule","Cutamesine","Cutamesine","C23H32N2O2","COC1=C(OC)C=C(CCN2CCN(CCCC3=CC=CC=C3)CC2)C=C1",null,"165377-43-5","368.521","Investigated for use/treatment in strokes and depression.",{"$nulls":3},"Indication associated"]
[1065,"DB06624","investigational","small molecule","Taranabant","Taranabant","C27H25ClF3N3O2","C[C@H](NC(=O)C(C)(C)OC1=CC=C(C=N1)C(F)(F)F)[C@@H](CC1=CC=C(Cl)C=C1)C1=CC=CC(=C1)C#N",null,"701977-09-5","515.96","Investigated for use/treatment in obesity.",{"$nulls":3},"Indication associated"]
[1066,"DB06630","investigational","small molecule","Anacetrapib","Anacetrapib","C30H25F10NO3","COC1=CC(F)=C(C=C1C1=CC=C(C=C1CN1[C@@H](C)[C@H](OC1=O)C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)C(F)(F)F)C(C)C",null,"875446-37-0","637.518","Investigated for use/treatment in hyperlipidemia.",{"$nulls":3},"Indication associated"]
[1067,"DB06641","investigational","small molecule","Perifosine","Perifosine","C25H52NO4P","CCCCCCCCCCCCCCCCCCOP([O-])(=O)OC1CC[N+](C)(C)CC1","Perifosine is a novel alkylphospholipid with antiproliferative properties attributed to protein kinase B inhibition.","157716-52-4","461.668","Investigated for use/treatment in solid tumors, multiple myeloma, leukemia (unspecified), lung cancer, and brain cancer.",null,"Targeting cellular membranes, perifosine modulates membrane permeability, membrane lipid composition, phospholipid metabolism, and mitogenic signal transduction, resulting in cell differentiation and inhibition of cell growth. This agent also inhibits the anti-apoptotic mitogen-activated protein kinase (MAPK) pathway and modulates the balance between the MAPK and pro-apoptotic stress-activated protein kinase (SAPK/JNK) pathways, thereby inducing apoptosis.","RAC-alpha serine/threonine-protein kinase; Mitogen-activated protein kinase 1; Protein kinase C alpha type","Therapeutic strategy associated"]
[1068,"DB06642","investigational","biotech","Bevasiranib","Bevasiranib",null,null,"Bevasiranib is a small interfering RNA (siRNA) targeting vascular endothelial growth factor A (VEGF-A).","959961-96-7",null,"Investigated for use/treatment in macular degeneration and diabetic retinopathy.","Bevasiranib represents the first drug in a promising new class of experimental medical treatments. It is a small interfering RNA (siRNA) drug, which silences the genes that produce Vascular Endothelial Growth Factor (VEGF), a protein that promotes blood vessel growth. The treatment slows the growth and leakage of abnormal blood vessels that are associated with the wet form of macular degeneration. The drug is injected directly into the eye.",null,"Vascular endothelial growth factor A","Indication associated"]
[1069,"DB06643","approved","biotech","Denosumab","Denosumab",null,null,"Denosumab is a novel, fully human IgG2 monoclonal antibody specific to receptor activator of nuclear factor kappa-B ligand (RANKL), suppresses bone resorption markers in patients with a variety of metastatic tumors and is being investigated in multiple clinical trials for the prevention and treatment of bone metastases. Chemically, it consists of 2 heavy and 2 light chains. Each light chain consists of 215 amino acids. Each heavy chain consists of 448 amino acids with 4 intramolecular disulfides. FDA approved on June 1, 2010.","615258-40-7",null,"Prolia is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture. It reduces the incidence of vertebral, nonvertebral, and hip fractures. Prolia is also indicated as a treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer. It can also be used in men with osteoporosis at high risk for fracture or in men receiving androgen deprivation therapy for nonmetastatic prostate cancer to increase bone mass. Xgeva is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors.","In clinical studies, treatment with 60 mg of Prolia resulted in reduction in the bone resorption marker serum type 1 C-telopeptide (CTX) by approximately 85% by 3 days. Consistent with the physiological coupling of bone formation and resorption in skeletal remodeling, subsequent reductions in bone formation markers (i.e. osteocalcin and procollagen type 1 N-terminal peptide ) were observed starting 1 month after the first dose of Prolia.","Denosumab is designed to target RANKL (RANK ligand), a protein that acts as the primary signal to promote bone removal/resorption. In many bone loss conditions, RANKL overwhelms the body's natural defense against bone destruction. Denosumab prevents RANKL from activating its receptor, RANK, on the surface of osteoclasts and their precursors. Prevention of the RANKL/RANK interaction inhibits osteoclast formation, function, and survival, thereby decreasing bone resorption and increasing bone mass and strength in both cortical and trabecular bone.","Tumor necrosis factor ligand superfamily member 11 antibody","Target associated"]
[1070,"DB06651","investigational","small molecule","DiaPep 277",null,"C106H180N28O34","[H][C@](C)(O)[C@]([H])(N=C(O)[C@]([H])(CC(C)C)N=C(O)[C@]([H])(CO)N=C(O)[C@]([H])(CC(O)=O)N=C(O)[C@]([H])(CC(C)C)N=C(O)[C@]([H])(C)N=C(O)[C@]1([H])CCCN1C(=O)[C@@]([H])(N=C(O)[C@@]([H])(N=C(O)[C@]([H])(CCCNC(N)=N)N=C(O)[C@]([H])(CC(C)C)N=C(O)[C@]([H])(CC(C)C)N=C(O)[C@]([H])(C)N=C(O)[C@@]([H])(N=C(O)CN=C(O)CN=C(O)CN=C(O)[C@]([H])(CC(C)C)N=C(O)[C@@]([H])(N)C(C)C)C(C)C)C(C)C)[C@@]([H])(C)CC)C(=O)N1CCC[C@@]1([H])C(O)=N[C@@]([H])(C)C(O)=N[C@@]([H])(CC(O)=N)C(O)=N[C@@]([H])(CCC(O)=O)C(O)=N[C@@]([H])(CC(O)=O)C(O)=O","DiaPep 277 is a 24-mer laboratory-made peptide derived from Hsp60(437-460).","179822-83-4","2390.768","Investigated for use/treatment in diabetes mellitus type 1, autoimmune diseases, and diabetes mellitus type 2.",{"$nulls":3},"Indication associated"]
[1071,"DB06652","investigational","small molecule","Vicriviroc","Vicriviroc","C28H38F3N5O2","COC[C@H](N1CCN(C[C@@H]1C)C1(C)CCN(CC1)C(=O)C1=C(C)N=CN=C1C)C1=CC=C(C=C1)C(F)(F)F","Vicriviroc, also known as SCH 417690 and SCH-D, is currently in clinical trials for the management of HIV-1. This pyrimidine based drug inhibits the interaction of HIV-1 with CCR5, preventing viral entry into cells. This drug was developed by Schering-Plough.","306296-47-9","533.6288","Investigated for use/treatment in HIV infection and viral infection.",null,"Vicriviroc is a once daily oral inhibitor of CCR5. It noncompetitively binds to a hydrophobic pocket between transmembrance helices by the extracellular side of CCR5. This allosteric antagonism causes a conformational change in the protein preventing binding of gp120 to CCR5. This prevents the entry of HIV into the cell.","C-C chemokine receptor type 5","Target associated"]
[1072,"DB06656","investigational","small molecule","TAS-106","3'-C-Ethynylcytidine; 4-Amino-1-((2R,3R,4R,5R)-4-ethynyl-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl)pyrimidin-2-one","C11H13N3O5","NC1=NC(=O)N(C=C1)[C@@H]1O[C@H](CO)[C@](O)(C#C)[C@H]1O","TAS-106 is a new nucleoside antimetabolite. TAS-106 has demonstrated strong antitumor activity without serious toxicity in nude rat models bearing human tumours .","180300-43-0","267.241","Investigated for use/treatment in solid tumors and cancer/tumors (unspecified).",null,"3'-C-ethynylcytidine is metabolized in tumor cells to ethynylcytidine triphosphate (ECTP), which inhibits RNA synthesis by competitive inhibition of RNA polymerases I, II and III; subsequently, RNase L is activated, resulting in apoptosis. RNase L is a potent antiviral and antiproliferative endoribonuclease that cleaves singled stranded RNA, causes 28s rRNA fragmentation, and activates Janus Kinase (JAK), a mitochondrial-dependent apoptosis signaling molecule.",null,"Therapeutic strategy associated"]
[1073,"DB06660","investigational","small molecule","Saredutant","Saredutant","C31H35Cl2N3O2","CN(C[C@@H](CCN1CCC(CC1)(NC(C)=O)C1=CC=CC=C1)C1=CC=C(Cl)C(Cl)=C1)C(=O)C1=CC=CC=C1","Saredutant (SR 48968) is a neurokinin-2 antagonist drug being developed as an antidepressant and anxiolytic by Sanofi-Aventis.","142001-63-6","552.54","Investigated for use/treatment in depression and anxiety disorders.",null,"Saredutant works by blocking the effects of Neurokinin A at the NK-2 receptor.","Substance-K receptor","Indication associated"]
[1074,"DB06669","investigational","small molecule","Arverapamil","(R)-norverapamil","C26H36N2O4","COC1=CC=C(CCNCCC[C@@](C#N)(C(C)C)C2=CC=C(OC)C(OC)=C2)C=C1OC",null,"123932-43-4","440.584","Investigated for use/treatment in irritable bowel syndrome (IBS) and diarrhea.",{"$nulls":3},"Indication associated"]
[1075,"DB06670","investigational","small molecule","Odanacatib","Odanacatib","C25H27F4N3O3S","CC(C)(F)C[C@H](N[C@@H](C1=CC=C(C=C1)C1=CC=C(C=C1)S(C)(=O)=O)C(F)(F)F)C(=O)NC1(CC1)C#N","Odanacatib is an inhibiter of cathepsin K which was originally developed be Merck & Co as a new treatment for osteoporosis . The drug made it to phase III trials before abandoned due to increased stroke.","603139-19-1","525.56","Investigated for use/treatment in osteoporosis .","Increases bone mineral density and reduces risk of fractures in osteoporosis .","Odanacatib inhibits cathepsin K, likely by binding to its active site . Cathepsin K is a cysteine protease enzyme which is secreted by osteoclasts . Cathepsin K is responsible for the breakdown of collagen in the bone matrix as part of bone resorption. The inhibition of this enzyme results in decreased bone resorption without affecting bone deposition resulting in increased bone mineral density. This increased bone mineral density strengthens the bone which leads to fewer fractures in osteoporosis.","Cathepsin K inhibitor","Indication associated"]
[1076,"DB06674","approved","biotech","Golimumab","Golimumab",null,null,"Golimumab is a human IgG1қ monoclonal antibody derived from immunizing genetically engineered mice with human TNFα. Golimumab binds and inhibits soluble and transmembrane human TNFα. Increased TNFα is associated with chronic inflammation. Thus golimumab is indicated for use in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) alone or as an adjunct to methotrexate treatment in patients with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS), and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. In the U.S. and Canada, golimumab is marketed under the brand name Simponi®. The FDA label includes a black box warning of serious infections and malignancy. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed.","476181-74-5",null,"Used in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) in patients 2 years old and above with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS) or in combination with methotrexate, and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. It is also indicated (v) for the treatment of active polyarticular juvenile idiopathic arthritis (pJIA) in patients 2 years of age and older.\r","Golimumab inhibits the activity of the cytokine, tumor necrosis factor alpha (TNFα). In areas such as the joints and blood, increased TNFα is associated with chronic inflammation seen in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Thus golimumab decreases the inflammation in these conditions. Concerning ulcerative colitis, the physiological effects of golimumab has yet to be determined.","As a human monoclonal antibody, golimumab binds and inhibits soluble and transmembrane human TNFα. Inhibition of TNFα prevents it binding to its receptors, which prevents both leukocyte infiltration through prevention of cell adhesion proteins such as E-selectin, ICAM-1 and VCAM-1, and pro-inflammatory cytokine secretion such as IL-6, IL-8, G-CSF and GM-CSF in vitro. Consequently, in patients with chronic inflammatory conditions, decreases in ICAM-1 and IL-6 as well as C-reactive protein (CRP), matrix metalloproteinase 3 (MMP-3), and vascular endothelial growth factor (VEGF) were observed.","Tumor necrosis factor antibody","Therapeutic strategy associated"]
[1077,"DB06677","investigational","small molecule","Clazosentan","Clazosentan","C25H23N9O6S","COC1=CC=CC=C1OC1=C(NS(=O)(=O)C2=CC=C(C)C=N2)N=C(N=C1OCCO)C1=CC=NC(=C1)C1=NN=NN1",null,"180384-56-9","577.58","Investigated for use/treatment in strokes.",null,null,"Endothelin-1 receptor","Indication associated"]
[1078,"DB06679","investigational","biotech","Amediplase","Amediplase",null,null,"Amediplase is a recombinant chimeric plasminogen activator, consisting of the kringle 2 domain from the A-chain of tissue plasminogen activator (t-PA) and the carboxy terminal region of pro-urokinase.","151912-11-7",null,"Investigated for use/treatment in myocardial infarction and thrombosis.",{"$nulls":3},"Indication associated"]
[1079,"DB06682","investigational","small molecule","Naproxcinod","(S)-2-(6-Methoxy-2-naphthyl)propanoic acid 4-nitrooxybutyl ester; Naproxen-N-butyl nitrate","C18H21NO6","COC1=CC2=CC=C(C=C2C=C1)[C@H](C)C(=O)OCCCCO[N+]([O-])=O",null,"163133-43-5","347.367","Investigated for use/treatment in pain (acute or chronic), inflammatory disorders (unspecified), osteoarthritis, and arthritis and arthritic pain.",{"$nulls":3},"Indication associated"]
[1080,"DB06689","approved","small molecule","Ethanolamine oleate","Ethamolin; Ethanolamine oleate; Monoethanolamine oleate; Oldamin","C20H41NO3","NCCO.CCCCCCCC\\C=C/CCCCCCCC(O)=O","Ethanolamine oleate is a mild sclerosing agent.  It is composed of ethanolamine, a basic substance, which when combined with oleic acid forms a clear, straw to pale yellow colored, deliquescent oleate.","2272-11-9","343.5444","For the treatment of patients with esophageal varices that have recently bled, to prevent rebleeding.","When injected intravenously, ethanolamine oleate acts primarily by irritation of the intimal endothelium of the vein and produces a sterile dose-related inflammatory response. This results in fibrosis and possible occlusion of the vein. Ethanolamine oleate also rapidly diffuses through the venous wall and produces a dose-related extravascular inflammatory reaction.","The oleic acid component of ethanolamine oleate is responsible for the inflammatory response, and may also activate coagulation in vivo by release of tissue factor and activation of Hageman factor. The ethanolamine component, however, may inhibit fibrin clot formation by chelating calcium, so that a procoagulant action of ethanolamine oleate has not been demonstrated.","Calcium ions chelator; Coagulation factor XII activator","Therapeutic strategy associated"]
[1081,"DB06692","approved; investigational; withdrawn","biotech","Aprotinin","Aprotinin; Aprotinin (bovine); Aprotinin biosynthetic; Aprotinin bovine; Aprotinin concentrated solution; Bovine aprotinin; Bovine pancreatic trypsin inhibitor; BPTI; Fibrinolysis inhibitor; Trypsin inhibitor, pancreatic basic",null,null,"Aprotinin is a protein-based drug that is also known as bovine pancreatic trypsin inhibitor (BPTI). Since it demonstrates the capacity to slow fibrinolysis, it has been employed to reduce bleeding during complex surgery such as heart and liver surgery. For this use, it is typically administered by injection. The goal of using of aprotinin was subsequently to minimize end-organ damage resulting from hypotension due to blood loss in surgery and to reduce the necessity for blood transfusions during surgery. Nevertheless, the drug was formally withdrawn worldwide in May of 2008 after studies confirmed that its use enhanced the risk of complications or death. The substance is consequently made available only for very restricted research use.","9087-70-1",null,"For prophylactic use to reduce perioperative blood loss and the need for blood transfusion in patients undergoing cardiopulmonary bypass in the course of coronary artery bypass graft surgery who are at an increased risk for blood loss and blood transfusion.","Aprotinin is a broad spectrum protease inhibitor which modulates the systemic inflammatory response (SIR) associated with cardiopulmonary bypass (CPB) surgery. SIR results in the interrelated activation of the hemostatic, fibrinolytic, cellular and humoral inflammatory systems. Aprotinin, through its inhibition of multiple mediators  results in the attenuation of inflammatory responses, fibrinolysis, and thrombin generation. Aprotinin inhibits pro-inflammatory cytokine release and maintains glycoprotein homeostasis. In platelets, aprotinin reduces glycoprotein loss (e.g., GpIb, GpIIb/IIIa), while in granulocytes it prevents the expression of pro-inflammatory adhesive glycoproteins (e.g., CD11b). The effects of aprotinin use in CPB involves a reduction in inflammatory response which translates into a decreased need for allogeneic blood transfusions, reduced bleeding, and decreased mediastinal re-exploration for bleeding.","Aprotinin inhibits serine proteases including trypsin, chymotrypsin and plasmin at a concentration of about 125,000 IU/mL, and kallikrein at 300,000 IU/mL. The inhibition of kallikrein inhibits formation of factor XIIa. This inhibits the intrinsic pathway of coagulation and fibrinolysis. Inhibition of plasmin also slows fibrinolysis.","Trypsin-1; Chymotrypsinogen B; Plasminogen; Kallikrein-1","Therapeutic strategy associated"]
[1082,"DB06693","experimental","small molecule","Mevastatin","Compactin; Mevastatin","C23H34O5","[H][C@]12[C@H](CCC=C1C=C[C@H](C)[C@@H]2CC[C@@H]1C[C@@H](O)CC(=O)O1)OC(=O)[C@@H](C)CC","Mevastatin or compactin is a cholesterol-lowering agent isolated from <i>Penicillium citinium</i>. It was the first discovered agent belonging to the class of cholesterol-lowering medications known as statins. During a search for antibiotic compounds produced by fungi in 1971, Akira Endo at Sankyo Co. (Japan) discovered a class of compounds that appeared to lower plasma cholesterol levels. Two years later, the research group isolated a compound structurally similar to hydroxymethylglutarate (HMG) that inhibited the incorporation of acetate. The compound was proposed to bind to the reductase enzyme and was named compactin. Mevastatin is a competitive inhibitor of HMG-Coenzyme A (HMG-CoA) reductase with a binding affinity 10,000 times greater than the HMG-CoA substrate itself. Mevastatin is a pro-drug that is activated by <i>in vivo</i> hydrolysis of the lactone ring. It has served as one of the lead compounds for the development of the synthetic compounds used today.","73573-88-3","390.52","Not used therapeutically due to its many side effects.","The primary cause of cardiovascular disease is atherosclerotic plaque formation. Mevastatin lowers hepatic production of cholesterol to reduce the risk of cardiovascular disease. Mevastatin competitively inhibits HMG-CoA reductase. This inhibition prevents the rate limiting step in cholesterol synthesis. Decreased hepatic cholesterol levels causes increased uptake of low density lipoprotein (LDL) cholesterol and reduces cholesterol levels in the circulation.","Mevastatin is structurally similar to the HMG, a substituent of the endogenous substrate of HMG-CoA reductase. Mevastatin is a prodrug that is activated <i>in vivo</i> via hydrolysis of the lactone ring. The hydrolyzed lactone ring mimics the tetrahedral intermediate produced by the reductase allowing the agent to bind with 10,000 times greater affinity than its natural substrate. The bicyclic portion of mevastatin binds to the coenzyme A portion of the active site.","3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor","Target associated"]
[1083,"DB06696","experimental; investigational","small molecule","Arbekacin","ABK; Arbekacin; Haberacin","C22H44N6O10","NCC[C@H](O)C(=O)N[C@@H]1C[C@H](N)[C@@H](O[C@H]2O[C@H](CN)CC[C@H]2N)[C@H](O)[C@H]1O[C@H]1O[C@H](CO)[C@@H](O)[C@H](N)[C@H]1O","An semisynthetic aminoglycoside antibiotic. Often used for treatment of multi-resistant bacterial infection such as methicillin-resistant _Staphylococcus aureus_ (MRSA).","51025-85-5","552.619","Arbekacin is used for the short term treatment of multi-resistant bacterial infections, such as methicillin-resistant <i>Staphylococcus aureus</i> (MRSA).","Arbekacin is an aminoglycoside. Aminoglycosides function by binding to bacterial 30S ribosomal subunits, causing t-RNA misreads, and preventing the production of proteins. Anaerobes are less susceptible to aminoglycosides because they do not spend as much energy as aerobes on taking up chemicals like aminoglycosides. Aminoglycosides are useful primarily in infections involving aerobic, gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter.","Arbekacin irreversibly binds bacterial 30S and 16S ribosomal subunits inhibiting protein synthesis. Arbekacin binds to 4 nucleotides of the 16S subunit and 1 amino acid of protein S12 to interfere with the decoding site around nucleotide 1400 in the 16S subunit. Interference with the decoding site interferes with its interaction with the wobble base of tRNA. This hindered interaction causes mRNA to be misread and the incorrect amino acids are inserted into protein. These error filled proteins are not able to function or may even be toxic.","30S ribosomal protein S12 inhibitor","Indication associated"]
[1084,"DB06703","approved","small molecule","Gadobutrol","gadolinium(III) 2,2',2''-(10-((2R,3S )-1,3,4-trihydroxybutan-2-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetate","C18H31GdN4O9","OC[C@H](O)[C@H](CO)[N+]12CC[N+]3(CC([O-])=O)CC[N+]4(CC([O-])=O)CC[N+](CC([O-])=O)(CC1)[Gd-]234","Intravenous gadobutrol is a second-generation extracellular non-ionic macrocyclic GBCA (gadolinium-based contrast agent) used in magnetic resonance imaging (MRI) in adults and children older than 2 years of age. It may help visualize and detect vascular abnormalities in the blood brain barrier (BBB) and central nervous system (CNS). \r\n\r\nIn patients with impaired renal function, gadolinium based contrast agents increase the risk of nephrogenic systemic fibrosis (NSF). A physician should be contacted if symptoms of NSF are encountered, such as dark or red patches on the skin; stiffness in joints; trouble moving, bending or straightening arms, hands, legs or feet; burning, itching, swelling, scaling, hardening and tightening of skin; pain in hip bones or ribs; or muscle weakness. \r\n\r\nCommon adverse reactions that may be experienced include headache, nausea, feeling hot, abnormal taste, and warmth, burning or pain local to the injection site. \r\n\r\nGeneral precautions should be taken in patients who are pregnant or breastfeeding, or who have a history of allergic reaction to contrast media, bronchial asthma or an allergic respiratory disorder.","770691-21-9","604.72","For diagnostic use only. Indicated for adults and children age 2 and over for contrast enhancement during cranial and spinal MRI, and for contrast-enhanced magnetic resonance angiography (CE-MRA). Gadobutrol is particularly suited for the detection of very small lesions and for the visualization of tumors that do not readily take up contrast media. It may be a desired agent when the exclusion or demonstration of an additional pathology may influence the choice of therapy or patient management. It may also be suitable for perfusion studies in the diagnosis of stroke, detection of focal cerebral ischemia, and in studies of tumor perfusion.","Even at low concentrations Gadobutrol can lead to distinct shortening of relaxation times of protons in plasma. At physiological conditions (pH=7, temperature=37°C), and 1.5T, the relaxivity (r1) is 5.2L/(mmol·sec) based on the relaxation times (T1), while the relativity (r2) is 6.1L/(mmol·sec) based on relaxation times (T2). \r\n\r\nMagnetic field strength has only slight influence on relaxivities.  \r\n\r\nDrug concentration and r1 relaxivity may contribute to a T1 shortening effect, which may improve tissue visualization.","MRI tissue visualization is dependent, in part, on variations in intensity of radiofrequency signals which occur due to differences in proton density, differences of the spin-lattice or longitudinal relaxation times (T1), and differences in the spin-spin or transverse relaxation times (T2).\r\n\r\nGadolinium shortens T1 and T2 relaxation times. Greater signal enhancement is achieved with increased shortening of T1 and T2. The extent to which Gadolinium can shorten T1 and T2 is influenced by concentration in tissue, MRI field strength, and the relative ratio of transverse and longitudinal relaxation times. \r\n\r\nThe recommended dose produced the greatest sensitivity of T1 shortening effect in T1-weighted magnetic resonance sequences. \r\nIn T2-weighted sequences, the large magnetic moment of gadolinium induced local magnetic field inhomogenenities. \r\n\r\nAt high concentrations used during bolus injections, T2-weighted sequences show a signal decrease.",null,"Indication associated"]
[1085,"DB06709","approved; investigational","small molecule","Methacholine","Acetyl-beta-methylcholine; Acetylmethylcholine; beta-Methylacetylcholine; MCh; Methacholine","C8H18NO2","CC(C[N+](C)(C)C)OC(C)=O","Asthma is a complex condition associated with phenomena such as airway hyperresponsiveness (AHR), in which the smooth muscle in the airways (ASM) excessively contracts in response to stimuli, reducing pulmonary function and causing symptoms such as difficulty breathing. Although the underlying pathology of AHR is complex, ASM contraction can be stimulated by cholinergic agonists that activate M<sub>3</sub> muscarinic receptors that stimulate ASM contraction. Methacholine is a non-specific cholinergic agonist (parasympathomimetic) that acts through muscarinic receptors in the lungs to induce bronchoconstriction. In patients with AHR, a lower dose of methacholine is required to induce bronchoconstriction, which forms the basis for the methacholine challenge test to diagnose AHR.\r\n\r\nMethacholine was granted FDA approval on October 31, 1986, and is marketed under the trademark PROVOCHOLINE® by Methapharm Inc.","55-92-5","160.234","Methacholine is indicated in adult and pediatric patients aged five years and older without clinically apparent asthma for the diagnosis of bronchial airway hyperactivity via the methacholine challenge test.","Methacholine is a non-specific cholinergic agonist (parasympathomimetic) that acts through muscarinic receptors in the lungs to induce bronchoconstriction, which is more significant in patients with asthma than those without. Therefore, methacholine carries a risk of severe bronchoconstriction, especially in patients with pre-existing reduced pulmonary function (typically baseline FEV<sub>1</sub> < 60% or < 1.5 L, at least in adults), clinically apparent asthma or wheezing, or other health conditions such as uncontrolled hypertension, aortic aneurysm, or history of myocardial infarction or stroke. Use in patients with epilepsy, vagotonia, peptic ulcer disease, thyroid disease, urinary tract obstruction or other conditions that could be adversely affected by a cholinergic agent is not recommended. Also, there is a potential risk to healthcare workers administering the methacholine challenge test; proper precautions and protective equipment should be used as needed.","Asthma is a complicated condition associated with airway remodelling, including the proliferation of airway smooth muscle (ASM) and altered extracellular matrix, aberrant pro-inflammatory immune responses, and excessive ASM contraction leading to decreased lung function. Excessive ASM contraction in response to contractile agonists, a phenomenon termed airway hyperresponsiveness (AHR), is a physical manifestation of the altered pulmonary physiology in asthma. Although numerous factors, such as increased ASM levels, pro-contractile molecules, pro-inflammatory cytokines, and growth factors, contribute to AHR, one of the key factors in determining ASM tone is regulated by vagal parasympathetic nerve innervation. The response to acetylcholine and other cholinergic agonists at these neuromuscular junctions is predominantly controlled by inhibitory G<sub>i</sub>-coupled M<sub>2</sub> and excitatory G<sub>q</sub>-coupled M<sub>3</sub> muscarinic acetylcholine receptors (mAChRs). Activation of M<sub>3</sub> receptors results in ASM contraction and resulting bronchoconstriction through downstream calcium-dependent signalling pathways, while M<sub>2</sub> activation inhibits neuronal acetylcholine release.\r\n\r\nMethacholine is a non-specific mAChR agonist, capable of acting on all mAChR subtypes. However, in the context of AHR, methacholine's ability to induce bronchoconstriction through M<sub>3</sub> receptors is clinically relevant. In addition, M<sub>3</sub> agonism may increase the release of pro-inflammatory cytokines, further contributing to AHR. The inhibitory effect of M<sub>2</sub> agonism by methacholine is likely also important, as shown by animal studies using mice with impaired M<sub>2</sub> function, and by observations that eosinophilic inflammation, such as occurs in asthma, negatively impacts M<sub>2</sub> function. Hence, asthmatic patients are more sensitive to inhaled cholinergic agonists such as methacholine; this forms the basis for the methacholine challenge test, which diagnoses AHR through an increased methacholine-induced response.","Muscarinic acetylcholine receptor M3 agonist; Muscarinic acetylcholine receptor M2 agonist; Muscarinic acetylcholine receptor M1 agonist; Muscarinic acetylcholine receptor M4 agonist; Muscarinic acetylcholine receptor M5 agonist","Therapeutic strategy associated"]
[1086,"DB06712","approved; investigational","small molecule","Nilvadipine","Nilvadipine","C19H19N3O6","COC(=O)C1=C(NC(C)=C(C1C1=CC(=CC=C1)[N+]([O-])=O)C(=O)OC(C)C)C#N","Nilvadipine is a calcium channel blocker (CCB) for the treatment of hypertension.","75530-68-6","385.3707","For the management of vasospastic angina, chronic stable angina and hypertension.","Nilvadipine is similar to other dihydropyridines including amlodipine, felodipine, isradipine, and nicardipine. Nilvadipine is used to treat Prinzmetal's angina, hypertension, and other vascular disorders such as Raynaud's phenomenon. By blocking the calcium channels, Nifedipine inhibits the spasm of the coronary artery and dilates the systemic arteries, results in a increase of myocardial oxygen supply and a decrease in systemic blood pressure.","Nilvadipine inhibits the influx of extracellular calcium through myocardial and vascular membrane pores by physically plugging the channel. The decrease in intracellular calcium inhibits the contractile processes of smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.","Voltage-dependent L-type calcium channel subunit alpha-1C inhibitor; Voltage-dependent calcium channel subunit alpha-2/delta-1 inhibitor; Voltage-dependent L-type calcium channel subunit beta-2 inhibitor; Voltage-dependent L-type calcium channel subunit alpha-1D inhibitor; Voltage-dependent L-type calcium channel subunit alpha-1S inhibitor; Voltage-dependent calcium channel subunit alpha-2/delta-3 inhibitor","Indication associated"]
[1087,"DB06725","approved; investigational","small molecule","Lornoxicam","Chlortenoxicam","C13H10ClN3O4S2","CN1C(C(=O)NC2=CC=CC=N2)=C(O)C2=C(C=C(Cl)S2)S1(=O)=O","Lornoxicam (chlortenoxicam) is a new nonsteroidal anti-inflammatory drug (NSAID) of the oxicam class with analgesic, anti-inflammatory and antipyretic properties. Lornoxicam differs from other oxicam compounds in its potent inhibition of prostaglandin biosynthesis, a property that explains the particularly pronounced efficacy of the drug. Lornoxicam is approved for use in Japan.","70374-39-9","371.81","For the treatment of acute mild to moderate pain, as well as pain and inflammation of the joints caused by certain types of rheumatic diseases.","Lornoxicam is a non-steroidal anti-inflammatory drug (NSAID) that belongs to the oxicam class. As with other NSAIDS, lornoxicam is a potent inhibitor of the cyclooxgenase enzymes, which are responsible for catalyzing the formation of prostaglandins (act as messenger molecules in the process of inflammation) and thromboxane from arachidonic acid. Unlike some NSAIDS, lornoxicam's inhibition of cyclooxygenase does not lead to an increase in leukotriene formation, meaning that arachidonic acid is not moved to the 5-lipoxygenase cascade, resulting in the minimization of the risk of adverse events.","Like other NSAIDS, lornoxicam's anti-inflammatory and analgesic activity is related to its inhibitory action on prostaglandin and thromboxane synthesis through the inhibition of both COX-1 and COX-2. This leads to the reduction of inflammation, pain, fever, and swelling, which are mediated by prostaglandins. However, the exact mechanism of lornoxicam, like that of the other NSAIDs, has not been fully determined.","Prostaglandin G/H synthase 1 inhibitor; Prostaglandin G/H synthase 2 inhibitor","Therapeutic strategy associated"]
[1088,"DB06729","approved","small molecule","Sulfaphenazole","1-phenyl-5-sulfanilamidopyrazole; 3-(p-aminobenzenesulfonamido)-2-phenylpyrazole; 5-sulfanilamido-1-phenylpyrazole; N'-(1-phenylpyrazol-5-yl)sulfanilamide; N(1)-(1-phenylpyrazol-5-yl)sulfanilamide; Sulfaphenazole; Sulphaphenazole","C15H14N4O2S","NC1=CC=C(C=C1)S(=O)(=O)NC1=CC=NN1C1=CC=CC=C1","Sulfaphenazole is a sulfonamide antibacterial.","526-08-9","314.362","For the treatment bacterial infections.",null,"Sulfaphenazole is a sulfonamide antibacterial. In bacteria, antibacterial sulfonamides act as competitive inhibitors of the enzyme dihydropteroate synthetase (DHPS), an enzyme involved in folate synthesis. As such, the microorganism will be \"starved\" of folate and die.","Dihydropteroate synthase inhibitor","Indication associated"]
[1089,"DB06736","approved; investigational","small molecule","Aceclofenac","2-[(2,6-dichlorophenyl)amino]benzeneacetic acid carboxymethyl ester; 2-[(2,6-dichlorophenyl)amino]phenylacetoxyacetic acid; 2-[(2',6'-dichlorophenyl)amino]phenylacetoxyacetic acid; Aceclofenac; Aceclofenac betadex; glycolic acid [o-(2,6-dichloroanilino)phenyl]acetate ester","C16H13Cl2NO4","OC(=O)COC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl","Aceclofenac is an oral non-steroidal anti-inflammatory drug (NSAID) with marked anti-inflammatory and analgesic properties used to treat osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. It is reported to have a higher anti-inflammatory action or at least comparable effects than conventional NSAIDs in double-blind studies . Aceclofenac potently inhibits the cyclo-oxygenase enzyme (COX) that is involved in the synthesis of prostaglandins, which are inflammatory mediators that cause pain, swelling, inflammation, and fever. Aceclofenac belongs to BCS Class II as it possesses poor aqueous solubility . It displays high permeability to penetrate into synovial joints where in patients with osteoarthritis and related conditions, the loss of articular cartilage in the area causes joint pain, tenderness, stiffness, crepitus, and local inflammation . Aceclofenac is also reported to be effective in other painful conditions such as dental and gynaecological conditions . In 1991, aceclofenac was developed as an analog of a commonly prescribed NSAID, , via chemical modification in effort to improve the gastrointestinal tolerability of the drug. It is a more commonly prescribed drug in Europe.","89796-99-6","354.18","Aceclofenac is indicated for the relief of pain and inflammation in osteoarthritis, rheumatoid arthritis and ankylosing spondylitis.","Aceclofenac is a NSAID that inhibits both isoforms of COX enzyme, a key enzyme involved in the inflammatory cascade. COX-1 enzyme is a constitutive enzyme involved in prostacyclin production and protective functions of gastric mucosa whereas COX-2 is an inducible enzyme involved in the production of inflammatory mediators in response to inflammatory stimuli. Aceclofenac displays more selectivity towards COX-2 (IC50 of 0.77uM) than COX-1 (IC50 of >100uM), which promotes its gastric tolerance compared to other NSAIDs. The primary metabolite, 4'-hydroxyaceclofenac, also minimally inhibits COX-2 with IC50 value of 36uM . Although the mode of action of aceclofenac is thought to mainly arise from the inhibition of synthesis of prostaglandins (PGE2), aceclofenac also inhibits the production of inflammatory cytokines, interleukins (IL-1β, IL-6), and tumor necrosis factors (TNF) . It is also reported that aceclofenac also affects the cell adhesion molecules from neutrophils . Aceclofenac also targets the synthesis of glycosaminoglycan and mediates chrondroprotective effects .","Through COX-2 inhibition, aceclofenac downregulates the production of various inflammatory mediators including prostaglandin E2 (PGE2), IL-1β, and TNF from the arachidonic acid (AA) pathway. Inhibition of IL-6 is thought to be mediated by diclofenac converted from aceclofenac . Suppressed action of inflammatory cytokines decreases the production of reactive oxygen species. Aceclofenac is shown to decreased production of nitrous oxide in human articular chondrocytes . In addition, aceclofenac interferes with neutrophil adhesion to endothelium by decreasing the expression of L-selectin (CD62L), which is a cell adhesion molecule expressed on lymphocytes . Aceclofenac is proposed to stimulate the synthesis of glycosaminoglycan in human osteoarthritic cartilage which may be mediated through its inhibitory action on IL-1 production and activity . The chrondroprotective effects are generated by 4'-hydroxyaceclofenac which suppresses IL-1 mediated production of promatrix metalloproteinase-1 and metalloproteinase-3 and interferes with the release of proteoglycan from chrondrocytes .","Prostaglandin G/H synthase 2 inhibitor; Prostaglandin G/H synthase 1 inhibitor","Therapeutic strategy associated"]
[1090,"DB06742","approved; investigational","small molecule","Ambroxol","Ambroxol; Bisolvon metabolite vIII; Bromhexine metabolite vIII; Bromhexine-metabolite vIII; Cyclohexanol, 4-((2-amino-3,5-dibromobenzyl)amino)- (E)-; N-(2-Amino-3,4-dibromociclohexil)-trans-4-aminociclohexanol; N-(2-Amino-3,4-dibromocyclohexyl)-trans-4-aminocyclohexanol; trans-4-((2-Amino-3,5-dibromobencil)amino)ciclohexanol; trans-4-((2-Amino-3,5-dibromobenzyl)amine)cyclohexanol; trans-4-((2-Amino-3,5-dibromobenzyl)amino)cyclohexanol","C13H18Br2N2O","NC1=C(Br)C=C(Br)C=C1CN[C@H]1CC[C@H](O)CC1","Ambroxol is a secretolytic agent used in the treatment of respiratory diseases associated with viscid or excessive mucus. It is the active ingredient of Mucosolvan, Lasolvan or Mucoangin. The substance is a mucoactive drug with several properties including secretolytic and secretomotoric actions that restore the physiological clearance mechanisms of the respiratory tract which play an important role in the body’s natural defence mechanisms. It stimulates synthesis and release of surfactant by type II pneumocytes. Surfactants acts as an anti-glue factor by reducing the adhesion of mucus to the bronchial wall, in improving its transport and in providing protection against infection and irritating agents.","18683-91-5","378.108","Ambroxol is indicated for secretolytic therapy in bronchoplmonary disease with abnormal mucus secretion and transport. It allows the mucus to be more easily cleared and ease a patient's breathing.",null,"Ambroxol is a mucolytic agent. Excessive Nitric oxide (NO) is associated with inflammatory and some other disturbances of airways function. NO enhances the activation of soluble guanylate cyclase and cGMP accumulation. Ambroxol has been shown to inhibit the NO-dependent activation of soluble guanylate cyclase. It is also possible that the inhibition of NO-dependent activation of soluble guanylate cyclase can suppress the excessive mucus secretion, therefore it lowers the phlegm viscosity and improves the mucociliary transport of bronchial secretions.",null,"Therapeutic strategy associated"]
[1091,"DB06755","approved; nutraceutical","small molecule","Beta carotene","all-trans-β-carotene; Beta carotene; beta-carotene; Betacarotene; β-Karotin","C40H56","C\\C(\\C=C\\C=C(/C)\\C=C\\C1=C(C)CCCC1(C)C)=C/C=C/C=C(\\C)/C=C/C=C(\\C)/C=C/C1=C(C)CCCC1(C)C","Beta-carotene, with the molecular formula C40H56, belongs to the group of carotenoids consisting of isoprene units. The presence of long chains of conjugated double bonds donates beta-carotene with specific colors. It is the most abundant form of carotenoid and it is a precursor of the vitamin A. Beta-carotene is composed of two retinyl groups. It is an antioxidant that can be found in yellow, orange and green leafy vegetables and fruits. Under the FDA, beta-carotene is considered as a generally recognized as safe substance (GRAS).","7235-40-7","536.888","Beta-carotene is FDA approved to be used as a nutrient supplement and to be even added in infant formula as a source of vitamin A. It is also approved to be used as a color additive for food products, drugs (with the label of \"only as a color additive\") and cosmetics.\r\n\r\nIt is used commonly for the reduction of photosensitivity in patients with erythropoietic protoporphyria and other photosensitivity diseases.","Oral administration of beta-carotene increases the serum concentration of beta-carotene by 60% but it does not change the concentration found in the heart, liver or kidneys. In vitro studies in hepatocytes have shown that beta-carotene ameliorates oxidative stress, enhances antioxidant activity and decreases apoptosis.\r\n\r\nOther than the antioxidant activities, some other actions have been correlated to beta-carotene. It is thought to have detoxifying properties, as well as to help increase resistance to inflammation and infection and increase immune response and enhance RNA production.","Beta-carotene is an antioxidant that presents significant efficacy against the reactive oxygen species singlet oxygen. Beta-carotene acts as a scavenger of lipophilic radicals within the membranes of every cell compartments. It also presents an oxidative modification of LDL. The presence of long chains of conjugated double bonds is responsible for its antioxidative properties by allowing beta-carotene to chelate oxygen-free radicals and dissipate their energy. The chelation of free radicals inhibits the peroxidation of lipids.\r\n\r\nThe effect of beta-carotene in the immune response is thought to be related to the direct effect on the thymus which increases the production of immune cells.","Free radicals binder","Therapeutic strategy associated"]
[1092,"DB06757","approved; nutraceutical","small molecule","Manganese",null,"Mn","[Mn++]","Manganese is a transition metal with a molar mass of 54.94g/mol. Manganese is considered critical for human health, and plays important roles in development, metabolism, and the antioxidant system. That said, excessive manganese intake is associated with manganism, a neurodegenerative disorder that causes dopaminergic neuronal death and parkinsonian-like symptoms.","7439-96-5","54.938","Indicated for use as a supplement to intravenous solutions given for Total Parenteral Nutrition (TPN). Administration helps to maintain plasma levels and to prevent depletion of endogenous stores and subsequent deficiency symptoms.",null,null,"Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial; Isocitrate dehydrogenase [NAD] subunit gamma, mitochondrial; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1; Arginase-1; Serotransferrin","Target associated"]
[1093,"DB06771","approved","small molecule","Besifloxacin","Besifloxacin","C19H21ClFN3O3","N[C@@H]1CCCCN(C1)C1=C(F)C=C2C(=O)C(=CN(C3CC3)C2=C1Cl)C(O)=O","Besifloxacin is a fourth generation fluoroquinolone-type opthalmic antibiotic for the treatment of bacterial conjunctivitis. FDA approved on May 28, 2009.","141388-76-3","393.84","Treatment of bacterial conjunctivitis. Bacterial isolates that are susceptible to besifloxacin include: CDC coryneform group G; Corynebacterium pseudodiphtheriticum; Corynebacterium striatum; Haemophilus influenzae; Moraxella lacunata; Staphylococcus aureus; Staphylococcus epidermidis; Staphylococcus hominis; Staphylococcus lugdunensis; Streptococcus mitis group; Streptococcus oralis; Streptococcus pneumoniae; Streptococcus salivarius*","Besifloxacin tear concentrations were higher than MIC90 (minimum inhibitory concentration) values for common bacterial pathogens and sustained for 24 hours or longer. Mean residence time in the conjunctiva was 4.7 hours.","Besifloxacin is a bactericidal fluroquinolone-type antibiotic that inhibits bacterial enzymes, DNA gyrase and topoisomerase IV. By inhibiting DNA gyrase, DNA replication, transcription, and repair is impaired. By inhibiting topoisomerase IV, decatenation during cell devision is impaired. Inhibiting these two targets also slows down development of resistance.","DNA topoisomerase 4 subunit A antagonist; DNA topoisomerase 4 subunit A antagonist; DNA gyrase subunit A antagonist; DNA gyrase subunit A antagonist","Indication associated"]
[1094,"DB06772","approved","small molecule","Cabazitaxel",null,"C45H57NO14","[H][C@]12[C@H](OC(=O)C3=CC=CC=C3)[C@]3(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C4=CC=CC=C4)C(C)=C([C@@H](OC)C(=O)[C@]1(C)[C@H](C[C@H]1OC[C@@]21OC(C)=O)OC)C3(C)C","Cabazitaxel is an anti-neoplastic used with the steroid medicine prednisone. Cabazitaxel is used to treat people with prostate cancer that has progressed despite treatment with docetaxel. Cabazitaxel is prepared by semi-synthesis with a precursor extracted from yew needles (10-deacetylbaccatin III). It was approved by the U.S. Food and Drug Administration (FDA) on June 17, 2010.","183133-96-2","835.9324","For treatment of patients with hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing treatment regimen.","Cabaitaxel has anti-tumour properties and is effective against docetaxel-sensitive and -insensitive tumours.","Cabazitaxel is a microtubule inhibitor. Cabazitaxel binds to tubulin and promotes its assembly into microtubules while simultaneously inhibiting disassembly. This leads to the stabilization of microtubules, which results in the interference of mitotic and interphase cellular functions. The cell is then unable to progress further into the cell cycle, being stalled at metaphase, thus triggering apoptosis of the cancer cell.","Tubulin alpha-4A chain binder; Tubulin beta-1 chain binder","Therapeutic strategy associated"]
[1095,"DB06777","approved","small molecule","Chenodeoxycholic acid","3alpha,7alpha-Dihydroxy-5beta-cholanic acid; 7α-hydroxylithocholic acid; Anthropodeoxycholic acid; Anthropodesoxycholic acid; CDCA; Chenic acid; Chenocholic acid; Chenodeoxycholate; Chenodeoxycholic acid; Chenodesoxycholic acid; Chenodiol; Gallodesoxycholic acid","C24H40O4","[H][C@@]1(CC[C@@]2([H])[C@]3([H])[C@H](O)C[C@]4([H])C[C@H](O)CC[C@]4(C)[C@@]3([H])CC[C@]12C)[C@H](C)CCC(O)=O","Chenodeoxycholic acid (or Chenodiol) is an epimer of ursodeoxycholic acid (DB01586). Chenodeoxycholic acid is a bile acid naturally found in the body. It works by dissolving the cholesterol that makes gallstones and inhibiting production of cholesterol in the liver and absorption in the intestines, which helps to decrease the formation of gallstones. It can also reduce the amount of other bile acids that can be harmful to liver cells when levels are elevated.","474-25-9","392.572","Chenodiol is indicated for patients with radiolucent stones in well-opacifying gallbladders, in whom selective surgery would be undertaken except for the presence of increased surgical risk due to systemic disease or age. Chenodiol will not dissolve calcified (radiopaque) or radiolucent bile pigment stones.","It acts by reducing levels of cholesterol in the bile, helping gallstones that are made predominantly of cholesterol to dissolve. Chenodeoxycholic acid is ineffective with stones of a high calcium or bile acid content.","Chenodiol suppresses hepatic synthesis of both cholesterol and cholic acid, gradually replacing the latter and its metabolite, deoxycholic acid in an expanded bile acid pool. These actions contribute to biliary cholesterol desaturation and gradual dissolution of radiolucent cholesterol gallstones in the presence of a gall-bladder visualized by oral cholecystography. Bile acids may also bind the the bile acid receptor (FXR) which regulates the synthesis and transport of bile acids.","Bile acid receptor other; Nuclear receptor subfamily 1 group I member 2; G-protein coupled bile acid receptor 1; Aldo-keto reductase family 1 member C2 substrate","Target associated"]
[1096,"DB06778","approved","small molecule","Cupric sulfate","Copper monosulfate; Copper monosulphate; Copper sulfate; Copper sulfate (1:1); Copper sulphate; Copper(2+) sulfate; Copper(II) sulphate; Cupric sulfate anhydrous; Cupric sulfate, anhydrous; Cupric sulphate anhydrous; Cupric sulphate, anhydrous","CuO4S","[Cu++].[O-]S([O-])(=O)=O","Cupric sulfate is a salt created by treating cupric oxide with sulfuric acid. This forms as large, bright blue crystals containing five molecules of water (CuSO4∙5H2O) and is also known as _blue vitriol_. The anhydrous salt is created by heating the hydrate to 150 °C (300 °F). Cupric sulfate is used primarily for agricultural purposes, as a pesticide, germicide, feed additive, and soil additive. Some of its secondary uses are as a raw material in the preparation of other copper compounds, as a reagent in analytic chemistry, as an electrolyte for batteries and electroplating baths, and in medical practice as a locally applied fungicide, bactericide, and astringent .\r\n\r\nCopper is an essential trace element and an important catalyst for heme synthesis and iron absorption. After zinc and iron, copper is the third most abundant trace element found in the human body. Copper is a noble metal and its properties include high thermal and electrical conductivity, low corrosion, alloying ability, and malleability.  Copper is a component of intrauterine contraceptive devices  (IUD) and the release of copper is necessary for their important contraceptive effects. The average daily intake of copper in the USA is approximately  1 mg Cu with the diet being a primary source .\r\n\r\nInterestingly, the dysregulation of copper has been studied with a focus on neurodegenerative diseases, such as Wilson’s disease, Alzheimer’s disease, and Parkinson’s disease. Data from clinical observations of the neurotoxic effects of copper may provide the basis for future treatments affecting copper and its homeostasis .","7758-98-7","159.609","Elemental use in copper deficiency \r\n\r\nCopper and copper containing compounds are broadly used in medical practice. Metallic copper is used already for many years in dental fillings and in copper intrauterine devices (IUD) for reversible contraception. Ointments containing copper, which release copper ions that are absorbed by the skin in the management of cramps, disturbances of renal function, peripheral, venous hypostatic circulatory disturbances, rheumatic disease and swelling associated with trauma. There are also cosmetic facial creams containing copper as their main active ingredient .","Copper is an essential mineral that plays a key role in many physiological processes, including angiogenesis, skin generation and expression and stabilization of skin proteins.  Copper is found naturally in many food sources including meats, vegetables, and grains. Copper has potent biocidal properties and is used to eliminate bacteria, viruses and parasites , .\r\n\r\nCopper is one of the nine essential minerals for humans, as it plays an imperative role in various physiological pathways in basically all human tissue, as well as in the health of the dermis and epidermis .\r\n \r\nIn addition to the above, copper is essential in wound healing, as it promotes angiogenesis and skin extracellular matrix formation and stabilization .","This drug is an essential trace element for the functioning of many metalloenzymes including ceruloplasmin, ferroxidase II, lysyl oxidase, monoamine oxidase, Zn-copper superoxide dismutase, tyrosinase, dopamine-β-hydroxylase, and cytochrome-c-oxidase.\r\n\r\nIt is involved in erythropoiesis & leukopoiesis, bone mineralization, elastin and collagen cross-linking, oxidative phosphorylation, catecholamine metabolism, melanin formation & antioxidant protection of cells .\r\n\r\nCupric sulfate may also have a role in iron turnover, ascorbic acid metabolism, phospholipid metabolism, myelin formation, glucose homeostasis, and cellular immune defense .\r\n\r\nAfter the metal passes through the basolateral membrane it is transported to the liver, attached to serum albumin. The liver is the critical organ for the homeostasis of copper. The copper is then prepared for excretion through the bile or incorporation into various proteins.  The transport of copper to the peripheral tissues is accomplished through the plasma attached to serum albumin, ceruloplasmin or low-molecular-weight complexes .\r\n\r\nIn the dermis, copper promotes dermal fibroblasts proliferation, upregulates collagen (types I, II, and V) and elastin fiber components (elastin, fibrillins) production by fibroblasts, through the induction of TGF-β, promotes heat shock protein-47, important for collagen fibril formation, serves as a cofactor of LOX enzyme required for extracellular matrix protein cross-linking, stabilizes the skin ECM once formed, as increased crosslinking of collagen and elastin matrices occurs in a copper dose dependant manner, serves as a cofactor of superoxide dismutase, an antioxidant enzyme in the skin, essential for protection against free radicals, inhibits cellular oxidative effects such as membrane damage and lipid peroxidation, acts as a cofactor of tyrosinase, a melanin biosynthesis essential enzyme responsible for skin and hair pigmentation .\r\n\r\nIn reference to its role as a biocide, copper is an essential nutrient for many organisms. It acts as a cofactor in respiration, and therefore copper is required for aerobic metabolism. Accumulation of copper ions or intracellular release of free copper ions from proteins lead to cell damage. Copper catalyzes reactions that result in the production of hydroxyl radicals through the Fenton and Haber-Weiss reactions. The highly reactive oxygen intermediates lead to lipid peroxidation and oxidation of proteins. Free copper ions oxidize sulfhydryl groups, such as cysteine, in proteins or the cellular redox buffer glutathione. In particular, copper ions inactivate proteins by damaging Fe-S clusters in cytoplasmic hydratases .",null,"Therapeutic strategy associated"]
[1097,"DB06779","approved","small molecule","Dalteparin","alpha-heparin",null,null,"Dalteparin, a low molecular weight heparin (LMWH) prepared by nitrous acid degradation of unfractionated heparin of porcine intestinal mucosa origin, is an anticoagulant. It is composed of strongly acidic sulphated polysaccharide chains with an average molecular weight of 5000 and about 90% of the material within the range of 2000-9000. LMWHs have a more predictable response, a greater bioavailability, and a longer anti-Xa half life than unfractionated heparin. Dalteparin can also be safely used in most pregnant women. Low molecular weight heparins are less effective at inactivating factor IIa due to their shorter length compared to unfractionated heparin.","9005-49-6",null,"Dalteparin is used as a prophylaxis for deep-vein thrombosis and pulmonary embolisms in patients undergoing general surgery (e.g., abdominal, gynecologic, urologic), and in patients with acute medical conditions (e.g. cancer, bed rest, heart failure, severe lung disease). It is also used in patients who have severely restricted mobility, which poses a risk for thromboembolic complications. \r\n\r\nDalteparin is also used concomitantly with aspirin and/or other therapy (e.g., nitrates, β-adrenergic blockers, clopidogrel, platelet glycoprotein  IIb/IIIa-receptor inhibitors) to reduce the risk of acute cardiac ischemic events. The patients who undergo this treatment combination have unstable angina or non-ST-segment elevation/non-Q-wave myocardial infarction (i.e., non-ST-segment elevation acute coronary syndromes).\r\n\r\nIt is also used in the prevention of clotting during hemodialysis and hemofiltration in connection with acute renal failure or chronic renal insufficiency.","Dalteparin has an antithrombin binding site that is essential for high affinity binding to the plasma protein antithrombin (ATIII). Anti-Xa activity of plasma is used as both as an estimate of clotting activity, and as a basis to determine dosage. Its use should be avoided in patients with a creatinine clearance less than 20mL/min. In these patients, unfractionated heparin should only be used. As for monitoring, active partial thromboplastin time (aPTT) will only increase at high doses of low molecular weight heparins (LMWH). Therefore, monitoring aPTT is not recommended. However, anti-Xa activity can be measured to monitor the efficacy of the LMWH.","Dalteparin potentiates the activity of ATIII, inhibiting the formation of both factor Xa and thrombin. The main difference between dalteparin and unfractionated heparin (UH) is that dalteparin preferentially inactivates factor Xa. As a result, only a slight increase in clotting time  is observed relative to UH. For this same reason, APTT is not used to monitor the effects of dalteparin except as an indicator for overdosage.","Antithrombin-III potentiator; Vascular endothelial growth factor A inhibitor; Tissue factor pathway inhibitor inhibitor; P-selectin inhibitor","Indication associated"]
[1098,"DB06781","approved","small molecule","Difluprednate","DFBA; Difluoroprednisolone butyrate acetate; Difluprednate","C27H34F2O7","[H][C@@]12CC[C@](OC(=O)CCC)(C(=O)COC(C)=O)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])C[C@H](F)C2=CC(=O)C=C[C@]12C","Difluprednate is a topical corticosteroid indicated for the treatment of infammation and pain associated with ocular surgery. It is a butyrate ester of 6(α), 9(α)-difluoro prednisolone acetate. Difluprednate is abbreviated DFBA, or difluoroprednisolone butyrate acetate. It is indicated for treatment of endogenous anterior uveiti.","23674-86-4","508.5515","For the treatment of inflammation and pain associated with ocular surgery.","Difluprednate is a corticosteroid used as an anti-inflammatory steroidal drug used primarily in ocular surgery.","Corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins (lipocortins). It is postulated that these proteins control the biosynthesis of potent mediators of infammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2.","Glucocorticoid receptor agonist","Therapeutic strategy associated"]
[1099,"DB06784","approved","small molecule","Gallium citrate Ga-67","Gallium (67 Ga) citrate; Gallium citrate Ga 67; Gallium citrate Ga-67; Gallium-67 Citrate","C6H5GaO7","[67Ga+3].OC(CC([O-])=O)(CC([O-])=O)C([O-])=O","Gallium citrate Ga 67 is the citrate salt of the radioisotope gallium Ga 67. Although the mechanism is unknown, gallium Ga 67 concentrates in lysosomes and is bound to a soluble intracellular protein in certain viable primary and metastatic tumors and focal sites of inflammation, allowing scintigraphic localization. Ga-67 scintigraphy (GS) cannot differentiate between tumor and acute inflammation.","41183-64-6","256.0279","Gallium Citrate Ga 67 Injection may be useful to demonstrate the presence and extent of Hodgkin's disease, lymphoma, and bronchogenic carcinoma. Positive gallium Ga-67 uptake in the absence of prior symptoms warrants follow-up as an indication of a potential disease state. Gallium Citrate Ga 67 Injection may be useful as an aid in detecting some acute inflammatory lesions.","It has been reported in the scientific literature that following intravenous injection, the highest tissue concentration of gallium Ga-67 - other than tumors and sites of infection - is the renal cortex. After the first day, the maximum concentration shifts to bone and lymph nodes and after the first week, to liver and spleen. Gallium Ga-67 is excreted relatively slowly from the body. The average whole body retention is 65 percent after seven days, with 26 percent having been excreted in the urine and 9 percent in the stools.","Gallium Citrate Ga 67, with no carrier added, has been found to concentrate in certain viable primary and metastatic tumors as well as focal sites of infection. The body generally handles Ga3+ as though it were ferric iron (Fe-III), and thus the free isotope ion is bound (and concentrates) in areas of inflammation, such as an infection site, and also areas of rapid cell division. Ga-67 binds to transferrin, leukocyte lactoferrin, bacterial siderophores, inflammatory proteins, and cell-membranes in neutrophils, both living and dead. Lactoferrin is contained within leukocytes. Ga-67 may bind to lactoferrin and be transported to sites of inflammation, or binds to lactoferrin released during bacterial phagocytosis at infection sites (and remains due to binding with macrophage receptors). Ga-67 also attaches to the siderophore molecules of bacteria themselves, and for this reason can be used in leukopenic patients with bacterial infection (here it attaches directly to bacterial proteins, and leukocytes are not needed). Uptake is thought to be associated with a range of tumour properties including transferring receptors, anaerobic tumor metabolism and tumor perfusion and vascular permeability.",null,"Therapeutic strategy associated"]
[1100,"DB06786","approved; investigational; withdrawn","small molecule","Halcinonide","(4aS,4bR,5S,6aS,6bS,9aR,10aS,10bS)-6b-(chloroacetyl)-4b-fluoro-5-hydroxy-4a,6a,8,8-tetramethyl-3,4,4a,4b,5,6,6a,6b,9a,10,10a,10b,11,12-tetradecahydro-2H-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-2-one","C24H32ClFO5","[H][C@@]12C[C@H]3OC(C)(C)O[C@@]3(C(=O)CCl)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])CCC2=CC(=O)CC[C@]12C","Halcinonide is a corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses, and is distributed as a cream and ointment. Halcinonide is marketed under the brand name Halog® by Ranbaxy Laboratories Inc. Research suggests that clobetasol propionate demonstrates superior pharmacologic efficacy in the treatment of psoriasis when compared to halcinonide.","3093-35-4","454.96","Indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses.",null,"The precise mechanism of action of topical corticosteroids is unclear. However they possess anti-inflammatory, antipruritic, and vasoconstrictive actions.\r\n\r\nNew research indicates that halcinonide activates MBP (myelin basic protein) expression via smoothened receptor activation. This finding suggests that halcinonide could be used in the treatment of multiple sclerosis therapy as an alternative to Dexamethasone or Methylprednisolone.","Smoothened homolog agonist&activator","Therapeutic strategy associated"]
[1101,"DB06789","approved; investigational","small molecule","Hydroxyprogesterone caproate","17-alpha-hydroxy-progesterone caproate; 17alpha-Caproyloxypregn-4-ene-3,20-dione; 17alpha-Hydroxyprogesterone hexanoate; Hydroxyprogesterone caproate; Hydroxyprogesterone hexanoate","C27H40O4","[H][C@@]12CC[C@](OC(=O)CCCCC)(C(C)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C","Hydroxyprogesterone caproate is a synthetic steroid hormone that is similar to medroxyprogesterone acetate and megestrol acetate. It is an ester derivative of 17α-hydroxyprogesterone formed from caproic acid (hexanoic acid). Hydroxyprogesterone caproate was previously marketed under the trade name Delalutin by Squibb, which was approved by the U.S. Food and Drug Administration (FDA) in 1956 and withdrawn from marketing in 1999. The U.S. FDA approved Makena from KV Pharmaceutical (previously named as Gestiva) on February 4, 2011 for prevention of preterm delivery in women with a history of preterm delivery, sparking a pricing controversy.","630-56-8","428.6041","Hydroxyprogesterone caproate is indicated for the prevention of spontaneous preterm births in singleton pregnancies in women who have previously had a spontaneous preterm birth. (1)","No specific pharmacodynamic studies have been performed to assess hydroxyprogesterone caproate injections. (4)  However, the mechanism of action is likely related to increased interaction between progesterone and progesterone receptors.  (5)","The mechanism by which progesterone prevents preterm birth is not well understood, but many pathways are likely involved. (1)  Progesterone plays a vital role in regulation of the female reproductive system and is important for successful implantation of the embryo and maintenance of pregnancy.  It acts by binding to progesterone receptors in the uterus, ovaries, breasts and in the central nervous system.  These receptors exist in 2 isoforms, PR-A and PR-B.  Progesterone binding to these receptors ultimately leads to regulation of gene transcription. (2)  This results in an anti-inflammatory effect which blunts the proinflammatory state that occurs with initiation of labor, and maintains uterine queiscence by stabilizing progesterone acting on the myometrium. (2)","Progesterone receptor agonist","Therapeutic strategy associated"]
[1102,"DB06791","approved","small molecule","Lanreotide","Lanreotide","C54H69N11O10S2","[H]N([H])CCCCC1N([H])C(=O)C(CC2=CN([H])C3=CC=CC=C23)N([H])C(=O)C(CC2=CC=C(O)C=C2)N([H])C(=O)C(CSSCC(N([H])C(=O)C(N([H])C1=O)C(C)C)C(=O)N([H])C(C(C)O)C(=O)N([H])[H])N([H])C(=O)C(CC1=CC2=CC=CC=C2C=C1)N([H])[H]","Lanreotide is a drug employed in the management of acromegaly (a hormonal condition caused by excess growth hormone) in addition to symptoms caused by neuroendocrine tumors, especially carcinoid syndrome. This drug is a long-acting analog of the drug somatostatin, a growth hormone inhibitor. Lanreotide is manufactured by the company, _Ipsen Pharmaceuticals_ as lanreotide acetate, and marketed as _Somatuline_. It is approved in several countries worldwide, including the United Kingdom, Australia, and Canada. Lanreotide was first approved for use in the United States by the FDA on August 30, 2007.","108736-35-2","1096.33","Lanreotide is a somatostatin analog approved for treatment of neuroendocrine tumours and acromegaly.","Lanreotide exhibits antisecretory effects through cAMP suppression, and activation of ion currents such as K+ and Ca2+ which leads to hyperpolarization of the membrane and inhibition of Ca2+ mediated depolarization. \r\nFurthermore, through direct and indirect mechanisms, Lanreotide has potent antiproliferative effects.","Lanreotide is a somatostatin analogue (SSA) and has mainly inhibitory effects which are mediated via somatostatin receptors (SSTRs) 2 and 5 and include inhibition of growth hormone release in the brain.  Tumor SSTR activation induces downstream cell cycle arrest and/or apoptosis, and also results in blunted production of substances that support tumor growth as well as tumor angiogenesis.  This leads to the anti-proliferative effects of Lanreotide.","Somatostatin receptor type 2 agonist; Somatostatin receptor type 5 agonist","Therapeutic strategy associated"]
[1103,"DB06795","approved; vet_approved","small molecule","Mafenide","4-(aminomethyl)benzenesulfonamide; 4-Homosufanilamide; Bensulfamide; Mafenide; Maphenidum","C7H10N2O2S","NCC1=CC=C(C=C1)S(N)(=O)=O","Mafenide is a sulfonamide-type antimicrobial agent used to treat severe burns. It acts by reducing the bacterial population present in the burn tissue and promotes healing of deep burns.","138-39-6","186.232","Indicated for use as an adjunctive topical antimicrobial agent to control bacterial infection when used under moist dressings over meshed autografts on excised burn wounds.",null,"The precise mechanism of mafenide is unknown. However, mafenide reduces the bacterial population in the avascular burn tissue and promotes spontaneous heeling of deep burns.","Carbonic anhydrase 6 antagonist","Indication associated"]
[1104,"DB06800","approved","small molecule","Methylnaltrexone","MNTX","C21H26NO4","C[N@+]1(CC2CC2)CC[C@]23[C@H]4OC5=C(O)C=CC(C[C@@H]1[C@]2(O)CCC4=O)=C35","Methylnaltrexone is a pheriphally-acting μ-opioid antagonist that acts on the gastrointestinal tract to decrease opioid-induced constipation without producing analgesic effects or withdrawal symptoms. It is also a weak CYP2D6 inhibitor. FDA approved in 2008.","916055-93-1","356.441","Treatment of opioids induced constipation in palliative patients that are inadequately responding to laxative therapy.","Use of opioids induces slowing of gastrointestinal motility and transit. Following remifentanil administration, the methylnaltrexone and placebo groups showed no change in pupiliary constriction while the naloxone group showed a marked change over the time interval tested.","Methylnaltrexone is a pheriphally-acting μ-opioid antagonists that acts on the gastrointestinal tract inhibit opioid-induced decrease in gastric motility and transit time. Because methylnaltrexone is a quaternary derivative of naltrexone, it produces its gastrointestinal effects without producing analgesic effects or withdrawal symptoms as it does not cross the blood-brain-barrier.","Mu-type opioid receptor antagonist; Kappa-type opioid receptor antagonist","Indication associated"]
[1105,"DB06812","approved","small molecule","Povidone-iodine","Iodopovidone; Povidone iodine; Povidone-iodine; Povidone, iodinated; PVP-I",null,null,"Povidone-iodine is a stable chemical complex of polyvinylpyrrolidone (povidone, PVP) and elemental iodine. It contains from 9.0% to 12.0% available iodine, calculated on a dry basis. This unique complex was discovered in 1955 at the Industrial Toxicology Laboratories in Philadelphia by H. A. Shelanski and M. V. Shelanski. During in vitro testing to demonstrate anti-bacterial activity it was found that the complex was less toxic in mice than tincture of iodine. Human clinical trials showed the product to be superior to other iodine formulations. Povidone-iodine was immediately marketed, and has since become the universally preferred iodine antiseptic.","25655-41-8",null,"For topical application in the treatment and prevention of infection in wounds.","Povidone iodine is a kind of iodine disinfectant which directly cause in vivo protein denaturation, precipitation of bacteria, and further resulting in the death of pathogenic microorganisms. Therefore, it is effective in disinfection and sterilization. It can kill viruses, bacteria, spores, fungi, and protozoa with low toxicity to human. Povidone-iodine aqueous solution has strong pharmacological activity against Staphylococcus aureus, Neisseria gonorrhoeae, Pseudomonas aeruginosa, syphilis, hepatitis B virus, HIV, and Trichomonas vaginalis.\r\nPovidone iodine gel is a gynecological topical semi-mobile colloidal agent made by povidone iodine and hydrophilic matrix. It is a system for maintaining its sustained release. Owing to the continuous release of free iodine, it can enable the skin and mucous membranes to maintain a certain effective concentration of iodine for killing bacteria. It is mainly used for gynecological vaginal infection. It exerted its effect through being miscible with vaginal secretions and further killing the inside pathogenic microorganisms, and thus blocking the spread of sexually transmitted diseases and invasion, as well as treating other infected vaginal diseases caused by other kinds of bacteria. \r\n\r\nPublished reports on the in vitro antimicrobial efficacy of iodophors demonstrate that iodophors are bactericidal, mycobactericidal, and virucidal but can require prolonged contact times to kill certain fungi and bacterial spores. Three brands of povidone-iodine solution have demonstrated more rapid kill (seconds to minutes) of S. aureus and M. chelonae at a 1:100 dilution than did the stock solution. The virucidal activity of 75–150 ppm available iodine was demonstrated against seven viruses. Other investigators have questioned the efficacy of iodophors against poliovirus in the presence of organic matter and rotavirus in distilled or tapwater. Manufacturers' data demonstrate that commercial iodophors are not sporicidal, but they are tuberculocidal, fungicidal, virucidal, and bactericidal at their recommended use-dilution.","Povidone-iodine is called iodophore which means povidone acts as a carrier of iodine. Iodine is considered as the active moiety that mediates microbicidal actions. When released from the complex, free iodine (I2) penetrates the cell wall of microorganisms quickly, and the lethal effects are believed to result from disruption of protein and nucleic acid structure and synthesis. While the full mechanism of action is not fully elucidated, iodine is thought to inhibit vital bacterial cellular mechanisms and structures, and oxidizes nucleotides fatty or amino acids in bacterial cell membranes . Additionally, free iodine disrupts the function of the cytosolic enzymes involved in the respiratory chain, causing them to become denatured and deactivated . _In vitro_ evidence suggests that iodine also counteracts inflammation elicited by both pathogens and the host response via multifactorial effects. In hosts, povidone-iodine was demonstrated to modulate the redox potential, inhibit the release of inflammatory mediators such as TNF-α and β-galactosidase, inhibit metalloproteinase production, and potentiate the healing signals from pro-inflammatory cytokines by activation of monocytes, T-lymphocytes, and macrophages, _in vitro_ .",null,"Therapeutic strategy associated"]
[1106,"DB06813","approved; investigational","small molecule","Pralatrexate","(2S)-2-((4-((1RS)-1-((2,4-Diaminopteridin-6-yl)methyl)but-3-ynyl)benzoyl)amino)pentanedioic acid; (2S)-2-({4-[1-(2,4-diaminopteridin-6-yl)pent-4-yn-2-yl]benzoyl}amino)pentanedioic acid; 10-Propargyl-10-deazaaminopterin; N-(4-(1-((2,4-Diamino-6-pteridinyl)methyl)-3-butynyl)benzoyl)-L-glutamic acid; PDX","C23H23N7O5","NC1=NC2=NC=C(CC(CC#C)C3=CC=C(C=C3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)N=C2C(N)=N1","Pralatrexate is an antimetabolite for the treatment of relapsed or refractory peripheral T-cell lymphoma. It is more efficiently retained in cancer cells than methotrexate. FDA approved on September 24, 2009.","146464-95-1","477.4726","Treatment of relapsed or refractory peripheral T-cell lymphoma.","Pralatrexate is a 10-deazaaminopterin analogue of methotrexate. Compared to methotrexate, pralatrexate binds to RTC-1 with 10-times the affinity and is a more potent substrate for FPGS. As a result, pralatrexate is better internalized and retained in cancer cells and is more cytotoxic. \r\nKm, pralatrexate = 0.3 μmol/L;\r\nKm, methotrexate = 4.8 μmol/L;\r\nVmax/Km (rate of intracellular transport), pralatrexate = 12.6 \r\nVmax/Km (rate of intracellular transport), methotrexate = 0.9","The selectivity of pralatrexate for cancer cells is based upon the observation that cancer cells generally have an overexpression of reduced folate carrier protein-1 (RTC-1) compared to normal somatic cells. This carrier protein allows the entrance of pralatrexate into the cell. Upon entering the cell, folypolyglutamate synthase FPGS catalyzes the polyglutamination of pralatrexate so that it is retained inside the cell.  \r\nOnce inside, pralatrexate competitively inhibits dihydrofolate reductase (DHFR) and thymidylate synthase. Subsequent depletion of thymidine monophosphate (TMP) occurs so that the cancer cell is unable to synthesize DNA and RNA. As a result, the cancer cell cannot proliferate and is forced to undergo apoptosis. Pralatrexate is more effective against cells that are actively dividing.","Dihydrofolate reductase inhibitor; Thymidylate synthase inhibitor","Therapeutic strategy associated"]
[1107,"DB06824","approved; investigational","small molecule","Triethylenetetramine","TETA; Trien; Trientine","C6H18N4","NCCNCCNCCN","Triethylenetatramine (TETA) is a highly selective divalent Cu(II) chelator and orphan drug that revereses copper overload in tissues. Its salt form, trientine (triethylenetetramine dihydrochloride or 2,2,2-tetramine) was introduced in 1969 as an alternative to D-penicillamine. It consists of a polyamine-like structure different from D-penicillamine, as it lack sulfhydryl groups. It was previously approved by FDA in 1985 as second-line pharmacotherapy for Wilson's disease. Although penicillamine treatment is believed to be more extensive, TETA therapy has been shown to be an effective initial therapy, even with patients with decompensated liver disease at the outset, and prolonged TETA treatment is not associated with adverse effects as expected in penicillamine treatment. Its clinical applications on cancer, diabetes mellitus, Alzheimer's disease and vascular demetia are being studied.","112-24-3","146.2339","Trientine is a copper chelator used in the treatment of Wilson's disease as an alternative to D-penicillamine. It tends to be used in patients who are experiencing serious adverse effects from penicillamine therapy or intolerance of penicillamine.","TETA is a selective copper (II) chelator. tightly binds and facilitates systemic elimination of Cu(II) into the urine whilst neutralizing its catalytic activity, but does not cause systemic copper deficiency even after prolonged use. It may also act as an antioxidant as it suppresses the copper-mediated oxidative stress. TETA not only increases urinary Cu excretion, but also decreases intestinal copper absorption by 80%.","Copper is chelated by forming a stable complex with the four constituent nitrogens in a planar ring as copper displays enhanced ligand binding properties for nitrogen compared to oxygen. It binds Cu(II) very tightly, having a dissociation constant from Cu(II) of 10^−15 mol/L at pH 7.0 . TETA reacts in a stoichiometric ratio 1:1 with copper and is also able to complex with iron and zinc in vivo. TETA is considered a potential chemotherapeutic agent as it could be a telomerase inhibitor because it is a ligand for G-quadruplex, and stabilizes both intra- and intermolecular G-quadruplexes. It may mediate a selective inhibitory effect or cytotoxicity on tumor growth. Chelating excess copper may affect copper-induced angiogenesis. Other mechanisms of action of TETA for alternative therapeutic implications include improved antioxidant defense against oxidative stress, pro-apoptosis, and reduced inflammation.",null,"Therapeutic strategy associated"]
[1108,"DB06826","approved; investigational","small molecule","Unoprostone","13,14-dihydro-15-keto-20-ethyl PGF2α; Unoprostone","C22H38O5","CCCCCCCC(=O)CC[C@H]1[C@H](O)C[C@H](O)[C@@H]1C\\C=C/CCCC(O)=O","Unoprostone isopropyl is a prostaglandin analogue. Ophthalmic Solution 0.15% is a synthetic docosanoid. Unoprostone isopropyl has the chemical name isopropyl (+)-(Z)-7--5-heptenoate.\r\nThe main indication of Unoprostane is treatment of glucoma.","120373-36-6","382.541","For the lowering of intraocular pressure in patients with open-angle glaucoma or ocular hypertension who are intolerant of other intraocular pressure lowering medications or insufficiently responsive (failed to achieve target IOP determined after multiple measurements over time) to another intraocular pressure lowering medication.","Unoprostone will begin to reduce IOP 30 minutes after ocular instillation.","Unoprostone  is believed to reduce elevated intraocular pressure (IOP), by increasing the outflow of aqueous humor. The mechanism of action for the IOP-lowering effect of unoprostone is controversial. Early studies showed that unoprostone increases aqueous humor outflow through the uveoscleral pathway similar to the 20-carbon prostaglandin analogs, such as latanoprost.8 More recent evidence, however, shows that it may work, at least in part, through stimulation of Ca2+-activated BK and CIC-2 type channels, leading to increased trabecular meshwork outflow.",null,"Indication associated"]
[1109,"DB06862","experimental","small molecule","2-HYDROXY-5-(2-MERCAPTO-ETHYLSULFAMOYL)-BENZOIC ACID",null,"C9H11NO5S2","OC(=O)C1=C(O)C=CC(=C1)S(=O)(=O)NCCS",null,null,"277.317",{"$nulls":3},"Caspase-3","Target associated"]
[1110,"DB06908","experimental","small molecule","(2S)-3-(1-{[2-(2-CHLOROPHENYL)-5-METHYL-1,3-OXAZOL-4-YL]METHYL}-1H-INDOL-5-YL)-2-ETHOXYPROPANOIC ACID",null,"C24H23ClN2O4","[H][C@@](CC1=CC2=C(C=C1)N(CC1=C(C)OC(=N1)C1=C(Cl)C=CC=C1)C=C2)(OCC)C(O)=O",null,null,"438.903",{"$nulls":3},"Nuclear receptor coactivator 1; Peroxisome proliferator-activated receptor gamma","Target associated"]
[1111,"DB06926","experimental","small molecule","(9Z,11E,13S)-13-hydroxyoctadeca-9,11-dienoic acid",null,"C18H32O3","[H][C@](O)(CCCCC)\\C=C\\C=C/CCCCCCCC(O)=O",null,null,"296.4449",{"$nulls":3},"Peroxisome proliferator-activated receptor gamma","Target associated"]
[1112,"DB07053","experimental","small molecule","2-{5-[3-(7-PROPYL-3-TRIFLUOROMETHYLBENZO[D]ISOXAZOL-6-YLOXY)PROPOXY]INDOL-1-YL}ETHANOIC ACID",null,"C24H23F3N2O5","CCCC1=C2ON=C(C2=CC=C1OCCCOC1=CC2=C(C=C1)N(CC(O)=O)C=C2)C(F)(F)F",null,null,"476.445",{"$nulls":3},"Peroxisome proliferator-activated receptor gamma","Target associated"]
[1113,"DB07070","experimental","small molecule","(2S)-2-{3-[({[2-fluoro-4-(trifluoromethyl)phenyl]carbonyl}amino)methyl]-4-methoxybenzyl}butanoic acid",null,"C21H21F4NO4","[H][C@](CC)(CC1=CC(CNC(=O)C2=C(F)C=C(C=C2)C(F)(F)F)=C(OC)C=C1)C(O)=O",null,null,"427.3894",{"$nulls":3},"Peroxisome proliferator-activated receptor delta","Target associated"]
[1114,"DB07111","experimental","small molecule","(4S,5E,7Z,10Z,13Z,16Z,19Z)-4-hydroxydocosa-5,7,10,13,16,19-hexaenoic acid",null,"C22H32O3","[H][C@](O)(CCC(O)=O)\\C=C\\C=C/C\\C=C/C\\C=C/C\\C=C/C\\C=C/CC",null,null,"344.4877",{"$nulls":3},"Peroxisome proliferator-activated receptor gamma","Target associated"]
[1115,"DB07172","experimental","small molecule","(5R,6E,8Z,11Z,14Z,17Z)-5-hydroxyicosa-6,8,11,14,17-pentaenoic acid",null,"C20H30O3","[H][C@@](O)(CCCC(O)=O)\\C=C\\C=C/C\\C=C/C\\C=C/C\\C=C/CC",null,null,"318.4504",{"$nulls":3},"Peroxisome proliferator-activated receptor gamma","Target associated"]
[1116,"DB07208","experimental","small molecule","(8E,10S,12Z)-10-hydroxy-6-oxooctadeca-8,12-dienoic acid",null,"C18H30O4","[H][C@](O)(C\\C=C/CCCCC)\\C=C\\CC(=O)CCCCC(O)=O",null,null,"310.4284",{"$nulls":3},"Peroxisome proliferator-activated receptor gamma","Target associated"]
[1117,"DB07209","experimental","small molecule","(8R,9Z,12Z)-8-hydroxy-6-oxooctadeca-9,12-dienoic acid",null,"C18H30O4","[H][C@@](O)(CC(=O)CCCCC(O)=O)\\C=C/C\\C=C/CCCCC",null,null,"310.4284",{"$nulls":3},"Peroxisome proliferator-activated receptor gamma","Target associated"]
[1118,"DB07215","investigational","small molecule","GW-590735",null,"C23H21F3N2O4S","CC1=C(SC(=N1)C1=CC=C(C=C1)C(F)(F)F)C(=O)NCC1=CC=C(OC(C)(C)C(O)=O)C=C1",null,"343321-96-0","478.484",{"$nulls":3},"Nuclear receptor coactivator 1; Peroxisome proliferator-activated receptor alpha","Target associated"]
[1119,"DB07302","experimental","small molecule","9(S)-HODE","(9S,10E,12Z)-9-hydroxyoctadeca-10,12-dienoic acid; 9S-Hode; alpha-Dimorphecolic acid","C18H32O3","CCCCC\\C=C/C=C/[C@@H](O)CCCCCCCC(O)=O",null,"73543-67-6","296.4449",{"$nulls":3},"Peroxisome proliferator-activated receptor gamma","Target associated"]
[1120,"DB07425","investigational","small molecule","Sobetirome","Sobetirome","C20H24O4","CC(C)C1=C(O)C=CC(CC2=C(C)C=C(OCC(O)=O)C=C2C)=C1",null,"211110-63-3","328.4022",{"$nulls":3},"Thyroid hormone receptor, alpha isoform 1 variant; Thyroid hormone receptor beta","Target associated"]
[1121,"DB07509","experimental","small molecule","difluoro(5-{2-[(5-octyl-1H-pyrrol-2-yl-kappaN)methylidene]-2H-pyrrol-5-yl-kappaN}pentanoato)boron",null,"C22H31BF2N2O2","CCCCCCCCC1=CC=C2C=C3C=CC(CCCCC(O)=O)=[N+]3[B-](F)(F)N12",null,null,"404.302",{"$nulls":3},"Peroxisome proliferator-activated receptor gamma","Target associated"]
[1122,"DB07565","approved","small molecule","Chloramphenicol succinate","Chloramphenicol hemisuccinate","C15H16Cl2N2O8","O[C@@H]([C@@H](COC(=O)CCC(O)=O)NC(=O)C(Cl)Cl)C1=CC=C(C=C1)[N+]([O-])=O","Chloramphenicol succinate is an ester prodrug of . Chloramphenicol is a bacteriostatic antibiotic. Use of chloramphenicol succinate and chloramphenicol has decreased due to the risk of potentially fatal blood dyscrasias.\r\n\r\nChloramphenicol succinate was granted FDA approval on 20 February 1959.","3544-94-3","423.202","Chloramphenicol succinate is indicated to treat serious and susceptible bacterial infections where less dangerous drugs are ineffective or contraindicated.","Chloramphenicol succinate is a prodrug of chloramphenicol, which binds to bacterial ribosomes and prevents translation. It has a narrow therapeutic index and a moderate duration of action. Patients should be counselled regarding the risk of serious fatal blood dyscrasias.","Chloramphenicol succinate is hydrolyzed into the active chloramphenicol. Chloramphenicol resembles uridine-5'-phosphate. It binds to the residues A2451 and A2452 in the 23S rRNA of the 50S ribosomal subunit of _E. coli_, which prevents translation.","Dr hemagglutinin structural subunit inhibitor","Indication associated"]
[1123,"DB07675","experimental","small molecule","(2S)-2-ETHOXY-3-{4-[2-(10H-PHENOXAZIN-10-YL)ETHOXY]PHENYL}PROPANOIC ACID",null,"C25H25NO5","[H][C@@](CC1=CC=C(OCCN2C3=C(OC4=C2C=CC=C4)C=CC=C3)C=C1)(OCC)C(O)=O",null,null,"419.4697",{"$nulls":3},"Peroxisome proliferator-activated receptor gamma","Target associated"]
[1124,"DB07691","experimental","small molecule","2-({[3-(3,4-dihydroisoquinolin-2(1H)-ylsulfonyl)phenyl]carbonyl}amino)benzoic acid",null,"C23H20N2O5S","OC(=O)C1=C(NC(=O)C2=CC=CC(=C2)S(=O)(=O)N2CCC3=CC=CC=C3C2)C=CC=C1",null,null,"436.48",{"$nulls":3},"Peroxisome proliferator-activated receptor delta","Target associated"]
[1125,"DB07696","experimental","small molecule","methyl (3S)-3-[(tert-butoxycarbonyl)amino]-4-oxopentanoate",null,"C11H19NO5","[H][C@@](CC(=O)OC)(NC(=O)OC(C)(C)C)C(C)=O",null,null,"245.2723",{"$nulls":3},"Caspase-3","Target associated"]
[1126,"DB07723","experimental","small molecule","3-(5-methoxy-1H-indol-3-yl)propanoic acid",null,"C12H13NO3","COC1=CC=C2NC=C(CCC(O)=O)C2=C1",null,null,"219.2365",{"$nulls":3},"Peroxisome proliferator-activated receptor gamma","Target associated"]
[1127,"DB07724","experimental","small molecule","Indeglitazar","Indeglitazar","C19H19NO6S","COC1=CC=C(C=C1)S(=O)(=O)N1C=C(CCC(O)=O)C2=CC(OC)=CC=C12",null,"835619-41-5","389.422",{"$nulls":3},"Nuclear receptor coactivator 1; Peroxisome proliferator-activated receptor alpha; Peroxisome proliferator-activated receptor delta; Peroxisome proliferator-activated receptor gamma","Target associated"]
[1128,"DB07733","experimental","small molecule","1-METHYL-3-TRIFLUOROMETHYL-1H-THIENO[2,3-C]PYRAZOLE-5-CARBOXYLIC ACID (2-MERCAPTO-ETHYL)-AMIDE",null,"C10H10F3N3OS2","CN1N=C(C2=C1SC(=C2)C(=O)NCCS)C(F)(F)F",null,null,"309.331",{"$nulls":3},"Caspase-1","Target associated"]
[1129,"DB07744","experimental","small molecule","Z-Val-Ala-Asp fluoromethyl ketone","N-[(Benzyloxy)carbonyl]-L-valyl-N-[(2S)-1-carboxy-4-fluoro-3-oxo-2-butanyl]-L-alaninamide; Z-VAD-FMK","C21H28FN3O7","CC(C)[C@H](NC(=O)OCC1=CC=CC=C1)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)CF","Non-methylated, competitive, and irreversible inhibitor of caspase 1, as well as other caspases,1 which can be used directly with purified enzymes. It does not require an esterase to hydrolyze the O-methyl ester like the cell-permeable form, Z-Val-Ala-Asp(O-Me) fluoromethyl ketone.","161401-82-7","453.467",{"$nulls":3},"Caspase-1","Target associated"]
[1130,"DB07842","experimental","small molecule","(2S)-2-(4-ethylphenoxy)-3-phenylpropanoic acid",null,"C17H18O3","[H][C@@](CC1=CC=CC=C1)(OC1=CC=C(CC)C=C1)C(O)=O",null,null,"270.323",{"$nulls":3},"Peroxisome proliferator-activated receptor gamma","Target associated"]
[1131,"DB07863","experimental","small molecule","2-chloro-5-nitro-N-phenylbenzamide",null,"C13H9ClN2O3","[O-][N+](=O)C1=CC=C(Cl)C(=C1)C(=O)NC1=CC=CC=C1",null,null,"276.675",{"$nulls":3},"Nuclear receptor coactivator 2; Peroxisome proliferator-activated receptor gamma; Retinoic acid receptor RXR-alpha","Target associated"]
[1132,"DB07870","experimental","small molecule","Haloxyfop-P","(+)-haloxyfop; (R)-haloxyfop; (R)-haloxyfop-acid; R-haloxyfop-acid","C15H11ClF3NO4","C[C@@H](OC1=CC=C(OC2=C(Cl)C=C(C=N2)C(F)(F)F)C=C1)C(O)=O",null,"95977-29-0","361.7",{"$nulls":3},"Acetyl-CoA carboxylase 2","Target associated"]
[1133,"DB07916","experimental","small molecule","3-{6-[(8-HYDROXY-QUINOLINE-2-CARBONYL)-AMINO]-2-THIOPHEN-2-YL-HEXANOYLAMINO}-4-OXO-BUTYRI ACID",null,"C24H25N3O6S","[H][C@@](CC(O)=O)(NC(=O)[C@@]([H])(CCCCNC(=O)C1=NC2=C(C=CC=C2O)C=C1)C1=CC=CS1)C=O",null,null,"483.537",{"$nulls":3},"Caspase-1","Target associated"]
[1134,"DB08078","experimental","small molecule","{4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy]phenoxy}acetic acid",null,"C22H26O7","CCCC1=C(OCCCOC2=CC=C(OCC(O)=O)C=C2)C=CC(C(C)=O)=C1O",null,null,"402.4376",{"$nulls":3},"Peroxisome proliferator-activated receptor delta","Target associated"]
[1135,"DB08085","experimental","small molecule","1-(4-HEXYLPHENYL)PROP-2-EN-1-ONE",null,"C15H20O","CCCCCCC1=CC=C(C=C1)C(=O)C=C",null,null,"216.3187",{"$nulls":3},"Thyroid hormone receptor beta","Target associated"]
[1136,"DB08121","experimental","small molecule","(2S)-2-(biphenyl-4-yloxy)-3-phenylpropanoic acid",null,"C21H18O3","[H][C@@](CC1=CC=CC=C1)(OC1=CC=C(C=C1)C1=CC=CC=C1)C(O)=O",null,null,"318.3658",{"$nulls":3},"Peroxisome proliferator-activated receptor gamma","Target associated"]
[1137,"DB08213","experimental","small molecule","1-METHYL-5-(2-PHENOXYMETHYL-PYRROLIDINE-1-SULFONYL)-1H-INDOLE-2,3-DIONE",null,"C20H20N2O5S","[H][C@@]1(COC2=CC=CC=C2)CCCN1S(=O)(=O)C1=CC2=C(C=C1)N(C)C(=O)C2=O",null,null,"400.448",{"$nulls":3},"Caspase-3","Target associated"]
[1138,"DB08220","experimental","small molecule","(8alpha,10alpha,13alpha,17beta)-17-[(4-hydroxyphenyl)carbonyl]androsta-3,5-diene-3-carboxylic acid",null,"C27H32O4","[H][C@@]1(CC[C@@]2([H])[C@]3([H])CC=C4C=C(CC[C@]4(C)[C@@]3([H])CC[C@]12C)C(O)=O)C(=O)C1=CC=C(O)C=C1",null,null,"420.5406",{"$nulls":3},"Nuclear receptor coactivator 1; Bile acid receptor","Target associated"]
[1139,"DB08229","experimental","small molecule","[N-(3-dibenzylcarbamoyl-oxiranecarbonyl)-hydrazino]-acetic acid",null,"C20H23N3O5","[H]N([H])N(CC(O)=O)C(=O)CC([H])(O)C(=O)N(CC1=CC=CC=C1)CC1=CC=CC=C1",null,null,"385.4137",{"$nulls":3},"Caspase-3","Target associated"]
[1140,"DB08231","experimental","small molecule","Myristic acid","1-tridecanecarboxylic acid; N-tetradecan-1-oic acid; N-tetradecanoic acid; Tetradecanoic acid","C14H28O2","CCCCCCCCCCCCCC(O)=O",null,"544-63-8","228.3709",{"$nulls":3},"Genome polyprotein; Genome polyprotein; Genome polyprotein; Genome polyprotein; cAMP-dependent protein kinase inhibitor alpha; cAMP-dependent protein kinase catalytic subunit alpha; Genome polyprotein; Genome polyprotein; Genome polyprotein; Genome polyprotein; Genome polyprotein; Fatty acid metabolism regulator protein; Enoyl-CoA delta isomerase 2, mitochondrial; Recoverin; Calmodulin; Non-fluorescent flavoprotein; Genome polyprotein; Tyrosine-protein kinase ABL1; UDP-3-O-[3-hydroxymyristoyl] N-acetylglucosamine deacetylase; Genome polyprotein; Hepatocyte nuclear factor 4-alpha; Nuclear receptor coactivator 1; Protein Nef; Ferrichrome-iron receptor; Peptidyl-prolyl cis-trans isomerase FKBP1A; Calcineurin subunit B type 1; Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform; Alpha-pyrone synthesis polyketide synthase-like Pks18; Gag-Pol polyprotein; Trafficking protein particle complex subunit 3; Insulin; Genome polyprotein; Polyprotein; Ganglioside GM2 activator; ADP-ribosylation factor 6; Lymphocyte antigen 96; Protein TonB; Gag polyprotein; Gag-Pol polyprotein; ADP-ribosylation factor 1; Guanylyl cyclase-activating protein 1; R2-like ligand binding oxidase; Poliovirus receptor; Toll-like receptor 4; Peroxisome proliferator-activated receptor alpha","Target associated"]
[1141,"DB08251","experimental","small molecule","4-[5-(2-CARBOXY-1-FORMYL-ETHYLCARBAMOYL)-PYRIDIN-3-YL]-BENZOIC ACID",null,"C17H14N2O6","[H][C@@](CC(O)=O)(NC(=O)C1=CN=CC(=C1)C1=CC=C(C=C1)C(O)=O)C=O",null,null,"342.3029",{"$nulls":3},"Caspase-3","Target associated"]
[1142,"DB08302","experimental","small molecule","3-[5-(2-nitropent-1-en-1-yl)furan-2-yl]benzoic acid",null,"C16H15NO5","CCC\\C(=C\\C1=CC=C(O1)C1=CC(=CC=C1)C(O)=O)[N+]([O-])=O",null,null,"301.294",{"$nulls":3},"Peroxisome proliferator-activated receptor gamma","Target associated"]
[1143,"DB08402","experimental","small molecule","2-[(2,4-DICHLOROBENZOYL)AMINO]-5-(PYRIMIDIN-2-YLOXY)BENZOIC ACID",null,"C18H11Cl2N3O4","OC(=O)C1=C(NC(=O)C2=C(Cl)C=C(Cl)C=C2)C=CC(OC2=NC=CC=N2)=C1",null,null,"404.204",{"$nulls":3},"Peroxisome proliferator-activated receptor gamma; Nuclear receptor coactivator 2; Retinoic acid receptor RXR-alpha","Target associated"]
[1144,"DB08435","experimental","small molecule","(5E,14E)-11-oxoprosta-5,9,12,14-tetraen-1-oic acid",null,"C20H28O3","[H][C@]1(C\\C=C\\CCCC(O)=O)C=CC(=O)\\C1=C/C=C/CCCCC",null,null,"316.4345",{"$nulls":3},"Peroxisome proliferator-activated receptor gamma","Target associated"]
[1145,"DB08497","experimental","small molecule","(1S)-2-oxo-1-phenyl-2-[(1,3,4-trioxo-1,2,3,4-tetrahydroisoquinolin-5-yl)amino]ethyl acetate",null,"C19H14N2O6","[H][C@@](OC(C)=O)(C(=O)NC1=CC=CC2=C1C(=O)C(=O)NC2=O)C1=CC=CC=C1",null,null,"366.3243",{"$nulls":3},"Caspase-3","Target associated"]
[1146,"DB08498","experimental","small molecule","(1S)-1-(3-chlorophenyl)-2-oxo-2-[(1,3,4-trioxo-1,2,3,4-tetrahydroisoquinolin-5-yl)amino]ethyl acetate",null,"C19H13ClN2O6","[H][C@@](OC(C)=O)(C(=O)NC1=CC=CC2=C1C(=O)C(=O)NC2=O)C1=CC=CC(Cl)=C1",null,null,"400.769",{"$nulls":3},"Caspase-3","Target associated"]
[1147,"DB08499","experimental","small molecule","N-[3-(2-fluoroethoxy)phenyl]-N'-(1,3,4-trioxo-1,2,3,4-tetrahydroisoquinolin-6-yl)butanediamide",null,"C21H18FN3O6","FCCOC1=CC=CC(NC(=O)CCC(=O)NC2=CC=C3C(=O)NC(=O)C(=O)C3=C2)=C1",null,null,"427.3825",{"$nulls":3},"Caspase-3","Target associated"]
[1148,"DB08560","experimental","small molecule","3-FLUORO-N-[1-(4-FLUOROPHENYL)-3-(2-THIENYL)-1H-PYRAZOL-5-YL]BENZENESULFONAMIDE",null,"C19H13F2N3O2S2","FC1=CC=C(C=C1)N1N=C(C=C1NS(=O)(=O)C1=CC=CC(F)=C1)C1=CC=CS1",null,null,"417.452",{"$nulls":3},"Peroxisome proliferator-activated receptor gamma","Target associated"]
[1149,"DB08604","approved; investigational","small molecule","Triclosan","2,4,4'-Trichloro-2'-hydroxydiphenyl ether; 5-Chloro-2-(2,4-dichloro-phenoxy)-phenol; Triclosan","C12H7Cl3O2","OC1=CC(Cl)=CC=C1OC1=C(Cl)C=C(Cl)C=C1","An aromatic ether that is phenol which is substituted at C-5 by a chloro group and at C-2 by a 2,4-dichlorophenoxy group. It is widely used as a preservative and antimicrobial agent in personal care products such as soaps, skin creams, toothpaste and deodorants as well as in household items such as plastic chopping boards, sports equipment and shoes.","3380-34-5","289.542","Triclosan is used in a variety of common household products, including soaps, mouthwashes, dish detergents, toothpastes, deodorants, and hand sanitizers.  It is also used in health care settings in surgical scrubs and personnel hand washes.",null,"Triclosan is a biocidal compound with multiple targets in the cytoplasm and membrane. At lower concentrations, however, triclosan appears bacteriostatic and is seen to target bacteria mainly by inhibiting fatty acid synthesis. Triclosan binds to enoyl-acyl carrier protein reductase enzyme (ENR). This complex has increased affinity for NAD+ and forms a ternary complex. This complex is unable to participate in fatty acid synthesis, weakening the cell membrane and causing cell death. Humans do not have an ENR enzyme, and thus are not affected.","Enoyl-[acyl-carrier-protein] reductase [NADH] FabI; Enoyl-[acyl-carrier-protein] reductase [NADH]; Enoyl-[acyl-carrier-protein] reductase [NADH] FabI; Enoyl-[acyl-carrier-protein] reductase [NADH]; Enoyl-[acyl-carrier-protein] reductase [NADPH] FabI; Nuclear receptor subfamily 1 group I member 2; Androgen receptor; Nuclear receptor subfamily 1 group I member 3 inverse agonist; Peroxisome proliferator-activated receptor gamma; Thyroid peroxidase weak inhibitor","Target associated"]
[1150,"DB08760","experimental","small molecule","(2S)-2-(4-chlorophenoxy)-3-phenylpropanoic acid",null,"C15H13ClO3","[H][C@@](CC1=CC=CC=C1)(OC1=CC=C(Cl)C=C1)C(O)=O",null,null,"276.715",{"$nulls":3},"Peroxisome proliferator-activated receptor gamma","Target associated"]
[1151,"DB08798","experimental","small molecule","Sulfamoxole","2-(p-Aminobenzenesulfonamido)-4,5-dimethyloxazole; 4-Amino-N-(4,5-dimethyl-2-oxazolyl)benzenesulfonamide; 4,5-Dimethyl-2-sulfanilamidooxazole; N(sup 1)-(4,5-Dimethyl-2-oxazolyl)sulfanilamide; N1-(4,5-Dimethyl-2-oxazolyl)sulfanilamide; Oxasulfa; p-Aminobenzenesulfonyl-2-amino-4,5-dimethyloxazole; Sulfadimethyloxazole; Sulfamoxole; Sulphamoxole","C11H13N3O3S","CC1=C(C)N=C(NS(=O)(=O)C2=CC=C(N)C=C2)O1","Sulfamoxole is an antibacterial in the sulfonamide class.","729-99-7","267.304","For the treatment of bacterial infection.","Sulfamoxole is a sulfonamide antibiotic. The sulfonamides are synthetic bacteriostatic antibiotics with a wide spectrum against most gram-positive and many gram-negative organisms. However, many strains of an individual species may be resistant. Sulfonamides inhibit multiplication of bacteria by acting as competitive inhibitors of <i>p</i>-aminobenzoic acid in the folic acid metabolism cycle. Bacterial sensitivity is the same for the various sulfonamides, and resistance to one sulfonamide indicates resistance to all. Most sulfonamides are readily absorbed orally. However, parenteral administration is difficult, since the soluble sulfonamide salts are highly alkaline and irritating to the tissues. The sulfonamides are widely distributed throughout all tissues. High levels are achieved in pleural, peritoneal, synovial, and ocular fluids. Although these drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections. Their antibacterial action is inhibited by pus.","Sulfamoxole is a competitive inhibitor of the bacterial enzyme dihydropteroate synthetase. This enzyme is needed for the proper processing of para-aminobenzoic acid (PABA) which is essential for folic acid synthesis. The inhibited reaction is necessary in these organisms for the synthesis of folic acid.","Dihydropteroate synthetase inhibitor","Indication associated"]
[1152,"DB08804","approved; illicit","small molecule","Nandrolone decanoate","19-nortestosterone decanoate; Nandrolone 17β-decanoate; Nandrolone decanoate","C28H44O3","[H][C@@]12CC[C@H](OC(=O)CCCCCCCCC)[C@@]1(C)CC[C@]1([H])[C@@]3([H])CCC(=O)C=C3CC[C@@]21[H]","Nandrolone decanoate, also known as nandrolone caprinate, is an alkylated anabolic steroid indicated in the management of anemia of renal insufficiency and as an adjunct therapy in the treatment of senile and postmenopausal osteoporosis. The process for creating esters of  was patented in Spain in 1959 and in 1960, it was described as having a long duration of action and strong anabolic effect compared to nandrolone and other esters.\r\n\r\nNandrolone decanoate was granted FDA approval on 5 October 1962.","360-70-3","428.6472","Nandrolone decanoate is indicated in the management of anemia of renal insufficiency. In Canada, it is also indicated as an adjunct therapy in the treatment of senile and postmenopausal osteoporosis.","Nandrolone decanoate is an alkylated anabolic steroid indicated in the management of anemia of renal insufficiency and as an adjunct therapy in the treatment of senile and postmenopausal osteoporosis. It has a long duration of action as it is given every 3-4 weeks, and a wide therapeutic window as acute overdoses are rare. Patients should be counselled regarding the risks of giving this drug to patients with cardiac, renal, or hepatic diseases.","Nandrolone decanoate is hydrolyzed to , possibly by PDE7B. Nandrolone is brought into cells by receptor mediated endocytosis, where it interacts with the androgen receptor. After binding to the androgen receptor, a conformational change occurs, the androgen receptor enters the nucleus, dimerizes, and can then bind to segments of DNA to regulate transcription. Androgens can also regulate transcription through activation of ERK, Akt, and MAPK; or binding to and competitively inhibiting transcription factors.","Androgen receptor agonist; Proto-oncogene c-Fos inducer; 5-hydroxytryptamine 2 receptor modulator; 5-hydroxytryptamine receptor 1B modulator; Insulin-like growth factor 1 receptor inducer; Dopamine receptor modulator","Indication associated"]
[1153,"DB08807","experimental","small molecule","Bopindolol","Bopindolol","C23H28N2O3","CC1=CC2=C(N1)C=CC=C2OCC(CNC(C)(C)C)OC(=O)C1=CC=CC=C1","Bopindolol (INN) is an ester prodrug for the beta blocker .","62658-63-3","380.48","For the management of hypertension, edema, ventricular tachycardias, and atrial fibrillation.","Bopindolol is a prodrug of pindolol. Pindolol is a non-selective beta-adrenergic antagonist (beta-blocker) which possesses intrinsic sympathomimetic activity (ISA) in therapeutic dosage ranges but does not possess quinidine-like membrane stabilizing activity. Pindolol impairs AV node conduction and decreases sinus rate and may also increase plasma triglycerides and decrease HDL-cholesterol levels. Pindolol is nonpolar and hydrophobic, with low to moderate lipid solubility. Pindolol has little to no intrinsic sympathomimetic activity and, unlike some other beta-adrenergic blocking agents, pindolol has little direct myocardial depressant activity and does not have an anesthetic-like membrane-stabilizing action.","Bopindolol (as pindolol) non-selectively blocks beta-1 adrenergic receptors mainly in the heart, inhibiting the effects of epinephrine and norepinephrine resulting in a decrease in heart rate and blood pressure. By binding beta-2 receptors in the juxtaglomerular apparatus, Pindolol inhibits the production of renin, thereby inhibiting angiotensin II and aldosterone production and therefore inhibits the vasoconstriction and water retention due to angiotensin II and aldosterone, respectively.","Beta-1 adrenergic receptor partial agonist; Beta-2 adrenergic receptor partial agonist; 5-hydroxytryptamine receptor 1A; 5-hydroxytryptamine receptor 1B; Beta-3 adrenergic receptor","Indication associated"]
[1154,"DB08808","experimental","small molecule","Bupranolol","Bupranolol","C14H22ClNO2","CC1=CC(OCC(O)CNC(C)(C)C)=C(Cl)C=C1","Bupranolol is a non-selective beta blocker with potency similar to . It does not have intrinsic sympathomimetic activity (ISA), but does have strong membrane stabilizing activity.","14556-46-8","271.783","Used to manage hypertension and tachycardia. Also used to treat glaucoma.","Bupranolol is a competitive, nonselective beta-blocker similar to propanolol without intrinsic sympathomimetic activity.","Bupranolol competes with sympathomimetic neurotransmitters such as catecholamines for binding at beta(1)-adrenergic receptors in the heart, inhibiting sympathetic stimulation. This results in a reduction in resting heart rate, cardiac output, systolic and diastolic blood pressure, and reflex orthostatic hypotension.","Beta-1 adrenergic receptor antagonist; Beta-2 adrenergic receptor antagonist; Beta-3 adrenergic receptor antagonist","Indication associated"]
[1155,"DB08813","approved; investigational","small molecule","Nadroparin","Nadroparine",null,null,"Nadroparin is a low molecular weight heparin (LMWH) which, when bound to antithrombin III (ATIII), accelerates the inactivation of factor II and factor Xa. Nadroparin halts the coagulation pathway by inhibiting the activation of thrombin (factor IIa) by factor Xa. The amplification of the fibrin clotting cascade is stopped once factors Xa and IIa are inactivated. It is derived from porcine sources and has a mean molecular size of 5000 daltons. Low molecular weight heparins are less effective at inactivating factor IIa due to their shorter length compared to unfractionated heparin.",null,null,"Nadroparin is used for prophylaxis of thromboembolic disorders and general surgery in orthopedic surgery, treatment of deep vein thrombosis, prevention of clotting during hemodialysis and treatment of unstable angina and non-Q wave myocardial infarction.","Nadroparin is a low molecular weight heparin that is composed of a heterogeneous mixture of sulfated polysaccaride glycosaminoglycan chains. Th mean molecular weight is approximately 4300 daltons. The ratio of anti-Xa activity to anti-IIa is 3.5:1 whereas it is about 1:1 for heparin. Its use should be avoided in patients with a creatinine clearance less than 40mL/min. In these patients, unfractionated heparin should only be used. As for monitoring, active partial thromboplastin time (aPTT) will only increase at high doses of low molecular weight heparins (LMWH). Therefore, monitoring aPTT is not recommended. However, anti-Xa activity can be measured to monitor the efficacy of the LMWH.","The mechanism of action for nadroparin is similar to all other LMWHs. Like all LMWHs, nadroparin has a pentasaccharide sequence which binds to ATIII, which potentiates the action of ATIII. This complex greatly accelerates the inactivation of factor Xa and factor IIa. As a result, the coagulation cascade is inhibited.","Antithrombin-III potentiator; P-selectin inhibitor; Proto-oncogene c-Fos inhibitor; Myc proto-oncogene protein inhibitor","Indication associated"]
[1156,"DB08814","approved; investigational","small molecule","Triflusal","Triflusal","C10H7F3O4","CC(=O)OC1=C(C=CC(=C1)C(F)(F)F)C(O)=O","Triflusal is a 2-acetoxy-4-trifluoromethylbenzoic acid and it is an aspirin chemically-related molecule but not a derivative. The benefits of this agent are the lack of action over the arachidonic acid pathway, the driven production of nitric oxide and the increase of cyclic nucleotide concentration on endothelial cells. The latest translates into the expansion of peripheral blood vessels. It is very important as a secondary prevention of ischemic stroke by offering a lower risk of bleeding. It was developed by  J. Uriach and Company and even though it is commercialized in different countries it is not approved by the FDA, EMA or HealthCanada.","322-79-2","248.157","Triflusal is indicated as prophylaxis of thromboembolic disorders. It has been registered in Spain and in other countries of Europe, South America and South Korea for the prevention of Stroke and myocardial infarction.","Triflusal is an antithrombotic anticoagulant. It irreversibly inhibits the production of thromboxane-B2 in platelets by acetylating cycloxygenase-1. Triflusal affects many other targets such as NF kappa B, which is a gene expression regulatory factor for cycloxygenase-a and cytokines. Numerous studies comparing the efficacy and safety profile (i.e. systemic hemorrhage) between triflusal and acetylsalsylic acid has shown either no significant difference or a better effacy and safety profile for triflusal. Triflusal has been shown to protect cerebral tissue due to its inhibition of lipid peroxidation resulting from anoxia-reoxygenation.","Triflusal is chemically related to acetylsalicylic acid (ASA) and irreversibly inhibits cycloxygenase-1 (COX-1) in platelets. Acetylation of the active group of COX-1 prevents the formation of thromboxane-B2 in platelets. However, it is unique because it spares the arachidonic acid metabolic pathway in endothelial cells. In addition, it favors the production of nitric oxide, a vasodilator.","Prostaglandin G/H synthase 1 antagonist; Nuclear factor NF-kappa-B p105 subunit antagonist; Nitric oxide synthase, inducible agonist; cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A antagonist","Indication associated"]
[1157,"DB08816","approved","small molecule","Ticagrelor","(1S,2S,3R,5S)-3-(7-((1R,2S)-2-(3,4-Difluorophenyl)cyclopropylamino)-5-(propylthio)-3H-(1,2,3)triazolo(4,5-d)pyrimidin-3-yl)-5-(2-hydroxyethoxy)cyclopentane-1,2-diol; Ticagrelor","C23H28F2N6O4S","CCCSC1=NC2=C(N=NN2[C@@H]2C[C@H](OCCO)[C@@H](O)[C@H]2O)C(N[C@@H]2C[C@H]2C2=CC(F)=C(F)C=C2)=N1","Ticagrelor, or AZD6140, was first described in the literature in 2003. Ticagrelor is an ADP derivative developed for its P2Y<sub>12</sub> receptor antagonism. Unlike , ticagrelor is not a prodrug. It is marketed by Astra Zeneca as Brilinta in the US and Brilique or Possia in the EU,.\r\n\r\nTicagrelor was granted EMA approval on 3 December 2010.\r\nTicagrelor was granted FDA approval on 20 July 2011.","274693-27-5","522.568","Ticagrelor is indicated to reduce the risk of cardiovascular death, myocardial infarction, and stroke in patients with acute coronary syndrome or a history of myocardial infarction. Ticagrelor is also indicated to reduce the risk of a first myocardial infarction or stroke in high risk patients with coronary artery disease.","Ticagrelor is a P2Y<sub>12</sub> receptor antagonist that inhibits the formation of thromboses to reduce the risk of myocardial infarction and ischemic stroke. It has a moderate duration of action as it is given twice daily, and a wide therapeutic index as high single doses are well tolerated. Patients should be counselled regarding the risk of bleeding, dyspnea, and bradyarrhythmias.","Ticagrelor is a P2Y<sub>12</sub> receptor antagonist.\r\n\r\nThe P2Y<sub>12</sub> receptor couples with Gα<sub>i2</sub> and other G<sub>i</sub> proteins which inhibit adenylyl cyclase. G<sub>i</sub> mediated signalling also activates PI3K, Akt, Rap1b, and potassium channels. The downstream effects of these activities mediate hemostasis and lead to platelet aggregation.\r\n\r\nAntagonism of the P2Y<sub>12</sub> receptor reduces development of occlusive thromboses, which can reduce the risk of myocardial infarction and ischemic stroke.","P2Y purinoceptor 12 inhibitor","Therapeutic strategy associated"]
[1158,"DB08818","approved; vet_approved","small molecule","Hyaluronic acid","Hyaluronan; Hyaluronate","C28H44N2O23","CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)C1O[C@@H]1O[C@@H]([C@@H](O[C@@H]2O[C@H](CO)[C@@H](O)C(O[C@@H]3O[C@@H]([C@@H](O)[C@H](O)[C@H]3O)C(O)=O)[C@H]2NC(C)=O)[C@H](O)[C@H]1O)C(O)=O","Hyaluronic acid (HA) is an anionic, nonsulfated glycosaminoglycan found in connective, epithelial, and neural tissues; it was first isolated in 1934. Karl Meyer and John Palmer obtained glycosaminoglycan (GAG) from the bovine eye, giving it the name “hyaluronic acid”. HA is involved in many important physiological processes, including but not limited to wound healing, tissue regeneration, and joint lubrication. It demonstrates unique viscoelasticity, moisturizing, anti-inflammatory qualities, and other important properties that prove beneficial in various clinical applications.  \r\n\r\nHA is used in drug delivery systems for the treatment of cancer, ophthalmological conditions, joint conditions, and aesthetic imperfections. Several preparations of hyaluronic acid have been approved by the FDA and are available in oral, topical, and injectable forms. A popular use of hyaluronic acid in recent years is cosmetic injection due to its ability to minimize the appearance of wrinkles and aging-related skin imperfections.","9004-61-9","776.6486","The intra-articular preparations of hyaluronic acid are indicated for knee pain associated with osteoarthritis. Hyaluronic acid is used in cosmetic applications to prevent and reduce the appearance of wrinkles on the face, and as a dermal filler to correct facial imperfections or other imperfections on other parts of the body. It is frequently an ingredient in topical applications for wound healing and symptomatic treatment of skin irritation from various causes. Hyaluronic acid may also be indicated in ophthalmological preparations or oral capsules to treat discomfort caused by dry eyes or conjunctivitis and for its protective qualities during and before eye surgery. Finally, hyaluronic acid can be used off-label to coat the bladder for relief of interstitial cystitis symptoms.","HA has long-acting lubricant, shock absorbing, joint stabilizing, and water balancing properties. It is similar to the naturally occurring glycosaminoglycan (GAG) in joints. Hyaluronic acid works by acting as a lubricant and shock absorber, facilitating joint mobility and thereby reducing osteoarthritic pain.  Hyaluronic acid has antioxidative, anti-inflammatory, and analgesic effects. The water-balancing properties and viscoelasticity of hyaluronic acid are beneficial in cosmetic injections, imparting volume and reducing the appearance of imperfections and wrinkles. Due to the abovementioned properties, HA has a protective effect on the eyes and cornea.","General principles and hyaluronic acid receptor binding \r\n\r\nHyaluronic acid works by two basic mechanisms: serving as a passive structural molecule or serving as signaling molecule, depending on the molecule size. The physicochemical properties of high molecular weight HA contribute to passive structural effects, demonstrating hygroscopicity and viscoelasticity and improving hydration, water balance, and structural integrity. As a signalling  molecule interacting with proteins, HA causes several opposing effects based on molecular weight: pro- or anti-inflammatory effects, promotion or inhibition of cell migration, and activating or inhibiting cell division. \r\n\r\nHyaluronic acid exerts its therapeutic effects through binding to three primary types of cell surface receptors: CD44 (a membrane glycoprotein), the receptor for hyaluronate-mediated motility (RHAMM), and the Intercellular Adhesion Molecule 1 (ICAM-1). CD44 is considered the most widely distributed receptor for hyaluronic acid, demonstrating cellular interactions with osteopontin, collagen, and matrix metalloproteinases (MMPs).  High and low molecular weight hyaluronic acids demonstrate differing molecular and cellular mechanisms in their interaction with CD44 receptors. Some examples of these effects include modification of chondrocyte survival pathways in addition to alteration of apoptosis pathways.  Lymphatic vessel endothelial hyaluronan receptor (LYVE-1), and hyaluronic acid receptor for endocytosis (HARE), (also known as Stabilin-2) also bind to hyaluronic acid. \r\n\r\nHyaluronic acid for skin conditions and cosmetics\r\n\r\nHyaluronic acid's anionic proprieties cause it to attract water and induce swelling, increasing tissue volume and skin structural integrity. The aging process is associated with reduced production of skin hyaluronic acid and collagen, causing the appearance of wrinkles and the loss of facial volume. Dermal fillers of hyaluronic acid replace lost tissue volume, imparting a full and youthful appearance to skin that has lost its elasticity. Hyaluronic acid fillers contain cross-linked hyaluronic acid particles, rendering a concentrated substance with resistance to various forms of physical and chemical breakdown. The cosmetic benefits of hyaluronic acid filler may last up to 6 months, depending on the brand and technique used for injection. Additionally, dermal hyaluronic acid fillers are known to increase the production of fibroblasts, supporting wound healing and offering relief from irritating and inflammatory skin conditions.\r\n\r\n\r\nHyaluronic acid for joint pain\r\n\r\nMost cells in the human body are capable of synthesizing HA. It is a primary component of the extracellular matrix (ECM) and can be found in bone marrow, cartilage, and synovial fluid in joints. In osteoarthritis, the concentration of naturally occurring hyaluronic acid gradually decreases, lowering the viscosity of synovial fluid that protects joints from excess friction. Administration of intra-articular hyaluronic acid increases viscosity of synovial joint fluid, reducing friction and subsequently relieving painful arthritic symptoms.\r\n\r\n\r\nHyaluronic acid for ophthalmic conditions and ophthalmological procedures\r\n\r\nSolutions of hyaluronic acid with a concentration greater than 0.1% moisturize the surface of the eyes to treat symptoms of dry eye while improving the stabilization of tear film, replenishing deficiencies of HA, reducing friction, and preventing binding of foreign substances to the ocular tissue. Hyaluronic acid is frequently used during and after ophthalmological surgeries and plays important roles by virtue of its moisturizing, viscoelastic, and protective properties. It promotes tissue healing of the corneal epithelium and other parts of the eye following ophthalmological surgery, minimizing the risk of adhesions and free radical formation.\r","CD44 antigen binder; Intercellular adhesion molecule 1 inhibitor&binder; Hyaluronan mediated motility receptor binder; Neurocan core protein binder; Versican core protein binder; Complement component 1 Q subcomponent-binding protein, mitochondrial binder; Hyaluronan and proteoglycan link protein 1 binder; Hyaluronan and proteoglycan link protein 3 binder; Hyaluronan-binding protein 2 binder; Layilin binder; Stabilin-2 binder; Tumor necrosis factor-inducible gene 6 protein binder; Interphotoreceptor matrix proteoglycan 2 binder; Intracellular hyaluronan-binding protein 4 binder; Lymphatic vessel endothelial hyaluronic acid receptor 1","Therapeutic strategy associated"]
[1159,"DB08819","approved","small molecule","Tafluprost","Tafluprost","C25H34F2O5","CC(C)OC(=O)CCC\\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\\C=C\\C(F)(F)COC1=CC=CC=C1","A prostaglandin analogue ester prodrug used topically (as eye drops) to control the progression of glaucoma and in the management of ocular hypertension. Chemically, tafluprost is a fluorinated analog of prostaglandin F2-alpha. Tafluprost was approved for use in the U.S. on February 10, 2012.","209860-87-7","452.5313","Tafluprost is indicated for reducing elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension.","Tafluprost is a novel prostaglandin analog with a high affinity for the fluoroprostaglandin (FP) receptor PGF2α. Tafluprost has an affinity for the FP receptor that is approximately 12 times higher than that of the carboxylic acid of latanoprost, but with almost no potential to bind to other receptors.","Tafluprost acid is a prostanoid selective FP receptor agonist that is believed to reduce the intraocular pressure (IOP) by increasing the outflow of aqueous humor. Studies in animals and humans suggest that the main mechanism of action is increased uveoscleral outflow.","Prostaglandin F2-alpha receptor agonist","Indication associated"]
[1160,"DB08820","approved","small molecule","Ivacaftor","N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide","C24H28N2O3","CC(C)(C)C1=CC(=C(O)C=C1NC(=O)C1=CNC2=CC=CC=C2C1=O)C(C)(C)C","Ivacaftor (also known as Kalydeco or VX-770) is a drug used for the management of Cystic Fibrosis (CF). It is manufactured and distributed by Vertex Pharmaceuticals. It was approved by the Food and Drug Administration on January 31, 2012, and by Health Canada in late 2012.  Ivacaftor is administered as a monotherapy and also administered in combination with other drugs for the management of CF.\r\n\r\nCystic Fibrosis is an autosomal recessive disorder caused by one of several different mutations in the gene for the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, an ion channel involved in the transport of chloride and sodium ions across cell membranes. CFTR is active in epithelial cells of organs such as of the lungs, pancreas, liver, digestive system, and reproductive tract. Alterations in the CFTR gene result in altered production, misfolding, or function of the protein and consequently abnormal fluid and ion transport across cell membranes. As a result, CF patients produce thick, sticky mucus that clogs the ducts of organs where it is produced making patients more susceptible to complications such as infections, lung damage, pancreatic insufficiency, and malnutrition.\r\n\r\nPrior to the development of ivacaftor, management of CF primarily involved therapies for the control of infections, nutritional support, clearance of mucus, and management of symptoms rather than improvements in the underlying disease process or lung function (FEV1). Notably, ivacaftor was the first medication approved for the management of the underlying causes of CF (abnormalities in CFTR protein function) rather than control of symptoms.","873054-44-5","392.4907","When used as monotherapy as the product Kalydeco, ivacaftor is indicated for the management of CF in patients age 2 years and older who have a mutation in the CFTR gene that is responsive to ivacaftor potentiation. Ivacaftor received expanded approval in May 2017 for the following 33 CFTR mutations: E56K, P67L, R74W, D110E, D110H, R117C, R117H, G178R, E193K, L206W, R347H, R352Q, A455E, S549N, S549R, G551D, G551S, D579G, S945L, S977F, F1052V, K1060T, A1067T, G1069R, R1070Q, R1070W, F1074L, D1152H, G1244E, S1251N, S1255P, D1270N, and G1349D.\r\n\r\nWhen used in combination with the drug  as the product Orkambi, ivacaftor is indicated for the management of CF patients age 6 years and older who are shown to be homozygous for the F508del mutation in the CFTR gene.\r\n\r\nWhen used in combination with  in the product Symdeko, it is used to manage CF in patients 12 years and older who have at least one mutation in the CFTR gene or patients aged 12 or older who are shown to be homozygous for the F508del mutation.\r\n\r\nWhen used in combination with tezacaftor and  in the product Trikafta, it is indicated for the treatment of cystic fibrosis in patients 12 years of age and older who have at least one _F508del_ mutation in the CFTR gene.","The use of Ivacaftor has been shown to both improve CF symptoms and modulate underlying disease pathology. This is achieved by potentiating the channel opening probability (or gating) of CFTR protein in patients with impaired gating mechanisms. This is in contrast to , another CF medication, that functions by preventing misfolding of the CFTR protein and thereby results in increased processing and trafficking of mature protein to the cell surface. \r\n\r\nResults from clinical trials indicated that treatment with ivacaftor results in improved lung function, reduced chance of experiencing a pulmonary exacerbation, reduced sweat chloride, increased weight gain, and improvements in CF symptoms and quality of life. When combined with tezacaftor, significant improvements in lung function have been observed in clinical studies. Ivacaftor was not found to increase the QTc interval in a clinically significant manner.\r\n\r\nAlthough ivacaftor given alone has not shown any significant improvements in patients with the delta-F508 mutation, it has shown significant improvements (>10% increase in FEV1 from baseline) in lung function for the following mutations: E56K, P67L, R74W, D110E, D110H, R117C, R117H, G178R, E193K, L206W, R347H, R352Q, A455E, S549N, S549R, G551D, G551S, D579G, S945L, S977F, F1052V, K1060T, A1067T, G1069R, R1070Q, R1070W, F1074L, D1152H, G1244E, S1251N, S1255P, D1270N, and G1349. This list was expanded by the FDA in May 2017 from 10 to 33 to accommodate more rare mutations.\r\n\r\nIt is important to note that this drug may cause an increase in liver transaminases (ALT, AST).  Ensure to assess liver transaminases before the initiation of treatment, every 3 months during the first year of administration, followed by every year thereafter.","A wide variety of CFTR mutations correlate to the Cystic Fibrosis phenotype and are associated with differing levels of disease severity. The most common mutation, affecting approximately 70% of patients with CF worldwide, is known as F508del-CFTR or delta-F508 (ΔF508), in which a deletion in the amino acid phenylalanine at position 508 results in impaired production of the CFTR protein, thereby causing a significant reduction in the amount of ion transporter present on cell membranes. Ivacaftor as monotherapy has failed to show a benefit for patients with delta-F508 mutations, most likely due to an insufficient amount of protein available at the cell membrane for interaction and potentiation by the drug. The next most common mutation, G551D, affecting 4-5% of CF patients worldwide is characterized as a missense mutation, whereby there is sufficient amount of protein at the cell surface, but opening and closing mechanisms of the channel are altered. Ivacaftor is indicated for the management of CF in patients with this second type of mutation, as it binds to and potentiates the channel opening ability of CFTR proteins on the cell membrane.\r\n\r\nIvacaftor exerts its effect by acting as a potentiator of the CFTR protein, an ion channel involved in the transport of chloride and sodium ions across cell membranes of the lungs, pancreas, and other organs. Alterations in the CFTR gene result in altered production, misfolding, or function of the protein and consequently abnormal fluid and ion transport across cell membranes . Ivacaftor improves CF symptoms and underlying disease pathology by potentiating the channel open probability (or gating) of CFTR protein in patients with impaired CFTR gating mechanisms. The overall level of ivacaftor-mediated CFTR chloride transport is dependent on the amount of CFTR protein at the cell surface and how responsive a particular mutant CFTR protein is to ivacaftor potentiation .","Cystic fibrosis transmembrane conductance regulator potentiator","Therapeutic strategy associated"]
[1161,"DB08822","approved; investigational","small molecule","Azilsartan medoxomil","Azilsartan; Azilsartan medoxomil","C30H24N4O8","CCOC1=NC2=C(N1CC1=CC=C(C=C1)C1=CC=CC=C1C1=NOC(=O)N1)C(=CC=C2)C(=O)OCC1=C(C)OC(=O)O1","Azilsartan medoxomil is a prodrug that is broken down to azilsartan, which belongs in the angiotensin-receptor blocking (ARB) drug class. It is a selective AT1 subtype angiotensin II receptor antagonist. Azilsartan medoxomil is a relatively recently-developed antihypertensive drug that was first approved by the FDA in February 2011. Many guidelines recommend the use of ARBs as first-line therapy when initiating antihypertensive therapy and indicate that the clinical efficacy of ARBs is comparable to angiotensin-converting enzyme (ACE) inhibitors that are also used as first-line treatment for hypertension.\r\n\r\nAzilsartan medoxomil is marketed under the brand name Edarbi. It is used to treat hypertension as monotherapy or in combination with other antihypertensive drugs. It is also available in a combination product with . As hypertension is a major risk factor for cardiovascular disease, early management of hypertension has several implications on patients' survival rate and quality of life in the future. Lowering blood pressure is associated with a reduced risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. Azilsartan medoxomil is thus speculated to lower mortality rates and the onset of cardiovascular disease. Although there is no clinical significance yet determined, azilsartan medoxomil may have potential off-label uses in patients with a history of myocardial infarction or heart failure.","863031-21-4","568.5336","Azilsartan medoxomil is indicated for the treatment of hypertension to lower blood pressure in patients over 18 years of age. It may be used either alone or in combination with other antihypertensive agents. Some antihypertensive drugs have lesser effects on blood pressure in black patients.\r\n\r\nAzilsartan medoxomil is available as a fixed-dose combination product with , which is indicated for the treatment of hypertension in patients whose hose blood pressure is not adequately controlled on monotherapy. It may be used as initial therapy if a patient is likely to need multiple drugs to achieve blood pressure goals.\r\n\r\nAzilsartan medoxomil belongs to the angiotensin-receptor blocking (ARB) class of drugs, which are used to decrease the progression of moderate-to-severe albuminuria and prevent the recurrence of atrial fibrillation as off-label uses in patients with diabetes mellitus and hypertension.","Pharmacodynamic effects of azilsartan medoxomil are mediated by its active metabolite, azilsartan. Azilsartan inhibits the pressor effects of an angiotensin II infusion in a dose-related manner. At a single 32 mg dose, azilsartan inhibited the maximal pressor effect by approximately 90% at peak plasma concentrations and by 60% at 24 hours after administration. In healthy subjects receiving single and repeated doses of azilsartan medoxomil, plasma angiotensin I and II concentrations and plasma renin activity increased, while plasma aldosterone concentrations decreased. Like other ARBs, azilsartan causes dose-dependent decrease in peripheral resistance and decreases smooth muscle vascular tone. As azilsartan blocks the angiotensin II receptor, the negative regulatory feedback of angiotensin II on renin secretion is inhibited; however, the resulting increased plasma renin activity and angiotensin II circulating levels do not overcome the blood pressure-lowering effect of azilsartan. Blood pressure-lowering effects of antihypertensive agents can be reduced in patients of African descent. However, there are no recommended dosage adjustment of azilsartan on the basis of a patient’s sex, race, or degree of renal or hepatic impairment.\r\n\r\nAzilsartan medoxomil has negligible effects on serum potassium or sodium levels. Azilsartan does not affect the biosynthesis of angiotensin II nor bradykinin levels. It also does not bind to any ion channels that are involved in cardiovascular regulation.","The renin-angiotensin-aldosterone system regulates blood pressure. Angiotensin II is a peptide hormone that is a principal pressor agent in the renin-angiotensin-aldosterone system. It is a potent, direct vasoconstrictor that binds to the angiotensin II type 1 receptor (AT1 receptor) to stimulate the synthesis and release of aldosterone and promote cardiac stimulation. Angiotensin II promotes renal tubular reabsorption of sodium, resulting in water retention. It also inhibits further secretion of renin. AT1 receptors are highly expressed in vascular smooth muscle and the adrenal gland.\r\n\r\nAzilsartan medoxomil is a prodrug that is hydrolyzed to its active metabolite, azilsartan, in the gastrointestinal tract following oral administration. Azilsartan selectively binds to AT1 receptors as an antagonist, blocking vasoconstrictor and aldosterone-secreting effects of angiotensin II. Azilsartan has more than a 10,000-fold greater affinity for the AT1 receptor than for the AT2 receptor, which is predominantly involved in cardiovascular homeostasis. Azilsartan appears to dissociate from AT1 receptors much more slowly than other ARBs, which explains its longer duration of action when compared to other ARBs.","Type-1 angiotensin II receptor antagonist","Target associated"]
[1162,"DB08827","approved; investigational","small molecule","Lomitapide",null,"C39H37F6N3O2","FC(F)(F)CNC(=O)C1(CCCCN2CCC(CC2)NC(=O)C2=C(C=CC=C2)C2=CC=C(C=C2)C(F)(F)F)C2=CC=CC=C2C2=CC=CC=C12","Lomitapide is a microsomal triglyceride transfer protein (MTP) inhibitor used in homozygous familial hypercholesterolemia (HoFH) patients. It is marketed under the name Juxtapid (R).","182431-12-5","693.7204","Used in homozygous familial hypercholesterolemia (HoFH) patients to reduce low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), apolipoprotein B (apo B), and non-high-density lipoprotein cholesterol (non-HDL-C).","Lomitapide directly inhibits microsomal triglyceride transfer protein (MTP).","Within the lumen of the endoplasmic reticulum, lomitapide inhibits microsomal triglyceride transfer protein (MTP), which prevents the formation of apolipoprotein B, and, thus, the formation of VLDL and chylomicrons as well. Altogether, this leads to a reduction of low-density lipoprotein cholesterol.","Microsomal triglyceride transfer protein large subunit antagonist","Indication associated"]
[1163,"DB08830","experimental","small molecule","Dehydroascorbic acid","dehydro-L-ascorbic acid; DHAA; L-dehydroascorbate; L-dehydroascorbic acid; L-threo-2,3-hexodiulosonic acid, γ-lactone; L-threo-hexo-2,3-diulosono-1,4-lactone; Oxidized ascorbic acid; Oxidized vitamin C","C6H6O6","[H][C@](O)(CO)[C@@]1([H])OC(=O)C(=O)C1=O","Dehydroascorbic acid is made from the oxidation of ascorbic acid. This reaction is reversible, but dehydroascorbic acid can instead undergo irreversible hydrolysis to 2,3-diketogulonic acid. Dehydroascorbic acid as well as ascorbic acid are both termed Vitamin C, but the latter is the main form found in humans. In the body, both dehydroascorbic acid and ascorbic acid have similar biological activity as antivirals but dehydroascorbic acid also has neuroprotective effects. Currently dehydroascorbic acid is an experimental drug with no known approved indications.","490-83-5","174.1082","There is no approved indication for dehydroascorbic acid, but it has potential therapeutic use in patients with certain viruses and ischemic stroke.","Dehydroascorbic acid has similar biological activity as ascorbic acid. Both compounds have been shown to have antiviral effects against herpes simplex virus type 1, influenza virus type A and poliovirus type 1 with dehydroascorbic acid having the stronger effect. In addition, unlike ascorbic acid, dehydroascorbic acid can cross the blood brain barrier and is then converted to ascorbic acid to enable retention in the brain. This is important because one study has found that after an ischemic stroke, dehydroascorbic acid has neuroprotective effects by reducing infarct volume, neurological deficits, and mortality.","Even though dehydroascorbic acid and ascorbic acid have similar effects, their mechanism of action seems to be different. The exact mechanism of action is still being investigated, but some have been elucidated. Concerning dehydroascorbic acid's antiviral effect against herpes simplex virus type 1, it is suggested that dehydroascorbic acid acts after replication of viral DNA and prevents the assembly of progeny virus particles.",null,"Indication associated"]
[1164,"DB08834","experimental; investigational","small molecule","Tauroursodeoxycholic acid","Tauroursodeoxycholate; Tauroursodesoxycholic acid; TUDCA; Ursodeoxycholyltaurine","C26H45NO6S","[H][C@@]12CC[C@H]([C@H](C)CCC(=O)NCCS(O)(=O)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])[C@@H](O)C[C@]2([H])C[C@H](O)CC[C@]12C","Tauroursodeoxycholic acid is the more hydrophilic form of ursodeoxycholic acid, which is the more abundant naturally produced bile acid in humans. Tauroursodeoxycholic acid, on the other hand, is produced abundantly in bears and has been used for centuries as a natural remedy in some Asian countries. It is approved in Italy and Turkey for the treatment of cholesterol gallstones and is an investigational drug in China, Unites States, and Italy. Tauroursodeoxycholic acid is being investigated for use in several conditions such as Primary Biliary Cirrhosis (PBC), insulin resistance, amyloidosis, Cystic Fibrosis, Cholestasis, and Amyotrophic Lateral Sclerosis. The only completed clinical trial thus far is a phase III clinical trial comparing tauroursodeoxycholic acid and ursofalk in PBC adult patients, but as of June 2013 no results of this trial have been published.","14605-22-2","499.71","Used in the treatment of cholesterol gallstones. Tauroursodeoxycholic acid is also being investigated for use in several conditions such as Primary Biliary Cirrhosis (PBC), insulin resistance, amyloidosis, Cystic Fibrosis, Cholestasis, and Amyotrophic Lateral Sclerosis.",null,"Tauroursodeoxycholic acid is the more hydrophilic form of ursodeoxycholic acid, which is naturally produced in the body. In patients with properly functioning gallbladders, both of these bile acids inhibit liver cholesterol secretion and synthesis as well as intestinal cholesterol absorption allowing for the promotion of cholesterol gallstone dissolution. The mechanism of action of tauroursodeoxycholic acid in the other conditions is still being investigated.\r\n\r",null,"Indication associated"]
[1165,"DB08835","experimental","small molecule","Spaglumic acid","N-Acetyl-L-β-aspartyl-L-glutamic acid; Spaglumic acid","C11H16N2O8","CC(=O)N[C@@H](CC(=O)N[C@@H](CCC(O)=O)C(O)=O)C(O)=O","Spaglumic acid is the β-aspartyl isoform of N-Acetyl-l-aspartylglutamate (isospaglumic Acid is N-(N-Acetyl-l-α-aspartyl)-l-glutamic acid). In eye drops, spaglumic acid is either a magnesium or sodium salt of N-Acetyl-l-aspartylglutamate. Spaglumic acid is a mast cell stabilizer. Thus it is used in allergic conditions such as allergic conjunctivitis. Specifically spaglumic acid is approved in Portugal under the brand name Naabak and in Greece under the brand name Naaxia for use in patients with allergic conjunctivitis.","4910-46-7","304.255","Used in patients with allergic conjunctivitis.",null,"Spaglumic acid is a mast cell stabilizer. Mast cells are involved in producing an allergic response by releasing inflammatory mediators such as histamine. Mast cell stablizers block the release of histamine and other mediators by inhibiting mast cell degranulation, which is the process of releasing these mediators. Inhibition occurs through inhibition of specific calcium channels to stabilize the mast cell and prevent degranulation.","Glutamate carboxypeptidase 2 ligand","Therapeutic strategy associated"]
[1166,"DB08836","experimental; investigational","small molecule","Temocapril","Temocapril","C23H28N2O5S2","CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@H]1CS[C@@H](CN(CC(O)=O)C1=O)C1=CC=CS1","Temocapril is a prodrug-type angiotensin-I converting enzyme (ACE) inhibitor not approved for use in the United States, but is approved in Japan and South Korea. Temocapril can also be used in hemodialysis patients without risk of serious accumulation.","111902-57-9","476.609","Temocapril is an ACE inhibitor primarily indicated in the treatment of hypertension and congestive heart failure, diabetic nephropathy, and improvement of prognosis for coronary artery diseases (including acute myocardial infarction).","Temocapril is a prodrug of its active metabolite (and diacid form) temocaprilat which contains a thiazepine ring. Temocaprilat has slightly higher potency than enalaprilat in ACE inhibition isolated from rabbit lung. ACE inhibitors exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility.). When compared with other Angiotensin-converting Enzyme Inhibitors, temocapril's advantages include a rapid onset of action and what research suggests is tighter vascular ACE binding than enalaprilat.",null,"Angiotensin-converting enzyme inhibitor","Indication associated"]
[1167,"DB08838","experimental","small molecule","Agmatine","(4-aminobutyl) guanidine; (4-aminobutyl)guanidine; 1-amino-4-guanidobutane; N-(4-aminobutyl)guanidine","C5H14N4","NCCCCNC(N)=N","Agmantine is a natural metabolite of the amino acid arginine. It is formed when arginine is decarboxylated by the enzyme arginine decarboxylase and is found naturally in ragweed pollen, ergot fungi, octopus muscle, herring sperm, sponges, and the mammalian brain. Agmatine is both an experimental and investigational drug. As an investigational drug, it is being studied in a non-blinded prospective case study in the United States looking at patients who have been diagnosed with small fiber peripheral neuropathy between the ages of 18 to 75 years. Up to now (July 2013), the results of this study have not yet been published. As an experimental drug, agmatine is being studied for several indications such as cardioprotection, diabetes, decreased kidney function, neuroprotection (stroke, severe CNS injuries, epilepsy, glaucoma, and neuropathic pain), and psychiatric conditions (depression, anxiety, schizophrenia, and cognition). The exact mechanism of action is still being investigated for all of the potential indications of agmatine.","306-60-5","130.1915","Agmatine is being studied experimentally for several indications such as cardioprotection, diabetes, decreased kidney function, neuroprotection (stroke, severe CNS injuries, epilepsy, glaucoma, and neuropathic pain), and psychiatric conditions (depression, anxiety, schizophrenia, and cognition). As an investigational drug, agamatine is being studied in a non-blinded prospective case study in the United States looking at patients who have been diagnosed with small fiber peripheral neuropathy.","Agmatine has several physiological effects. Its cardiovascular effects include mildly reducing heart rate and blood pressure. Also it promotes a mild hypoglycemic state, reduces cellular oxidative stress, and enhances glomerular filtration rate.","The exact mechanism of action is still being investigated for all of the potential indications of agmatine. Some of the biochemical mechanisms discovered so far concern agmatine's indication for diabetes, neuroprotection, and psychiatric conditions. In diabetes, agmatine produces hypoglycemia by increasing the release of insulin form pancreatic islet cells and increasing glucose uptake by the cells through increased endorphin release from the adrenal glands. Concerning neuroprotection, agmatine's effects are thought to involve modulation of receptors (NMDA, alpha 2, and imidazoline) and ion channels (ATP sensitive potassium channels and voltage-gated calcium channels) as well as blocking nitric oxide synthesis. Agmatine blocks nitric oxide synthesis by reducing the nitric oxide synthase -2 (NOS-2) protein in astroglial cells and macrophages. With respect to agmatine's benefit in psychiatric disorders, it is suggested that the mechanism involves neurotransmitter receptor modulation of the NMDA, alpha-2, serotonin, opioid, and imidazoline receptors. Specifically when agmatine binds to the imidazoline and alpha 2 receptors, it acts as a neurotransmitter and releases catecholamines from the adrenal gland.","Alpha-2C adrenergic receptor agonist; Nischarin agonist; Acetylcholine receptor subunit alpha antagonist; Glutamate receptor ionotropic, NMDA 1 antagonist; ATP-sensitive inward rectifier potassium channel 1 antagonist; Voltage-dependent N-type calcium channel subunit alpha-1B antagonist; Acid-sensing ion channel 3 agonist","Therapeutic strategy associated"]
[1168,"DB08842","approved; investigational","small molecule","Acetylcarnitine","acetyl-L-carnitine; O-acetyl-L-carnitine ; O-Acetylcarnitine","C9H17NO4","CC(=O)O[C@H](CC([O-])=O)C[N+](C)(C)C","Acetylcarnitine is an investigational drug in the United states, Italy, United Kingdom, China, Israel, and Norway, and it is approved in Italy, Portugal, Argentina, Chile, Philippines, Australia, and India. Acetylcarnitine can be synthesized, but it is also naturally found in adequate amounts in healthy humans. In human plasma and tissues, acetylcarnitine is the most predominant acylated ester of carnitine, which is an amino acid derivative that is made in the kidney, liver, and brain from lysine and methionine. The main role of acetylcarnitine is to help transport fatty acids into the mitochondrial matrix where fatty acid metabolism occurs.","3040-38-8","203.238","Acetylcarnitine is not approved for any indication in the United states and Canada, but it is approved and indicated in Italy for cerebrovascular disorders, mental function disorders, peripheral nerve disorders, diabetic neuropathy, and nutritional supplementation; Portugal for mental function disorders; Argentina for cerebral vasculopathy, nutritional supplementation, and peripheral neuropathy; Chile for dementia; Philippines for cerebrovascular disorders and mental function disorders; Australia for nutritional supplementation; and India for nutritional supplementation to increase sperm count. Acetylcarnitine also has several potential therapeutic indications for which it is still being investigated: in Norway, acetylcarnitine is in a phase IV trial for prophylactic treatment of migraines; in Italy acetylcarnitine is in a phase II trial for use in patients with type 2 Diabetes Mellitus, a phase III trial for alleviating fatigue in patients with chronic hepatitis C, and for use in patients with Minimal Hepatic Encephalopathy; in the United States acetylcarnitine is in a phase II trial for the neurodegenerative disorder Progressive Supranuclear Palsy, a phase II and III trial for reducing peripheral neuropathy in cancer patients as an adjunct to chemotherapy, a phase I and II trial for treating patients in septic shock, a phase II trial for bipolar depression, a phase II trial to reduce oxidative stress in patients with Sickle Cell disease, a phase I and II trial for chronic fatigue syndrome, and a study for preventing nerve damage in HIV patients; in China acetylcarnitine is in a phase III trial for reducing peripheral neuropathy in cancer patients as an adjunct to chemotherapy; in the United Kingdom acetylcarnitine is being investigated for preventing nerve damage in HIV patients; and in Israel acetylcarnitine is being studied for the treatment of male infertility.\r\n\r\n \r","The complete physiological effects of acetycarnitine are still being studied. What has been discovered so far is that acetylcarinitine has positive effects on mental fatigue, neurodegenerative disorders, cognitive functions, peripheral neuropathy, and sperm motility. Specifically, in one study involving patients with HIV, patients on acetylcarnitine supplementation had increased CD4 cells, decreased lymphocyte apoptosis, improved polyneuropathy and cardiovascular damage, and decreased triglyceride and TNF alpha levels in the blood. Another study showed that acetylcarnitine increased glucose disposal in type 2 diabetic patients through possibly increasing the activity of glycogen synthase.","The mechanisms of action of acetylcarnitine have not been fully elucidated, but it seems that the main role of acetylcarnitine is to donate an acetyl group during fatty acid metabolism to help transport fatty acids, such as acetyl CoA, into the mitochondrial matrix where fatty acid metabolism occurs. Additionally several studies have found that separate from its metabolic role, acetylcarnitine has neuromodulatory, neurotrophic, and neuroprotective effects that most likely are involved in its positive effects in neurological diseases. In its role in treating male infertility, acetylcarnitine increases the active movement of sperm cells. One study has also mentioned a role for acetylcarnitine as an antioxidant. The study found that through the receptor, tyrosine kinase A, acetylcarnitine was able to decrease the production of free radicals, peroxidation of lipids, and oxidation of proteins as well as decrease glutathione levels and increase thioredoxin.",null,"Therapeutic strategy associated"]
[1169,"DB08844","investigational","small molecule","Uric acid","2,6,8-trihydroxypurine; 2,6,8-trioxopurine; 2,6,8-trioxypurine; 7,9-dihydro-1H-purine-2,6,8(3H)-trione; Lithic acid; Purine-2,6,8(1H,3H,9H)-trione; Urate","C5H4N4O3","O=C1NC2=C(N1)C(=O)NC(=O)N2","Uric acid is the last product of purine metabolism in humans. The formation of uric acid is through the enzyme xanthine oxidase, which oxidizes oxypurines. Normally a small amount of uric acid is present in the body, but when there is an excess amount in the blood, called hyperuricemia, this can lead to gout and formation of kidney stones. As a therapeutic agent, it is known that uric acid is increased in response to oxidative stress, and as such, uric acid acts as an antioxidant. At present (August 2013), there is no approved formulation or indication for uric acid. In one country, Spain, uric acid is an investigational drug in a phase 3 trial studying its effects as an adjunct to alteplase in acute ischemic stroke.","69-93-2","168.1103","At present (August 2013), there is no approved indication for uric acid.  The potential therapeutic use for uric acid is as an adjunct in acute ischemic stroke.","Uric acid is a strong reducing agent (donates electrons) and an antioxidant. Normally in humans, one of the main antioxidants in plasma is uric acid. Several animal studies have found that animals given exogenous uric acid within 3 hours after a stroke had decreased infarct volume, improved neurologic function, and diminished inflammatory responses providing evidence for the neuroprotective effects of uric acid. In some early human studies, uric acid has so far shown similar neuroprotective effects, in both the cortex and subcortex areas, due to its antioxidant effects such as decreased lipid peroxidation, and there appears to be no significant toxicities.","The exact mechanism of action for uric acid's antioxidant effects have not yet been elucidated.","Glycogen phosphorylase, liver form","Therapeutic strategy associated"]
[1170,"DB08862","approved; investigational","small molecule","Cholecystokinin","CCK-PZ; Human CCK-33; Human cholecystokinin-33; Pancreozymin",null,null,"Cholecystokinin ( also known as _CCK or CCK-PZ_) is a peptide hormone of the gastrointestinal system which is responsible for stimulating the digestion of fat and protein. Cholecystokinin, previously called _pancreozymin_, is synthesized and secreted by enteroendocrine cells in the duodenum (the first portion of the small intestine) and leads to the release of bile and digestive enzymes. CCK also acts as an appetite suppressant and has been studied for weight management regimens . \r\n\r\nNormally, it is an endogenous hormone but is available commercially for diagnostic processes and replacement in pancreatic insufficiency . in the octapeptide form.\r\n\r\n\r\n\r\nCholecystokinin is one of the first gastrointestinal hormones discovered, identified more than 90 years ago due to its ability to stimulate gallbladder contraction in 1928. Soon after, it was recognized to be identical to the factor responsible for stimulating pancreatic exocrine secretion in 1943 . This hormone has also been shown to have positive effects on enteric smooth muscle contraction and on nerve activity at multiple locations in the peripheral and central nervous system. In addition to its roles in promoting smooth muscle cell contraction/exocrine cell secretion, CCK promotes cell growth, energy production, gene expression and protein synthesis, processes that have profound for drug development .  This drug has also been investigated for possible antipsychotic properties, owing to its effect on CCK receptors in the brain .\r\n\r\nRecent studies have suggested that cholecystokinin also plays a major role in inducing drug tolerance to opioids such as morphine and heroin, and is partially implicated in experiences of pain hypersensitivity during opioid withdrawal .","9011-97-6",null,"For use as a diagnostic aid for evaluation of gallbladder disorders.  It is also used in conjunction with secretin in pancreatic insufficiency .","Cholecystokinin (CCK) plays an imperative role in facilitating digestion within the small intestine. The activation of the CCK1 receptor by CCK has demonstrated to be responsible for a wide variety of important physiologic functions, including the stimulation of gallbladder, contraction and exocrine pancreatic enzyme secretion, delay of gastric emptying, relaxation of the sphincter of Oddi, inhibition of gastric acid secretion, and induction of satiety . Cholecystokinin is also produced by neurons in the enteric nervous system and is found to be widely distributed in the brain .  An interesting function of CCK is the role it plays in stimulating the CCK receptor and subsequently regulating food consumption, which may prove to be a highly useful treatment for obesity .   Exogenous administration CCK has been widely studied . \r\n\r\n\r\nDiseases resulting from excessive or deficient secretion of cholecystokinin are rare. Cholecystokinin deficiency has been described in humans as part of autoimmune polyglandular syndrome, characterized as a malabsorption syndrome clinically similar to pancreatic exocrine insufficiency. Additionally, there is increasing evidence that alterations in expression of cholecystokinin or its receptor within the brain may possibly play a role in the pathogenesis of various types of anxiety disorders and schizophrenia .\r\n\r\nFoodstuffs flowing into the small intestine are mostly made up of large macromolecules (proteins, polysaccharides, and triglyceride) that require digestion into small molecules (amino acids, monosaccharides, fatty acids) in order to be absorbed. Digestive enzymes from the pancreas and bile salts from the liver (which are stored in the gallbladder) are necessary for  digestion. Cholecystokinin is the primary stimulus for the release of pancreatic enzymes and bile secretion into the small intestine. Additionally, cholecystokinin,  induces contraction of the gallbladder muscle, resulting in the reduction of gallbladder size and evacuation of bile .","Cholecystokinin (CCK) is a peptide hormone discovered in the small intestine. Together with secretin and gastrin, CCK constitutes the classical gut hormone triad. In addition to gallbladder contraction, CCK also regulates pancreatic enzyme secretion and growth, intestinal motility, satiety signaling and the inhibition of gastric acid secretion. CCK is, however, also a transmitter in central and intestinal neurons. Notably, CCK is the most ubiquitously found neuropeptide in the human brain. Owing to difficulties in developing accurate assays for the hormone, knowledge about CCK secretion in disease is limited. Available data indicate, however, that proCCK is expressed in certain malignant neuroendocrine tumors and sarcomas, whereas the secretion of CCK is affected in celiac disease and the eating disorder bulimia nervosa. Stimulation with exogenous CCK has proved this protein useful in diagnostic imaging of gallbladder and pancreatic diseases, as well as testing of medullary thyroid carcinomas .\r\n\r\n\r\nCholecystokinin, a natural polypeptide which is formed in the amine precursor uptake and decarboxylation (APUD) cells of the proximal mucosa of the small intestine, promotes contraction of the gallbladder muscle, resulting in the reduction of gallbladder size and the expression of bile . Cholecystokinin stimulates secretion of pancreatic digestive enzymes and secretion from the glands of Brunner .\r\n\r\nCCK is composed of a five amino acid sequence at the carboxyl terminus that is identical to that of gastrin. The carboxyl terminus confers the biologic activity of CCK; as a result, gastrin has CCK-mimicking activity and CCK has gastrin-mimicking activity. The amino acid sequence similarity has made the creation of assays for CCK cumbersome, due to the fact that antibodies specific for the biologically active portion the molecule often cross-react with gastrin. This hormone circulates in the blood at concentrations 10 to 100 times greater than that of CCK .\r\n\r","Cholecystokinin receptor type A agonist; RAF proto-oncogene serine/threonine-protein kinase agonist; Mitogen-activated protein kinase 3; Pro-epidermal growth factor; Protein kinase C beta type agonist; Gastrin/cholecystokinin type B receptor agonist","Therapeutic strategy associated"]
[1171,"DB08867","approved","small molecule","Ulipristal","Ulipristal","C28H35NO3","CN(C)C1=CC=C(C=C1)[C@H]1C[C@@]2(C)[C@@H](CC[C@]2(O)C(C)=O)[C@@H]2CCC3=CC(=O)CCC3=C12","Ulipristal is a selective progesterone receptor modulator used for the purposes of emergency contraception (Ella) and for the treatment of uterine fibroids (Fibristal).  It is a derivative of 19-norprogesterone and has both antagonistic and partial agonist activity at the progesterone receptor. It also binds to glucocorticoid receptor, however compared to mifepristone (a progesterone receptor antagonist), ulipristal is more tolerable and has lower glucocorticoid activity and better binding affinity. \r\n\r\nUlipristal is currently recommended as first line therapy for emergency contraception, due to improved efficacy and similar side effect profile as compared to the traditional use of levonorgestrel or the Yuzpe regimen. The exact mechanism of action for ulipristal is still currently debated, though there is evidence that it functions by inhibiting ovulation. A recent systematic review proclaimed that the majority of available evidence demonstrates an inhibitory effect on ovulation rather than a post-fertilization effect on the endometrium, which has been heavily debated due to ethical concerns related to abortion (Rosato et al, 2016). Nevertheless, current and ongoing research into the agent's mechanism of action as an emergency contraceptive continue to provide potentially plausible evidence that ulipristal may, in fact, elicit activity on the endometrium that prevents embryo implantation .","159811-51-5","433.592","As the product Ella (available in Canada and the US), ulipristal is indicated for use as emergency contraception after unprotected intercourse or possible contraceptive failure when administered within 120 hours (5 days) after unprotected intercourse or a known or suspected contraceptive failure. As the product Fibristal (available in Canada), ulipristal is indicated for treatment of the signs and symptoms of uterine fibroids in adult women.","Ulipristal is a selective, reversible progestin receptor modulator and its tissue targets include the uterus, cervix, ovaries, and hypothalamus. Ulipristal may act as an agonist or antagonist in the presence or absence of progesterone based on the tissue target. If given mid-follicular phase, development of the follicle growth is delayed and estradiol concentrations decrease. If given at the time when luteinizing hormone peaks, follicular rapture is delayed by several days.  If given early-luteal phase, a decrease in endometrial thickness can be observed.","The exact mechanism of action of ulipristal has been heavily debated  . On one hand, the majority of official prescribing information labels, monographs, and prior research studies for ulipristal indicated as an emergency contraceptive suggest that its primary mechanism of action revolves around inhibiting or delaying ovulation by suppressing surges in LH that result in the postponement of follicular rupture .\r\n\r\nConversely, some of the latest investigations pertaining to ulipristal's mechanism of action as an emergency contraceptive propose that it principally elicits its action by preventing embryo implantation, as opposed to preventing ovulation . Although previous investigations have shown that ulipristal essentially has the ability to prevent ovulation equivalent to placebo (ie. null effect or ability) when administered during LH peaks one to two days before ovulation, the agent still demonstrates a stable and consistently high contraceptive effect of approximately >=80% when used at this time . Subsequently, current studies attempt to investigate how ulipristal could elicit emergency contraception via ovulation prevention under circumstances where ovulation had already clearly been observed . Endometrial biopsy samples studied from such circumstances in such investigations subsequently show that the administered ulipristal causes endometrial tissue to become inhospitable and unsuitable for embryo implantation where a variety of genes characteristic of receptive, pro-gestational endometrium are downregulated . \r\n\r\nNevertheless, most if not all proposed mechanisms commonly agree that ulipristal ultimately demonstrates its pharmacological effects by binding to human progesterone receptors and prevents natural, endogenous progesterone from occupying such receptors . Regardless, however, considering current and on-going research into ulipristal's ability to prevent embryo implantation, the notion that the medication can elicit post-fertilization effects potentially raises alerts and/or ethical debates over the use of ulipristal owing to potential abortifacient activity , which is considered to be on par or equipotent to that of mifepristone . Attention should be drawn to the fact that some prescribing information, however, such as the US FDA label for ulipristal indicated for emergency contraception, has included new supplementary commentary since 2018 that directly warns about ulipristal not being indicated for termination of existing pregnancies and suggesting that ulipristal use may confer alterations to the endometrium that may affect implantation and contribute to efficacy . \r\n\r\nIn the treatment of fibroids, ulipristal has been shown to exert direct actions on fibroids reducing their size through inhibition of cell proliferation and induction of apoptosis.","Progesterone receptor modulator; Glucocorticoid receptor antagonist; Androgen receptor","Therapeutic strategy associated"]
[1172,"DB08870","approved; investigational","biotech","Brentuximab vedotin","Brentuximab; Brentuximab vedotin; Brentuximab vedotin brentuximab; cAC10-vcMMAE; Moab, chimeric, SGN-30, to CD30 antigen; Monoclonal antibody SGN-30",null,null,"Brentuximab vedotin, also known as Adcetris®, is an antibody-drug conjugate that combines an anti-CD30 antibody with the drug monomethyl auristatin E (MMAE). It is an anti-neoplastic agent used in the treatment of Hodgkin's lymphoma and systemic anaplastic large cell lymphoma. Brentuximab vedotin was initially approved in 2011. In January 2012, the drug label was revised with a boxed warning of a condition known as progressive multifocal leukoencephalopathy and death due to opportunistic JC virus infection post treatment . \r\n\r\nThe U.S. Food and Drug Administration approved Adcetris in March 2018 to treat adult patients with previously untreated stage III or IV classical Hodgkin lymphoma (cHL) in combination with chemotherapy .\r\n\r\nAdcetris has also been previously approved by the FDA to treat Hodgkin's lymphoma after relapse, Hodgkin's lymphoma after stem cell transplantation when a patient has a high risk of relapse or progression, systemic anaplastic large cell lymphoma (ALCL) after the failure of other treatment regimens, and primary cutaneous ALCL after failure of other treatment regimens .\r\n\r\nLymphoma is a malignancy that begins in the lymphatic system, which helps to combat infection and disease. Lymphoma may begin anywhere in the body and can spread to nearby lymph nodes. The two main types of lymphoma are Hodgkin lymphoma (also called Hodgkin disease) and non-Hodgkin lymphoma. Most individuals with Hodgkin's lymphoma have the classical type. In this type of lymphoma, large, abnormal lymphocytes (a type of white blood cell) are found in the lymph nodes called Reed-Sternberg cells. With early diagnosis and intervention, patients with Hodgkin lymphoma normally experience long-term remission .\r\n\r\nThe ECHELON-1 study results demonstrated superior efficacy of the drug combined with a chemotherapy regimen when it is compared to the previous standard of care. Importantly, removing the drug bleomycin, a highly toxic agent, was completely removed from the regimen. This demonstrates meaningful progress in treatment for patients affected by this disease .","914088-09-8",null,"Seattle Genetics Announced FDA Approval of ADCETRIS® (Brentuximab Vedotin) in combination with chemotherapy for adults with previously untreated stage III or IV Classical Hodgkin Lymphoma in March 2018  .\r\n\r\nHodgkin lymphoma after failure of autologous stem cell transplant (ASCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates , .\r\n\r\nSystemic anaplastic large cell lymphoma after failure of at least one prior multi-agent chemotherapy regimen .","Brentuximab vedotin causes apoptosis of tumor cells by preventing cell cycle progression of the G2 to M phase through disruption of the cytosolic microtuble network, thus preventing tumor growth and proliferation .\r\n\r\nHodgkin lymphoma (HL) is characterized by malignant Reed-Sternberg cells which express CD30, a marker of large cell lymphoma . Until March 2018, USA National Comprehensive Cancer Network guidelines for patients with advanced HL (stage III/IV disease) recommend treatment with  adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD), or escalated bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) as first-line regimens . \r\n\r\nABVD appears to be as effective, with fewer side effects, as escalated BEACOPP. Escalated BEACOPP leads to a greater progression-free survival but no difference in overall survival. Recent progress in technology has enabled a new shift to cancer therapy targeting specific molecules. Brentuximab vedotin, a CD30-directed antibody conjugate, selectively targets malignant HL cells .\r\n\r\nThe effect of Brentuximab vedotin (1.8 mg/kg) on the QTc interval was studied in an open-label, single-group study in 46 patients diagnosed with CD30-expressing hematologic malignancies.  Ingestion of brentuximab vedotin did not prolong the mean cardiac QTc interval >10 ms from baseline levels.  Smaller increases in the mean QTc interval (<10 ms) cannot be ruled out because this study did not include a placebo arm and a positive control arm .","Brentuximab vedotin is composed of 3 parts: a chimeric human-murine IgG1 that selectively targets CD30, monomethyl auristatin E (MMAE), which is a microtubule-disrupting agent, and a protease-susceptible linker that links the antibody and MMAE. The IgG1 antibody enables Brentuximab vedotin to target tumor cells expressing CD30 on their surface.  Following this Brentuximab vedotin enters the cell. Once inside, the linker is cleaved releasing MMAE which binds disrupts the microtubule network .\r\n\r\nThe antibody component of this drug is a chimeric IgG1 directed against CD30.  The small molecule, MMAE, is a microtubule-disrupting particle.  MMAE is covalently attached to the antibody by a linker. Data suggest that the anticancer activity of Adcertris is due to the binding of the ADC to CD30-expressing cells, followed by internalization of the ADC-CD30 complex, and the subsequent release of MMAE by proteolytic cleavage.  Binding of MMAE to tubulin disrupts the microtubule network within the cell, inducing cell cycle arrest and apoptotis of the malignant cells .\r","Tumor necrosis factor receptor superfamily member 8 binder","Target associated"]
[1173,"DB08874","approved","small molecule","Fidaxomicin","Difimicin ; Fidaxomicin; Lipiarmicin; Lipiarmycin; Lipiarrmycin; Tiacumicin B","C52H74Cl2O18","[H][C@@]1(O[C@@H]2[C@@H](CC)\\C=C(C)\\[C@@H](O)C\\C=C\\C=C(CO[C@@H]3O[C@H](C)[C@@H](OC(=O)C4=C(CC)C(Cl)=C(O)C(Cl)=C4O)[C@H](O)[C@@H]3OC)\\C(=O)O[C@@H](C\\C=C(/C)\\C=C2/C)[C@@H](C)O)OC(C)(C)[C@@H](OC(=O)C(C)C)[C@H](O)[C@@H]1O","Fidaxomicin is a novel macrolide antibiotic used in the treatment of diarrhea caused by _Clostridioides_ (formerly _Clostridium_) _difficile_ in adult and pediatric patients over the age of 6 months. Fidaxomicin is a naturally-occurring 18-member macrocycle derived from fermentation. Because fidaxomicin contains an 18-membered lactone ring in its structure, it is referred to as a macrocyclic lactone antibiotic drug. The antibacterial activity of fidaxomicin is distinct from macrolides and rifamycins, as the bactericidal activity is time-dependent, and not concentration-dependent. Fidaxomicin was the first macrocyclic lactone antibiotic with activity against _C. difficile_, and it displays a narrow spectrum of activity against gram-positive anaerobes. It mediates its potent bactericidal action on the bacteria by inhibiting the bacterial RNA synthase, thereby disrupting bacterial transcription. The minimum inhibitory concentration (MIC<sub>90</sub>) for fidaxomicin is four times less than that of , which was the primary drug of choice for _C. difficile_ infection before the approval of fidaxomicin. Unlike vancomycin, however, fidaxomicin has a negligible effect on normal colonic microflora.\r\n\r\nThe FDA initially approved fidaxomicin in May 2011 for the treatment of _C. difficile_-associated diarrhea in adult patients over the age of 18. Later that year in December, the drug was also approved by the European Medicine Agency. In June 2012, fidaxomicin was also granted approval by Health Canada. The approved indication of fidaxomicin was expanded by the FDA in January 2020 to include pediatric patients over the age of 6 months in the treatment population.","873857-62-6","1058.05","Fidaxomicin is indicated for the treatment of _Clostridioides_ (formerly _Clostridium_) _difficile_-associated diarrhea in adult and pediatric patients 6 months of age and older.\r\n\r\nFidaxomicin should only be used in patients with proven or strongly suspected _C. difficile_ infection to reduce the risk of development of drug-resistant bacteria and maximize the therapeutic effectiveness of fidaxomicin and other antimicrobial agents.","Fidaxomicin has a narrow-spectrum antibacterial profile, with potent bactericidal activity specifically against C. difficile. The minimum inhibitory concentration for 90% of organisms for fidaxomicin against _C. difficile_ ranged from 0.0078 to 2 μg/mL _in vitro_. The bactericidal activity of fidaxomicin is time-dependent. Other than _C. difficile_, fidaxomicin has moderate inhibitory activity against Gram-positive bacteria (_S. aureus_ and _Enterococcus spp._)  and poor activity against normal colonic flora, including anaerobes and enteric Gram-negative bacilli. Isolates of _C. difficile_ that are resistant to rifamycins or other antimicrobial classes (such as cephalosporins, fluoroquinolones, clindamycin) were not shown to be cross-resistant to fidaxomicin.","_Clostridium difficile_ is a Gram-positive bacterium that causes various gastrointestinal complications, such as antibiotic-associated diarrhea. _C. difficile_ infection can be caused by antibiotic therapy, resulting in the disruption of the human gut flora leads to an overgrowth of _C. difficile_. The consequences of _C. difficile_ infection can be mild to severe and sometimes fatal. \r\n\r\nFidaxomicin gets hydrolyzed to its active metabolite, OP-1118, upon oral administration. Both compounds mediate a bactericidal activity against _C. difficile_ by inhibiting bacterial RNA polymerase at the initiation phase of the transcription cycle. The RNA polymerase is an essential bacterial enzyme that regulates gene expression, catalyzes nucleic acid interactions, and promotes several bacterial enzymatic reactions critical for bacterial survival. The core RNA polymerase is composed of a complex of different subunits and contains the active site. To initiate bacterial transcription, the active site of the core RNA polymerase binds to a promoter-specificity σ initiation factor, which locates and binds to a promoter region of the DNA. The DNA-RNA polymerase interaction promotes subsequent steps of transcription, which involves the separation of DNA strands. Fidaxomicin binds to the DNA template-RNA polymerase complex, thereby preventing the initial separation of DNA strands during transcription and inhibiting messenger RNA synthesis. The narrow spectrum of antimicrobial activity of fidaxomicin may be explained by the unique target site of fidaxomicin and differing σ subunits of the core structure of RNA polymerase among bacterial species.","RNA polymerase sigma factor inhibitor","Therapeutic strategy associated"]
[1174,"DB08877","approved","small molecule","Ruxolitinib","Ruxolitinib","C17H18N6","N#CC[C@H](C1CCCC1)N1C=C(C=N1)C1=C2C=CNC2=NC=N1","Ruxolitinib, formerly known as INCB018424 or INC424, is an anticancer drug and a Janus kinase (JAK) inhibitor. It is a potent and selective inhibitor of JAK1 and JAK2, which are tyrosine kinases involved in cytokine signalling and hematopoiesis. Myeloproliferative neoplasms, such as myelofibrosis and polycythemia vera, are often characterized by aberrant activation of the JAK-STAT pathway, leading to abnormal blood cell counts and thrombotic complications. By inhibiting JAK1 and JAK2, ruxolitinib works to block the dysregulated cell signalling pathways and prevents abnormal blood cell proliferation. Due to a large number of patients with myeloproliferative neoplasms who have JAK2 mutations, ruxolitinib was the first ATP-competitive inhibitor of JAK1 and JAK2 ever developed.\r\n\r\nRuxolitinib was first approved for the treatment of adult patients with myelofibrosis by the FDA in 2011, followed by EMA's approval in 2012. In 2014, it was approved for the treatment of polycythemia vera in adults who have an inadequate response to or are intolerant of  and in 2019, ruxolitinib was approved for use in steroid-refractory acute graft-versus-host disease in adults and children. In 2021, ruxolitinib was approved for treatment of mild to moderate atopic dermatitis in patients 12 years and older whose disease was not adequately controlled by topical prescription therapies or when those therapies were not advisable. Available as oral tablets, ruxolitinib is commonly marketed under the trade name Jakafi. Ruxolitinib has been investigated to treat patients with coronavirus disease 2019 (COVID-19) accompanied by severe systemic hyperinflammation. In phase II clinical trials, ruxolitinib improved chest computed tomography and improved recovery in patients with lymphopenia. However, phase III clinical trials later determined that ruxolitinib was inadequate in meeting its primary endpoint of reducing the number of hospitalized COVID-19 patients who experienced severe complications. Ruxolitinib was not approved as a treatment for COVID-19. The topical formulation of ruxolitinib was investigated to treat vitiligo, atopic dermatitis, and psoriasis, where it showed promising preliminary results in improving the symptoms of inflammatory skin conditions.","941678-49-5","306.365","Ruxolitinib is indicated for the treatment of inte1mediate or high-risk myelofibrosis (MF), including prima1y MF, post-polycythemia vera MF and post-essential thrombocythemia MF in adults. It is also indicated to treat disease-related splenomegaly or symptoms in adult patients with these conditions.\r\n\r\nRuxolitinib is indicated for the treatment of polycythemia vera (PV) in adults who have had an inadequate response to or are intolerant of hydroxyurea.\r\n\r\nRuxolitinib is indicated for the treatment of steroid-refracto1y acute graft-versus-host disease (GVHD) in adult and pediatric patients 12 years and older.\r\n\r\nRuxolitinib is indicated for topical non-continuous and short-term treatment of mild to moderate atopic dermatitis in immunocompetent patients who are 12 years and older and whose disease is not adequately controlled with topical prescription therapies or when the topical prescription therapies are not advisable.","Ruxolitinib is an antineoplastic agent that inhibits cell proliferation, induces apoptosis of malignant cells, and reduces pro-inflammatory cytokine plasma levels by inhibiting JAK-induced phosphorylation of signal transducer and activator of transcription (STAT). Inhibition of STAT3 phosphorylation, which is used as a marker of JAK activity,  by ruxolitinib is achieved at two hours after dosing which returned to near baseline by 10 hours in patients with myelofibrosis and polycythemia vera. In clinical trials, ruxolitinib reduced splenomegaly and improved symptoms of myelofibrosis. In a mouse model of myeloproliferative neoplasms, administration of ruxolitinib was associated with prolonged survival. Ruxolitinib inhibits both mutant and wild-type JAK2 ; however, JAK2V617F mutation, which is often seen in approximately 50% of patients with myelofibrosis, was shown to reduce ruxolitinib sensitivity, which may also be associated with possible resistance to JAK inhibitor treatment.","The Janus kinase (JAK) family of protein tyrosine kinases comprises JAK1, JAK2, JAK3, and non-receptor tyrosine kinase 2 (TYK2). JAKs play a pivotal role in intracellular signalling pathways of various cytokines and growth factors essential to hematopoiesis, such as interleukin, erythropoietin, and thrombopoietin. JAKs have diverse functions: JAK1 and JAK3 promote lymphocyte differentiation, survival, and function, while JAK2 promotes signal transduction of erythropoietin and thrombopoietin. JAKs are in close proximity to the cytokine and growth factor receptor’s cytoplasmic region. Upon binding of cytokines and growth factors, JAKs are activated, undergoing cross-phosphorylation and tyrosine phosphorylation. This process also reveals selective binding sites for STATs, which are DNA-binding proteins that also bind to the cytoplasmic region of cytokine or growth factor receptors. Activated JAKs and STATs translocate to the nucleus as transcription factors to regulate gene expression of pro-inflammatory cytokines such as IL-6, IL-10, and nuclear factor κB (NF-κB). They also activate downstream pathways that promote erythroid, myeloid, and megakaryocytic development. \r\n\r\nThe molecular pathogenesis of myeloproliferative neoplasms is not fully understood; however, JAK2 is constitutively activated and the JAK-STAT signalling pathway becomes deregulated and aberrant. Ruxolitinib is a selective and potent inhibitor of JAK2 and JAK1, with some affinity against JAK3 and TYK2. Anticancer effects of ruxolitinib are attributed to its inhibition of JAKs and JAK-mediated phosphorylation of STAT3. By downregulating the JAK-STAT pathway, ruxolitinib inhibits myeloproliferation and suppresses the plasma levels of pro-inflammatory cytokines such as IL-6 and TNF-α. \r\n\r\nActivated JAKs are also implicated in graft-versus-host-disease (GVHD), which is a severe immune complication of allogeneic hematopoietic cell transplantation GVHD is associated with significant morbidity and mortality, especially for patients who do not respond well to corticosteroid therapy. Activated JAKS stimulate T-effector cell responses, leading to increased proliferation of effector T cells and heightened production of pro-inflammatory cytokines. By blocking JAK1 and JAk2, ruxolitinib inhibits donor T-cell expansion and suppresses pro-inflammatory responses.","Tyrosine-protein kinase JAK2 inhibitor; Tyrosine-protein kinase JAK1 inhibitor; Tyrosine-protein kinase JAK3 inhibitor; Non-receptor tyrosine-protein kinase TYK2 inhibitor","Therapeutic strategy associated"]
[1175,"DB08879","approved","biotech","Belimumab","Belimumab",null,null,"Belimumab is an intravenous immunosupressant for the adjunctive treatment of systemic lupus erythematosus (SLE). More specifically, it is a fully human recombinant IgG1λ monoclonal antibody produced from a recombinant NS0 cell line stably transfected with the belimumab heavy chain and light chain genes. It is the first biological treatment approved for the indication of SLE. Concomitant use with live or inactivated vaccines must be avoided. Belimumab was FDA approved on March 9, 2011. Belimumab consists of 2 heavy chains, and 2 light chains of the lambda subclass. Each heavy chain contains 452 amino acid residues and each light chain contains 214 amino acid residues. There are 3 post-translational modifications: a conserved N-linked glycosylation on the CH2 domain at Asn 303 of the heavy chain, the conversion of the N-terminal glutamine residue of the heavy chain into pyroglutamate, and loss of C-terminal lysine residue of the heavy chain.","356547-88-1",null,"Adjunct treatment for auto-antibody-positive active systemic lupus erythematosus (SLE). The intravenous injectable form is the only FDA approved treatment for pediatric patients with SLE.","By the 52nd week of treatment with belimumab, a reduction in CD19+, CD20+, naive and activated B cells, plasma cells, plasmacytoid cells, and SLE B-cell subset can be observed. Reductions in plasma cells and SLE B-cell subset can be seen by the eighth week and these levels were maintained to week 52. Belimumab also reduced levels of IgG and anti-dsDNA.","Belimumab selectively binds to soluble human B lymphocyte stimulator protein (BLyS) so that BLyS is unable to bind to receptors on B lymphocytes. The binding of BLyS to its receptor is essential for the survival of B lymphocytes. Consequently, belimumab reduces B-cell mediated immunity and the autoimmune response.\r","Tumor necrosis factor ligand superfamily member 13B neutralizer","Target associated"]
[1176,"DB08880","approved","small molecule","Teriflunomide","(Z)-2-cyano-alpha,alpha,alpha-trifluoro-3-hydroxy-p-crotonotoluidide; Teriflunomide","C12H9F3N2O2","C\\C(O)=C(/C#N)C(=O)NC1=CC=C(C=C1)C(F)(F)F","Teriflunomide is the active metabolite of leflunomide, and it acts as an immunomodulatory agent by inhibiting pyrimidine synthesis. It is marketed under the name Aubagio® and is indicated for the treatment of multiple sclerosis, specifically relapsing forms. The FDA label states an important warning about the risk of hepatoxicity and teratogenicity for patients using teriflunomide.","163451-81-8","270.2073","Used in the treatment of relapsing forms of multiple sclerosis (MS).","Teriflunomide is an immunomodulatory agent that decreases the amount of activated CNS lymphocytes, which results in anti-inflammatory and antiproliferative effects.\r","The exact mechanism by which teriflunomide acts in MS is not known. What is known is that teriflunomide prevents pyrimidine synthesis by inhibiting the mitochondrial enzyme dihydroorotate dehydrogenase, and this may be involved in its immunomodulatory effect in MS.","Dihydroorotate dehydrogenase (quinone), mitochondrial inhibitor","Therapeutic strategy associated"]
[1177,"DB08881","approved","small molecule","Vemurafenib",null,"C23H18ClF2N3O3S","CCCS(=O)(=O)NC1=C(F)C(C(=O)C2=CNC3=NC=C(C=C23)C2=CC=C(Cl)C=C2)=C(F)C=C1","Vemurafenib is a competitive kinase inhibitor with activity against BRAF kinase with mutations like V600E. It exerts its function by binding to the ATP-binding domain of the mutant BRAF. Vemurafenib was co-developed by Roche and Plexxikon and it obtained its FDA approval on August 17, 2011, under the company Hoffmann La Roche. After approval, Roche in collaboration with Genentech launched a broad development program.","918504-65-1","489.922","Vemurafenib is approved since 2011 for the treatment of metastatic melanoma with a mutation on BRAF in the valine located in the exon 15 at codon 600, this mutation is denominated as V600E. The V600E mutation, a substitution of glutamic acid for valine, accounts for 54% of the cases of cutaneous melanoma. \r\nVemurafenib approval was extended in 2017, for its use as a treatment of adult patients with Erdheim-Chester Disease whose cancer cells present BRAF V600 mutation. Erdheim-Chester disease is an extremely rare histiocyte cell disorder that affects large bones, large vessels, central nervous system, as well as, skin and lungs. It is reported an association of Erdheim-Chester disease and V600E mutation.","BRAF activation results in cell growth, proliferation, and metastasis. BRAF is an intermediary molecule in MAPK whose activation depends on ERK activation, elevation of cyclin D1 and cellular proliferation. The mutation V600E produces a constitutively form of BRAF. Vemurafenib has been shown to reduce all activation markers related to BRAF; in clinical trials, vemurafenib treatment showed a reduction of cytoplasmic phosphorylated ERK and a cell proliferation driven by Ki-67. Studies also reported decrease in MAPK-related metabolic activity. All the different reports indicate thet Vemurafenib generates an almost complete inhibition of the MAPK pathway.","Vemurafenib is an orally available inhibitor of mutated BRAF-serine-threonine kinase. Vemurafenif is a small molecule that interacts as a competitive inhibitor of the mutated species of BRAF. It is especially potent against the BRAF V600E mutation. Vemurafenib blocks downstream processes to inhibit tumour growth and eventually trigger apoptosis. Vemurafenib does not have antitumour effects against melanoma cell lines with the wild-type BRAF mutation.","Serine/threonine-protein kinase B-raf inhibitor","Therapeutic strategy associated"]
[1178,"DB08887","approved; investigational; nutraceutical","small molecule","Icosapent ethyl","(all-Z)-5,8,11,14,17-Eicosapentaenoic acid ethyl ester; all-cis-ethyl 5,8,11,14,17-icosapentaenoate; cis-Eicosapentaenoic acid ethyl ester; E-EPA; Eicosapentaenoic acid ethyl ester; ethyl (5Z,8Z,11Z,14Z,17Z)-eicosa-5,8,11,14,17-pentaenoate; ethyl (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate; ethyl (5Z,8Z,11Z,14Z,17Z)-icosapentaenoate; Ethyl (all cis)-5,8,11,14,17-icosapentaenoate; Ethyl all-cis-5,8,11,14,17-icosapentaenoate; Ethyl eicosapentaenoate; Ethyl icosapentate ; ethyl-eicosapentaenoic acid; Ethyl-EPA; Icosapent ethyl; Timnodonic acid ethyl ester","C22H34O2","CCOC(=O)CCC\\C=C/C\\C=C/C\\C=C/C\\C=C/C\\C=C/CC","Icosapent ethyl or ethyl eicosapentaenoic acid is a synthetic derivative of the omega-3 fatty acid eicosapentaenoic acid (EPA). It is used as adjunct therapy for severe hypertriglyceridemia (TG levels > 500 mg/dL). FDA approved on July 26, 2012.","86227-47-6","330.5042","Icosapent ethyl is used as adjunct therapy to reduce triglyceride (TG) levels in adults with severe (>500 mg/dL) hypertriglyceridemia.",null,"Studies suggest that EPA reduces hepatic very low-density lipoprotein triglycerides (VLDL-TG) synthesis and/or secretion and enhances TG clearance from circulating VLDL particles. Potential mechanisms of action include increased β-oxidation; inhibition of acyl-CoA:1,2-diacylglycerol acyltransferase (DGAT); decreased lipogenesis in the liver; and increased plasma lipoprotein lipase activity.",null,"Therapeutic strategy associated"]
[1179,"DB08889","approved; investigational","small molecule","Carfilzomib","Carfilzomib","C40H57N5O7","CC(C)C[C@H](NC(=O)[C@H](CCC1=CC=CC=C1)NC(=O)CN1CCOCC1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(=O)[C@@]1(C)CO1","Carfilzomib is an injectable antineoplastic agent (IV only). Chemically, it is a modified tetrapeptidyl epoxide and an analog of epoxomicin. It is also a selective proteasome inhibitor. FDA approved carfilzomib in July 2012 for the treatment of adults with relapsed or refractory multiple myeloma as monotherapy or combination therapy.","868540-17-4","719.9099","Carfilzomib is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy in combination with lenalidomide and dexamethasone; or dexamethasone; or daratumumab and dexamethasone; or daratumumab and hyaluronidase-fihj and dexamethasone. It is also indicated as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.","Intravenous carfilzomib administration resulted in suppression of proteasome chymotrypsin-like activity when measured in blood 1 hour after the first dose. On Day 1 of Cycle 1, proteasome inhibition in peripheral blood mononuclear cells (PBMCs) ranged from 79% to 89% at 15 mg/m2, and from 82% to 83% at 20 mg/m2. In addition, carfilzomib administration resulted in inhibition of the LMP2 and MECL1 subunits of the immunoproteasome ranging from 26% to 32% and 41% to 49%, respectively, at 20 mg/m2.  Proteasome inhibition was maintained for ≥ 48 hours following the first dose of carfilzomib for each week of dosing. Resistance against carfilzomib has been observed and although the mechanism has not been confirmed, it is thought that up-regulation of P-glycoprotein may be a contributing factor. Furthermore, studies suggest that carfilzomib is more potent than bortezomib.","Carfilzomib is made up of four modified peptides and acts as a proteasome inhibitor. Carfilzomib irreversibly and selectively binds to N-terminal threonine-containing active sites of the 20S proteasome, the proteolytic core particle within the 26S proteasome.  This 20S core has 3 catalytic active sites: the chymotrypsin, trypsin, and caspase-like sites. Inhibition of the chymotrypsin-like site by carfilzomib (β5 and β5i subunits) is the most effective target in decreasing cellular proliferation, ultimately resulting in cell cycle arrest and apoptosis of cancerous cells. At higher doses, carfilzomib will inhibit the trypsin-and capase-like sites.","Proteasome subunit beta type-5 inhibitor; Proteasome subunit beta type-8 inhibitor; Proteasome subunit beta type-1 inhibitor; Proteasome subunit beta type-9 inhibitor; Proteasome subunit beta type-2 inhibitor; Proteasome subunit beta type-10 inhibitor","Therapeutic strategy associated"]
[1180,"DB08890","approved","small molecule","Linaclotide","Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (disulfide bridge: 1-6; 2-10; 5-13); Linaclotide","C59H79N15O21S6","[H][C@]1(CSSC[C@]2([H])NC(=O)[C@H](CC3=CC=C(O)C=C3)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]3CSSC[C@H](NC(=O)[C@H](C)NC(=O)[C@@H]4CCCN4C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CSSC[C@H](N)C(=O)N3)NC2=O)C(=O)N[C@@]([H])([C@@H](C)O)C(=O)NCC(=O)N1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O","Linaclotide is an orally administered, peptide agonist of guanylate cyclase 2C for the treatment of irritable bowel syndrome. Chemically, it is a heterodetic cyclic peptide and consists of fourteen amino acids. The protein sequence is as follows: Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr. There are three disulfide bonds which are located between Cys1 and Cys6; between Cys2 and Cys10; and between Cys5 and Cys13. FDA approved on August 30, 2012.","851199-59-2","1526.736","Treatment of irritable bowel syndrome (IBS) with constipation and chronic idiopathic constipation.","Changes in the appearance and consistency of stools as measured by the Bristol Stool Form Scale (BSFS) have been noted after taking linaclotide.","Linaclotide is an agonist of guanylate cyclase-C (GC-C). Once linaclotide and its active metabolite binds to GC-C, it has local effect on the luminal surface of the intestinal epithelium. Activation of GC-C by linaclotide results in the intra- and extracellular increase of cyclic guanosine monophosphate concentrations (cGMP). This elevation of cGMP levels stimulates the secretion of chloride and bicarbonate into the intestinal lumen via activation of cystic fibrosis transmembrane conductance regulator (CFTR) ion channel. Ultimately, linaclotide helps patients with IBS (especially with constipation) as GI transit is accelerated and the release of intestinal fluid is increased. In animal models, a decrease in visceral pain after administration of linaclotide may be observed. A decrease in the activity of pain-sensing nerves occurs as a result of an increase in extracellular cGMP.","Heat-stable enterotoxin receptor agonist","Therapeutic strategy associated"]
[1181,"DB08895","approved; investigational","small molecule","Tofacitinib","Tasocitinib","C16H20N6O","C[C@@H]1CCN(C[C@@H]1N(C)C1=NC=NC2=C1C=CN2)C(=O)CC#N","Tofacitinib is an inhibitor of Janus kinases, a group of intracellular enzymes involved in signalling pathways that affect hematopoiesis and immune cell function. It is approved by the FDA for treatment of moderate to severe rheumatoid arthritis that responds inadequately to methotrexate or in those who are intolerant to methotrexate. \r\nBesides rheumatoid arthritis, tofacitinib has also been studied in clinical trials for the prevention of organ transplant rejection, and is currently under investigation for the treatment of psoriasis. Known adverse effects include nausea and headache as well as more serious immunologic and hematological adverse effects. Tofacitinib is marketed under the brand name Xeljanz by Pfizer.","477600-75-2","312.3696","For the treatment of moderate to severe rheumatoid arthritis which is resistant or intolerant to methotrexate therapy. It may also be used as an adjunct to methotrexate therapy, or other non-biologic disease-modifying antirheumatic drugs (DMARDS), when methotrexate alone is not sufficient.  \r\n\r\nTofacitinib has also been investigated as a preventative therapy for kidney transplant rejections, and as a treatment for psoriasis, ulcerative colitis, and ankylosing spondylitis. \r\n\r\nIt is not to be initiated in patients with a history of chronic or recurrent infections, or in the presence of active infection, even if localized, due to reports of serious and sometimes fatal infections (commonly pneumonia, herpes zoster and urinary tract infections). Use of tofacitinib is also discouraged in those who have been, or are likely to be, exposed to TB. An increased likelihood of exposure may be encountered by traveling to certain areas. In addition, tofacitinib is not to be used in patients with severe hepatic impairment, or low hemoglobin (less than 9g/dL). Cautioned is advised when using tofacitinib in patients at risk of gastrointestinal perforation, and in the elderly who are more susceptible to infection.","Tofacitinib targets inflammation present in rheumatoid arthritis by inhibiting the janus kinases involved in the inflammatory response pathway. \r\n\r\nIn placebo controlled trials of rheumatoid arthritis patients receiving 5mg or 10mg of tofacitinib twice daily, higher ACR20 responses were observed within 2 weeks in some patients (with ACR20 being defined as a minimum 20% reduction in joint pain or tenderness and 20% reduction in arthritis pain, patient disability, inflammatory markers, or global assessments of arthritis by patients or by doctors, according to the American College of Rheumatology (ACR) response criteria list), and improvements in physical functioning greater than placebo were also noted. \r\n\r\nCommon known adverse effects of tofacitinib include headaches, diarrhea, nausea, nasopharyngitis and upper respiratory tract infection. More serious immunologic and hematological adverse effects have also been noted resulting in lymphopenia, neutropenia, anemia, and increased risk of cancer and infection. \r\n\r\nBefore initiations of tofacitinib patients should be tested for latent infections of tuberculosis, and should be closely monitored for signs and symptoms of infection (fungal, viral, bacterial, or mycobacterial) during therapy. Therapy is not to be started in the presence of active infection, systemic or localized, and is to be interrupted if a serious infection occurs. \r\n\r\nTofacitinib has been associated with an increased risk of lymphomas, such as Epstein-Barr virus associated lymphomas, and other malignancies (including lung, breast, gastric, and colorectal cancers). It is recommended to monitor lymphocytes, neutrophils, hemoglobin, liver enzymes, and lipids. \r\n\r\nTofacitinib use is associated with a rapid decrease in C-reactive protein (CRP), dose dependent decreases in natural killer cells, and dose dependent increases in B cells. Depression in C-reactive protein levels continue after 2 weeks of tofacitinib discontinuation and suggest that pharmacodynamic activity last longer than pharmacokinetic half life.","Rheumatoid arthritis is an autoimmune disease characterized by a dysregulation of pro-inflammatory cytokines including IL7, IL15, IL21, IL6, IFN-alpha, and IFN-beta. (3) Cytokines signalling results in tissue inflammation and joint damage by stimulating the recruitment and activation of immune cells via the janus kinase signalling pathway.\r\n\r\nTofacitinib is a partial and reversible janus kinase (JAK) inihibitor that will prevent the body from responding to cytokine signals. By inhibiting JAKs, tofacitinib prevents the phosphorylation and activation of STATs. The JAK-STAT signalling pathway is involved in the transcription of cells involved in hematopoiesis, and immune cell function. Tofacitinib works therapeutically by inhibiting the JAK-STAT pathway to decrease the inflammatory response. However, there is evidence to suggest that it may also achieve efficacy via other pathways as well. \r\n\r\n\r","Tyrosine-protein kinase JAK1 inhibitor; Tyrosine-protein kinase JAK2 antagonist&inhibitor; Tyrosine-protein kinase JAK3 inhibitor; Non-receptor tyrosine-protein kinase TYK2","Therapeutic strategy associated"]
[1182,"DB08899","approved","small molecule","Enzalutamide","Enzalutamide","C21H16F4N4O2S","CNC(=O)C1=C(F)C=C(C=C1)N1C(=S)N(C(=O)C1(C)C)C1=CC=C(C#N)C(=C1)C(F)(F)F","Enzalutamide is an androgen receptor inhibitor for the treatment of castration-resistant prostate cancer. FDA approved on August 31, 2012.","915087-33-1","464.436","Enzalutamide is indicated for the treatment of patients with metastatic castration-resistant prostate cancer who have previously received docetaxel.","Resitance to enzalutamide therapy has been observed. This may occurred due to an upregulation of NF-κB2/p52.","Enzalutamide is a competitive androgen receptor inhibitor that effects multiple stages of the signalling pathway. It is able to inhibit androgen binding to its receptor, androgen receptor nuclear translocation, and subsequent interaction with DNA. As a result, proliferation of prostate cancer cells decreases which ultimately leads to apoptosis and decreased tumour volume.","Androgen receptor inhibitor","Therapeutic strategy associated"]
[1183,"DB08904","approved","biotech","Certolizumab pegol","Certolizumab pegol",null,null,"Certolizumab pegol is a pegylated monoclonal antibody against the tumor necrosis factor-alpha (TNF-alpha). It is formed with a humanized Fab fragment of 50 kDa, from an IgG 1 isotype, fused to a 40 kDa polyethylene glycol moiety replacing the Fc antibody region. The absence of the Fc region was ideated to prevent complement fixation and antibody-mediated cytotoxicity as well as to markedly increase its half-life. \r\n\r\nCertolizumab does not require glycosylation for active function and hence, its production is significantly more affordable when compared to other existing TNF-alpha therapies as it can be done directly in bacterial hosts such as _E. coli_. It was developed and manufactured by UCB Pharma, first FDA approved in 2008 and updated for a new indication on March 28, 2019.","428863-50-7",null,"Certolizumab pegol has been approved for several different conditions listed below:\r\n\r\n- Symptomatic management of Chron's disease patients and for the maintenance of clinical response in patients with moderate to severe disease with inadequate response to conventional therapy.\r\n- Treatment of adult patients with moderate to severely active rheumatoid arthritis.\r\n- Treatment of adult patients with active psoriatic arthritis.\r\n- Treatment of adult patients with active ankylosing spondylitis.\r\n- Treatment of adult patients with moderate-to-severe plaque psoriasis that are candidates for systemic therapy or phototherapy.\r\n- Treatment of adult patients with active non-radiographic axial spondyloarthritis with objective signs of inflammation.\r\n\r\nIn Canada, certolizumab pegol is additionally approved in combination with  for the symptomatic treatment, including major clinical response, and for the reduction of joint damage in adult patients with moderately to severely active rheumatoid arthritis and psoriatic arthritis.\r\n\r\nInflammation is a biological response against a potential threat. This response can be normal but in certain conditions, the immune system can attack the body's normal cells or tissues which causes an abnormal inflammation. TNF-alpha has been identified as a key regulator of the inflammatory response. The signaling cascades of this inflammatory mediator can produce a wide range of reactions including cell death, survival, differentiation, proliferation and migration.","As part of the mechanism of action and nature of the drug, certolizumab does not induce apoptosis in cultured lymphocytes and monocytes. However, as a piece of the inhibition of inflammation, certolizumab pegol inhibits lipopolysaccharide-induced production of IL-1 beta and it induces nonapoptotic cell death via signaling transmembrane TNF-alpha. \r\n\r\nIn vitro studies with certolizumab pegol in human tissue did not show any unexpected binding at 3 mcg/ml nor at 10 mcg/ml. Due to the drug class, certolizumab pegol is not expected to present adverse effects on the major vital systems.\r\n\r\nIn phase III clinical trials in psoriatic arthritis patients, certolizumab pegol was reported to generate improvements in skin disease, joint involvement, dactylitis, enthesitis and general life quality. The clinical effect of certolizumab was paired to a comparable safety profile to other TNF-alpha inhibitors.\r\n\r\nThe clinical effectiveness of certolizumab pegol was mainly studied in six randomized controlled trials that compared its effect versus placebo. In a comparative study, the efficacy for certolizumab pegol registered ranged from 30-65% while in placebo ranged from 4-25%. However, in other additional trials, certolizumab was proven to present a similar clinical efficacy to other disease-modifying antirheumatic drugs in patients with inadequate response to TNF inhibitors.","Certolizumab targets the activation of TNF-alpha with high affinity (KD 90 pM and IC90 0.004 mcg/ml) which in order, inhibits the downstream inflammatory process. It acts by binding and neutralizing the soluble and membrane portions of TNF-alpha without inducing complement or antibody-dependent cytotoxicity due to the lack of the Fc region. The inhibition of TNF-alpha is achieved in a dose-dependent manner and it does not present activity against lymphotoxin alpha (TNF-beta).\r\n\r\nOne additional feature od certolizumab pegol is that, due to the presence of the PEGylation, it is more significantly distributed into inflamed tissues when compared to other TNF-alpha inhibitors such as  and .","Tumor necrosis factor neutralizer","Therapeutic strategy associated"]
[1184,"DB08908","approved; investigational","small molecule","Dimethyl fumarate","(E)-But-2-enedioic acid dimethyl ester; 1,2-bis(methoxycarbonyl)-trans-ethylene; Dimethyl fumarate; Dimethyl trans-ethylenedicarboxylate; Fumaric acid, dimethyl ester; trans-1,2-Ethylenedicarboxylic acid dimethyl ester; trans-Butenedioic acid dimethyl ester","C6H8O4","[H]\\C(=C(\\[H])C(=O)OC)C(=O)OC","Dimethyl fumarate is an anti-inflammatory. It is indicated for multiple sclerosis patients with relapsing forms and is also being investigated for the treatment of psoriasis. The mechanism of action of dimethyl fumarate in multiple sclerosis is not well understood. It is thought to involve dimethyl fumarate degradation to its active metabolite monomethyl fumarate (MMF) then MMF up-regulates the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway that is activated in response to oxidative stress. Dimethyl fumarate is marketed under the brand name Tecfidera.","624-49-7","144.1253","Used in multiple sclerosis patients with relapsing forms.","The physiological effects dimethyl fumarate has on the body is not well understood. It is known that dimethyl fumarate has anti-inflammatory and cytoprotective effects, which both are likely involved in its actions in multiple sclerosis patients.","The mechanism of action of dimethyl fumarate in multiple sclerosis is not well understood. It is thought to involve dimethyl fumarate degradation to its active metabolite monomethyl fumarate (MMF). MMF up-regulates the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway that is activated in response to oxidative stress. As well MMF is an agonist at the nicotinic acid receptor, but the relevance of this is not known.","Kelch-like ECH-associated protein 1 binder; Transcription factor p65","Therapeutic strategy associated"]
[1185,"DB08910","approved","small molecule","Pomalidomide","Pomalidomide","C13H11N3O4","NC1=CC=CC2=C1C(=O)N(C1CCC(=O)NC1=O)C2=O","Pomalidomide, an analogue of thalidomide, is an immunomodulatory antineoplastic agent. FDA approved on February 8, 2013.","19171-19-8","273.2441","Pomalidomide is indicated for patients with multiple myeloma who have received at least two prior therapies including lenalidomide and bortezomib and have demonstrated disease progression on or within 60 days of completion of the last therapy.","Pomalidomide is more potent than thalidomide (100-times) and lenalidomide (10-times).","Promalidomide is an immunomodulatory agent with antineoplastic activity. It is shown to inhibit the proliferation and induce apoptosis of various tumour cells. Furthermore, promalidomide enhances T cell and natural killer (NK) cell-mediated immunity and inhibited the production of pro-inflammatory cytokines, like TNF-alpha or IL-6, by monocytes. The primary target of promalidomide is thought to be the protein cereblon. It binds to this target and inhibits ubiquitin ligase activity. It is also a transcriptional inhibitor of COX2.","Protein cereblon inhibitor; Tumor necrosis factor inhibitor; Prostaglandin G/H synthase 2 inhibitor","Therapeutic strategy associated"]
[1186,"DB08911","approved","small molecule","Trametinib",null,"C26H23FIN5O4","CN1C(=O)C(C)=C2N(C(=O)N(C3CC3)C(=O)C2=C1NC1=CC=C(I)C=C1F)C1=CC(NC(C)=O)=CC=C1","Trametinib dimethyl sulfoxide is a kinase inhibitor. Each 1-mg tablet contains 1.127 mg trametinib dimethyl sulfoxide equivalent to 1 mg of trametinib non-solvated parent. FDA approved on May 29, 2013 .\r\n\r\nThe U.S. Food and Drug Administration approved (Tafilnar) and Mekinist (trametinib), administered together, for the treatment of anaplastic thyroid cancer (ATC) that cannot be removed by surgery or has spread to other parts of the body (metastatic), and has a type of abnormal gene, BRAF V600E (BRAF V600E mutation-positive) .\r\n\r\nThyroid cancer is a disease in which cancer cells form in the tissues of the thyroid. Anaplastic thyroid cancer is a rare, aggressive type of thyroid cancer. The National Institutes of Health (NIH) estimates there will be 53,990 new cases of thyroid cancer and an estimated 2,060 deaths from the disease in the United States in 2018. Anaplastic thyroid cancer accounts for approximately 1 to 2 percent of all thyroid cancers .","871700-17-3","615.3948","Trametinib is indicated for the treatment of unresectable or metastatic melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test .\r\n\r\nIn May 2018, it was approved for use with  for the treatment of treat anaplastic thyroid cancer caused by an abnormal BRAF V600E gene .","Trametinib is an anticancer agent which causes apoptosis (or programmed cell death) and inhibits cell proliferation, which are both important in the treatment of malignancies .","Trametinib is a reversible, allosteric inhibitor of mitogen-activated extracellular signal regulated kinase 1 _(MEK1)_ and _MEK2_ activation and of_ MEK1_ and _MEK2_ kinase activity. MEK proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway, which promotes cellular proliferation. Trametinib helps with melanoma with the BRAF V600E or V600K as the mutation results in the constitutive activation of the BRAF pathway which includes MEK1 and MEK2 .","Dual specificity mitogen-activated protein kinase kinase 1 antagonist&inhibitor; Dual specificity mitogen-activated protein kinase kinase 2 antagonist&inhibitor","Therapeutic strategy associated"]
[1187,"DB08915","investigational","small molecule","Aleglitazar","Aleglitazar","C24H23NO5S","CO[C@@H](CC1=CC=C(OCCC2=C(C)OC(=N2)C2=CC=CC=C2)C2=C1SC=C2)C(O)=O","Aleglitazar is an investigational drug from the company Hoffmann–La Roche and is currently in a phase III clinical trial called ALECARDIO. It is being investigated for use in patients with type II diabetes to reduce their risks of cardiovascular mortality and morbidity. Aleglitazar is an agonist at the peroxisome proliferator-activated receptor (PPAR) for both the PPARα and PPARγ receptor subtypes. In the phase II clinical trial called SYNCHRONY, with type II diabetic patients, aleglitazar was able to control both lipid and glucose levels in a synergistic manner while also having limited side effects and toxicity.","475479-34-6","437.508","Investigated for use in patients with type II diabetes to reduce their risks of cardiovascular mortality and morbidity.",null,"Aleglitazar was rationally designed to be an agonist at the peroxisome proliferator-activated receptor (PPAR) for both the PPARα and PPARγ receptor subtypes. Agonistic action at PPARα controls lipid levels, which improves dyslipidemia, and agonistic action at PPARγ controls glucose levels, which improves insulin sensitivity in diabetes.","Peroxisome proliferator-activated receptor alpha agonist; Peroxisome proliferator-activated receptor gamma agonist; Nuclear receptor coactivator 1","Target associated"]
[1188,"DB08931","approved","small molecule","Riociguat","Methyl N-[4,6-Diamino-2-[1-[(2-fluorophenyl)methyl]-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinyl]-N-methyl-carbaminate","C20H19FN8O2","COC(=O)N(C)C1=C(N)N=C(N=C1N)C1=NN(CC2=C(F)C=CC=C2)C2=C1C=CC=N2","Riociguat is a soluble guanylate cyclase (sGC) agonist approved in the USA, Europe and several other regions for patients with group I PAH (pulmonary arterial hypertension) in WHO FC II or III; and for the treatment of patients with inoperable CTEPH (chronic thromboembolic pulmonary hypertension), or persistent/recurrent PH (pulmonary hypertension) after pulmonary endarterectomy in WHO FC II or III. Riociguat is marketed under the brand Adempas® by Bayer HealthCare Pharmaceuticals. Treatment with riociguat costs USD $7,500 for 30 days of treatment.","625115-55-1","422.4157","Riociguat is indicated for the treatment of adults with persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH), (WHO Group 4) after surgical treatment, or inoperable CTEPH, to improve exercise capacity and WHO functional class.\r\nRiociguat is indicated for the treatment of adults with pulmonary arterial hypertension (PAH), (WHO Group 1), to improve exercise capacity, WHO functional class and to delay clinical worsening. Efficacy was shown in patients on Riociguat monotherapy or in combination with endothelin receptor antagonists or prostanoids. Studies establishing effectiveness included predominately patients with WHO functional class II–III and etiologies of idiopathic or heritable PAH (61%) or PAH associated with connective tissue diseases (25%).",null,"Riociguat is a stimulator of soluble guanylate cyclase (sGC), an enzyme in the cardiopulmonary system and the receptor for nitric oxide (NO). When NO binds to sGC, the enzyme catalyzes synthesis of the signaling molecule cyclic guanosine monophosphate (cGMP). Intracellular cGMP plays an important role in regulating processes that influence vascular tone, proliferation, fibrosis and inflammation. Pulmonary hypertension is associated with endothelial dysfunction, impaired synthesis of nitric oxide and insufficient stimulation of the NO-sGC-cGMP pathway. \r\n\r\nRiociguat has a dual mode of action. It sensitizes sGC to endogenous NO by stabilizing the NO-sGC binding. Riociguat also directly stimulates sGC via a different binding site, independently of NO. Riociguat stimulates the NO-sGC-cGMP pathway and leads to increased generation of cGMP with subsequent vasodilation.","Guanylate cyclase soluble subunit alpha-2 agonist&stimulator","Therapeutic strategy associated"]
[1189,"DB08932","approved","small molecule","Macitentan",null,"C19H20Br2N6O4S","CCCNS(=O)(=O)NC1=C(C(OCCOC2=NC=C(Br)C=N2)=NC=N1)C1=CC=C(Br)C=C1","Macitentan is a dual endothelin receptor antagonist used in the treatment of pulmonary arterial hypertension. It was first approved by the FDA in 2013. Macitentan differs from its predecessor  due to its lower risk of hepatotoxicity.","441798-33-0","588.273","Macitentan is indicated for the treatment of WHO group 1 pulmonary arterial hypertension (PAH) both alone and in combination with tadalafil.","Macitentan acts primarily by reducing vasoconstriction and cell proliferation due to endothelin overexpression.","Macitentan is an antagonist which binds to the endothelin A and B receptors (E<sub>A</sub> and E<sub>B</sub>) and blocks signaling from endothelin-1 and -2. Pulmonary arterial hypertension has many different mechanisms which contribute to the development of endothelial dysfunction including elevated cytosolic calcium, genetic factors, epigenetic changes, and mitochondrial dysfunction. The focus of macitentan's mechanism relates to the role of overexpressed endothelin from the vascular endothelium. Endothelins are released in both a constitutive fashion from secretory vesicles and in response to stimuli via Weibel-Palade storage granules. Endothelins bind to the E<sub>A</sub> and E<sub>B</sub> receptors, with endothelins -1 and -2 having more affinity than endothelin-3. Binding to the Gq coupled E<sub>A</sub> receptor triggers Ca2+ release from the sarcoplasmic reticulum of smooth muscle cells via the phospholipase C (PLC) pathway. Downstream protein kinase C activation may also contribute to increased Ca2+ sensitivity of the contractile apparatus. E<sub>A</sub> receptor activation is also known to contribute to pulmonary artery smooth muscle cell proliferation. The binding of endothelins to the E<sub>B</sub> receptors acts in opposition to E<sub>A</sub> signaling by activating the same PLC cascade in endothelial cells to activate endothelial nitric oxide synthase. The subsequent release of nitric oxide produces vasodilation through the cyclic guanosine monophosphate cascade. Despite the greater presence of E<sub>B</sub> receptors on endothelial cells, they are still present on smooth muscle cells and may contribute to cell proliferation through the same mechanisms as E<sub>A</sub> receptors. Macitentan is thought to provide its therapeutic effect primarily via blocking signaling through E<sub>A</sub> which produces both decreased vasoconstriction via reduced smooth muscle cell contractility and attenuation of the hyperproliferation of smooth muscle cells found in PAH. Blockade of E<sub>B</sub> is less likely to contribute to a therapeutic effect as this signaling is responsible for the counter-regulatory vasodilatory signal.","Endothelin-1 receptor antagonist; Endothelin B receptor antagonist","Indication associated"]
[1190,"DB08949","approved; withdrawn","small molecule","Inositol nicotinate","hexanicotol; Inositol hexanicotinate; Inositol niacinate; Inositol nicotinate; mesoinositol hexanicotinate; myo-inositol hexanicotinate","C42H30N6O12","O=C(O[C@H]1[C@H](OC(=O)C2=CC=CN=C2)[C@@H](OC(=O)C2=CC=CN=C2)[C@H](OC(=O)C2=CC=CN=C2)[C@H](OC(=O)C2=CC=CN=C2)[C@@H]1OC(=O)C1=CC=CN=C1)C1=CC=CN=C1","Inositol nicotinate, also known as Inositol hexaniacinate/hexanicotinate or \"no-flush niacin\", is a niacin ester and vasodilator. It is used in food supplements as a source of niacin (vitamin B3), where hydrolysis of 1 g (1.23 mmol) inositol hexanicotinate yields 0.91 g nicotinic acid and 0.22 g inositol. Niacin exists in different forms including nicotinic acid, nicotinamide and other derivatives such as inositol nicotinate. It is associated with reduced flushing compared to other vasodilators by being broken down into the metabolites and inositol at a slower rate. Nicotinic acid plays an essential role in many important metabolic processes and has been used as lipid-lowering agent. Inositol nicotinate is prescribed in Europe under the name Hexopal as a symptomatic treatment for severe intermittent claudication and Raynaud’s phenomenon.","6556-11-2","810.732","Indicated as a dietary supplement for the source of niacin. Has been investigated for potential beneficial effects on serum lipids. In Europe, inositol hexanicotinate is indicated as a patented drug known as Hexopal, which is therapeutically indicated for the symptomatic relief of severe intermittent claudication and Raynaud’s phenomenon.","Inositol nicotinate mediates a vasodilatory, lipid-lowering and fibrinolytic effect on the cardiovascular system. Like other niacins, inositol nicotinate is a lipid-regulating agent that reduces the levels of plasma triglycerides, atherogenic apolipoprotein B (apoB)-containing lipoproteins (VLDL, LDL and lipoprotein a) while increasing antiatherogenic apoA-I-containing HDL levels .","Inositol nicotinate and other niacins directly and noncompetitively inhibit microsomal enzyme diacylglycerol acyltransferase 2 (DGAT2) responsible for esterification of fatty acids to form triglycerides, resulting in decreased triglyceride synthesis and hepatic atherogenic lipoprotein secretion. Inhibitied triglyceride synthesis results in accelerated intracellular hepatic apo B degradation and the decreased secretion of VLDL and LDL particles . Niacin also inhibits hepatic expression of beta-chain adenosine triphosphate synthase which inhibits the removal or uptake of HDL–apo A-I. It is also suggested that niacin increases vascular endothelial cell redox state, resulting in the inhibition of oxidative stress and vascular inflammatory genes or key cytokines involved in atherosclerosis. It acts as a ligand on G-protein coupled receptor 109A (HCAR2/HM74A) and 109B (HCAR3/HM74) which mediates the anti-lipolytic and lipid-lowering effects of nicotinic acid. Niacin-mediated signalling of GPR109A expressed on adipocytes and G(i)-mediated decrease in cAMP levels result in decreased lipolysis, fatty acid mobilization, and triglyceride synthesis. The action of inositol nicotinate on GPR109A expressed on skin and macrophages to cause increased prostaglandin D2/E2 activity is thought to be less significant compared to other niacin molecules as it involves sustained release that leads to less flushing .","Hydroxycarboxylic acid receptor 3 agonist; Hydroxycarboxylic acid receptor 2 agonist","Therapeutic strategy associated"]
[1191,"DB08995","approved; investigational","small molecule","Diosmin","3',5,7-trihydroxy-4'-methoxyflavone 7-rhamnoglucoside; 3',5,7-trihydroxy-4'-methoxyflavone-7-rutinoside; diosmetin 7-neohesperidoside; Diosmetin 7-O-rutinoside","C28H32O15","COC1=C(O)C=C(C=C1)C1=CC(=O)C2=C(O)C=C(O[C@@H]3O[C@H](CO[C@@H]4O[C@@H](C)[C@H](O)[C@@H](O)[C@H]4O)[C@@H](O)[C@H](O)[C@H]3O)C=C2O1","Chronic venous insufficiency is a common condition the western population. Compression and pharmacotherapy are frequently used to manage chronic venous insufficiency, improving circulation and symptoms of venous disease.\r\n\r\nDiosmin is a bioflavonoid isolated from various plants or synthesized from . It is used for the improvement of capillary fragility or venous insufficiency, including chronic venous insufficiency (CVI) and hemorrhoids. Diosmin is widely available over-the-counter and demonstrates a favourable a favorable safety profile.","520-27-4","608.5447","Diosmin is used over-the-counter alone or with ingredients such as  and  to support vein and capillary function.","Diosmin is a venoactive drug supporting  circulatory health through various actions on blood vessels; it supports lymphatic drainage and improves microcirculation while increasing  venous tone and elasticity. For these reasons, diosmin is frequently taken by individuals with chronic venous disease to support vascular health and has been demonstrated to improve quality of life. In addition to the above effects, diosmin exerts antioxidant activity and scavenges oxygen free radicals, reducing levels of oxidative stress normally detected through biomarkers such as prostaglandins isoprostane precursors.\r\n\r\nIn one clinical study, mean content of TNF alpha, VEGF-C, VEGF-A IL-6, in addition to FGF2 were decreased by after the therapy with diosmin; findings were statistically significant. Additionally, a decrease in edema and mean leg circumference of patients taking diosmin for three months was observed in a clinical study. Diosmin has been demonstrated to enhance the metabolism of glucose in diabetic disorders.\r","Diosmin helps to maintain circulatory system structure and function, particularly vein strength and competence. The molecular mechanism of action of diosmin has not been established. Several resources indicate that diosmin binds to the  aryl hydrocarbon receptor, however clinical relevance to vascular function is unknown. One study demonstrates that oral diosmin exerts effects on the in vitro metabolism of noradrenaline by varicose veins, potentially benefitting vascular health.","Aryl hydrocarbon receptor agonist","Therapeutic strategy associated"]
[1192,"DB09006","experimental","small molecule","Clinofibrate","Clinofibrate","C28H36O6","CCC(C)(OC1=CC=C(C=C1)C1(CCCCC1)C1=CC=C(OC(C)(CC)C(O)=O)C=C1)C(O)=O","Clinofibrate is a fibrate drug sold and marketed in Japan.","30299-08-2","468.59",{"$nulls":3},"Peroxisome proliferator-activated receptor alpha; Peroxisome proliferator-activated receptor gamma; Peroxisome proliferator-activated receptor delta","Target associated"]
[1193,"DB09012","experimental; withdrawn","small molecule","Carbazochrome","3-Hydroxy-1-methyl-5,6-inodlindionsemicarbazon; Adchnon; Adedolon; Adrenostan; Carbazochrome","C10H12N4O3","CN1CC(O)C2=C\\C(=N\\NC(N)=O)C(=O)C=C12","Carbazochrome is a hemostatic agent that promotes clotting, preventing blood loss from open wounds. It is an oxidation product of adrenaline which enhances the microcirculatory tone . In the future this may prevent excessive blood flow during surgical operations and the treatment of hemorrhoids, but research on effectiveness and severity of side effects remains inconclusive. It is not FDA-approved but is available as tablets or IM/SC injections in the treatment of hemorrhages in a number of countries.\r\n\r\nCarbazochrome has been investigated for use in the treatment of non-surgical acute uncomplicated hemorrhoids in a mixture with , and this combination therapy demonstrated efficacy and safe tolerability either at a local or systemic level .","69-81-8","236.231","Indicated for capillary and parenchymal hemorrhage (trauma, tonsillectomy, during surgery), intestinal bleeding, and thrombocytopenic purpura.","Carbazochrome is an anti-bleeding agent that increases platelet aggregation and forms a platelet plug by interacting with α-adrenoreceptors on surface of platelets . It is shown to improve the structure of local capillary vessels in haemorrhage caused by fragility of capillaries. Carbazochrome capillary stabilizer that reverses pulmonary vascular hyperpermeability and decreases arterial PaO2 in experimental models .","Carbazochrome interacts with platelet surface α-adrenoreceptors which are Gq-coupled receptors that leads to activation of PLC IP3/DAG pathway and increase in intracellular calcium levels. Elevated calcium ions bind to calmodulin and activates Ca2+/calmodulin-dependent myosin light chain kinase, allowing the myosin crossbridge to bind to the actin filament and polymerisation of globular actin (G-actin) to filamentous actin (F-actin) . Subsequent contraction of endothelial cells changes the shape of platelets and promotes the release of factors such as serotonin, ADP, Von Willebrand and platelet activating factor by platelets that induce aggregation and platelet adherence . Carbazochrome is reported to inhibit vascular hyperpermeability by inhibiting agonist-induced phosphoinositides hydrolysis caused by various vasoactive agents such as tryptase, thrombin and bradykinin .",null,"Therapeutic strategy associated"]
[1194,"DB09020","approved","small molecule","Bisacodyl","Phenol, 4,4'-(2-pyridinylmethylene)bis-, diacetate (ester)","C22H19NO4","CC(=O)OC1=CC=C(C=C1)C(C1=CC=C(OC(C)=O)C=C1)C1=CC=CC=N1","Bisacodyl, a diphenylmethane derivative, is a commonly used over the counter stimulant laxative for occasional constipation. Both bisacodyl and  are metabolized to the same active metabolite bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM).\r\n\r\nBisacodyl was patented on 25 September 1956 but has been used as a laxative since 1952.","603-50-9","361.3906","Bisacodyl is indicated to relieve occasional constipation and irregularity.","Patients should be counselled regarding abdominal pain, nausea, vomiting, or a change in bowel function that lasts longer than 2 weeks. It has a wide therapeutic index, as patients can take 5-15 mg orally. Patients taking bisacodyl should be counselled before taking the medication if they are already experiencing abdominal pain, nausea, vomiting, or a change in bowel function lasting longer than 2 weeks. Patients should also be counselled to stop taking the medication if they experience rectal bleeding or no bowel movement in 12 hours.","Bisacodyl is deacetylated to the active bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM) by an intestinal deacetylase. BHPM can stimulate parasympathetic nerves in the colon directly to increase motility and secretions.\r\n\r\nBisacodyl stimulates adenylate cyclase, increasing cyclic AMP, leading to active transport of chloride and bicarbonate out of cells. Sodium ions, potassium ions, and water passively leave the cell; while sodium and chloride ions are unable to be reabsorbed.\r\n\r\nWater is also be transported from the luminal side of cells into the vasculature by aquaporin 3. Bisacodyl decreases expression of aquaporin 3, preventing water from moving into the vasculature, which may contribute to increased water in the colon.\r\n\r\nBisacodyl directly stimulates parasympathetic nerves in the colon, stimulating contraction of longitudinal smooth muscle but not circular smooth muscle.","Aquaporin-3 negative modulator; Sodium/Potassium Transporting ATPase subunits inhibitor","Indication associated"]
[1195,"DB09026","approved; investigational","small molecule","Aliskiren","Aliskiren","C30H53N3O6","COCCCOC1=C(OC)C=CC(C[C@@H](C[C@H](N)[C@@H](O)C[C@@H](C(C)C)C(=O)NCC(C)(C)C(N)=O)C(C)C)=C1","Aliskiren is the first drug in the renin inhibitor drug class and is used for the treatment of hypertension. It was developed by Speedel and Novartis and initially approved by the FDA in early 2007. Aliskiren has been proven to efficacious in reducing blood pressure when used alone or in conjunction with other antihypertensive agents.","173334-57-1","551.7583","Aliskiren is used for the treatment of hypertension in children above 6 years and adults. This drug may also be used in conjunction with antihypertensives such as calcium channel blockers and thiazides in products form to provide additional blood pressure control.","Aliskiren reduces blood pressure by inhibiting renin. This leads to a cascade of events that decreases blood pressure, lowering the risk of fatal and nonfatal cardiovascular events including stroke and myocardial infarction.","Aliskiren is a renin inhibitor. Renin is secreted by the kidneys when blood volume and renal perfusion decrease. It normally cleaves the protein angiotensinogen to form angiotensin I. Angiotensin I is then converted to angiotensin II, an active protein. Angiotensin II is a potent vasoconstrictor that causes the release of catecholamines into the circulation.  It also promotes the secretion of aldosterone in addition to sodium reabsorption, increasing blood pressure. Additionally, angiotensin II acts on the adrenal cortex where it stimulates aldosterone release. Aldosterone increases sodium reabsorption and potassium excretion in the nephron. \r\n\r\nAliskiren prevents the above process via binding to renin at its active site, stopping the cleavage of angiotensin, in turn inhibiting the formation of angiotensin I. This ends the cascade of angiotensin II mediated mechanisms that normally increase blood pressure. \r\n\r","Renin inhibitor","Indication associated"]
[1196,"DB09030","approved","small molecule","Vorapaxar","Carbamic acid, [(1R,3aR,4aR,6R,8aR,9S,9aS)-9-[(1E)-2-[5-(3-fluorophenyl)-2- pyridinyl]ethenyl]dodecahydro-1-methyl-3-oxonaphtho[2,3-c]furan-6-yl]-, ethyl ester; Carbamic acid, N-[(1R,3aR,4aR,6R,8aR,9S,9aS)-9-[(E)-2-[5-(3-fluorophenyl)-2-pyridinyl]ethenyl]dodecahydro-1-methyl-3-oxonaphtho[2,3-c]furan-6-yl]-, ethyl ester; Ethyl N-[(3R,3aS,4S,4aR,7R,8aR,9aR)-4-[(E)-2-[5-(3-fluorophenyl)-2-pyridyl]vinyl]-3-methyl-1-oxo-3a,4,4a,5,6,7,8,8a,9,9a-decahydro-3H-benzo[f]isobenzofuran-7-yl]carbamate; Vorapaxar","C29H33FN2O4","[H][C@@]12C[C@]3([H])C[C@@H](CC[C@@]3([H])[C@H](\\C=C\\C3=CC=C(C=N3)C3=CC(F)=CC=C3)[C@]1([H])[C@@H](C)OC2=O)NC(=O)OCC","Vorapaxar is a tricyclic himbacine-derived selective inhibitor of protease activated receptor (PAR-1) indicated for reducing the incidence of thrombotic cardiovascular events in patients with a history of myocardial infarction (MI) or with peripheral arterial disease (PAD). By inhibiting PAR-1, a thrombin receptor expressed on platelets, vorapaxar prevents thrombin-related platelet aggregation.","618385-01-6","492.5817","Vorapaxar is indicated for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction (MI) or peripheral arterial disease (PAD). It is usually co-administered with acetylsalicylic acid (ASA) and/or clopidogrel, and should therefore be administered as an addition to these medications as it has not been studied alone.",null,"Vorapaxar inhibits platelet aggregation through the reversible antagonism of protease-activated receptor 1 (PAR-1), also known as thrombin receptor. PARs are a family of G-protein coupled receptors highly expressed on platelets and activated by serine protease activity of thrombin to mediate thrombotic response. By blocking PAR-1 activating, vorapaxar inhibits thrombin-induced platelet aggregation and thrombin receptor agonist peptide (TRAP)-induced platelet aggregation. Vorapaxar does not inhibit platelet aggregation induced by other agonists such as adenosine diphosphate (ADP), collagen or a thromboxane mimetic.","Proteinase-activated receptor 1 antagonist","Therapeutic strategy associated"]
[1197,"DB09031","approved; investigational","small molecule","Miltefosine","HDPC; hexadecyl 2-(trimethylazaniumyl)ethyl phosphate; Hexadecylphosphocholine; Hexadecylphosphorylcholine; Miltefosine; Monohexadecylphosphocholine; Monohexadecylphosphorylcholine","C21H46NO4P","CCCCCCCCCCCCCCCCOP([O-])(=O)OCC[N+](C)(C)C","Miltefosine is a broad spectrum antimicrobial, anti-leishmanial, phospholipid drug that was originally developed in the 1980s as an anti-cancer agent. It is currently the only recognized oral agent used to treat visceral, cutaneous, and mucosal forms of leishmaniasis, a neglected tropical disease. It can be administered topically or orally and is only indicated in patients aged 12 years or older. The CDC has also recommended it as a first line treatment for free-living amebae (FLA) infections such as primary amebic meningoencephalitis and granulomatous amebic encephalitis.","58066-85-6","407.576","For the treatment of mucosal (caused by Leishmania braziliensis), cutaneous (caused by L. braziliensis, L. guyanensis, and L. panamensis), and visceral leishmaniasis (caused by L. donovani). In comparing Leishmania drug susceptibility, it has been found that L. donovani is the most susceptible to miltefosine while L. major is the least susceptible.  Off-label use includes treatment of free-living amebae (FLA) infections (unlabeled use; CDC, 2013).","Little is known about the clinical pharmacodynamics of miltefosine and other antileishmanial drugs.","Miltefosine has demonstrated activity against Leishmania parasites and neoplastic cells primarily due to its effects on apoptosis and disturbance of lipid-dependent cell signalling pathways. Several potential antileishmanial mechanisms of action have been proposed, however no mechanism has been identified definitely. Within the mitochondria, miltefosine inhibits cytochrome-c oxidase leading to mitochondrial dysfunction and apoptosis-like cell death. Antineoplastic mechanisms of action are related to antileishmanial targets and include inhibition of phosphatidylcholine biosynthesis and inhibition of Akt (also known as protein kinase B), which is a crucial protein within the PI3K/Akt/mTOR intracellular signalling pathway involved in regulating the cell cycle. Animal studies also suggest it may be effective against Trypanosome cruzi (the organism responsible for Chagas' disease), metronidazole-resistant strains of Trichonomas vaginalis, and it may have broad-spectrum anti-fungal activity.","P-glycoprotein 1","Therapeutic strategy associated"]
[1198,"DB09033","approved","biotech","Vedolizumab","Vedolizumab",null,null,"Vedolizumab is a recombinant humanized IgG1 monoclonal antibody directed against the human lymphocyte α4β7 integrin, a key mediator of gastrointestinal inflammation. It is used in the treatment of moderate to severe active ulcerative colitis and Crohn's disease for patients who have had an inadequate response with, lost response to, or were intolerant to inhibitors of tumor necrosis factor-alpha (TNF-alpha) or other conventional therapies. By blocking its primary target, α4β7 integrin, vedolizumab reduces inflammation in the gut. Vedolizumab is administered by IV infusion over a period of 30 minutes; after the first dose, it is given again at two and six weeks and then every 8 weeks thereafter.","943609-66-3",null,"Vedolizumab is indicated for adult patients with moderately to severely active UC or CD who have had an inadequate response with, lost response to, or were intolerant to a tumor necrosis factor (TNF) blocker or immunomodulator; or had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroids.","Non-clinical studies have shown that the pharmacodynamic effects of vedolizumab are reversible upon removal of the antibody: pharmacologic activity of cells inhibited by vedolizumab could be partially restored within 24 hours after removal, with near complete restoration within 4 days. There are no known drug interactions as vedolizumab is a humanized antibody and does not modulate production of cytokines, which is known to affect drug metabolism.","Vedolizumab binds to α4β7 integrin, a key mediator of gastrointestinal inflammation expressed on the surfaces of T and B lymphocytes. By selectively inhibiting the α4β7 integrin, vedolizumab inhibits adhesion of lymphocytes to its natural ligand, mucosal addressin cell adhesion molecule-1 (MAdCAM-1), thereby preventing lymphocytic cells from entering the gut lamina propria and gut-associated lymphoid tissue (GALT). Specifically inhibiting this pathway alleviates GI inflammation without impairing systemic immune responses.","Integrin alpha-4 antibody; Integrin beta-7 antibody","Therapeutic strategy associated"]
[1199,"DB09042","approved","small molecule","Tedizolid phosphate","[(5R)-3-{3-fluoro-4-[6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl]phenyl}-2-oxo-1,3-oxazolidin-5-yl]methyl dihydrogen phosphate; Tedizolid phosphate; Torezolid phosphate","C17H16FN6O6P","CN1N=NC(=N1)C1=CC=C(C=N1)C1=CC=C(C=C1F)N1C[C@H](COP(O)(O)=O)OC1=O","Drug-resistant bacteria, such as methicillin-resistant _Staphylococcus aureus_, vancomycin-resistant _Enterococcus faecium_, and penicillin-resistant _Streptococcus penumoniae_, represent a massive public health threat. Tedizolid is a member of the oxazolidinone class of antibiotics, which includes the previously approved  and is generally effective against multidrug-resistant Gram-positive bacteria. Tedizolid is indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and is generally more effective and more tolerable than .\r\n\r\nTedizolid was approved by the FDA on June 20, 2014, for sale by Cubist Pharmaceuticals as tedizolid phosphate (SIVEXTRO®). This product is currently available as both an oral tablet and as a powder for intravenous injection.","856867-55-5","450.323","Tedizolid is indicated for the treatment of acute bacterial infections of the skin and skin structure (ABSSSI). To prevent drug resistance, tedizolid should only be used for infections that are caused by susceptible bacteria.","Tedizolid is an oxazolidinone antibiotic that works by inhibiting protein synthesis by bacterial ribosomes. However, oxazolidinone antibiotics can also bind to human mitochondrial, but not cytoplasmic, ribosomes. Mitochondrial protein synthesis inhibition is associated with adverse patient effects such as neurological, hematological, and gastrointestinal toxicity, although tedizolid is tolerated better than the related . Alternative therapies should be considered when treating neutropenic patients with ABSSSI. _Clostridium difficile_-associated diarrhea has been reported in patients treated with tedizolid.","Despite renewed efforts to combat the spread of antimicrobial resistance, multidrug-resistant organisms, including gram-positive bacteria such as methicillin-resistant _Staphylococcus aureus_, remain a threat. Oxazolidinones represent a relatively new class of antibacterials inhibiting protein synthesis that is generally capable of overcoming resistance to other bacterial protein synthesis inhibitors.\r\n\r\nProtein synthesis involves the action of ribosomes, multi-subunit complexes composed of both protein and ribosomal RNA (rRNA) substituents. Translocation along the length of a messenger RNA and concomitant protein synthesis involves the action of the A, P, and E sites of the peptidyltransferase centre (PTC), which accepts charged aminoacyl-tRNAs and catalyzes the formation of peptide bonds between them. The bacterial 70S ribosome comprises a small (30S) and a large (50S) subunit.\r\n\r\nEarly studies into the mechanism of action of oxazolidinone antibiotics suggested that they inhibit a step in the initiation of protein synthesis. However, this mechanism was inconsistent with mapped resistance mutations, and later studies involving cross-linking and direct structural determination of the binding site revealed that oxazolidinones, including both  and tedizolid, bind in the A site of the PTC by interacting with the 23S rRNA component. The structural studies also revealed that oxazolidinone binding alters the conformation of a conserved nucleotide in the 23S rRNA (U2585 in _Escherichia coli_), which renders the PTC non-productive for peptide bond formation. Hence, tedizolid exerts its effect through inhibiting bacterial protein synthesis.","23S ribosomal RNA inhibitor","Indication associated"]
[1200,"DB09043","approved","biotech","Albiglutide","Albiglutide",null,null,"Albiglutide is a glucagon-like peptide-1 agonist (GLP-1) biologic drug indicated in the treatment of type 2 diabetes. It is marketed under the brands Eperzan and Tanzeum by GSK (GlaxoSmithKline). It is a dipeptidyl peptidase-4-resistant glucagon-like peptide-1 dimer fused to human albumin. Albiglutide was approved on April 15, 2014 by the FDA.","782500-75-8",null,"Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.",null,"Albiglutide is an agonist of the GLP-1 (glucagon-like peptide 1) receptor and augments glucose-dependent insulin secretion. Albiglutide also slows gastric emptying.","Glucagon-like peptide 1 receptor agonist","Target associated"]
[1201,"DB09049","approved","small molecule","Naloxegol","(5α,6α)-17-Allyl-6-[(20-hydroxy-3,6,9,12,15,18-hexaoxaicos-1-yl)oxy]-4,5-epoxymorphinan-3,14-diol; Naloxegol","C34H53NO11","COCCOCCOCCOCCOCCOCCOCCO[C@H]1CC[C@@]2(O)[C@H]3CC4=CC=C(O)C5=C4[C@@]2(CCN3CC=C)[C@H]1O5","Naloxegol, for \"PEGylated naloxol\" is a peripherally-selective opioid antagonist developed by AstraZeneca. It was approved by the FDA in September 2014 and is indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non‑cancer pain. The advantage of naloxegol over the opioid antagonist naloxone is that its PEGylated structure allows for high selectivity for peripheral opioid receptors and lack of entry into the central nervous system through the blood-brain barrier.","854601-70-0","651.794","Indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain.","Use of opioids induces slowing of gastrointestinal motility and transit. Patients do not develop tolerance to these effects, unlike many other opioid side effects. Naloxegol antagonizes mu, delta, and kappa opioid receptors, having the highest affinity for mu. Antagonism of gastrointestinal mu-opioid receptors by naloxegol inhibits opioid-induced delay of gastrointestinal transit time.","Naloxegol is an antagonist of opioid binding at the mu-opioid receptor. When administered at the recommended dose levels, naloxegol functions as a peripherally-acting mu-opioid receptor antagonist in tissues such as the gastrointestinal tract, thereby decreasing the constipating effects of opioids. Naloxegol has shown more than 6000 fold selectivity for the peripheral mu receptors, and its PEGylated form restricts its action only to the periphery, not affecting the pain-relieving mechanism of opioids in the central nervous system.","Mu-type opioid receptor antagonist","Indication associated"]
[1202,"DB09050","approved; investigational","small molecule","Ceftolozane","(6R,7R)-3-([3-Amino-4-(2-aminoethylcarbamoylamino)-2-methylpyrazol-1-ium-1-yl]methyl)-7-([(2Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(2-carboxypropan-2-yloxyimino)acetyl]amino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate; Ceftolozane","C23H30N12O8S2","CN1C(N)=C(NC(=O)NCCN)C=[N+]1CC1=C(N2[C@H](SC1)[C@H](NC(=O)C(=N/OC(C)(C)C(O)=O)\\C1=NSC(N)=N1)C2=O)C([O-])=O","Ceftolozane is a semi-synthetic broad-spectrum fifth generation cephalosporin. It was approved by the FDA in 2014 for use in combination with  for the treatment of serious infections, such as intra-abdominal infections and complicated urinary tract infections. The manufacturer of this drug is Cubist Pharmaceuticals. Most recently, in June 2019, ceftolozane-tazobactam was approved for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia.\r\n\r\nHospital-acquired pneumonia and ventilator-associated pneumonia are major causes of morbidity and mortality in hospitalized patients and the use of ceftolozane-tazobactam offers effective activity against various organisms causing these infections, such as Pseudomonas aeruginosa.","689293-68-3","666.69","This drug is administered in combination with tazobactam for the treatment of complicated intra-abdominal infections (in combination with metronidazole) and complicated urinary tract infections, which may include pyelonephritis. Ceftolozane-tazobactam is also indicated in the treatment of bacterial ventilator-associated pneumonia and bacterial hospital-acquired pneumonia.","Ceftolozane exerts bactericidal activities against susceptible gram-negative and gram-positive infections by interfering with bacterial cell wall synthesis. When it is combined with tazobactam, it exerts further activity against beta-lactamase enzyme producing bacteria, which are normally resistant to beta-lactam antibiotics and interfere with infection treatment. The addition of tazobactam strengthens the therapeutic response to ceftolozane, giving it the ability to treat a broader range of bacterial infections and resistant organisms.","Ceftolozane belongs to the cephalosporin class of antibacterial drugs. Ceftolozane exerts antibacterial effects, preventing the formation of cell walls that protect bacteria from injury and confer resistance to some antibiotics. Its antibacterial activity is also mediated through ceftolozane binding to penicillin-binding proteins (PBPs), which are required for peptidoglycan cross-linking for bacterial cell wall synthesis. As a result of cell wall synthesis inhibition, bacterial cells are killed, treating various infections. Ceftolozane has a particularly high affinity to the penicillin-binding proteins for Pseudomonas aeruginosa and Escherichia coli as well as Klebsiella pneumoniae and other enteric bacteria. In particular, a high affinity has been seen in vitro for penicillin-binding proteins 1b, 1c, 2, and 3 when compared to other antibiotics, ceftazidime and imipenem.","Penicillin-binding protein 1B inhibitor; Penicillin-binding protein 3 inhibitor; Penicillin-binding protein; Penicillin-binding protein 1C inhibitor; Penicillin-binding protein 2 inhibitor","Indication associated"]
[1203,"DB09052","approved; investigational","biotech","Blinatumomab","Blinatumomab",null,null,"Blinatumomab is a BiTE-class (bi-specific T-cell engagers) constructed monoclonal antibody indicated for the treatment of Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). Blinatumomab is manufactured by Amgen Inc. and marketed under the brand Blincyto™. A full treatment regimen consisting of two cycles of four weeks each, is priced at $178 000 USD. Blinatumomab was approved in December 2014 under the FDA’s accelerated approval program, which allows approval of a drug to treat a serious or life-threatening disease based on clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients.","853426-35-4",null,"Indicated for the treatment of Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).",null,"Blinatumomab is a bispecific CD19-directed CD3 T-cell engager that binds to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells. It activates endogenous T cells by connecting CD3 in the T-cell receptor (TCR) complex with CD19 on benign and malignant B cells. Blinatumomab mediates the formation of a synapse between the T cell and the tumor cell, upregulation of cell adhesion molecules, production of cytolytic proteins, release of inflammatory cytokines, and proliferation of T cells, which result in redirected lysis of CD19+ cells.","B-lymphocyte antigen CD19 activator; T-cell surface glycoprotein CD3 delta chain activator","Therapeutic strategy associated"]
[1204,"DB09053","approved","small molecule","Ibrutinib","1-[(3R)-3-[4-Amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]prop-2-en-1-one","C25H24N6O2","NC1=NC=NC2=C1C(=NN2[C@@H]1CCCN(C1)C(=O)C=C)C1=CC=C(OC2=CC=CC=C2)C=C1","Ibrutinib is a small molecule that acts as an irreversible potent inhibitor of Burton's tyrosine kinase. It is designated as a targeted covalent drug and it presents a very promising activity in B cell malignancies. Ibrutinib was developed by Pharmacyclics Inc and in November 2013 was FDA-approved for the treatment of mantle cell lymphoma. Later, in February 2014, ibrutinib was approved for the treatment of chronic lymphocytic leukemia and it is also indicated for the treatment of patients with Waldenström's Macroglobulinemia. Ibrutinib has also been approved by the EMA for the treatment of chronic lymphocytic leukemia and mantle cell lymphoma. Ibrutinib was approved for use in chronic graft versus host disease in August 2017 .","936563-96-1","440.507","Ibrutinib acquired an accelerated approval for the treatment of mantle cell lymphoma who have received at least one prior therapy. Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma that develops in the outer edge of a lymph node. MCL is usually diagnosed at late stages and it is easily spread into bone marrow, spleen, liver and gastrointestinal tract.\r\n\r\nIbrutinib is indicated for the treatment of chronic lymphocytic leukemia (CLL) who have at least one prior therapy. CLL is a type of cancer caused by an overproduction of lymphocytes by the bone marrow. Some of the symptoms include swollen lymph nodes and tiredness.\r\n\r\nIbrutinib is indicated for the treatment of chronic lymphocytic leukemia (CLL) with 17p deletion. CLL with 17p is a type of leukemia in which a deletion in 17p disrupts the tumor suppressor p53 by deleting one allele of the TP53 gene. The remaining allele is mainly inactivated and thus, this type of leukemia is unresponsive to p53-dependent treatments.\r\n\r\nIbrutinib is indicated for the treatment of patients with Waldenstrom's Macroglobulinemia (WM). WM, also called lymphoplasmacytic lymphoma, is a type of non-Hodgkin lymphoma in which the cancer cells make large amounts of macroglobulin. The macroglobulin is a monoclonal protein that corresponds to the type of IgM antibodies and the unrestricted formation of this protein causes typical symptoms such as excessive bleeding and effects in vision and nervous system.","In vitro studies have shown an induction of CLL cell apoptosis even in presence of prosurvival factors. It has also been reported an inhibition of CLL cell survival and proliferation as well as an impaired in cell migration and a reduction in the secretion of chemokines such as CCL3 and CCL4. The latter effect has been shown to produce regression in xenograft mouse models.\r\n\r\nClinical studies for relapsed/refractory CLL in phase I and II showed an approximate 71% of overall response rate.. In the case of relapsed/refractory mantle cell lymphoma, approximately 70% of the tested patients presented a partial or complete response.. In clinical trials for relapsed/refractory diffuse large B-cell lymphoma, a partial response was found in between 15-20% of the patients studied; while for patients with relapsed/refractory Waldenstrom's macroglobulinemia, a partial response was observed in over 75% of the patients tested. Finally, for patients with relapsed/refractory follicular lymphoma, a partial to complete response was obtained in approximately 54% of the patients.","Ibrutinib is an inhibitor of Bruton’s tyrosine kinase (BTK). It forms a covalent bond with a cysteine residue in the active site of BTK (Cys481), leading to its inhibition. The inhibition of BTK plays a role in the B-cell receptor signaling and thus, the presence of ibrutinib prevents the phosphorylation of downstream substrates such as PLC-γ.","Tyrosine-protein kinase BTK inhibitor","Therapeutic strategy associated"]
[1205,"DB09054","approved","small molecule","Idelalisib","5-Fluoro-3-phenyl-2-((S)-1-(9H-purin-6-ylamino)-propyl)-3H-quinazolin-4-one; 5-fluoro-3-phenyl-2-[(1S)-1-(3H-purin-6-ylamino)propyl]quinazolin-4(3H)-one; Idelalisib","C22H18FN7O","[H][C@@](CC)(NC1=NC=NC2=C1N=CN2)C1=NC2=CC=CC(F)=C2C(=O)N1C1=CC=CC=C1","Idelalisib is a phosphoinositide 3-kinase inhibitor indicated in the treatment of chronic lymphocytic leukemia (CLL), relapsed follicular B-cell non-Hodgkin lymphoma (FL), and relapsed small lymphocytic lymphoma (SLL). For the treatment of relapsed CLL, it is currently indicated as a second-line agent in combination with rituximab in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities, while in the treatment of FL and SLL it is intended to be used in patients who have received at least two prior systemic therapies. More specifically, idelalisib targets P110δ, the delta isoform of the enzyme phosphatidylinositol-4,5-bisphosphate 3-kinase, also known as PI-3K. The PI-3Ks are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer. In contrast to the other class IA PI3Ks p110α and p110β, p110δ is principally expressed in leukocytes (white blood cells) and is important for the function of T cells, B cell, mast cells and neutrophils. By inhibiting this enzyme, idelalisib induces apoptosis of malignant cells and inhibits several cell signaling pathways, including B-cell receptor (BCR) signaling and C-X-C chemokine receptors type 5 and type 4 signalling, which are involved in trafficking and homing of B-cells to the lymph nodes and bone marrow. Treatment of lymphoma cells with idelalisib has been shown to result in inhibition of chemotaxis and adhesion, and reduced cell viability.","870281-82-6","415.432","Idelalisib is indicated in the treatment of chronic lymphocytic leukemia (CLL), relapsed follicular B-cell non-Hodgkin lymphoma (FL), and relapsed small lymphocytic lymphoma (SLL). For the treatment of relapsed CLL, it is currently indicated as a second-line agent in combination with rituximab in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities, while in the treatment of FL and SLL it is intended to be used in patients who have received at least two prior systemic therapies.",null,"Idelalisib specifically inhibits P110δ, the delta isoform of the enzyme phosphatidylinositol-4,5-bisphosphate 3-kinase, also known as PI-3K. The PI-3Ks are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer. In contrast to the other class IA PI3Ks p110α and p110β, p110δ is principally expressed in leukocytes (white blood cells) and is important for the function of T cells, B cell, mast cells and neutrophils. By inhibiting this enzyme, idelalisib induces apoptosis of malignant cells and inhibits several cell signaling pathways, including B-cell receptor (BCR) signaling and C-X-C chemokine receptors type 5 and type 4 signalling, which are involved in trafficking and homing of B-cells to the lymph nodes and bone marrow. Treatment of lymphoma cells with idelalisib has been shown to result in inhibition of chemotaxis and adhesion, and reduced cell viability.","Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform inhibitor","Therapeutic strategy associated"]
[1206,"DB09059","approved; investigational","small molecule","Atosiban","Atosiban","C43H67N11O12S2","[H][C@]1(NC(=O)[C@@]([H])(NC(=O)[C@@H](CC2=CC=C(OCC)C=C2)NC(=O)CCSSC[C@H](NC(=O)[C@H](CC(N)=O)NC1=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN)C(=O)NCC(N)=O)[C@@H](C)CC)[C@@H](C)O","Atosiban is an inhibitor of the hormones oxytocin and vasopressin. It is used intravenously to halt premature labor. Although initial studies suggested it could be used as a nasal spray and hence would not require hospital admission, it is not used in that form. Atobisan was developed by the Swedish company Ferring Pharmaceuticals. It was first reported in the literature in 1985. Atosiban is licensed in proprietary and generic forms for the delay of imminent pre-term birth in pregnant adult women.","90779-69-4","994.19","Atosiban is indicated for use in delaying imminent pre-term birth in pregnant adult women with: \r\n\r\n- regular uterine contractions of at least 30 s duration at a rate of at least 4 per 30 min\r\n- a cervical dilation of 1-3cm (0-3cm for nulliparas) and effacement of  at least 50%\r\n- a gestational age of 24-33 weeks\r\n- a normal fetal heart rate","Atosiban reduces the frequency of uterine contractions to delay pre-term birth in adult females and induces uterine quiescence .","Atosiban is a synthetic peptide oxytocin antagonist . It resembles oxytocin with has modifications at the 1, 2, 4, and 8 positions. The N-terminus of the cysteine residue is deaminated to form 3-mercaptopropanic acid at position 1, at position 2 L-tyrosine is modified to D-tyrosine with an ethoxy group replacing the phenol , threonine replaces glutamine at postion 4, and ornithine replaces leucine at position 8.\r\n\r\nIt binds to membrane bound oxytocin receptors on the myometrium and prevents oxytocin-stimulated increases in inositol triphosphate production . This ultimately prevents release of stored calcium from the sarcoplasmic reticulum and subsequent opening of voltage gated calcium channels. This shutdown of cytosolic calcium increase prevents contractions of the uterine muscle, reducing the frequency of contractions and inducing uterine quiescence.\r\n\r\nAtosiban has more recently been found to act as a biased ligand at oxytocin receptors . It acts as an antagonist of Gq coupling, explaining the inhibition of the inositol triphosphate pathway thought to be responsible for the effect on uterine contraction, but acts as an agonist of Gi coupling. This agonism produces a pro-inflammatory effect in the human amnion, activating pro-inflammatory signal tranducer NF-κB . It is thought that this reduces atosiban's effectiveness compared to agents which do not produce inflammation as inflammatory mediators are known to play a role in the induction of labour.","Oxytocin receptor antagonist; Vasopressin V1a receptor antagonist; Vasopressin V1b receptor antagonist; Vasopressin V2 receptor antagonist","Therapeutic strategy associated"]
[1207,"DB09060","approved","small molecule","Avibactam","Avibactam","C7H11N3O6S","NC(=O)[C@@H]1CC[C@@H]2CN1C(=O)N2OS(O)(=O)=O","Avibactam is a non-β-lactam β-lactamase inhibitor that is available in combination with ceftazidime (Avycaz). This combination was approved by the FDA on February 25, 2015 for the treatment of complicated intra-abdominal infections in combination with metronidazole, and the treatment of complicated urinary tract infections, including pyelonephritis caused by antibiotic resistant-pathogens, including those caused by multi-drug resistant gram-negative bacterial pathogens. As there is limited clinical safety and efficacy data, Avycaz should be reserved for patients over 18 years old who have limited or not alternative treatment options.","1192500-31-4","265.24","AVYCAZ (ceftazidime-avibactam), in combination with metronidazole, is indicated for the treatment of complicated intra-abdominal infections caused by the following susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Providencia stuartii, Enterobacter cloacae, Klebsiella oxytoca, and Pseudomonas aeruginosa in patients 18 years or older.\r\nAVYCAZ is also indicated for the treatment of complicated urinary tract infections including pyelonephritis caused by the following susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, Citrobacter koseri, Enterobacter aerogenes, Enterobacter cloacae, Citrobacter freundii, Proteus spp., and Pseudomonas aeruginosa in patients 18 years or older.",null,"Avibactam is a non-β lactam β-lactamase inhibitor that inactivates some β-lactamases (Ambler class A β-lactamases, including Klebsiella pneumoniae carbapenemases, Ambler class C and some Ambler class D β-lactamases) by a unique covalent and reversible mechanism, and protects ceftazidime from degradation by certain β-lactamases. Avibactam rapidly reaches the periplasm of bacteria at high enough concentrations to restore activity of ceftazidime against ceftazidime-resistant, β-lactamase-producing strains. Avibactam does not decrease the activity of ceftazidime against ceftazidime­ susceptible organisms.","Beta-lactamase TEM inhibitor; Beta-lactamase CTX-M inhibitor; Beta-lactamase inhibitor; Beta-lactamase SHV-1 inhibitor; Beta-lactamase SHV-2 inhibitor; Beta-lactamase SHV-1 inhibitor; Class D OXA-48 carbapenemase inhibitor; Carbapenem-hydrolyzing beta-lactamase KPC inhibitor; Beta-lactamase CTX-M-15 inhibitor; Extended-spectrum beta-lactamase PER-1 inhibitor","Indication associated"]
[1208,"DB09061","approved; investigational","small molecule","Cannabidiol","(−)-trans-2-p-mentha-1,8-dien-3-yl-5-pentylresorcinol; (−)-trans-cannabidiol; (1'R,2'R)-5'-methyl-4-pentyl-2'-(prop-1-en-2-yl)-1',2',3',4'-tetrahydrobiphenyl-2,6-diol; CBD; Δ1(2)-trans-cannabidiol","C21H30O2","CCCCCC1=CC(O)=C([C@@H]2C=C(C)CC[C@H]2C(C)=C)C(O)=C1","Cannabidiol, or CBD, is one of at least 85 active cannabinoids identified within the Cannabis plant. It is a major phytocannabinoid, accounting for up to 40% of the Cannabis plant's extract, that binds to a wide variety of physiological targets of the endocannabinoid system within the body. Although the exact medical implications are currently being investigated, CBD has shown promise as a therapeutic and pharmaceutical drug target. In particular, CBD has shown promise as an analgesic, anticonvulsant, muscle relaxant, anxiolytic, antipsychotic and has shown neuroprotective, anti-inflammatory, and antioxidant activity, among other currently investigated uses . CBD's exact place within medical practice is still currently hotly debated, however as the body of evidence grows and legislation changes to reflect its wide-spread use, public and medical opinion have changed significantly with regards to its usefulness in a number of medical conditions ranging from anxiety to epilepsy.\r\n\r\nFrom a pharmacological perspective, Cannabis' (and CBD's) diverse receptor profile explains its potential application for such a wide variety of medical conditions. Cannabis contains more than 400 different chemical compounds, of which 61 are considered cannabinoids, a class of compounds that act upon endogenous cannabinoid receptors of the body . Cannabinoid receptors are utilized endogenously by the body through the endocannabinoid system, which includes a group of lipid proteins, enzymes, and receptors that are involved in many physiological processes. Through its modulation of neurotransmitter release, the endocannabinoid system regulates cognition, pain sensation, appetite, memory, sleep, immune function, and mood among many other bodily systems. These effects are largely mediated through two members of the G-protein coupled receptor family, cannabinoid receptors 1 and 2 (CB1 and CB2). CB1 receptors are found in both the central and peripheral nervous systems, with the majority of receptors localized to the hippocampus and amygdala of the brain. Physiological effects of using cannabis make sense in the context of its receptor activity as the hippocampus and amygdala are primarily involved with regulation of memory, fear, and emotion. In contrast, CB2 receptors are mainly found peripherally in immune cells, lymphoid tissue, and peripheral nerve terminals .\r\n\r\nTetrahydrocannabinol (THC) and cannabidiol (CBD) are two types of cannabinoids found naturally in the resin of the marijuana plant, both of which interact with the cannabinoid receptors that are found throughout the body. Although THC and CBD have been the most studied cannabinoids, there are many others identified to date including cannabinol (CBN), cannabigerol (CBG),  (CBDV), and  (THCV) that can be found within the medical cannabis . While both CBD and THC are used for medicinal purposes, they have different receptor activity, function, and physiological effects. If not provided in their activated form (such as through synthetic forms of THC like  or ), THC and CBD are obtained through conversion from their precursors, tetrahydrocannabinolic acid-A (THCA-A) and cannabidiolic acid (CBDA), through decarboxylation reactions. This can be achieved through heating, smoking, vaporization, or baking of dried unfertilized female cannabis flowers.\r\n\r\nThe primary psychoactive component of Cannabis, delta 9-tetrahydrocannabinol (Δ9-THC), demonstrates its effects through weak partial agonist activity at Cannabinoid-1 (CB1R) and Cannabinoid-2 (CB2R) receptors. This activity results in the well-known effects of smoking cannabis such as increased appetite, reduced pain, and changes in emotional and cognitive processes. In contrast to THC's weak agonist activity, CBD has been shown to act as a negative allosteric modulator of the cannabinoid CB1 receptor, the most abundant G-Protein Coupled Receptor (GPCR) in the body . Allosteric regulation is achieved through the modulation of receptor activity on a functionally distinct site from the agonist or antagonist binding site which is clinically significant as direct agonists (such as THC) are limited by their psychomimetic effects such as changes to mood, memory, and anxiety. \r\n\r\nIn addition to the well-known activity on CB1 and CB2 receptors, there is further evidence that CBD also activates 5-HT1A/2A/3A serotonergic and TRPV1–2 vanilloid receptors, antagonizes alpha-1 adrenergic and µ-opioid receptors, inhibits synaptosomal uptake of noradrenaline, dopamine, serotonin and gamma-aminobutyric acid (GABA), and cellular uptake of anandamide, acts on mitochondria Ca2+ stores, blocks low-voltage-activated (T-type) Ca2+ channels, stimulates activity of the inhibitory glycine-receptor, and inhibits activity of fatty amide hydrolase (FAAH) .\r\n\r\nCBD is currently available in Canada within a 1:1 formulation with tetrahydrocannbinol (THC) (as the formulation known as \"nabiximols\") as the brand name product Sativex. It is approved for use as adjunctive treatment for symptomatic relief of spasticity in adult patients with multiple sclerosis (MS). Sativex was also given a conditional Notice of Compliance (NOC/c) for use as adjunctive treatment for the symptomatic relief of neuropathic pain in adult patients with multiple sclerosis and as adjunctive analgesic treatment for moderate to severe pain in adult patients with advanced cancer .\r\n\r\nIn April 2018, a Food and Drug Administration advisory panel unanimously recommended approval of Epidiolex (cannabidiol oral solution) for the treatment of two rare forms of epilepsy - Lennox-Gastaut syndrome and Dravet syndrome, which are among the two most difficult types of epilepsy to treat . Epidiolex was granted Orphan Drug designation as well as Fast Track Approval from the FDA for further study in these hard to treat conditions. Notably, phase 3 clinical trials of Epidiolex have demonstrated clinically significant improvement in Lennox-Gastaut syndrome and Dravet syndrome . On June 25th, 2018, Epidiolex was approved by the FDA to be the first CBD-based product available on the US market.","13956-29-1","314.469","When used in combination with delta-9-tetrahydrocannabinol as the product Sativex, cannabidiol was given a standard marketing authorization (ie. a Notice of Compliance (NOC)) by Health Canada for the following indications: \r\n1) as adjunctive treatment for symptomatic relief of spasticity in adult patients with multiple sclerosis (MS) who have not responded adequately to other therapy and who demonstrate meaningful improvement during an initial trial of therapy ;\r\n\r\nDue to the need for confirmatory studies to verify the clinical benefit coupled with the promising nature of the clinical evidence, Sativex was also given a Notice of Compliance with Conditions (NOC/c) by Health Canada for the following indications: \r\n1) as adjunctive treatment for the symptomatic relief of neuropathic pain in adult patients with multiple sclerosis; \r\n2) as adjunctive analgesic treatment in adult patients with advanced cancer who experience moderate to severe pain during the highest tolerated dose of strong opioid therapy for persistent background pain .","Although the exact mechanism and magnitude of effects of THC and CBD are not fully understood, CBD has been shown to have analgesic, anticonvulsant, muscle relaxant, anxiolytic, neuroprotective, anti-oxidant, and anti-psychotic activity. This wide variety of effects is likely due to it's complex pharmacological mechanisms. In addition to binding to CB1 and CB2 receptors of the endocannabinoid system, there is evidence that CBD activates 5-HT1A serotonergic and TRPV1–2 vanilloid receptors, antagonizes alpha-1 adrenergic and µ-opioid receptors, inhibits synaptosomal uptake of noradrenaline, dopamine, serotonin and gaminobutyric acid and cellular uptake of anandamide, acts on mitochondria Ca2 stores, blocks low-voltage-activated (T-type) Ca2 channels, stimulates activity of the inhibitory glycine-receptor, and inhibits activity of fatty amide hydrolase (FAAH) .","The exact mechanism of action of CBD and THC is not currently fully understood. However, it is known that CBD acts on cannabinoid (CB) receptors of the endocannabinoid system, which are found in numerous areas of the body, including the peripheral and central nervous systems, including the brain. The endocannabinoid system regulates many physiological responses of the body including pain, memory, appetite, and mood. More specifically, CB1 receptors can be found within the pain pathways of the brain and spinal cord where they may affect CBD-induced analgesia and anxiolysis, and CB2 receptors have an effect on immune cells, where they may affect CBD-induced anti-inflammatory processes. \r\n\r\nCBD has been shown to act as a negative allosteric modulator of the cannabinoid CB1 receptor, the most abundant G-Protein Coupled Receptor (GPCR) in the body . Allosteric regulation of a receptor is achieved through the modulation of the activity of a receptor on a functionally distinct site from the agonist or antagonist binding site. The negative allosteric modulatory effects of CBD are therapeutically important as direct agonists are limited by their psychomimetic effects while direct antagonists are limited by their depressant effects .","Cannabinoid receptor 1 antagonist&modulator; Cannabinoid receptor 2 antagonist; G-protein coupled receptor 12 inverse agonist; Glycine receptor subunit alpha-1; Glycine receptor (alpha-1/beta) allosteric modulator; Glycine receptor subunit alpha-3 potentiator; N-arachidonyl glycine receptor; G-protein coupled receptor 55 antagonist; 5-hydroxytryptamine receptor 1A agonist; 5-hydroxytryptamine receptor 2A agonist; Neuronal acetylcholine receptor subunit alpha-7; Delta-type opioid receptor; Mu-type opioid receptor; Peroxisome proliferator-activated receptor gamma activator; Transient receptor potential cation channel subfamily V member 1 activator; Voltage-dependent T-type calcium channel subunit alpha-1G; Voltage-dependent T-type calcium channel subunit alpha-1H; Voltage-dependent T-type calcium channel subunit alpha-1I; Transient receptor potential cation channel subfamily A member 1 agonist; Transient receptor potential cation channel subfamily M member 8; Transient receptor potential cation channel subfamily V member 2 activator; Transient receptor potential cation channel subfamily V member 3 activator; Transient receptor potential cation channel subfamily V member 4 activator; Voltage-dependent anion-selective channel protein 1; 5-hydroxytryptamine receptor 3A antagonist; Adenosine receptor A1 activator; Prostaglandin G/H synthase 1 inhibitor; Prostaglandin G/H synthase 2 inhibitor; Acetyl-CoA acetyltransferase, mitochondrial inhibitor; Steroid 17-alpha-hydroxylase/17,20 lyase inhibitor; 3-hydroxy-3-methylglutaryl-coenzyme A reductase stimulator; Glutathione reductase, mitochondrial stimulator; Glutathione peroxidase 1 stimulator; Indoleamine 2,3-dioxygenase 1 inhibitor; Cytochrome P450 1B1 inhibitor; NAD(P)H dehydrogenase [quinone] 1 inhibitor; Catalase inhibitor; Cytochrome P450 3A5 inhibitor; Cytochrome P450 2D6 inhibitor; Superoxide dismutase [Cu-Zn] inhibitor; Cytochrome P450 1A2 inhibitor; Cytochrome P450 3A7 inhibitor; Arylalkylamine N-acetyltransferase inhibitor; N-acylethanolamine-hydrolyzing acid amidase inhibitor","Therapeutic strategy associated"]
[1209,"DB09064","approved; investigational","small molecule","Ciprofibrate","Ciprofibrate","C13H14Cl2O3","CC(C)(OC1=CC=C(C=C1)C1CC1(Cl)Cl)C(O)=O",null,"52214-84-3","289.15",{"$nulls":3},"Peroxisome proliferator-activated receptor alpha","Target associated"]
[1210,"DB09069","approved; investigational","small molecule","Trimetazidine","1-[2,3,4-trimethoxybenzyl] piperazine dihydrochloride; Trimetazidine","C14H22N2O3","COC1=C(OC)C(OC)=C(CN2CCNCC2)C=C1","Trimetazidine is a piperazine derivative indicated for the symptomatic treatment of stable angina pectoris in patients inadequately controlled or intolerant to first line therapies. Trimetazidine has been studied as a treatment for angina pectoris since the late 1960s.\r\n\r\nAcidic conditions, caused by anaerobic metabolism and fatty acid oxidation, in response to myocardial ischemia, activate sodium-hydrogen and sodium-calcium antiport systems. The increased intracellular calcium decreases contractility. It is hypothesized that trimetazidine inhibits 3-ketoacyl coenzyme A thiolase, which decreases fatty acid oxidation but not glucose metabolism, preventing the acidic conditions that exacerbate ischemic injury. However, evidence for this mechanism is controversial.\r\n\r\nTrimetazidine is not FDA approved. However, it has been approved in France since 1978.","5011-34-7","266.341","Trimetazidine is indicated for the symptomatic treatment of stable angina pectoris in patients inadequately controlled or intolerant to first line therapies.","Trimetazidine is indicated for the symptomatic treatment of stable angina pectoris in patients inadequately controlled or intolerant to first line therapies. Patients should be counselled regarding the risk of use with reduced renal or hepatic function, worsening of extrapyramidal symptoms or other movement disorders, and risk of falls.","During myocardial ischemia, anaerobic metabolism takes over, increasing levels of lactic acid. The decreased intracellular pH and increased concentration of protons activates sodium-hydrogen and sodium-calcium antiport systems, raising intracellular calcium concentrations, finally leading to decreased contractility.\r\n\r\nThis injury to the myocardium raises concentrations of catecholamines, which activate hormone sensitive lipase, and increasing fatty acid concentrations in plasma. When the myocardium is repurfused, fatty acid oxidation becomes the dominant form of ATP production, maintaining an acidic pH, and further exacerbating the injury.\r\n\r\nThe mechanism of action of trimetazidine is not fully understood. Trimetazidine may inhibit mitochondrial 3-ketoacyl coenzyme A thiolase, decreasing long chain fatty acid β-oxidation but not glycolysis in the myocardium. The decreased long chain fatty acid β-oxidation is compensated for by increased use of glucose, preventing a lowered myocardial pH, and further decreases in contractility. However, another study suggests that 3-ketoacyl coenzyme A thiolase may not be trimetazidine's target, and that this mechanism may be incorrect.","3-ketoacyl-CoA thiolase, mitochondrial inhibitor","Indication associated"]
[1211,"DB09070","approved; investigational","small molecule","Tibolone","17-hydroxy-7alpha-methyl-19-nor-17alpha-pregn-5(10)-en-20-yn-3-one; Tibolone","C21H28O2","[H][C@@]12CC[C@@](O)(C#C)[C@@]1(C)CC[C@]1([H])C3=C(CC(=O)CC3)C[C@@]([H])(C)[C@@]21[H]","Tibolone is a synthetic steroid hormone drug, which is mainly non-selective in its binding profile, acting as an agonist primarily at estrogen receptors (ER), with a preference for ER alpha .\r\n\r\nTibolone (Livial, Org OD 14), produced by Organon (West Orange, NJ), is a synthetic steroid that possesses estrogenic, androgenic and progestogenic properties. It has been used in Europe for almost 2 decades, primarily for the prevention of postmenopausal osteoporosis and the treatment of post-menopausal symptoms .  Tibolone is approved in 90 countries to manage menopausal symptoms and in 45 countries to prevent the development of osteoporosis .\r\n\r\nIn June 2006, Organon Pharmaceuticals announced the receipt of a Not Approvable Letter from the U.S. Food and Drug Administration (FDA), advising the company that the New Drug Application (NDA) for tibolone had not been approved .\r\n\r\nInterestingly, the use of tibolone in the treatment cardiovascular disease has been studied with inconclusive results . Tibolone has been to have anti-resorptive effects on bone .","5630-53-5","312.453","For the relief of post-menopausal symptoms and for the prevention of osteoporosis .","Tibolone prevents bone loss and treating post-menopausal symptoms without stimulating the endometrial tissues, which may lead to malignancy. Typical, drugs that treat post-menopausal symptoms such as estrogen, have a proliferative effect on the endometrium, increasing the risk of endometrial carcinoma . The effects on the bone, brain and vaginal tissues can be explained by the estrogenic activity of tibolone.  It is important to note that activity is not expressed in the endometrium. Tibolone behaves differently from estrogen plus progesterone combinations on the breast. Therefore, tibolone can be characterized as a selective estrogen activity regulator .\r\n\r\nTibolone has been demonstrated to be an effective agent in treating symptoms associated with menopause. A 16 week trial in 1189 women examined the effect of tibolone 2.5 mg once daily on climacteric symptoms. Women treated with tibolone showed improvement from baseline in typical menopausal symptoms including hot flashes, sweating, insomnia, and anxiety .","This drug's effects are owed to the activity of its metabolites in various tissues .\r\n\r\nUpon ingestion, tibolone is quickly converted into three major metabolites: _3 alpha- and 3 beta-hydroxy-tibolone_, which have oestrogenic effects, and the _Delta(4)-isomer_, which has progestogenic and androgenic effects. The specific tissue-selective effects of tibolone occur due to the metabolism, regulation of enzymes and receptor activation that varies in different tissues of the body.\r\n \r\nThe bone-conserving effects occur due to estradiol receptor activation, while the progesterone and androgen receptors are not involved in this process. Breast tissue of monkeys is not found to be stimulated after tibolone administration,  as occurs with estrogen plus progesterone used in combination. This is explained by the fact that tibolone and its metabolites inhibit _sulphatase and 17 beta-hydroxysteroid dehydrogenase_ (HSD) type I and _stimulate sulphotransferase and 17 beta-HSD type II_.  The combined effects of this process prevent the conversion to active estrogens.\r\n\r\nIn the uterus, the progestogenic activity of the _Delta(4)-metabolite_ and the effect on estrogen-inactivating enzymes prevent estrogenic stimulation. The mammary gland is not stimulated in currently used animal models. Tibolone has been shown to regulate estrogenic activity in several tissue types by influencing the availability of estrogenic compounds for the estradiol receptor in a selective manner .\r\n\r\nAdditionally, tibolone modulates cellular homeostasis in the breast by preventing breast tissue proliferation and stimulating cell apoptosis. Tibolone does not stimulate the endometrium because of the action of its highly stable progestogenic metabolite (Delta(4)-isomer) in combination with an effect on the sulfatase (inhibition)-sulfotransferase (stimulation) system. The estrogenic metabolites of tibolone have direct, favorable effects on the cardiovascular system and, in animal models, this drug has shown no adverse consequences. \r\n\r\n\r\nThe tissue-selective effects of tibolone are the result of metabolism, enzyme regulation and receptor activation that vary in different tissues. The bone-preserving effects of tibolone are the result of estradiol receptor activation, while other steroid receptors, mainly the progesterone and androgen receptors, are not involved in this process. \r\n\r\nIn a study of monkeys, breast tissue was not stimulated, which occurs with estrogen and progesterone, because tibolone and its metabolites inhibit _sulfatase and 17 beta-hydroxysteroid _dehydrogenase (HSD) type I and stimulate _sulfotransferase and 17 beta-HSD type II_. The simultaneous effects of this process halt conversion to active estrogens. Additionally, tibolone affects cellular homeostasis in the breast by preventing proliferation and stimulating apoptosis. Tibolone does not stimulate the endometrium due to the action of the highly stable progestogenic metabolite (Delta(4)-isomer) in combination with an effect on the sulphatase (inhibition)-sulphotransferase (stimulation) pathway .\r\n\r\nThe levels of tibolone metabolites and the alteration of hormonal activities vary according to the tissue type. In endometrial tissue the _Δ4-isomer_ functions as a progestagen, however, in the brain and liver, it shows androgenic effects. In breast tissue, the primary actions of tibolone are strong inhibition of sulfatase activity and weak inhibition of 17β-hydroxysteroid dehydrogenase activity, which leads to blocking the conversion estrone sulfate to E2 .","Estrogen receptor alpha antagonist&agonist","Therapeutic strategy associated"]
[1212,"DB09075","approved","small molecule","Edoxaban","Edoxaban","C24H30ClN7O4S","CN(C)C(=O)[C@H]1CC[C@H](NC(=O)C(=O)NC2=NC=C(Cl)C=C2)[C@@H](C1)NC(=O)C1=NC2=C(CN(C)CC2)S1","Edoxaban is a member of the Novel Oral Anti-Coagulants (NOACs) class of drugs, and is a rapidly acting, oral, selective factor Xa inhibitor. By inhibiting factor Xa, a key protein in the coagulation cascade, edoxaban prevents the stepwise amplification of protein factors needed to form blood clots. It is indicated to reduce the risk of stroke and systemic embolism (SE) in patients with nonvalvular atrial fibrillation (NVAF) and for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) following 5-10 days of initial therapy with a parenteral anticoagulant. Traditionally, warfarin, a vitamin K antagonist, was used for stroke prevention in these individuals but effective use of this drug is limited by it's delayed onset, narrow therapeutic window, need for regular monitoring and INR testing, and numerous drug-drug and drug-food interactions. This has prompted enthusiasm for newer agents such as dabigatran, apixaban, and rivaroxaban for effective clot prevention. In addition to once daily dosing, the benefits over warfarin also include significant reductions in hemorrhagic stroke and GI bleeding, and improved compliance, which is beneficial as many patients will be on lifelong therapy.","480449-70-5","548.06","Edoxaban is indicated for reducing the risk of stroke and systemic embolism (SE) in patients with nonvalvular atrial fibrillation (NVAF). However, it should not be used in patients with creatinine clearance (CrCL) > 95 mL/min because of increased risk of ischemic stroke compared to warfarin at the highest dose studied (60 mg). It is also indicated for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) following 5-10 days of initial therapy with a parenteral anticoagulant.","Administration of edoxaban results in prolongation of clotting time tests such as aPTT (activated partial thromboplastin time), PT (prothrombin time), and INR (international normalized ratio).","Edoxaban is a selective inhibitor of factor Xa, a serine endopeptidase of the clotting cascade required for cleavage of prothrombin into thrombin.","Coagulation factor X inhibitor","Indication associated"]
[1213,"DB09077","approved; investigational","biotech","Dinutuximab","Dinutuximab; Dinutuximab beta; Monoclonal antibody ch14.18",null,null,"Dinutuximab is an IgG1 monoclonal human/mouse chimeric antibody against GD2, a disialoganglioside expressed on tumors of neuroectodermal origin, including human neuroblastoma and melanoma, with highly restricted expression on normal tissues. It is composed of the variable heavy- and light-chain regions of the murine anti-GD2 mAb 14.18 and the constant regions of human IgG1 heavy-chain and kappa light-chain. By binding to GD2, dinutiximab induces antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity of tumor cells thereby leading to apoptosis and inhibiting proliferation of the tumour. It is indicated, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and 13-cis-retinoic acid (RA), for the treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to prior first-line multiagent, multimodality therapy. Despite a high clinical response seen after first-line treatment, the complete eradication of neuroblastoma is rarely achieved and the majority of patients with advanced disease suffer a relapse. Current strategies for treatment include immunotherapy with drugs such as dinutuximab to target surviving neuroblastoma cells and to prevent relapse.","1363687-32-4",null,"Dinutuximab is indicated, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and 13-cis-retinoic acid (RA), for the treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to prior first-line multiagent, multimodality therapy. Despite a high clinical response seen after first-line treatment, the complete eradication of neuroblastoma is rarely achieved and the majority of patients with advanced disease suffer a relapse. Current strategies for treatment include immunotherapy with drugs such as dinutuximab to target surviving neuroblastoma cells and to prevent relapse.","In vitro dinutuximab binds to neuroblastoma tumour cells and mediates the lysis of tumour cells via cell-mediated and complement-mediated cytotoxicity.","Dinutuximab is an IgG1 monoclonal human/mouse chimeric antibody against GD2, a disialoganglioside expressed on tumors of neuroectodermal origin, including human neuroblastoma and melanoma, with highly restricted expression on normal tissues. It is composed of the variable heavy- and light-chain regions of the murine anti-GD2 mAb 14.18 and the constant regions of human IgG1 heavy-chain and kappa light-chain. By binding to GD2, dinutiximab induces antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity of tumor cells thereby leading to apoptosis and inhibiting proliferation of the tumour.","GD2 disialoganglioside inhibitor","Therapeutic strategy associated"]
[1214,"DB09079","approved","small molecule","Nintedanib","methyl (3Z)-3-[(4-{methyl[(4-methylpiperazin-1-yl)acetyl]amino}anilino)(phenyl)methylidene]-2-oxo-2,3-dihydro-1H-indole-6-carboxylate; Nintedanib","C31H33N5O4","COC(=O)C1=CC=C2C(NC(=O)\\C2=C(/NC2=CC=C(C=C2)N(C)C(=O)CN2CCN(C)CC2)C2=CC=CC=C2)=C1","Nintedanib is a small molecule kinase inhibitor used in the treatment of pulmonary fibrosis, systemic sclerosis-associated interstitial lung disease, and non-small cell lung cancer (NSCLC). It was first approved for use in the United States in 2014. Within the spectrum of idiopathic pulmonary fibrosis treatment options, nintedanib is currently one of only two disease-modifying therapies available and indicated for the condition (the other being ) and as such is  used as a first-line treatment following diagnosis to slow down the progressive loss of lung function. As a chemotherapeutic agent for NSCLC, nintedanib, in combination with , is reserved for patients who have tried and failed first-line chemotherapeutic options.","656247-17-5","539.6248","In the US, nintedanib is indicated for the treatment of idiopathic pulmonary fibrosis (IPF) and to slow declining pulmonary function in patients with systemic sclerosis-associated interstitial lung disease. In the EU, nintedanib is indicated in combination with docetaxel for the treatment of adult patients with metastatic, locally advanced, or locally recurrent non-small cell lung cancer of adenocarcinoma histology who have already tried first-line therapy.","Nintedanib is a small molecule kinase inhibitor that inhibits upstream kinase activity to ultimately inhibit lung fibroblast proliferation and migration, as well as signalling pathways that promote the proliferation and survival of endothelial and perivascular cells in tumour tissues.\r\n\r\nNintedanib poses a risk of drug-induced liver injury, especially within the first three months of therapy. Liver function tests should be conducted at baseline prior to beginning therapy, at regular intervals for the first three months of therapy, and as indicated thereafter in patients exhibiting symptoms of hepatic injury such as jaundice or right upper quadrant pain. It is not recommended to be used in patients with pre-existing moderate to severe hepatic impairment (Child Pugh class B or C).","Nintedanib is a small molecule, competitive, triple angiokinase inhibitor that targets multiple receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (nRTKs). Many of these RTKs are implicated in lung fibrosis and tumour angiogenesis, so nintedanib is therefore used in the treatment of proliferative diseases such as idiopathic pulmonary fibrosis, non-small cell lung cancer, and systemic sclerosis-associated interstitial lung disease. The specific RTKs that nintedanib inhibits are platelet-derived growth factor (PDGFR) α and β, fibroblast growth factor receptor (FGFR) 1-3, vascular endothelial growth factor receptor (VEGFR) 1-3, and Fns-Like tyrosine kinase-3 (FLT3). Nintedanib binds to the ATP-binding pocket of these receptors and inhibits their activity, thereby blocking signalling cascades that result in the proliferation and migration of lung fibroblasts. Nintedanib also inhibits kinase signalling pathways in various cells within tumour tissues, including endothelial cells, pericytes, smooth muscle cells, and cells contributing to angiogenesis, culminating in an inhibition of cell proliferation and apoptosis of affected tumour cells.\r\n\r\nIn addition to RTK inhibition, nintedanib also prevents the actions of the nRTKs Lck, Lyn, and Src. The contribution of the inhibition of Lck and Lyn towards the therapeutic efficacy of nintedanib is unclear, but inhibition of the Src pathway by nintedanib has been shown to reduce lung fibrosis.","Vascular endothelial growth factor receptor 1 inhibitor; Vascular endothelial growth factor receptor 2 inhibitor; Vascular endothelial growth factor receptor 3 inhibitor; Platelet-derived growth factor receptor alpha inhibitor; Platelet-derived growth factor receptor beta inhibitor; Fibroblast growth factor receptor 1 inhibitor; Fibroblast growth factor receptor 2 inhibitor; Fibroblast growth factor receptor 3 inhibitor; Receptor-type tyrosine-protein kinase FLT3 inhibitor; Tyrosine-protein kinase Lck inhibitor; Tyrosine-protein kinase Lyn inhibitor; Proto-oncogene tyrosine-protein kinase Src inhibitor","Therapeutic strategy associated"]
[1215,"DB09083","approved","small molecule","Ivabradine","3-[3-({[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}(methyl)amino)propyl]-7,8-dimethoxy-2,3,4,5-tetrahydro-1H-3-benzazepin-2-one","C27H36N2O5","COC1=C(OC)C=C2[C@@H](CN(C)CCCN3CCC4=CC(OC)=C(OC)C=C4CC3=O)CC2=C1","Ivabradine is a novel heart rate lowering medicine for the symptomatic management of stable angina pectoralis and symptomatic chronic heart failure.  Ivabradine, brand name Corlanor, was approved by the FDA in April 2015 for the treatment of chronic heart failure in patients with an ejection fraction of ≤35%, in sinus rhythm with resting heart rate ≥70 beats per minute, who are not on beta-blockers due to contraindications or already receiving maximum beta-blocker dose. Recently a new indication was added to treat symptomatic heart failure from dilated cardiomyopathy for patients 6 months or more in age. Ivabradine acts by selectively inhibiting the \"funny\" channel pacemaker current (If) in the sinoatrial node in a dose-dependent fashion, resulting in a lower heart rate and thus more blood to flow to the myocardium. Although non-dihydropyridine calcium channel blockers and beta blockers also effectively lower heart rate, they exhibit adverse events due to their negative ionotropic effects. Therefore, as ivabradine is designed as a \"pure\" heart rate-lowering drug by selectively acting on the If channels, it may offer a more favorable side effect profile due to its lower likelihood of causing serious adverse effects.","155974-00-8","468.594","Ivabradine is indicated by the FDA to reduce the risk of hospitalization for worsening heart failure in adult patients with stable, symptomatic chronic heart failure with left ventricular ejection fraction ≤35%, who are in sinus rhythm with resting heart rate ≥70 beats per minute and either are on maximally tolerated doses of beta-blockers or have a contraindication to beta-blocker use. It is also indicated for treatment of stable symptomatic heart failure as a result of dilated cardiomyopathy for pediatric patients 6 months of age or more.","The funny channels (If) open during repolarization and close during depolarization, making ivabradine's activity dependent on heart rate or the closing and opening of the channels. Therefore ivabradine exhibits use-dependence and is more pharmacologically active at higher heart rates. Ivabradine exhibits a linear dose-dependent heart-rate lowering activity (bradycardic effect) until a maximum dose of 30-40mg. At higher doses, the concentration of ivabradine tends to plateau, reducing risk of serious sinus bradycardia.  It has been shown that the metabolite of ivabradine lowers heart rate as well, contributing to ivabradine's overall effect.","Ivabradine lowers heart rate by selectively inhibiting If channels (\"funny channels\") in the heart in a concentration-dependent manner without affecting any other cardiac ionic channels (including calcium or potassium). Ivabradine binds by entering and attaching to a site on the channel pore from the intracellular side and disrupts If ion current flow, which prolongs diastolic depolarization, lowering heart rate. The If currents are located in the sinoatrial node and are the home of all cardiac pacemaker activity. Ivabradine therefore lowers the pacemaker firing rate, consequently lowering heart rate and reducing myocardial oxygen demand. This allows for an improved oxygen supply and therefore mitigation of ischemia, allowing for a higher exercise capacity and reduction in angina episodes.","Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 inhibitor","Indication associated"]
[1216,"DB09084","approved","small molecule","Benzydamine","Benzydamine","C19H23N3O","CN(C)CCCOC1=NN(CC2=CC=CC=C2)C2=CC=CC=C12","Benzydamine (also known as Tantum Verde or Difflam), available as the hydrochloride salt, is a locally-acting nonsteroidal anti-inflammatory drug (NSAID) with local anaesthetic and analgesic properties. It is used topically for pain relief and anti-inflammatory treatment of the mouth, throat, or muscoskeletal system.\r\n\r\nAlthough the indazole analogue benzydamine is a non-steroidal anti-inflammatory drug (NSAID), it has various physicochemical properties and pharmacologic activities that are different from those of traditional aspirin-like NSAIDs but facilitate benzydamine's mechanism of action as an effective locally-acting NSAID with local anaesthetic and analgesic properties. Moreover, unlike aspirin-like NSAIDs which are acids or metabolised to acids, benzydamine is in fact a weak base.","642-72-8","309.413","Available predominantly as a liquid mouthwash, oromucosal spray, or topical cream, benzydamine is most frequently employed as a locally acting analgesic and anti-inflammatory treatment for the relief of painful inflammatory conditions. \r\n\r\nWhen formulated as a mouthwash or spray, benzydamine may be used to treat traumatic conditions like pharyngitis following tonsillectomy or the use of a naso-gastric tube, inflammatory conditions like pharyngitis, aphthous ulcers and oral ulceration due to radiation therapy, dentistry operations and procedures, or more general conditions like sore throat, sore tongue, sore gums, mouth ulcers, or discomfort caused by dentures.  \r\n\r\nWhen used as a topical cream, benzydamine may be employed to relieve symptoms associated with painful inflammatory conditions of the muscolo-skeletal system including acute inflammatory disorders such as myalgia and bursitis or traumatic conditions like sprains, strains, bruises, sore muscles, stiff joints, or even the after-effects of fractures.","Benzydamine is a non-steroidal anti-inflammatory drug (NSAID) designed to elicit local anesthetic and analgesic effects mainly for the mouth and throat. It specifically acts on the local mechanisms of inflammation such as pain, oedema, or granuloma. Typically applied topically, the drug demonstrates anti-inflammatory activity reducing oedema as well as exudate and granuloma formation. Moreover, benzydamine exhibits analgesic properties and local anaesthetic activity if pain is caused by an inflammatory condition. Benzydamine can be absorbed into the oral mucosa and intact skin. Once absorbed in the local area of pain or inflammation, benzydamine binds selectively to local inflamed tissues, usually allowing it to act with few adverse systemic effects. On average a period of 2 to 4 hours is necessary for the substance to reach peak plasma concentration. \r\n \r\nBenzydamine can be synthesized with the reaction of the N-benzyl derivative from methyl anthranilate with nitrous acid to give N-nitoso derivative. This is next reduced by sodium thiosulfate to give transient hydrazine. This hydrazine can then undergo spontaneous internal hydrazide formation. Treating this resultant enolate with 3-chloro-1-dimethylamkino propane ultimately yields benzydamine.","Despite being categorized as a non-steroidal anti-inflammatory drug (NSAID), benzydamine demonstrates various mechanisms of action that differ from those of traditional aspirin-like NSAIDs. In particular, benzydamine predominantly acts by inhibiting the synthesis of pro inflammatory cytokines like tumour necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) without largely affecting other pro inflammatory cytokines (ie. such as IL-6 and IL-8) or anti-inflammatory cytokines (ie. like IL-10 or IL-1 receptor antagonist). \r\n\r\nMoreover, benzydamine is largely a weak inhibitor of prostaglandin synthesis as it has been shown to effectively inhibit cyclooxygenase (COX) and lipoxygenase enzyme activity only at concentrations of 1mM or greater. Considering most contemporary usages of benzydamine are topical applications that are generally not well absorbed through the skin and/or non-specialized mucosae, benzydamine does not often achieve the kind of absorption or blood concentrations necessary to cause any extraneous distant systemic effects or COX inhibition, allowing it to localize its action. \r\n\r\nAdditionally, it is also hypothesized that benzydamine is capable of inhibiting the oxidative burst of neutrophils and membrane stabilization. These actions are exhibited by the substance’s ability to inhibit the release of granules from neutrophils and to stabilize lysosomes. \r\n\r\nFurthermore, benzydamine is capable of a local anaesthetic effect that may be related to its capability for inhibiting the release of inflammatory mediators like substance P and calcitonin gene related peptide from sensory nerve endings. Since substance P is capable of causing the release of histamine from mast cells, benzydamine’s prevention of substance P release further contributes to an anti-inflammatory effect. \r\n\r\nBenzydamine also demonstrates a non-specific antibacterial activity against various bacterial strains that are resistant to broad-spectrum antibiotics such as ampicillin, chloramphenicol, and tetracycline at concentrations of about 3 mmol/L. Combinatorial use of benzydamine and other antibiotics like tetracycline and chloramphenicol are also synergistic against antibiotic resistant strains of *Staphylococcus aureus* and *Pseudomonas aeruginosa*.",null,"Therapeutic strategy associated"]
[1217,"DB09086","approved","small molecule","Eugenol","Eugenol","C10H12O2","COC1=C(O)C=CC(CC=C)=C1","Eugenol is a naturally occurring phenolic molecule found in several plants such as cinnamon, clove, and bay leaves. It has been used as a topical antiseptic as a counter-irritant and in dental preparations with zinc oxide for root canal sealing and pain control. Although not currently available in any FDA-approved products (including OTC), eugenol has been found to have anti-inflammatory, neuroprotective, antipyretic, antioxidant, antifungal and analgesic properties. Its exact mechanism of action is unknown, however, it has been shown to interfere with action potential conduction. \r\nThere are a number of unapproved OTC products available containing eugenol that advertise its use for the treatment of toothache.","97-53-0","164.2011","Eugenol is not currently available in any FDA-approved drug products. There are a number of unapproved OTC products that advertise it for the use of toothache.  Eugenol is is also commonly used in combination with zinc oxide in dental procedures for the cementation of temporary prostheses and the temporary restoration of teeth and cavities.",null,"The exact mechanism of action of eugenol is unknown. However, eugenol has been shown to interrupt action potentials, which may be involved in its anti-pain activity. Research has also shown eugenol to have anti-inflammatory, neuroprotective, antipyretic, antioxidant, antifungal and analgesic properties.","Estrogen receptor alpha; Estrogen receptor beta; Androgen receptor antagonist; Transient receptor potential cation channel subfamily V member 3","Therapeutic strategy associated"]
[1218,"DB09087","approved","small molecule","Potassium alum","Alum, potassium; Aluminium potassium bis(sulphate); Aluminium potassium sulfate; Aluminum potassium alum; Aluminum potassium disulfate; Aluminum potassium sulfate; Aluminum potassium sulfate anhydrous; Burnt potassium alum; Potash alum; Potassium aluminium sulfate; Potassium aluminum disulfate","AlKO8S2","[Al+3].[K+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O","Potassium alum is considered by the FDA as a generally recognized as safe (GRAS) substance. It is an inorganic salt, also called potassium aluminum sulfate with a formula of AlK(SO4)2 that is predominantly produced in the dodecahydrate form (AlK(SO4)2 * 12H2O). Potassium alum is formed by large, transparent crystals that are used in different products like food or drugs as a buffer, neutralizing or forming agent.","10043-67-1","258.205","Potassium alum is considered safe by the FDA and its use is in homepathic or OTC products. Due to its presence in several different drugs, the main indications for the use of potassium alum are:\r\n\r\n-Constipation\r\n-Cosmetic or drug astringent, helping the shrinkage of tissues and the dry of secretions\r\n-Oral health care drug\r\n-Part of formulation in cleansing products, skin-care products, mosturizers, face powders and deodorants\r\n-Antiperspirant\r\n-Antifungal","The presence of potassium alum reduces swollen mucous membranes that result from inflammation of the nasal, gastrointestinal and urinary passages as well as in the presence of excessive secretions. The induction of the coagulation cascade will also stop bleeding.","The main functions of potassium alum in drugs are as an astringent, antiseptic or adjuvant agent. The astringent action is performed by the induction of coagulation in the superficial tissue layers until the formation of a crust. The formation of alum ions neutralize the charges on plasma proteins, causing the blood to coagulate. Similar effect is observed in disinfectants where these ions react with the free organic acid and thiol groups of proteins on microbes and free proteins, resulting in protein precipitation. This action will generate the contraction of the tissue and dry up secretions. Its adjuvant properties are mainly used in the production of vaccines where the presence of this chemical enhances the immune response.",null,"Indication associated"]
[1219,"DB09089","approved","small molecule","Trimebutine","2-Dimethylamino-2-phenylbutyl 3,4,5-trimethoxybenzoat; Trimebutine","C22H29NO5","CCC(COC(=O)C1=CC(OC)=C(OC)C(OC)=C1)(N(C)C)C1=CC=CC=C1","Trimebutine is a spasmolytic agent that regulates intestinal and colonic motility and relieves abdominal pain with antimuscarinic and weak mu opioid agonist effects. It is marketed for the treatment of irritable bowel syndrome (IBS) and lower gastrointestinal tract motility disorders, with IBS being one of the most common multifactorial GI disorders . It is used to restore normal bowel function and is commonly present in pharmaceutical mixtures as trimebutine maleate salt form. Trimebutine is not a FDA-approved drug, but it is available in Canada and several other international countries.","39133-31-8","387.476","Indicated for symptomatic treatment of irritable bowel syndrome (IBS) and treatment of postoperative paralytic ileus following abdominal surgery.","Trimebutine is a spasmolytic agent that acts directly on smooth muscle to modulate gastric motility. It shows a \"dual function\" that stimulates or inhibits spontaneous contractions depending on the concentration and prior contractile activity in the preparation. Targeting ion conductance that regulates GI motility, trimebutine inhibits the inward calcium currents and calcium-dependent potassium currents in a concentration-dependent manner . At lower concentrations (1-10uM), trimebutine depolarizes the resting membrane potential without affecting the amplitude of contractions, which is thought to be mediated by inhibition of outward potassium currents. It is also shown to activate T-type Ca2+ channel and increase gastric emptying, intestinal and colonic contractility . At higher concentrations (100-300uM), reduced amplitude of spontaneous contractions and action potentials is thought to be mediated by inhibition of L-type Ca2+ channels and inward calcium current . Trimebutine mediates a local anesthetic action by acting as a weak agonist at mu opioid receptors.","At high concentrations, trimebutine is shown to inhibit the extracellular Ca2+ influx in the smooth muscle cells through voltage dependent L-type Ca2+ channels and further Ca2+ release from intracellular Ca2+ stores . Trimebutine is suggested to bind to the inactivated state of the calcium channel with high affinity. Reduced calcium influx attenuates membrane depolarization and decrease colon peristalsis. It also inhibits outward K+ currents in response to membrane depolarization of the GI smooth muscle cells at resting conditions through inhibition of delayed rectifier K+ channels and Ca2+ dependent K+ channels, which results in induced muscle contractions . Trimebutine binds to mu opioid receptors with more selectivity compared to delta or kappa opioid receptors but with lower affinity than their natural ligands. Its metabolites (N-monodesmethyl-trimebutine or nor-trimebutine), are also shown to bind to opoid receptors on brain membranes and myenteric synaptosomes .","Mu-type opioid receptor agonist; Voltage-dependent L-type calcium channel inhibitor; Calcium-activated potassium channel inhibitor; Voltage-dependent T-type calcium channel activator; Muscarinic acetylcholine receptor M1 antagonist; Muscarinic acetylcholine receptor M2 antagonist; Muscarinic acetylcholine receptor M3 antagonist; Muscarinic acetylcholine receptor M4 antagonist","Indication associated"]
[1220,"DB09090","approved","small molecule","Pinaverium",null,"C26H41BrNO4","COC1=C(OC)C=C(C[N+]2(CCOCCC3CCC4CC3C4(C)C)CCOCC2)C(Br)=C1","Pinaverium is a spasmolytic agent used for functional gastrointestinal disorders. It is a quaternary ammonium compound that acts as an atypical calcium antagonist to restore normal bowel function. It is shown to relieve GI spasm and pain, transit disturbances and other symptoms related to motility disorders  and may be considered as effective first-lline therapy for patients with irritable bowel syndrome (IBS) . Pinaverium bromide is the common ingredient in formulations, mostly as oral tablets. Although it is not a currently approved drug by the FDA, pinaverium is available in over 60 countries including Canada.","59995-65-2","511.52","Pinaverium is indicated for the symptomatic treatment of irritable bowel syndrome (IBS) and functional disorders of the biliary tract.","Pinaverium is a selective and specific voltage-dependent calcium channel blocker located on intestinal smooth muscle cells to inhibit calcium influx. It mediates various effects on the GI tract: it causes oesophageal, gastric and duodenal relaxation, relaxes the colon and intestines, inhibits colonic motility in response to food, hormonal or pharmacological stimuli, accelerates gastric emptying, and reduces contractions of the gallbladder and phasic contractions of sphincter of Oddi . At higher concentrations, pinaverium also exhibits very weak anticholinergic effects  but is not shown to display vasodilatory or anti-arrythmic actions .","Pinaverium interacts with the 1,4-dihydropyridine binding sites on voltage dependent L-type calcium channels located on GI smooth muscle cells in a competitve manner . The binding site is located in the alpha 1S subunit and pinaverium most likely antagonizes the action of calcium ions by stabilizing a non-conducting channel state . Pinaverium inhibits smooth muscle contractions of the GI tract by inhibiting inward calcium current and calcium influx. It is suggested that pinaverium may be able to bind to both closed or inactivates states of the calcium channel with similar affinity .","Voltage-dependent L-type calcium channel subunit alpha-1S antagonist&inhibitor","Indication associated"]
[1221,"DB09092","approved; withdrawn","small molecule","Xanthinol","Xantinol","C13H21N5O4","CN(CCO)CC(O)CN1C=NC2=C1C(=O)N(C)C(=O)N2C","Xanthinol is a very potent water-soluble derivative of niacin that can be found in diet supplements. It is also known as xanthinol nicotinate.  Xaninthol is known to be a potent vasodilator that can easily pass through the cell membrane and once inside the cell it causes an increase in glucose metabolism resulting in an increased energy.  It was approved as a drug in 1998 in Canada and nowadays its status is cancelled post marketing.","2530-97-4","311.342","Xanthinol is primarily used in diet supplements to increase the brain metabolism of glucose and obtain ATP. Xanthinol is also used as an agent to reduced cholesterol as it is a vasodilator. Its action allows having an elevated rate of blood flow in the brain which helps improve memory function, concentration and awareness. Thus, due to his actions, xanthinol is indicated to improve cerebrovascular and peripheral vascular disorders as well as hyperlipidaemias.","Reports indicate that xanthinol increases blood flow in the vascular beds. The use of xanthinol in clinical trials have reported improvements in the performance of healthy elderly individuals in short- and long-term memory tests. The later effect is explained by the enhancing on the cell metabolism and oxygen supply in the brain by the rise of ATP in erythrocytes which allows penetration into capillaries easier and a higher oxygen pressure in the capillary blood which improves oxygenation of surrounding tissue.","The positively charged xanthinol ion is thought to help the transportation of the nicotinic acid into the cell since the later cannot freely diffuse through the cell membrane. The mechanism of action is thought to be related to present influence in the cell metabolism through the nucleotides NAD and NADP. Also, the nicotinic acid is a coenzyme for a lot of proteins involved in tissue respiration (Embden-Meyerhof and citrate cycle). The effect of xanthinol nicotinate causes an increase in glucose metabolism and energy gain.","60S ribosomal protein L3 binder; NAD(P) transhydrogenase, mitochondrial cofactor; Glyceraldehyde-3-phosphate dehydrogenase cofactor; Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial cofactor; 2-oxoglutarate dehydrogenase, mitochondrial cofactor; Malate dehydrogenase, mitochondrial cofactor","Indication associated"]
[1222,"DB09095","approved; investigational; withdrawn","small molecule","Difluocortolone","Diflucortolone","C22H28F2O4","[H][C@@]12C[C@@H](C)[C@H](C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])C[C@H](F)C2=CC(=O)C=C[C@]12C","Difluocortolone is a potent topical corticosteroid. It is commonly used in dermatology for the reduction of inflammation and itching. It was submitted to the FDA in July 1984 by the pharmaceutical company Schering AG.","2607-06-9","394.459","Difluocortolone is used as a topical treatment of the symptoms of inflammatory skin disorders like eczema, seborrheic eczema, lichen planus and psoriasis. All these disorders present as a common characteristic the occurrence of symptoms as itching, swelling, redness and scaling.","Diflucortolone is a steroid with the properties of being an anti-inflammatory, antipruritic and vasoconstrictive. Its activity causes the vasoconstriction of the blood vessels and thus a decrease in the release of inflammatory substances. These actions produce the effect of skin soothed and elimination of the symptoms.","Diflucortolone performs its action by the induction of lipocortins which are phospholipase A2 inhibitory proteins and sequentially inhibiting the release of arachidonic acid. The absence of arachidonic acid translates to the inhibition of the formation, release and activity of endogenous chemical inflammatory mediators. Another mechanism of action is the transrepression in which diflucortolone binds to the glucocorticoid receptor which induces its migration to the nucleus where it stimulates the transcription of anti-inflammatory genes like tyrosine aminotransferase, phophoenolpyruvate carboxykinase, IL-10, etc. and suppress the expression of proinflammatory genes like cytokines, growth factors, adhesion molecules, etc.","Annexin A3 inducer; Glucocorticoid receptor binder","Therapeutic strategy associated"]
[1223,"DB09099","approved; investigational","small molecule","Somatostatin","Somatostatin; Synthetic growth hormone release-inhibiting hormone; Synthetic somatostatin-14","C76H104N18O19S2","C[C@@H](O)[C@@H]1NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC2=CNC3=C2C=CC=C3)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](CO)NC1=O)C(O)=O)NC(=O)CNC(=O)[C@H](C)N)[C@@H](C)O","Somatostatin, also known as growth hormone-inhibiting hormone, is a naturally-occurring peptide hormone of 14 or 28 amino acid residues  that regulates the endocrine system. It is secreted by the D cells of the islets to inhibit the release of insulin and glucagon, and is also generated in the hypothalamus, where it inhibits the release of growth hormone and thyroid-stimulating hormones from the anterior pituitary . Somatostatin is initially secreted as a 116 amino acid precursor, preprosomatostatin, which undergoes endoproteolytic cleavage to prosomastatin. Prosomastatin is further process into two active forms, somatostatin-14 (SST-14) and somatostatin-28 (SST-28), an extended SST-14 sequence to the N-terminus . The actions of somatostatin are mediated via signalling pathways of G protein-coupled somatostatin receptors. \r\n\r\nAntineoplastic effects and potential uses of somatostatin on various tumours, including pituitary adenomas, GEP-NETs, paragangliomas, carcinoids, breast cancers, malignant lymphoma and small-cell lung cancers, have been extensively investigated . Somatostatin has been used in the clinical setting for the diagnosis of acromegaly and gastrointestinal tract tumours. Its analogues have been developed to achieve more favourable kinetics for efficiency use in the management of acute conditions, such as esophageal varices.  is a long-acting analogue of somatostatin that inhibits the release of a number of hormones, and is clinically used to relieve symptoms of uncommon gastroenteropancreatic endocrine tumours, as well as treat acromegaly .","38916-34-6","1637.9","For the symptomatic treatment of acute bleeding from esophageal varices. Other treatment options for long-term management of the condition may be considered if necessary, once initial control has been established.","Somatostatin is an endogenous peptide hormone that is secreted by the central nervous system, gastrointestinal tract, retina, peripheral neurons and pancreatic D cells of the islets of Langerhans. It exhibits several biological roles but predominantly exerts an inhibitory effect on secretion of other hormones and transmitters . While distribution of two active isoforms of somatostatin is similar, SST-14 is more predominant in the enteric neurons and peripheral nerves whereas SST-28 is more prominent in the retina and intestinal mucosal cells .\r\n\r\n**Anterior pituitary gland and brain:** It inhibits the release of growth hormones and thyroid-stimulating hormones, such as thyroid stimulating hormone (TSH) and thyrotrophin, from the anterior pituitary while inhibiting the release of dopamine from the midbrain, norepinephrine, TRH and corticotrophin-releasing hormone in the brain . \r\n\r\n**Pancreas:** In the pancreas, somatostatin reduces the secretion of glucagon and insulin as well as bicarbonate ions and other enzymes .\r\n\r\n**Thyroid gland:** Somatosatin reduces secretion of T3, T4, and calcitonin . Somatostatin regulates the thyroid function by reducing basal TSH release .\r\n\r\n**Gastrointestinal tract:** It attenuates the release of most gastrointestinal hormones such as gastrin, secretin, motilin, gastric acid, enteroglucagon, cholecystokinin (CCK), vasoactive intestinal peptide (VIP), gastric inhibitory polypeptide (GIP), intrinsic factor, pepsin, neurotensin, as well as bile secretion and colonic fluid secretion .\r\n\r\n**Adrenal gland:** It inhibits angiotensin II-stimulated aldosterone secretion and acetylcholine-induced medullary catecholamine secretion .\r\n\r\n**Eye/retina:** Somatostatin inhibits the production of vascular endothelial growth factor .\r\n\r\n**Inflammatory cells and sensory nerves:** The expression of somatostatin has been found in inflammatory cells such as lymphocytes, monocytes, macrophages and endothelial cells to act as an autocrine or paracrine regulator in local immune responses. Findings suggest that somatostatin may play a role in exerting local and systemic anti-inflammatory and antinociceptive effects . On primary afferent neurons, somatostatin reduces the responses to thermal stimulation in C-mechanoheat sensitive fibers in a dose-dependent fashion and reduces the responses of C-mechanoheat fibers to bradykinin-induced excitation and sensitization to heat . Somatostatin is reported to elicit an analgesic effect when applied intrathecally; there is evidence supporting that similar effects may occur when systemically used to treat endocrine disorders . \r\n\r\nSomatostatin is thought to reduce bleeding from esophageal varices by causing splanchnic vasoconstriction . Somatostatin elicits anti-neoplastic actions on various tumours via direct or indirect effects, or a combination of both .","Somatostatin binds to 5 subtypes of somatostatin receptors (SSTRs), which are all Gi-protein-coupled transmembrane receptors that inhibits adenylyl cyclase upon activation . By inhibiting intracellular cyclic AMP and Ca2+ and by a receptor-linked distal effect on exocytosis, SSTRs block cell secretion . The common pathway shared by the receptors involve the activation of phosphotyrosine phosphatase (PTP), and modulation of mitogen-activated protein kinase (MAPK) . With the exception of SSTR3, activation of SSTRs lead to activation of voltage-gated potassium channels accompanied by increased K+ currents. This result in membrane hyperpolarization and inhibits depolarization-induced Ca2+ influx through voltage-sensitive Ca2+ channels . Depending on the receptor subtype, signalling cascades involve activation of other downstream targets such as Na+/H+ exchanger, Rho GTPase, and nitric oxide synthase (NOS) . SSTRs 1 to 4 bind both somatostatin isoforms with equal nanomolar binding affinity whereas SSTR5 exhibits a 5- to 10-fold higher binding affinity for SST-28 . \r\n\r\n**Effects of SSTR1:** Upon biding of somatostatin and activation, SSTR1 mediates an antisecretory effect on growth hormone, prolactin and calcitonin . \r\n\r\n**Effects of SSTR2:** SSTR2 subtype dominates in endocrine tissues. By binding to SST2 receptors, somatostatin exerts paracrine inhibitory actions on gastrin release from G cells, histamine release from ECL cells, and directly on parietal cell acid output . SSTR2 receptor signalling cascades also inhibit the secretion of growth hormone and that of adrenocorticotropin, glucagon, insulin, and interferon-γ . \r\n\r\n**Effects of SSTR3:** Activation of these receptors lead to reduction in cell proliferation . SSTR3 triggers PTP-dependent cell apoptosis accompanied by activation of p53 and the pro-apoptotic protein Bax . A study of the matrigel sponge assay suggests that through SSTR3-mediated inhibition of both NOS and MAPK activities may lead to the antitumor effects of somatostatin in inhibiting tumor angiogenesis .\r\n\r\n**Effects of SSTR4:** The functions of SSTR4 remain largely unknown .\r\n\r\n**Effects of SSTR5:** Like SSTR2, SSTR5 subtype also predominates in endocrine tissues. Upon activation, SSTR5 signalling cascades exert an inhibitory action on growth hormone, adrenocorticotropin, insulin, and glucagon-like peptide-1 as well as the secretion of amylase .\r\n\r\nThe presence of somatostatin receptors has been identified in most neuroendocrine tumours, endocrine gastroenteropancreatic (GEP) tumors, paragangliomas, pheochromocytomas, medullary thyroid carcinomas (MTC) and small cell lung carcinomas . The antitumor effects of somatostatin were also effective in various malignant lymphomas and breast tumours . Gastrointestinal hormones, such as gastrin, secretin, and cholecystokinin (CCK), as well as growth hormones and growth factors are thought to be elevated in gastrointestinal tract and neuroendocrine tumours and are inhibited by somatostatin . _In vitro_, somatostatin inhibited epidermal growth factor (EGF)-induced DNA synthesis and replication following  which suggest that somatostatin may have direct anti-proliferative effects via SSTR signalling . Acromegaly is characterized as the endocrine disorder caused by a functioning tumour of cells that secrete growth hormone from the anterior pituitary . Somatostatin analogue therapies serve to normalize the elevated levels of GH and insulin-like growth factor 1 (IGF-1) and attenuate tumour growth.  \r\n\r\nIn the vascular system this likely produces vasoconstriction by inhibiting adenylate cyclase leading to a lowering the concentration of cyclic adenosine monophosphate in the endothelial cells which ultimately blocks vasodilation through this pathway. This vasoconstriction is though the be responsible for reducing blood flow to the esophageal tissues and so reduces bleeding from esophageal varices . \r\n\r\nSomatostatin mediates an analgesic activity by reducing vascular and nociceptive components of inflammation . Studies indicate that somatostatin may be present in nociceptive DRG neurons with C-fibers and primary afferent neurons to inhibit the release of transmitters at the presynaptic junctions of the sensory-efferent nerve terminals . Exogenous somatostatin has shown to inhibit the release of Substance P from central and peripheral nerve ending .","Somatostatin receptor type 1 agonist; Somatostatin receptor type 2 agonist; Somatostatin receptor type 3 agonist; Somatostatin receptor type 4 agonist; Somatostatin receptor type 5 agonist","Therapeutic strategy associated"]
[1224,"DB09100","approved","biotech","Thyroid, porcine","Pig thyroid; Porcine thyroid; Sus scrofa thyroid; Thyroid (pork); Thyroid extract, porcine",null,null,"Thyroid extract is dried and powdered thyroid glands from pigs containing tiiodothyronine (T3) and thyroxine (T4) used to supplement low or absent thyroid activity. Thyroid extract has been described in literature to treat hypothyroidism since 1891 but its use dates back as far as the 6th century. Thyroid extract is no longer considered a first line therapy as it delivers a dose that is inconsistent with the stated strength of the tablet. Currently, patients are more likely to be treated with .\r\n\r\nThyroid extracts were never FDA approved as their use in the United States predates the FDA.",null,null,"Thyroid extract is indicated for replacement therapy in decreased or absent thyroid function.","Thyroid extract increases the metabolic rate of patients with hypothyroidism. The therapeutic index of thyroid extract is wide, as patients can be given varying doses. The duration of action is long as thyroid extract is generally given once daily. Patients should not use thyroid extract for weight loss.","T3 binding to the thyroid hormone receptor (TR), changes the conformation of the TR, allowing it to bind to the retinoid X receptor (RXR) and form a coactivator complex. The coactivator complex has histone acetyltransferase activity, which activates genes. In the absence of T3, TR and RXR form a corepressor complex with histone deacetylase activity, which represses genes. The macroscopic effects of thyroid hormones is an increase in the metabolic rate. T4 has similar but weaker activity to T3.","Thyroid hormone receptor alpha substrate; Thyroid hormone receptor beta substrate","Target associated"]
[1225,"DB09104","approved; investigational","small molecule","Magnesium hydroxide","Magnesium dihydroxide; Magnesium hydroxide; Milk of magnesia","H2MgO2","[OH-].[OH-].[Mg++]","Magnesium hydroxide is an inorganic compound. It is naturally found as the mineral brucite. Magnesium hydroxide can be used as an antacid or a laxative in either an oral liquid suspension or chewable tablet form. \r\nAdditionally, magnesium hydroxide has smoke suppressing and flame retardant properties and is thus used commercially as a fire retardant. \r\nIt can also be used topically as a deodorant or for the relief of canker sores (aphthous ulcers).","1309-42-8","58.32","Magnesium hydroxide can be used as an antacid or a laxative depending on the administered dose.\r\n\r\nAs an antacid, it is used for the temporary relief of heartburn, upset stomach, sour stomach or acid indigestion.\r\n\r\nAs a laxative, it is used for the relief of occasional constipation by promoting bowel movements for 30 minutes and up to 6 hours.\r","As an antacid, magnesium hydroxide suspension neutralizes gastric acid by reacting with hydrochloric acid in the stomach to form magnesium chloride and water. It is practically insoluble in water and does not have any effect until it reacts with the hydrochloric acid in the stomach. There, it decreases the direct acid irritant effect and increases the pH in the stomach leading to inactivation of pepsin. Magnesium hydroxide enhances the integrity of the mucosal barrier of the stomach as well as improving the tone of both the gastric and esophageal sphincters. \r\n\r\nAs a laxative, the magnesium hydroxide works by increasing the osmotic effect in the intestinal tract and drawing water in. This creates distension of the colon which results in an increase in peristaltic movement and bowel evacuation.","The suspension of magnesium hydroxide is ingested and enters the stomach. According to the amount ingested, the magnesium hydroxide will either act as an antacid or a laxative. \r\n\r\nThrough the ingestion of 0.5-1.5 grams (in adults) the magnesium hydroxide will act by simple acid neutralization in the stomach. The hydroxide ions from the magnesium hydroxide suspension will combine with the acidic H+ ions of the hydrochloric acid made by the stomachs parietal cells. This neutralization reaction will result in the formation of magnesium chloride and water. \r\n\r\nThrough the ingestion of 2-5 grams (in adults) the magnesium hydroxide acts as a laxative in the colon. The majority of the suspension is not absorbed in the intestinal tract and will create an osmotic effect to draw water into the gut from surrounding tissues. With this increase of water in the intestines, the feces will soften and the intraluminal volume of the feces will increase. These effects still stimulate intestinal motility and induce the urge to defecate. Magnesium hydroxide will also release cholecystokinin (CKK) in the intestines which will accumulate water and electrolytes in the lumen and furthermore increase intestinal motility.",null,"Therapeutic strategy associated"]
[1226,"DB09110","approved; investigational","small molecule","Coenzyme M","2-Mercaptoethane; 2-Mercaptoethanesulfonate; 2-mercaptoethanesulfonic acid; 2-mercaptoethanesulphonic acid; 2-mercaptoethylsulfonate; 2-sulfanylethylsulfonate; CoM; HS-CoM; reduced coenzyme M; reduced CoM; β-mercaptoethanesulfonic acid","C2H6O3S2","OS(=O)(=O)CCS","Coenzyme M (commonly known by its salt form, Mesna) is a synthetic sulfhydryl (thiol) compound and is used for prophylaxis of Ifosfamide and cyclophosphamide induced hemorrhagic cystitis.","3375-50-6","142.197","Mesna is a uroprotective agent and is used prophylactically to reduce ifosfamide and cyclophosphamide induced hemorrhagic cystitis.","Mesna binds to and inactivates acrolein there by preventing or reducing bladder problems","A metabolite called acrolein is produced when ifosfamide and cyclophosphamide are metabolized. This metabolite concentrates in the bladder and causes cell death via upregulation of reactive oxygen species (ROS), and activates inducible nitric oxide synthase (iNOS) which leads to production of nitric oxide (NO). Both ROS and NO produce products which are detrimental to lipids, proteins and DNA strands. Furthermore, ROS stimulate gene expression of pro-inflammatory cytokines such as TNF-α AND IL-1β. Acrolein may also lead to ulceration of the bladder urothelium. Mesna protects against cyclophosphamide and ifosfamide induced hemorrhagic cystitis by binding to their toxic metabolites. Mesna is metabolized to dimesna and excreted by the kidneys. Glutathione dihydrogenase acts on the reabsorbed portion and produces free sulfhydryl groups. These free sulfhydryl  groups bind acrolein in the bladder, allowing effective excretion and prevention  of toxic effects. In addition, Mesna binds to and detoxifies a urotoxic ifosfamide metabolite called 4-hydroxy-ifosfamide.",null,"Therapeutic strategy associated"]
[1227,"DB09114","approved; investigational; withdrawn","small molecule","Colfosceril palmitate","Colfosceril palmitate; Dipalmitoylphosphatidylcholine","C40H80NO8P","CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCC","Colfosceril palmitate is a synthetic pulmonary surfactant administered in infants with respiratory distress syndrome. It was part of the first generation of commercially available artificial surfactants. It was developed by Burroughs Wellcome and it was FDA approved on August 6, 1990. Nowadays colfosceril palmitate is under the state of canceled post-marketing.","63-89-8","734.0389","Colfosceril palmitate is indicated for the treatment of respiratory distress syndrome (RDS) in premature infants. The official label is referred as a intratracheal suspension for prophylactic treatment of infants of less than 1350 grams of birth weight under risk of developing RDS, or in infants with birth weight greater than 1350 grams with pulmonary immaturity, or as rescue treatment of infants that already developed RDS. The central feature of RDS is a surfactant deficiency due to lung immaturity. This lung condition is more frequently presented due to risk factors like prematurity, delayed lung maturation caused by maternal diabetes or male gender, or surfactant dysfuntion due to perinatal asphyxia, pulmonary infection or delivery without labor.","Colfosceril palmitate has shown to significantly reduce the risk of pneumothoraces, pulmonary interstitial emphysema and mortality. Unlike naturals surfactants, colfosceril palmitate reduces the risk of bronchopulmonary dysplasia, intraventricular hemorrhage and patent ductus arteriosus. In clinical placebo-controlled trials, there was a significant reduction in the number of deaths attributed to hyaline membrane disease, the incidence of pulmonary air leaks, oxygen requirements and mean airway pressure. Some reports have indicated a lack of therapeutic effect due to the absence of surfactant protein.","Treatment with colfosceril palmitate aims to reinflate a collapsed area of the lung, improve compliance and reduce intrapulmonary shunting. The actions of colfosceril palmitate are perfomed by replacing the defficient or innefective endogenous lung surfactant and thus, reducing the tension and stabilizing the alveoli from collapsing. Colfosceril palmitate will form a very thin film that will cover the surface of the alveolar cells and therefore it will reduce surface tension.",null,"Indication associated"]
[1228,"DB09120","approved; investigational","small molecule","Zucapsaicin","(Z)-Capsaicin; cis-Capsaicin; Civamide; Zucapsaicin","C18H27NO3","COC1=C(O)C=CC(CNC(=O)CCCC\\C=C/C(C)C)=C1","Zucapsaicin, the cis-isomer of capsaicin, is a topical analgesic used to treat osteoarthritis of the knee and other neuropathic pain. It is a modulator of transient receptor potential cation channel subfamily V member 1 (TRPV-1), also known as the vanilloid or capsaicin receptor 1, that reduces pain and improves articular functions. Zucapsaicin has also been evaluated for the management of several conditions manifested by chronic nerve pain. These conditions include herpes simplex (HSV) infections, cluster headaches, migraine, and osteoarthritis of the knee. Zucapsaicin was approved by the Health Canada in 2010 as topical cream marketed under the brand name Zuacta but currently not FDA-approved.","25775-90-0","305.4119","Indicated to be used in conjunction with oral COX-2 inhibitors or NSAIDs for the relief of severe pain in adult patients with osteoarthritis of the knee, not controlled with oral COX-2 inhibitors or NSAIDs alone, for a duration of no more than three months.","Zucapsaicin mediates an antinociceptive action via acting as an agonist at TRPV1. TRPV1 play an important physiological role of transducing chemical, mechanical and thermal stimuli as well as pain transduction, and participate in pain modulation and perception. They are mainly distributed in C sensory nerve fibers as well as Aẟ fibers to transmit sensory information involving inflammatory and neuropathic pain, and activation of these channels releasesomatostatin, calcitonin gene-related peptide (CGRP) and other neuropeptides (neurokinin A, kassinin), leading to neurogenic inflammation . Zucapsaicin is also reported to affect the peptidergic afferent neurons via a desensitization mechanism to decrease the levels of dorsal root ganglia and sciatic calcitonin gene-related peptide (CGRP) and substance P (SP) .","Zucapsaicin excites and desensitizes C-fibers via agonist at TRPV1 on nociceptive neurons. It binds to intracellular sites and initially stimulates the channels, causing burning sensation. Activation of TRPV1 results in calcium influx and sodium, which leads to cell depolarization. Hypersensitization by zucapsaicin is then followed by reduced sensitivity and persistent desensitization (tachyphylaxis) of the channels via various pathways. Densentiziation is thought to be dependent on intraceullar levels of calcium . Decreased TRPV1 channel action and release of inflammatory neuropeptides induces an analgesic effect, and pain relief . Zucapsaicin activates calcineurin and calcium-dependent protein kinase C isoforms which results in phosphorylation of TRPV1. Phosphorylation of TRPV1 enhances reponsivity to zucapsaicin by potentiating capsaicin- or proton-evoked responses and reducing the temperature threshold for TRPV1 activation . Studies suggest that zucapsaicin is involved in activation of phospholipase C with the subsequent phosphatidylinositol 4,5-biphosphate (PIP2) hydrolysis, which results in TRPV1 inactivation . \r\nTachyphylaxis or persistent desensitization is reversible, and involves the downregulation of proalgesic substances (such as SP) and upregulation of analgesic peptides .","Transient receptor potential cation channel subfamily V member 1 agonist&activator","Therapeutic strategy associated"]
[1229,"DB09121","approved; withdrawn","small molecule","Aurothioglucose","Auromyose; Aurothioglucose; Gold thioglucose","C6H11AuO5S","OC[C@H]1O[C@H](S[Au])[C@H](O)[C@@H](O)[C@@H]1O","Aurothioglucose, also known as gold thioglucose, was formerly used to treat rheumatoid arthritis.\r\n\r\nContemporary research on the effect of gold salts treatment began in 1935, primarily to reduce inflammation and to slow disease progression in patients with rheumatoid arthritis . The use of gold compounds has decreased since the 1980s owing to numerous side effects, limited efficacy, and slow onset of action. Many if not most gold compounds that were indicated for rheumatoid arthritis therapy have since been replaced with the use of various current disease modifying anti-rheumatic drugs (DMARDs) like methotrexate and others, which are far more effective.","12192-57-3","392.18","Aurothioglucose is indicated for the adjunctive treatment of early active adult and juvenile type rheumatoid arthritis that is not adequately controlled by other anti-inflammatory agents and conservative measures like salicylate, glucocorticoids, etc. . In chronic, advanced cases of rheumatoid arthritis, such gold therapy is not demonstrated to be as valuable .\r\n\r\nAntirheumatic measures such as salicylate and other anti-inflammatory drugs (both steroidal and non steroidal) may be continued after initiation of gold therapy . After improvement commences, these measures may be discontinued slowly as symptoms permit .","After administration, patient serum levels of gold rise sharply but decline over the following week . Peak levels with aqueous preparations are higher and decline faster than those with oily preparations . Regular weekly administration produces a continuous rise in the basal value for several months, after which the serum level becomes relatively stable . After a standard weekly dose, considerable individual variation in the levels of gold can be observed . A steady decline in gold levels occurs when the interval between injections is lengthened, and small amounts may be found in the serum for months after discontinuation of therapy . The incidence of toxic reactions is seemingly unrelated to the plasma level of gold, but may perhaps be more associated with the total cumulative content of gold in the body .","Rheumatoid arthritis is an autoimmune disease in which the body's immune system mistakenly attacks the lining of various skeletal bone joints of the body . These attacks are facilitated by various pro-inflammatory immune cells and agents like cytokines, histamines, mast cells, macrophages, monocytes, lymphocytes, leukocytes, and many others . The longterm result of this unwanted immune response is chronic inflammation and painful tissue damage . The cause of the malfunctioning immune system in rheumatoid arthritis is unknown and there is no definitive cure for the condition .\r\n\r\nSimilarly, the mechanism of action of aurothioglucose is also not well elucidated. Nevertheless, some studies have suggested that the combination of both the sulfhydryl ligand and aureus cation present in aurothioglucose elicits an inhibitory effect on adenylyl cyclase activity in human lymphocyte membranes and in membranes of T and B lymphocyte subsets . In particular, such inhibition of the activity of adenylyl cyclase and its various isoforms would theoretically also limit the cyclases' ability to induce mast cell degranulation and histamine release, to enhance respiratory burst effects, to stimulate the action of resting macrophages, to induce and activate phagocytes, to induce neutrophil chemotaxis, etc. - all of which are pro-inflammatory actions .","Adenylate cyclase type 1; Adenylate cyclase type 2; Adenylate cyclase type 5","Therapeutic strategy associated"]
[1230,"DB09124","approved; withdrawn","small molecule","Medrogestone","Medrogestone","C23H32O2","[H][C@@]12CC[C@](C)(C(C)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])C=C(C)C2=CC(=O)CC[C@]12C","Medrogestone (INN), also known as 6,17α-dimethyl-6-dehydroprogesterone, is a progestational agent derived from 17-methylprogesterone. It was conceived as an alternative for an orally effective contraceptive option. It was developed by Ayerst, approved in Canada in 1969 and its current status is cancelled post-marketing. It was never approved by the FDA.","977-79-7","340.507","Medrogestone is indicated as adjunct to treat endometial shedding in menopausal women, to treat secondary amenorrhea, to induce menses and to treat dysfunctional uterine bleeding in adult and adolescent women.","Medrogestone was created as a more potent and orally active option of progesterone. In pre-clinical trials, medrogestone was proven to have four times more progestational activity than progesterone with a similar duration effect than the one found for 17-hydroxyprogesterone. Medrogestone was also able to maintain pregnancy and prevented ovulation in ovariectomized rats. Administration of medrogestone, alone or with premarin, prevented pregnancy, as well as it suppressed ovarian weight increase by nearly 100% of the tested individuals. Medrogestone does not produce any androgenic effect but it presented a marked anti-androgenic effect. It did not present an oestrogenic effect, nor changes in organ weight or histological appearance in adrenal glands or thymus and it does not present any anti-inflammatory effects.","Medrogestone is a progestogen, thus its action is done under the same profile. These type of molecules are steroid hormones that bind and activate the progesterone receptor. Its action may involve the suppression of gonadotropic hormones from the anterior portion of the pituitary gland and secondary suppression of testosterone. Medrogestone presents structural similarities to testosterone which allows it to compete for the androgen-receptor-protein receptor sites in prostatic cells. Administration of medrogestone diminishes the response to endogenous hormones in tumor cells due to a reduction in hormone steroid receptors; this effect will translate into cytotoxic or antiproliferative effects.","Progesterone receptor ligand","Therapeutic strategy associated"]
[1231,"DB09130","approved; investigational","small molecule","Copper",null,"Cu","[Cu]","Copper is a transition metal and a trace element in the body. It is important to the function of many enzymes including cytochrome c oxidase, monoamine oxidase and superoxide dismutase . Copper is commonly used in contraceptive intrauterine devices (IUD) .","7440-50-8","63.546","For use in the supplementation of total parenteral nutrition and in contraception with intrauterine devices  .","Copper is incorporated into many enzymes throughout the body as an essential part of their function . Copper ions are known to reduce fertility when released from copper-containing IUDs .","Copper is absorbed from the gut via high affinity copper uptake protein and likely through low affinity copper uptake protein and natural resistance-associated macrophage protein-2 . It is believed that copper is reduced to the Cu1+ form prior to transport. Once inside the enterocyte, it is bound to copper transport protein ATOX1 which shuttles the ion to copper transporting ATPase-1 on the golgi membrane which take up copper into the golgi apparatus. Once copper has been secreted by enterocytes into the systemic circulation it remain largely bound by ceruloplasmin (65-90%), albumin (18%), and alpha 2-macroglobulin (12%). \r\n\r\nCopper is an essential element in the body and is incorporated into many oxidase enzymes as a cofactor . It is also a component of zinc/copper super oxide dismutase, giving it an anti-oxidant role. Copper defiency occurs in Occipital Horn Syndrome and Menke's disease both of which are associated with impaired development of connective tissue due to the lack of copper to act as a cofactor in protein-lysine-6-oxidase. Menke's disease is also associated with progressive neurological impairment leading to death in infancy. The precise mechanisms of the effects of copper deficiency are vague due to the wide range of enzymes which use the ion as a cofactor.\r\n\r\nCopper appears to reduce the viabilty and motility of spermatozoa . This reduces the likelihood of fertilization with a copper IUD, producing copper's contraceptive effect . The exact mechanism of copper's effect on sperm are unknown.","Amyloid beta A4 protein binder; Adenosylhomocysteinase allosteric modulator; Histone H2B type 1-C/E/F/G/I; Glyceraldehyde-3-phosphate dehydrogenase; Nucleoside diphosphate kinase A; Histone H1.4; Peroxiredoxin-1; Protein S100-A8; 40S ribosomal protein SA; Actin, cytoplasmic 2; Alpha-enolase; Elongation factor 1-alpha 1; Keratin, type II cytoskeletal 8; Protein disulfide-isomerase; Protein disulfide-isomerase A3; 60 kDa heat shock protein, mitochondrial; Heat shock 70 kDa protein 13; 78 kDa glucose-regulated protein; Endoplasmin; Serotransferrin; Cell growth-regulating nucleolar protein; 40S ribosomal protein S2; Serine/arginine-rich splicing factor 1; Heterogeneous nuclear ribonucleoproteins A2/B1; Heterogeneous nuclear ribonucleoprotein H; Heterogeneous nuclear ribonucleoprotein H3; Cobalt-precorrin-5B C(1)-methyltransferase; Heterogeneous nuclear ribonucleoprotein L; Splicing factor, proline- and glutamine-rich; Splicing factor 3A subunit 2; Receptor of activated protein C kinase 1; Alpha-actinin-1; Aminoacylase-1; Annexin A4; Annexin A5; Calreticulin; Pyruvate kinase PKM; Alcohol dehydrogenase [NADP(+)]; NADH-cytochrome b5 reductase 3; Glutathione reductase, mitochondrial; Transketolase; Peroxiredoxin-2; Peroxiredoxin-6; Peptidyl-prolyl cis-trans isomerase A; Heat shock cognate 71 kDa protein; Heat shock protein HSP 90-alpha; Prostaglandin E synthase 3; Stress-induced-phosphoprotein 1; Translation elongation factor 1 alpha 1-like 14; Eukaryotic translation initiation factor 6; Eukaryotic initiation factor 4A-I; Glucose-6-phosphate isomerase; L-lactate dehydrogenase A chain; Phosphoglycerate kinase 1; Tubulin alpha-3C/D chain; Tubulin beta chain; Cofilin-1; 14-3-3 protein beta/alpha; Aspartate aminotransferase, cytoplasmic; Glutathione synthetase; Hepatoma-derived growth factor; Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial; Chloride intracellular channel protein 1; Proteasome activator complex subunit 1; Phosphatidylethanolamine-binding protein 1; Phosphoglycerate mutase 1; Ran-specific GTPase-activating protein; UDP-glucose 6-dehydrogenase; Beta-2-microglobulin; Protein SCO1 homolog, mitochondrial; Alternative prion protein; Glycine receptor subunit alpha-1; Huntingtin; Endonuclease 8-like 1; Endonuclease 8-like 2; Hephaestin-like protein 1 cofactor; Plasminogen activator inhibitor 1; Protein S100-A2; Protein S100-A4; Alpha-synuclein; Brain-derived neurotrophic factor cofactor; Protein DJ-1; Islet amyloid polypeptide; Tachykinin-3; Alpha-1B-glycoprotein; Afamin; Angiotensinogen; Alpha-2-HS-glycoprotein; Serum amyloid P-component; Apolipoprotein A-I; Apolipoprotein A-II; Apolipoprotein A-IV; Apolipoprotein B receptor; Apolipoprotein C-II; Apolipoprotein C-III; Apolipoprotein D; Apolipoprotein E; Beta-2-glycoprotein 1; Zinc-alpha-2-glycoprotein; Complement C1q subcomponent subunit C; Complement C1s subcomponent; Complement C3; Complement C4-B; C4b-binding protein alpha chain; Complement C5; Complement component C8 beta chain; Complement component C9; Complement factor H; Complement factor I; Tetranectin; Clusterin; Prothrombin; Complement component 1 Q subcomponent-binding protein, mitochondrial; Gelsolin; Hemoglobin subunit alpha; Hemoglobin subunit beta; Chromobox protein homolog 5; Haptoglobin-related protein; Insulin-like growth factor-binding protein complex acid labile subunit; Ig gamma-1 chain C region; Ig gamma-4 chain C region; Ig kappa chain V-III region GOL; Immunoglobulin lambda-like polypeptide 1; Inter-alpha-trypsin inhibitor heavy chain H2; Kininogen-1; Keratin, type II cytoskeletal 1; Keratin, type I cytoskeletal 10; Keratin, type II cytoskeletal 2 epidermal; Keratin, type I cytoskeletal 9; Leucine-rich alpha-2-glycoprotein; Lumican; N-acetylmuramoyl-L-alanine amidase; Plasminogen; Serum paraoxonase/arylesterase 1; Platelet basic protein; Alpha-1-antitrypsin; Kallistatin; Corticosteroid-binding globulin; Thyroxine-binding globulin; Antithrombin-III; Heparin cofactor 2; Pigment epithelium-derived factor; Alpha-2-antiplasmin; Plasma protease C1 inhibitor; Transthyretin; Vitronectin; Amyloid-like protein 1 cofactor","Therapeutic strategy associated"]
[1232,"DB09134","approved","small molecule","Ioversol","Ioversol; N,N'-Bis (2,3-dihydroxypropyl)-5-[N-(2-hydroxyethyl) -glycolamido] -2,4,6-triiodoisophthalamide; Optiray","C18H24I3N3O9","OCCN(C(=O)CO)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I","Ioversol is classified as an _organoiodine_ compound and is used as a contrast dye in diagnostic procedures. It contains high levels of iodine in addition to various hydrophilic groups.","87771-40-2","807.115","Optiray 350 is indicated in adults for peripheral and coronary arteriography and left ventriculography. Optiray 350 is also indicated for contrast enhanced computed tomographic imaging of the head and body, intravenous excretory urography, intravenous digital subtraction angiography and venography. Optiray 350 is indicated in children for angiocardiography.\r\nOptiray 320 is indicated in adults for angiography throughout the cardiovascular system. The uses include cerebral, coronary, peripheral, visceral and renal arteriography, venography, aortography, and left ventriculography. Optiray 320 is also indicated for contrast enhanced computed tomographic imaging of the head and body, and intravenous excretory urography.\r\nOptiray 320 is indicated in children for angiocardiography, contrast enhanced computed tomographic imaging of the head and body, and intravenous excretory urography.\r\nOptiray 300 is indicated for cerebral angiography and peripheral arteriography. Optiray 300 is also indicated for contrast enhanced computed tomographic imaging of the head and body, venography, and intravenous excretory urography.\r\nOptiray 240 is indicated for cerebral angiography and venography. Optiray 240 is also indicated for contrast enhanced computed tomographic imaging of the head and body and intravenous excretory urography.",null,"Intravascular injection of ioversol opacifies those vessels in the path of the flow of the contrast medium, permitting radiographic visualization of the internal structures until significant hemodilution occurs. Optiray enhances computed tomographic imaging through augmentation of radiographic efficiency with the degree of density enhancement directly related to the iodine content in an administered dose.",null,"Indication associated"]
[1233,"DB09139","approved","small molecule","Technetium Tc-99m oxidronate","99mtc-HDP; Oxidronic acid 99mtc-complex; Technetium (99mTc) oxidronate; Technetium 99mtc oxidronate; Technetium Tc 99m oxidronate","CH6O7P2Tc","[99Tc].OC(P(O)(O)=O)P(O)(O)=O","Technetium Tc-99m oxidronate, also known as 99mTc-methylene diphosphonate, is a radiopharmaceutical agent. A radiopharmaceutical is defined as a medicinal formulation containing radioisotopes that are used in major clinical areas for diagnosis and/or therapy. The radiopharmaceuticals based on technetium-99m are widely used for diagnostic purposes because 99mTc has a versatile chemistry which allows it to produce an extense variety of complexes with specific characteristics. These complexes are formed by the binding of 99mTc to metal atoms of an organic molecule. The group oxidronate falls into the category of diphosphonates whose structure allows them to bind to calcium. Thus, technetium Tc-99m oxidronate is a powerful detection tool for abnormal osteogenesis by skeletal scintigraphy. It was developed by Mallinkrodt nuclear and FDA approved on February 18, 1981.","72945-61-0","290.906","Technetium Tc-99m oxidronate is indicated in adult and pediatric patients to be used in skeletal imaging for diagnosis of areas that can present altered osteogenesis. When administered intravenously, it is able to generate a clear image of the bones which allows the physician to diagnose any bone problem. It is important to point out that this drug has to be manipulated only under the service of a nuclear specialist. The approved indications for a bone scan are 1) visualization of tumor metastasis in bone, 2) osteomyelitis, 3) fracture, 4) stress fracture, 5) avascular necrosis, 6) osteoporosis and 7) prosthetic joint evaluation. From all the major indications, the detection of a metastatic disease is the most common because it presents a 95% of sensitivity and lesion detection can be done 6 months earlier than with X-ray studies.","The technetium is generated in a molibdene generator. Technetium Tc-99m presents a reduction of gamma emission after 6 hours and it is considered a quasi-stable molecule. The visualization of bone lesions is possible since there is an altered uptake in areas of abnormal osteogenesis. The principal photon used for detection is the gamma-2 with an energy of 140.5 keV. Its use for bone examination should be performed 2 hours after initial injection with a recommended activity on the range of 370-740 MBq.","The exact mechanism for bone uptake of technetium Tc-99m oxidronate is unknown. The most accepted mechanism is the localization of 99m-Tc on the surface of hydroxyapatite crystals of bone by chemisorption. Chemisorption is explained as a type of adsorption that involves a chemical reaction between the surface and the adsorbate in which new strong interactions form electronic bonds at the adsorbent surface. The presented chemisorption are regulated by the blood flow and blood concentration because it restrains the delivery of the agent in the uptake sites.",null,"Indication associated"]
[1234,"DB09140","approved; vet_approved","small molecule","Oxygen","Dioxygen; Molecular oxygen; Oxygen; Oxygen USP; Pure oxygen","O2","O=O","Oxygen is an element displayed by the symbol O, and atomic number 8.  It is an essential element for human survival. Decreased oxygen levels may be treated with medical oxygen therapy. Treatment with oxygen serves to increase blood oxygen levels and also exerts a secondary effect of decreasing blood flow resistance in the diseased lung, leading to decreased cardiovascular workload in an attempt to oxygenate the lungs. Oxygen therapy is used to treat emphysema, pneumonia, some heart disorders (congestive heart failure), some disorders that cause increased pulmonary artery pressure, and any disease that impairs the body's ability to take up and use gaseous oxygen. Higher level of oxygen than ambient air (hyperoxia) can be introduced under normobaric or hyperbaric conditions.","7782-44-7","31.9988","Oxygen therapy in clinical settings is used across diverse specialties, including various types of anoxia, hypoxia or dyspnea and any other disease states and conditions that reduce the efficiency of gas exchange and oxygen consumption such as respiratory illnesses, trauma, poisonings and drug overdoses. Oxygen therapy tries to achieve hyperoxia  to reduce the extent of hypoxia-induced tissue damage and malfunction.","Oxygen therapy improves effective cellular oxygenation, even at a low rate of tissue perfusion. Oxygen molecules adjust hypoxic ventilatory drive by acting on chemoreceptors on carotid bodies that sequentially relay sensory information to the higher processing centers in brainstem. It also attenuates hypoxia-induced mitochondrial depolarization that generates reactive oxygen species and/or apoptosis.\r\nStudies investigating on hyperbaric oxygen therapy has shown that oxygen supplementation can induce neural stem cell proliferation in neonatal rats thus promoting neurological regeneration after injuries .  CD34+, CD45-dim leukocytes are also potential targets for hyperbaric oxygen therapy benefit as their mobilization was increased in vitro which could facilitate the acceleration of recovery at peripheral sites .","Oxygen therapy increases the arterial pressure of oxygen and is effective in improving gas exchange and oxygen delivery to tissues, provided that there are functional alveolar units. Oxygen plays a critical role as an electron acceptor during oxidative phosphorylation in the electron transport chain through activation of cytochrome c oxidase (terminal enzyme of the electron transport chain). This process achieves successful aerobic respiration in organisms to generate ATP molecules as an energy source in many tissues. Oxygen supplementation acts to restore normal cellular activity at the mitochondrial level and reduce metabolic acidosis. There is also evidence that oxygen may interact with O2-sensitive voltage-gated potassium channels in glomus cells and cause hyperpolarization of mitochondrial membrane .","Cytochrome c oxidase subunit 1 agonist&activator; NADPH oxidase 1 agonist&activator","Therapeutic strategy associated"]
[1235,"DB09163","approved","small molecule","Technetium Tc-99m exametazime","(99m)Tc HM-PAO; (99m)Tc HMPAO; [(99m)Tc] HM-PAO; Technetium (99mTc) exametazime; Technetium (99mTc) HMPAO; Technetium tc 99m exametazime; Technetium tc 99m HMPAO; Technetium Tc-99m exametazime",null,null,"Technetium Tc-99m exametazime is a radiopharmaceutical sold under the trade name Ceretec used in the detection of altered regional cerebral perfusion in stroke and other cerebrovascular diseases. It can also be used for the labelling of leukocytes to localise intra-abdominal infections and inflammatory bowel disease. Exametazime, also known as hexamethylpropyleneamine oxime or HMPAO, acts as a chelating agent for the Tc-99m radioisotope.","99944-78-2",null,"Technetium Tc99m exametazime scintigraphy (with or without methylene blue stabilization) may be useful as an adjunct in the detection of altered regional cerebral perfusion in stroke. Tc99m exametazime without methylene blue stabilization is indicated for leukocyte labeled scintigraphy as an adjunct in the localization of intra-abdominal infection and inflammatory bowel disease.","During the first hour following injection of Tc99m labeled leukocytes, activity is seen in the lungs, liver, spleen, blood pool, bone marrow and the bladder. The kidneys (parenchyma and/or renal pelvis) and gall bladder may also be visualized. Over the first 1-6 hours, the Tc99m is visualized in the bowel. At 24 hours post-injection substantial colonic activity is seen.",null,null,"Indication associated"]
[1236,"DB09165","approved","small molecule","Technetium Tc-99m pyrophosphate","Technetium (99mTc) pyrophosphate; Technetium TC 99M Pyrophosphate","O7P2Tc","[99Tc+4].[O-]P([O-])(=O)OP([O-])([O-])=O","A radionuclide imaging agent used primarily in scintigraphy or tomography of the heart to evaluate the extent of the necrotic myocardial process. It has also been used in noninvasive tests for the distribution of organ involvement in different types of amyloidosis and for the evaluation of muscle necrosis in the extremities.","52997-54-3","272.847","For use as a skeletal imaging agent used to demonstrate areas of altered osteogenesis, and a cardiac imaging agent used as an adjunct in the diagnosis of acute myocardial infarction . May also be used to image gated blood pools and detect gastrointetinal bleeding.","Technetium Tc-99m pyrophosphate collects in areas of altered osteogenesis and injured myocardium. It also has an affinity for red blood cells, enabling imaging of blood pools.","It is thought that technetium Tc-99m pyrophosphate is adsorbed onto the surface of amorphous calcium phosphate deposits , insoluble hydroxyapatite crystals, and possibly other organic macromolecules. This would result in selective localization to necrotic muscle tissue such as that of a myocardial infarction where calcium deposition has begun as a result of cell damage. In areas of altered osteogenesis where hydroxyapatite formation is actively occuring, the surface area to volume ratio is high and favors a greater amount of technetium Tc-99m pyrophosphate to the surface of the crystals than in other areas of bone where crystal formation is less active. The localization of technetium Tc-99m pyrophosphate to these areas allows for their specific radioimaging.","Hydroxyapatite ligand; Amorphous calcium phosphate ligand","Indication associated"]
[1237,"DB09166","experimental","small molecule","Etizolam","4-(o-Chlorophenyl)-2-ethyl-9-methyl-6H-thieno(3,2-f)-s-triazolo(4,3-a)(1,4)diazepine; Etizolam","C17H15ClN4S","CCC1=CC2=C(S1)N1C(C)=NN=C1CN=C2C1=CC=CC=C1Cl","Etizolam is a thienodiazepine which is chemically related to benzodiazepine (BDZ) drug class; it differs from BDZs in having a benzene ring replaced with a thiophene ring. It is an agonist at GABA-A receptors and possesses amnesic, anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties. Initially introduced in 1983 in Japan as treatment for neurological conditions such as anxiety and sleep disorders, etizolam is marketed in Japan, Italy and India. It is not approved for use by FDA in the US; however it remains unscheduled in several states and is legal for research purposes.","40054-69-1","342.846","Indicated for the treatment of generalized anxiety disorder with depression, panic disorder and insomnia.","Etizolam is a CNS depressant with anxiolytic, anticonvulsant, sedative-hypnotic and muscle relaxant effects. It acts on the benzodiazepine site of the GABA-A receptor as an agonist to increase inhibitory GABAergic transmission throughout the central nervous system. Studies indicate that etizolam mediates its pharmacological actions with 6 to 10 times more potency than that of diazepam. Clinical human studies performed in Italy showed clinical effectiveness of etizolam in relieving symptoms in patients with generalized anxiety disorders with depressive symptoms . Etizolam also mediates imipramine-like neuropharmacological and behavioral effects, as well as minor effects on cognitive functioning. It is shown to substitute the actions of a short-acting barbiturate, pentobarbitol, in a drug discrimination study . \r\nEtizolam is an antagonist at platelet-activating-factor (PAF) receptor and attenuates the recurrence of chronic subdural hematoma after neurosurgery in clinical studies . It is shown to inhibit PAF-induced bronchoconstriction and hypotension .","Etizolam is selectively a full agonist at GABA-A receptors to increase GABAergic transmission and enhance GABA-induced Cl- currents . It is reported to bind to the benzodiazepine binding site which is located across the interface between the alpha and gamma subunits. Benzodiazapines are reported to only bind to receptors that contain gamma 2 and alpha 1/2/3/5 subunits . Alpha-1-containing receptors mediate the sedative effects of etizolam whereas alpha-2 and alpha-3 subunit-containing receptors mediate the anxiolytic effect . Etizolam shows high potency and affinity towards GABA-A receptor with alpha 1 beta 2 gamma 2S subunit combination . By binding to the regulatory site of the receptor, etizolam potentiates GABA transmission by facilitating the opening of GABA-induced chloride channels .\r\nEtizolam is a specific antagonist at PAFR. It inhibits PAF-induced platelet aggregation by inhibiting PAF binding to the receptors located on the surface of platelets with an IC50 of 22nM .","Platelet-activating factor receptor antagonist; GABA(A) Receptor positive allosteric modulator; GABA(A) Receptor Benzodiazepine Binding Site ligand","Therapeutic strategy associated"]
[1238,"DB09185","approved; investigational; withdrawn","small molecule","Viloxazine","2-((2-Ethoxyphenoxy)methyl)morpholine; Viloxazine","C13H19NO3","CCOC1=CC=CC=C1OCC1CNCCO1","Viloxazine is a selective norepinephrine reuptake inhibitor (NRI) that was used in some European countries as an antidepressant drug. It structurally differs from conventional tri- or tetra-cyclic antidepressants and it does not produce sedative anticholinergic or adrenergic effects in man . While displaying amphetamine-like CNS stimulant effects, there is little evidence of drug dependence from viloxazine therapy. Viloxazine hydrochloride is a common active ingredient in drug formulation. It was discovered and brought to market in 1976 by Imperial Chemical Industries and in early 2000's, it was withdrawn from the market.","46817-91-8","237.299","Indicated for the treatment of clinical depression.","Viloxazine is a selective noradrenaline reuptake inhibitor (NRI) with minimal inhibitory effect on the reuptake of 5-HT. It is also shown to upregulate the levels of GABA-B receptors in the rat frontal cortex. It is shown to form a complex with the human norepinephrine transporter (hNET) .\r\nThe S(-)-stereoisomer of viloxazine exhibits more potent pharmacological actions .","Viloxazine inhibits noradrenaline uptake in rat and mouse heart tissue and has a weak effect on the uptake of 5-HT . In a docking study, the amino group of viloxazine points towards Asp75 in the drug binding pocket of the transporter and forms hydrogen bonds with Phe72, Asp75 and Phe317. The rest of the drug molecule forms hydrophobic interactions with other key residues in the binding pocket .","Sodium-dependent noradrenaline transporter inhibitor","Indication associated"]
[1239,"DB09194","withdrawn","small molecule","Etoperidone","Etoperidone","C19H28ClN5O","CCN1C(=O)N(CCCN2CCN(CC2)C2=CC=CC(Cl)=C2)N=C1CC","Etoperidone is an atypical antidepressant introduced in Europe in 1977. It is a phenylpiperazine-substituted triazole derivative with a composition that classifies it as an analog of tradozone and presents a similar pharmacological profile. Etoperidone was developed by Angelini Francesco ACRAF.","52942-31-1","377.92","Etoperidone has been studied for the treatment of depression, tremors in Parkinson, extrapyramidal symptoms and male impotence. It is not certain if it was ever approved and marketed but its current status is withdrawn.","Etoperidone has a biphasic effect on the central transmission of serotonin. It presents the capacity to inhibit serotonin receptor but also to inhibit the reuptake of serotonin, norepinephrine and dopamine. As part of its actions, etoperidone also inhibits the α-adrenergic receptors which directly corresponds to the sedative and cardiovascular effects. The presence of both effects caused that the effective dose of etoperidone was poorly tolerated thus, efforts have been made to separate the serotonergic and adrenergic functions in order to generate etoperidone-derivatives like nefazodone.","The activity of etoperidone is made mainly by its major metabolite 1-(3'-chlorophenyl)piperazine (mCPP). mCPP binds with different affinity to most of the serotonergic receptors and adrenergic receptors. This metabolite is an agonist of 5-HT2c and an antagonist of 5-HT2a. Part of etoperidone structure contibutes to the activity in the α-adrenergic receptors.","Alpha-1 adrenergic receptors antagonist; Alpha-2 adrenergic receptors antagonist; Dopamine D2 receptor antagonist; Muscarinic acetylcholine receptor antagonist; 5-hydroxytryptamine receptor 2A antagonist; 5-hydroxytryptamine receptor 2C agonist","Indication associated"]
[1240,"DB09201","experimental","small molecule","Ciglitazone","Ciglitazone","C18H23NO3S","CC1(COC2=CC=C(CC3SC(=O)NC3=O)C=C2)CCCCC1","Developed by Takeda Pharmaceuticals in the early 1980s, it is considered the prototypical compound for the thiazolidinedione class.\r\n\r\nCiglitazone was never used as a medication, but it sparked interest in the effects of thiazolidinediones. Several analogues were later developed, some of which—such as pioglitazone and troglitazone—made it to the market.\r\n\r\nCiglitazone significantly decreases VEGF production by human granulosa cells in an in vitro study, and may potentially be used in ovarian hyperstimulation syndrome. Ciglitazone is a potent and selective PPARγ ligand with an EC50 of 3.0 µM. It is also an anti-hyperglycemic agent in the ob/ob murine model in vivo. Ciglitazone increases adipogenesis, decreases differentiation and angiogenesis in human umbilical vein endothelial cell (HUVEC), and osteoblastogenesis in human mesenchymal stem cells.","74772-77-3","333.45",{"$nulls":3},"Peroxisome proliferator-activated receptor gamma","Target associated"]
[1241,"DB09204","investigational","small molecule","Arotinolol","Arotinolol","C15H21N3O2S3","CC(C)(C)NCC(O)CSC1=NC(=CS1)C1=CC=C(S1)C(N)=O","Arotinolol is an alpha- and beta-receptor blocker developed in Japan. It is a thiopropanolamine with a tertiary butyl moiety. It has been studied for its potential to be an antihypertensive therapy. Artinolol is being developed by Sumitomo Pharmaceutical Co., Ltd. and it is currently under clinical trials.","68377-92-4","371.53","Artinolol was introduced to be used as an antihypertensive agent since 1986. It has been studied for other functions like tremor control for patients with Parkinson disease and it is currently in clinical trials for its use in the control of blood pressure and heart rate.","Preclinical studies showed a lack of intrinsic sympathomimetic activities or membrane-establishing properties. It is confirmed that arotinolol presents vasorelaxant activity. This characteristic is also proved to be mainly mediated by its α1-blocking property. In preclinical hypertension trials, there is a specific acute bradycardiac and antihypertensive activity with a pronounced reduction in heart rate. Some reports indicate a delayed development of hypertension when arotinolol is administered daily. Arotinolol has a dose-dependent decrease in cardiac contractility and coronary blood flow as well as an increase in total peripheral resistance. The effects of arotinolol have been confirmed in clinical trials where this drug was able to decrease cardiac index and thus, blood pressure.","Arotinolol binds to the β1-, β2- and α1- adrenergic receptor sites with a very high affinity. Radioligand studies have shown that arotinolol presents a higher affinity to the β-receptor compared to the α-receptor. The elucidated mechanism of action seems to be the result of a reduction in the cardiac output via the β-blockade and an additional inhibition of the counter-regulatory increase in peripheral resistance mediated by the α-blockade.","Beta-1 adrenergic receptor antagonist; Beta-2 adrenergic receptor antagonist; Alpha-1 adrenergic receptors antagonist","Therapeutic strategy associated"]
[1242,"DB09210","approved; investigational","small molecule","Piracetam","Piracetam","C6H10N2O2","NC(=O)CN1CCCC1=O","Piracetam is a nootropic drug in the racetams group, with chemical name 2-oxo-1-pyrrolidine acetamide. It shares the same 2-oxo-pyrrolidone base structure with pyroglutamic acid and is a cyclic derivative of the neurotransmitter γ-aminobutyric acid (GABA). However its mechanism of action differ from that of endogenous GABA. Piracetam has neuroprotective and anticonvulsant properties and is reported to improve neural plasticity . Its efficacy is documented in cognitive disorders and dementia, vertigo, cortical myoclonus, dyslexia, and sickle cell anemia although the clinical application in these conditions is not yet established. Piracetam has effects on the vascular system by reducing erythrocyte adhesion to the vascular endothelium, hindering vasospasms and facilitating microcirculation .\r\n\r\nOriginally marketed by UCB Pharma in 1971, piracetam was the first nootropic drug to modulate cognitive function without causing sedation or stimulation . It is not approved for any medical or dietary use by the FDA. In the UK, piracetam is prescribed mainly for myoclonus, but is used off-label for other conditions such as learning difficulties in children, memory loss or other cognitive defects in the elderly, and sickle-cell vaso-occlusive crises . Evidence to support its use for many conditions is unclear.","7491-74-9","142.1558","Indicated in adult patients suffering from myoclonus of cortical origin, irrespective of aetiology, and should be used in combination with other anti-myoclonic therapies .","Piracetam is known to mediate various pharmacodynamic actions:\r\n\r\n**Neuronal effects**: \r\n\r\nPiracetam modulates the cholinergic, serotonergic, noradrenergic, and glutamatergic neurotransmission although the drug does not display high affinity to any of the associated receptors (Ki >10μM). Instead, piracetam increases the density of postsynaptic receptors and/or restore the function of these receptors through stabilizing the membrane fluidity . In the forebrain of aging mice, the density of NMDA receptors was increased by approximately 20% following 14 days of piracetam treatment. Based on the findings of various animal and human studies, the cognitive processses including learning, memory, attention and consciousness were enhanced from piracetam therapy without inducing sedation and psychostimulant effects . Piracetam mediate neuroprotective effects against hypoxia-induced damage, intoxication, and electroconvulsive therapy . \r\n\r\nIn two studies involving alcohol-treated rats with evidences of withdrawal-related neuronal loss, piracetam was shown to reduce the extent of neuronal loss and increase the numbers of synapses in the hippocampus by up to 20% relative to alcohol-treated or alcohol-withdrawn rats . This suggests that piracetam is capable in promoting neuroplasticity when recoverable neural circuits are present . Although the mechanism of action is not fully understood, administration of piracetam prior to a convulsant stimulus reduces the seizure severity and enhances the anticonvulsant effectiveness of conventional antiepileptics such as carbamazepine and diazepam . \r\n\r\n**Vascular effects**: \r\n\r\nPiracetam is shown to increase the deformability of erythrocytes, reduce platelet aggregation in a dose-dependent manner, reduce the adhesion of erythrocytes to vascular endothelium and capillary vasospasm. In healthy volunteers, piracetam mediated a direct stimulant effect on prostacycline synthesis and reduced the plasma levels of fibrinogen and von Willebrand’s factors (VIII: C; VIII R: AG; VIII R: vW) by 30 to 40% . Potentiated microcirculation is thought to arise from a combination of effects on erythrocytes, blood vessels and blood coagulation .","Piracetam interacts with the polar heads in the phospholipids membrane and the resulting mobile drug-lipid complexes are thought to reorganize the lipids and influence membrane function and fluidity . Such interaction has been reported in a study that investigated the effects of neuronal outgrowth induced by beta amyloid peptides; while amyloid peptides cause lipid disorganization within the cell membranes leading to neuronal death, piracetam demonstrated to decrease the destabilizing effects of amyloid peptide . The authors suggest that piracetam induces a positive curvature of the membrane by occupying the polar groups in the phospholipids to counteract the negative curvature induced by amyloid peptides , which in turn would decrease the likelihood of membrane fusion . This mechanism of action is thought to improve membrane stability, allowing the membrane and transmembrane proteins to maintain and recover the three-dimensional structure or folding for normal function  such as membrane transport, chemical secretion, and receptor binding and stimulation . \r\n\r\nThrough restored membrane fluidity, piracetam promotes restored neurotransmission such as glutamatergic and cholinergic systems, enhances neuroplasticity and mediates neuroprotective and anticonvulsant effects at the neuronal level . It is also demonstrated that piracetam also improves the fluidity of platelet membranes. At the vascular level, piracetam decreases adhesion of erythrocytes to cell wall and reduces vasospasm which in turn improves microcirculation including cerebral and renal blood flow .",null,"Therapeutic strategy associated"]
[1243,"DB09212","approved","small molecule","Loxoprofen","Loxoprofen","C15H18O3","CC(C(O)=O)C1=CC=C(CC2CCCC2=O)C=C1","Loxoprofen is a propionic acid derivative non-steroidal anti-inflammatory drug. It is marketed under the trade name Loxonin in Brazil, Mexico and Japan by Sankyo, as Loxomac in India, and as Oxeno in Argentina. A transdermal preparation was approved for use in Japan in January 2006.","68767-14-6","246.3016","Loxoprofen is non-steroidal anti-inflammatory medication (NSAID) indicated for pain and inflammation related to musculoskeletal and joint disorders. In addition to its effects on pain, it is an antipyretic and anti-inflammatory medication.","Loxoprofen is a non-selective inhibitor of cyclooxygenase enzymes, which are responsible for the formation of various biologically active pain, fever, and inflammatory mediators. These include prostaglandins, prostacyclin, thromboxane, and arachidonic acid.","Loxoprofen itself is a prodrug and carries little-to-no pharmacological activity - it is rapidly metabolized to its trans-alcohol form, which is a potent and non-selective inhibitor of cyclooxygenase. Cyclooxygenase (COX) is present in 2 forms, COX-1 and COX-2, with each serving different functions. COX-1 is present in human cells and is constitutively released,  performing cellular housekeeping functions such as mucus production and platelet aggregation.  COX-2 is induced in human cells post-injury or due to other stimuli, is triggered to appear in large quantities at the sites of injury/stimuli, and is ultimately responsible for the mediation of inflammation and pain.\r\n\r\nLoxoprofen's active metabolite inhibits both COX isoforms, resulting in reduced expression of several mediators of pain, inflammation, and fever (e.g. prostaglandins, prostacyclin, thromboxane, etc).","Prostaglandin G/H synthase 2 antagonist; Prostaglandin G/H synthase 1 antagonist","Therapeutic strategy associated"]
[1244,"DB09213","approved; investigational","small molecule","Dexibuprofen","(+)-(S)-p-isobutylhydratropic acid; (2S)-2-(4-isobutylphenyl)propanoic acid; (S)-α-methyl-4-(2-methylpropyl)benzeneacetic acid; d-ibuproten; Dexibuprofen","C13H18O2","CC(C)CC1=CC=C(C=C1)[C@H](C)C(O)=O","Dexibuprofen, S(+)-ibuprofen, is a non-steroidal anti-inflammatory drug (NSAID). It is a pharmacologically effective enantiomer of racemic ibuprofen that differs in physicochemical properties. It is proposed to be more pharmacologically active and tolerable with a better safety profile than ibuprofen due to higher concentration of active S enantiomer. Dexibuprofen has a slower dissolution rate in the simulated gastric and enteric juices compared with the racemic ibuprofen and displays improved oral bioavilability . For Metabolism, Enzymes, Carriers, Transporters Sections, refer to .","51146-56-6","206.2808","For more information, refer to .","For more information, refer to .","Like common NSAIDs, dexibuprofen is an active enantiomer of  that suppresses the prostanoid synthesis in the inflammatory cells via inhibition of the COX-2 isoform of the arachidonic acid COX. For more information, refer to .","Prostaglandin G/H synthase 2 inhibitor; Prostaglandin G/H synthase 1 inhibitor; Apoptosis regulator Bcl-2 negative modulator; Thrombomodulin modulator; Tissue-type plasminogen activator modulator; Fatty acid-binding protein, intestinal binder; Peroxisome proliferator-activated receptor gamma activator; Cystic fibrosis transmembrane conductance regulator inhibitor; Solute carrier family 15 member 1; Peroxisome proliferator-activated receptor alpha; Platelet glycoprotein Ib alpha chain; Protein S100-A7","Therapeutic strategy associated"]
[1245,"DB09214","approved; investigational","small molecule","Dexketoprofen","Dexketoprofen","C16H14O3","[H][C@@](C)(C(O)=O)C1=CC(=CC=C1)C(=O)C1=CC=CC=C1","Dexketoprofen is a non-steroidal anti-inflammatory drug. It is available in the various countries in Europe, Asia and Latin America. It has analgesic, antipyretic and anti-inflammatory properties .","22161-81-5","254.2806","For short-term treatment of mild to moderate pain, including dysmenorrhoea, musculoskeletal pain and toothache .","This drug is an isomer of ketoprofen.   Dexketoprofen a propionic acid derivative with analgesic, anti-inflammatory, and antipyretic properties .","It is a non-steroidal anti-inflammatory drug (NSAID) that reduces prostaglandin synthesis via inhibition of cyclooxygenase pathway (both COX-1 and COX-2) activity .","Prostaglandin G/H synthase 1 antagonist; Prostaglandin G/H synthase 2 antagonist","Therapeutic strategy associated"]
[1246,"DB09215","withdrawn","small molecule","Droxicam",null,"C16H11N3O5S","CN1C2=C(OC(=O)N(C2=O)C2=CC=CC=N2)C2=CC=CC=C2S1(=O)=O","Droxicam is an oxicam non-steroidal anti-inflammatory drug and a prodrug of . It is used to reduce pain and inflammation in musculoskeletal disorders such as rheumatoid arthritis and osteoarthritis.","90101-16-9","357.34","Droxicam is an NSAID previously used for the treatment of inflammation and rheumatoid arthritis .","Droxicam is a prodrug of  . Droxicam administration produces anti-inflammatory, antirheumatic, analgesic, and antipyretic effects similar to .","Droxicam is converted to  via hydrolysis of the ester group in the intestine . Droxicam administration inhibits the synthesis of prostaglandins by cyclooxygenase enzymes .","Prostaglandin G/H synthase 1 inhibitor; Prostaglandin G/H synthase 2 inhibitor","Therapeutic strategy associated"]
[1247,"DB09216","approved; investigational","small molecule","Tolfenamic acid","Tolfenamic acid","C14H12ClNO2","CC1=C(Cl)C=CC=C1NC1=CC=CC=C1C(O)=O","Tolfenamic acid, with the formula N-(2-methyl-3-chlorphenyl)-anthranilic acid, is a nonsteroidal anti-inflammatory agent. It was discovered by scientists at Medica Pharmaceutical Company in Finland. It is used in the UK as a treatment for migraine under the name of Clotam. In the US, it presents a Status class I by the FDA. By the European Medicine Agency, it was granted in 2016 with the status of orphan for the treatment of supranuclear palsy.","13710-19-5","261.704","In the information for tolfenamic acid, it is stated that this drug, being an NSAID, is effective in treating the pain associated with the acute attack of migraines in adults.","Studies have shown that tolfenamic acid presents a non-dose dependent partial inhibition of irritant-induced temperature rise as well as a dose-dependent inhibition of skin edema. By studying its NSAID properties more closely, it was noted a dose-related inhibition of serum thromboxane which indicated the inhibition of COX-1. In the same line, there was noted a inhibition of prostaglandin E2 synthesis which marks a related COX-2 inhibition. The maximal inhibition of thromboxane was greater than 80% as well as is proven to be a potent prostaglandin E inhibitor.","Tolfenamic acid inhibits the biosynthesis of prostaglandins, and it also presents inhibitory actions on the prostaglandin receptors. As commonly thought, the mechanism of action of tolfenamic acid is based on the major mechanism of NSAIDs which consists of the inhibition of COX-1 and COX-2 pathways to inhibit prostaglandin secretion and action and thus, to exert its anti-inflammatory and pain-blocking action. Nonetheless, some report currently indicates that tolfenamic acid inhibits leukotriene B4 chemotaxis of human polymorphonuclear leukocytes leading to an inhibition of even 25% of the chemotactic response. This activity is a not ligand specific additional anti-inflammatory mechanism of tolfenamic acid.","Prostaglandin G/H synthase 1 antagonist; Prostaglandin G/H synthase 2 antagonist","Therapeutic strategy associated"]
[1248,"DB09218","experimental","small molecule","Clonixin","Clonixin","C13H11ClN2O2","CC1=C(NC2=C(C=CC=N2)C(O)=O)C=CC=C1Cl","Clonixin is a non-steroidal anti-inflammatory drug.","17737-65-4","262.69","Indicated for use in the management of chronic arthritic conditions and certain soft tissue disorders associated with pain and inflammation.","Clonixin is a non-steroidal anti-inflammatory drug (NSAID) similar in structure to . It produces vasodilation and analgesia.","The mechanism of clonixin does not appear to have been investigated on a molecular level. It is presumed to function similarly to other NSAIDs by inhibiting cycloxygenase enzymes 1 and 2 resulting in a reduction in prostaglandin production.",null,"Therapeutic strategy associated"]
[1249,"DB09219","approved","small molecule","Bisoxatin","Bisoxatin","C20H15NO4","OC1=CC=C(C=C1)C1(OC2=CC=CC=C2NC1=O)C1=CC=C(O)C=C1","Bisoxatin is a stimulant laxative which increases peristalsis and inhibits absorbtion of water and ions in the intestine . It is marketed in Belgium under the tradename Wylaxine and used for the treatment of constipation and for preparation of the colon for surgical procedures.","17692-24-9","333.343","For use in the treatment of constipation in the absence of bowel obstruction and for surgical preparation of the colon .","Bisoxatin is a stimulant laxative which increases peristalsis and inhibits the absorbtion of water and ions in the intestine . This increases the water content of the feces and increases its movement through the intestine.","The precise mechanism of the bisoxatin's stimulant effect and inhibition of water and ion movement is unknown.",null,"Indication associated"]
[1250,"DB09220","approved; investigational","small molecule","Nicorandil","2-Nicotinamidoethyl nitrate; N-(2-Hydroxyethyl)nicotinamide nitrate; N-(2-Hydroxyethyl)nicotinamide nitrate (ester)","C8H9N3O4","[O-][N+](=O)OCCNC(=O)C1=CC=CN=C1","Nicorandil is an orally efficacious vasodilatory drug and antianginal agent marketed in the UK, Australia, most of Europe, India, Philippines, Japan, South Korea, and Taiwan. It is not an approved drug by FDA. It is a niacinamide derivative that induces vasodilation of arterioles and large coronary arteries by activating potassium channels. It is often used for patients with angina who remain symptomatic despite optimal treatment with other antianginal drugs . Nicorandil is a dual-action potassium channel opener that relaxes vascular smooth muscle through membrane hyperpolarization via increased transmembrane potassium conductance and increased intracellular concentration of cyclic GMP. It is shown to dilate normal and stenotic coronary arteries and reduces both ventricular preload and afterload .","65141-46-0","211.177","Indicated for the prevention and treatment of chronic stable angina pectoris and reduction in the risk of acute coronary syndromes.","Nicorandil is a potassium channel opener with nitrovasodilator (NO donor) actions, making it both an arterial and a venous dilator . It causes sustained dilation of both the arterial resistance and conductive vessels that increases coronary blood flow, however the effect of the drug on coronary arteries does not involve the coronary steal phenomenon . Activation of potassium channels lead to hyperpolarization of the smooth muscle cells, followed by arterial dilation and afterload reduction. Nicorandil is shown to increase pooling in the capacitance vessels with a decrease in preload through relaxing the venous vascular system. Overall, improved blood flow and reduced infarct size are achieved through reduction of end-diastolix pressure and decreased extravascular component of vascular resistance . Open studies showed the effectiveness of nicorandil treatment on various types of angina pectoris .","Nicorandil mediates its therapeutic efficacy via two main mechanisms. Nicorandil is an activator and opener of ATP-sensitive (ATP-dependent) potassium channels (KATP channels) that are composed of Kir6.x-type subunits and sulfonylurea receptor (SUR) subunits. Nicorandil binding sites are located in the sulfonylurea receptor 2 (SUR2) in the ATP-sensitive potassium channel , which are regulatory subunits of the channel that exhibit an ATPase activitiy . There are 2 types of SUR2 subunits (2A/2B) that have identical nucleotide binding domains (NBD), where SUR2A is more predominantly expressed in skeletal and cardiac myocytes and SUR2B in smooth muscle cells . Nicorandil more potently activates SUR2B/Kir6.2 than SUR2A/Kir6.2 channels to cause hyperpolarization. ATP-NBD1 interaction influences the channel signalling by nicorandil, and the response of the channel to nicorandil is also facilitated and heightened by the interaction of ATP or ADP with NBD2 . Potentiated activity of ATP-sensitive channels have cardioprotective role by limiting the duration of action potentials and preventing intraceullar calcium overload . This attenuates cellular injury by preserving cellular energetics and ultimately cell survival . KATP channel-dependent membrane hyperpolarization can also lead to vasodilation via reduction in Ca2+ influx through the voltage-gated Ca2+ channels and regulation of intracellular Ca2+ mobilization in smooth muscle cells . \r\nNicorandil contain a nitrate moiety in its structure, making it a good dilator of vascular smooth muscle like other nitroglycerin esters . Direct relaxation of venous vascular system arises from NO-donor mediated stimulation of guanylyl cyclase and increased levels of intracellular cyclic GMP (cGMP). Elevated levels of cGMP contributes to the total relaxing effect of nicorandil at higher concentrations of the drug .","ATP-binding cassette sub-family C member 9 activator","Indication associated"]
[1251,"DB09221","experimental","small molecule","Polaprezinc","beta-Alanyl-L-histidinato zinc; Polaprezinc; Zinc L-carnosine","C9H12N4O3Zn","NCCC(=O)N1[Zn]OC(=O)[C@@H]1CC1=CN=CN1","Polaprezinc is a chelated form of zinc and L-carnosine. It is a zinc-related medicine approved for the first time in Japan, which has been clinically used to treat gastric ulcers .  It was determined that polaprezinc may be effective in pressure ulcer treatment . A study in 2013 showed that CO-administration of polaprezinc may be effective against small intestine mucosal injury associated with long-term aspirin therapy .","107667-60-7","289.6","Peptic ulcer disease, dyspepsia .","Used to treat/manage peptic ulcer disease or irritation of the gastrointestinal tract by promoting tissue healing by the elimination of free radicals .","Polaprezinc increases the expression of various antioxidant enzymes, including superoxide dismutase 1 (SOD-1), SOD-2, heme oxygenase-1 (HO-1), glutathione S-transferase (GST), glutathione peroxidase (GSH-px), peroxidredoxin-1 (PRDX1; PRXI) and PRXD5 (PRXV). \r\n\r\nThis process occurs in the gastric mucosa, defending mucosal cells against reactive oxygen species. This drug inhibits the activity of the transcription factor nuclear factor-kappaB (NF-kB) and decreases the expression of various inflammatory cytokines, including interleukin (IL) 1beta, IL-6, IL-8, and tumor necrosis factor alpha (TNF-a). \r\n\r\nPolaprezinc also promotes the expression of numerous growth factors, including as platelet-derived growth factor-B (PDGF-B), vascular endothelial growth factor (VEGF), and nerve growth factor (NGF), in addition to various heat shock proteins (HSPs), including HSP90, HSP70, HSP60, HSP47, HSP27, and HSP10. This process promotes tissue growth and protects against damage the gastric mucosa .","Tumor necrosis factor inhibitor; Interleukin-6 inhibitor; Interleukin-3 inhibitor; Vascular endothelial growth factor receptor 1 agonist; Beta-nerve growth factor agonist; Platelet-derived growth factor receptor beta agonist; Heat shock protein HSP 90-alpha agonist; Heat shock protein HSP 90-beta agonist","Therapeutic strategy associated"]
[1252,"DB09227","experimental","small molecule","Barnidipine","Barnidipine; Mepirodipine","C27H29N3O6","COC(=O)C1=C(C)NC(C)=C([C@H]1C1=CC(=CC=C1)[N+]([O-])=O)C(=O)O[C@H]1CCN(CC2=CC=CC=C2)C1","Barnidipine is a long-acting novel calcium antagonist that belongs to the dihydropyridine (DHP) group of calcium channel blockers. Used in the treatment of hypertension, barnidipine displays high affinity for the calcium channels of the smooth muscle cells in the vascular wall  and selectivity against cardiovascular L-type calcium channels . Barnidipine contains two chiral centres thus can have four possible enantiomers. The active component is composed of a single optical isomer (*3'S, 4S* configuration), which is the most potent and longest-acting of the four enantiomers . Compared to several other calcium antagonists which are racemates, the barnidipine compound consisting of a single enantiomer may offer a high degree of pharmacological selectivity .\r\n\r\nAccording to a dose-ranging, multicentre, placebo-controlled, double-blind study in patients with mild to moderate hypertension, the antihypertensive response from barnidipine treatment was maintained after a 1-year and 2-year follow-up period in 91% of the patients who had an initial response to the drug . In two European multicentre randomized, double-blind trials, barnidipine was shown to possess equivalent antihypertensive efficacy to amlodipine and nitrendipine, but produced fewer class-specific side-effects . It also demonstrated clinical efficacy which is similar to that of atenolol, enalapril and hydrochlorothiazide . \r\n\r\nIt is available in modified-release oral tablets under the brand name Vasexten to be taken once daily in the morning. Barnidipine has a gradual onset of action and is shown to be well tolerated in patients. It does not produce reflex tachycardia .","104713-75-9","491.544","Indicated for the treatment of mild to moderate essential hypertension and management of chronic stable angina.","Barnidipine reduces peripheral resistance and lowers blood pressure. The chronic use of the drug is not reported to lead to an increase in basic heart frequency. The antihypertensive effects of barnidipine are reported to remain during the entire 24-hour dose interval. Barnidipine does not exert any negative effect on serum lipids profile, glucose level or blood electrolytes .","Barnidipine is a lipophilic 1,4-dihydropyridine calcium antagonist that is characterized by a slow onset of action and a strong and long-lasting binding to the L-type calcium channels . It displays high affinity for the channels expressed in the smooth muscle cells in the vascular wall. Its main mechanism of action arises from the reduction of peripheral vascular resistance secondary to its vasodilatory actions. \r\n\r\nCalcium ion influx via L-subtype ‘voltage-operated’ channels in the excitable membranes of the smooth muscle cells promotes the formation of calcium-dependent formation of cross-bridges between myosin and actin which are the two major contractile proteins that drive contraction. By blocking the L-type 'voltage-dependent' calcium channels, barnidipine selectively blocks the calcium ion influx in the smooth muscle cells and inhibits the activation of contractile proteins . It is suggested that barnidipine displays a high affinity to the inactivated state of the channel . Like other dihydropyridine calcium antagonists, barnidipine is predicted to interact with the alpha 1-C subunit of the L-type calcium channels. Alpha 1-C subunit of the channel is predicted to reside within the bilayer or channel pore at a location closer to the extracellular rather than the intracellular face of the membrane . Its lipophilicity is likely a reason why barnidipine displays a slow onset and long duration of action. Being a highly lipophilic molecule with an octanol/water partition coefficient of 2000, barnidipine is expected to accumulate in the cell membrane and consequently, gains access to its target receptor in a slow manner .","Voltage-dependent L-type calcium channel subunit alpha-1C antagonist","Therapeutic strategy associated"]
[1253,"DB09229","experimental","small molecule","Aranidipine","Aranidipine","C19H20N2O7","COC(=O)C1=C(C)NC(C)=C(C1C1=CC=CC=C1[N+]([O-])=O)C(=O)OCC(C)=O","Aranidipine is a novel dihydropyridine derivative that gives rise to two active metabolites (M-1α and M-1β) that exhibit hypotensive activity. It is a calcium antagonist with the formula methyl 2-oxopropyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate. It was developed by Maruko Seiyaku, introduced by Taiho and launched in Japan in 1997.","86780-90-7","388.376","Aranidipine has been used for many years to treat angina pectoris and hypertension.","Pre-clinical studies with aranidipine and its two metabolites have shown production of increases in femoral blood flow. It has been shown to present potent and long-lasting vasodilating actions. Aranidipine and its metabolites are shown to inhibit calcium-induced contraction in isolated rabbit arteries. Studies have shown that aranidipine is more potent to reduce blood pressure than other dihydropyridines. Aranidipine produce changes in renal blood flow, this effect may be explained by its effect on alpha-2-adrenoreceptor-mediated vasoconstriction.","The high potential of aranidipine is thought to be related to the additional calcium antagonistic activity of its metabolite. The mechanism is thought to be related to the capacity of aranidipine and its metabolites to vasodilate afferent and efferent arterioles. this action is performed through the inhibition of voltage-dependent calcium channels. The typical mechanism of action of aranidipine, as all dihydropyridines, is based on the inhibition of L-type calcium channels, decreasing calcium concentration and inducing smooth muscle relaxation. It is a selective alpha2-adrenoreceptor antagonist which inhibits vasoconstrictive responses.","Voltage-dependent L-type calcium channel subunit alpha-1C antagonist; Voltage-dependent L-type calcium channel subunit alpha-1D antagonist; Voltage-dependent L-type calcium channel subunit alpha-1F antagonist; Voltage-dependent L-type calcium channel subunit alpha-1S antagonist; Alpha adrenergic receptor agonist","Indication associated"]
[1254,"DB09230","investigational","small molecule","Azelnidipine","Azelnidipine","C33H34N4O6","CC(C)OC(=O)C1=C(C)NC(N)=C(C1C1=CC=CC(=C1)[N+]([O-])=O)C(=O)OC1CN(C1)C(C1=CC=CC=C1)C1=CC=CC=C1","Azelnidipine is a dihydropyridine calcium channel blocker. It is marketed by Daiichi-Sankyo pharmaceuticals, Inc. in Japan.  It has a gradual onset of action and produces a long-lasting decrease in blood pressure, with only a small increase in heart rate, unlike some other calcium channel blockers . It is currently being studied for post-ischemic stroke management .","123524-52-7","582.657","For the treatment of hypertension.","Azelnidipine is a vasodilator that induces a gradual decrease in blood pressure in hypertensive patients. Unlike other members of its drug class, azelnidipine does not induce reflex tachycardia due to vasodilation. This is likely due to the fact that it elicits a gradual fall in blood pressure\r\n\r\nIt also exhibits a prolonged hypotensive effect and has been shown to have a strong anti-arteriosclerotic action in vessels due to its high affinity for vascular tissue and antioxidative activity . \r\n\r\nClinical studies have demonstrated that azelnidipine markedly reduced heart rate and proteinuria in hypertensive patients by inhibiting sympathetic nerve activity. Azelnidipine has also been confirmed to have cardio-protective, neuroprotective, and anti-atherosclerotic properties, and has also been found to prevent insulin resistance .","Azelnidipine inhibits trans-membrane Ca2+ influx through the voltage-dependent channels of smooth muscles in vascular walls. Ca2+ channels are classified into various categories, including L-type, T-type, N-type, P/Q-type, and R-type Ca2+ channels. The L-type Ca2+ channels .    Normally, calcium induces smooth muscle contraction, contributing to hypertension.  When calcium channels are blocked, the vascular smooth muscle does not contract, resulting in relaxation of vascular smooth muscle walls and decreased blood pressure.","Voltage-dependent L-type calcium channel subunit beta-1 agonist","Therapeutic strategy associated"]
[1255,"DB09231","experimental","small molecule","Benidipine","Benidipine","C28H31N3O6","COC(=O)C1=C(C)NC(C)=C([C@@H]1C1=CC=CC(=C1)[N+]([O-])=O)C(=O)O[C@@H]1CCCN(CC2=CC=CC=C2)C1","Benidipine has the formula 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid methyl 1-(phenylmethyl)-3-piperidinyl ester hydrochloride. It is a synthetic dihydropyridine derivative that has anti-hypertensive and anti-anginal actions. It was originated in Japan by Kyowa Hakko, it is submitted for FDA approval and it is currently available in some Asian countries like India and Japan.","105979-17-7","505.571","Benidipine is a potent and long-lasting drug indicated for the treatment of cardiovascular diseases such as hypertension, renoparenchymal hypertension and angina pectoris.","Benidipine reduces systolic and diastolic blood pressure as well as to present decreases in heart rate pulse after treatment. It is reported also a decrease urinary protein excretion and serum triglycerides. Different studies have shown benidipine anti-oxidative activity, stimulation of NO production, suppression of adhesion molecules expression, stimulation of osteoblast differentiation, suppression of the proliferation of vascular smooth muscle cells and mesangial cells, as well as myocardial protection. The enhancement of NO production is associated with the cardioprotective and antiartheriosclerotic effects of benidipine.","Benidipine is a tripe calcium channel inhibitor by inhibiting L, N and T type calcium channel. It presents a very long-lasting activity that can be explained by its high affinity for cell membranes from the DHP binding site; this characteristic indicated a long-lasting pharmacological activity of benidipine. The additional property of benidipine is the vascular selectivity towards peripheral blood vessels.","Voltage-dependent L-type calcium channel antagonist; Voltage-dependent N-type calcium channel subunit alpha-1B antagonist; Voltage-dependent T-type calcium channel antagonist","Indication associated"]
[1256,"DB09232","investigational","small molecule","Cilnidipine","Cilnidipine","C27H28N2O7","COCCOC(=O)C1=C(C)NC(C)=C(C1C1=CC=CC(=C1)[N+]([O-])=O)C(=O)OC\\C=C\\C1=CC=CC=C1","Cilnidipine is a dihydropyridine calcium antagonist. It was jointly developed by Fuji Viscera Pharmaceutical Company, Japan and Ajinomoto, Japan and approved in 1995. Compared with other calcium antagonists, cilnidipine can act on the N-type calcium channel that existing sympathetic nerve end besides acting on L-type calcium channel that similar to most of the calcium antagonists. This drug is approved in China, Japan, Korea, India, and several countries in the European Union.","132203-70-4","492.528","Cilnidipine is indicated for the management of hypertension for end-organ protection. It is reported to be useful in elderly patients and in those with diabetes and albuminuria. Cilnidipine has been increasingly used in patients with chronic kidney disease \r\n\r\nHypertension is the term used to describe the presence of high blood pressure. The blood pressure is generated by the force of the blood pumped from the heart against the blood vessels. Thus hypertension is caused when there is too much pressure on the blood vessels and this effect can damage the blood vessel.","Administration of cilnidipine has been shown to present an antisympathetic profile in vitro and in vivo. It decreases blood pressure safely and effectively without excessive blood pressure reduction or tachycardia.","Cilnidipine acts on the L-type calcium channels of blood vessels by blocking the incoming calcium and suppressing the contraction of blood vessels, thereby reducing blood pressure. Cilnidipine also works on the N-type calcium channel located at the end of the sympathetic nerve, inhibiting the emission of norepinephrine and suppressing the increase in stress blood pressure.","Voltage-dependent N-type calcium channel subunit alpha-1B antagonist; Voltage-dependent L-type calcium channel antagonist","Indication associated"]
[1257,"DB09235","experimental","small molecule","Efonidipine","Efonidipine","C34H38N3O7P","CC1=C(C(C2=CC=CC(=C2)[N+]([O-])=O)C(=C(C)N1)P1(=O)OCC(C)(C)CO1)C(=O)OCCN(CC1=CC=CC=C1)C1=CC=CC=C1","Efonidipine is a calcium channel blocker of the _dihydropyridine class_, commercialized by Shionogi & Co. (Japan). Initially, it was marketed in 1995 under the trade name, _Landel_. The drug has been shown to block T-type in addition to L-type calcium channels . It has also been studied in atherosclerosis and acute renal failure . This drug is also known as NZ-105, and several studies have been done on its pharmacokinetics in animals .","111011-63-3","631.666","For the treatment of hypertension.","Dihydropyridines (DHPs), act mainly on L-type calcium channels, essentially causing reflex tachycardia, which negatively affects cardiac function.  This leads to a decrease in blood pressure and an increase in heart rate. Efonidipine acts on both L-type and T-type calcium channels. Because inhibition of T-type calcium channels in the sinoatrial (SA node) node attenuate reflex tachycardia, this drug favorably affects cardiac pacing. The effect of efonidipine on heart rate deserves special recognition with regard to reflex tachycardia, due to its unique effects in relation to other drugs in its class .","This drug inhibits the L-type and T-type calcium channels, thereby leading to vasodilation and decreased automaticity of the heart. Efonidipine exerts negative chronotropic effects, decreasing heart rate. Acting on SA node cells by inhibiting T-type calcium channel activity, Efonidipine prolongs the late phase-4 depolarization of the sinoatrial node action potential, decreasing heart rate. This is associated with decreased myocardial oxygen demand and increases of blood flow to the coronary arteries and thereby attenuates myocardial ischemia.  Efonidipine increases glomerular filtration rate (GFR) without increasing intra-glomerular pressure and filtration fraction  . This increase leads to the prevention of renal damage that is normally associated with hypertension.\r\n\r\nEfonidipine increases the rate of renal sodium excretion via the suppression of aldosterone synthesis and aldosterone secretion from the adrenal glands. Aldosterone-induced renal parenchymal fibrosis is said to be suppressed by efonidipine .\r\n\r\nL-type calcium channel blockers, such as efonidipine, preferentially dilate afferent arterioles in the kidney, whereas both L-/T-type and L-/N-type calcium channel blockers potently dilate both afferent and efferent arterioles. The distinct actions of calcium channel blockers on the renal microcirculation are demonstrated by changes in glomerular capillary pressure and subsequent renal injury: L-type calcium channel blockers favor an increase in glomerular capillary pressure, whereas L-/T-type and L-/N-type CCBs alleviate glomerular hypertension. This supports the theory that L-Type/T-type calcium channel blockers may be of benefit in renal hypertension . Efonidipine is a long-acting medication due to a low dissociation constant .   \r\n\r\nRecent studies suggest that efonidipine reduces plasma aldosterone levels in patients on regular hemodialysis, which is of additional benefit to the cardiovascular protection by antihypertensive therapy with efonidipine in patients with end-stage renal disease .","Voltage-dependent T-type calcium channel subunit alpha-1I antagonist; Voltage-dependent L-type calcium channel subunit alpha-1C","Therapeutic strategy associated"]
[1258,"DB09236","approved; investigational","small molecule","Lacidipine","Lacidipine","C26H33NO6","CCOC(=O)C1=C(C)NC(C)=C(C1C1=CC=CC=C1\\C=C\\C(=O)OC(C)(C)C)C(=O)OCC","Lacidipine is a lipophilic dihydropyridine calcium antagonist with an intrinsically slow onset of activity. Due to its long duration of action, lacidipine does not lead to reflex tachycardia . It displays specificity in the vascular smooth muscle, where it acts as an antihypertensive agent to dilate peripheral arterioles and reduce blood pressure. Compared to other dihydropyridine calcium antagonists, lacidipine exhibits a greater antioxidant activity which may confer potentially beneficial antiatherosclerotic effects . Lacidipine is a highly lipophilic molecule that interacts with the biological membranes. Through radiotracer analysis, it was determined that lacidipine displays a high membrane partition coefficient leading to accumulation of the drug in the membrane and slow rate of membrane washout . When visualized by small-angle X-ray diffraction with angstrom resolution to examine its location within the membranes, lacidipine was found deep within the membrane's hydrocarbon core . These results may explain the long clinical half-life of lacidipine . \r\n\r\nIn randomised, well-controlled trials, administration of daily single-dose lacidipine ranging from 2-6 mg demonstrated comparable antihypertensive efficacy similar to that of other long-acting dihydropyridine calcium antagonists, thiazide diuretics, atenolol (a beta-blocker) and enalapril (an ACE inhibitor) . It is available as once-daily oral tablets containing 2 or 4 mg of the active compound commonly marketed as Lacipil or Motens. It is not currently FDA-approved.","103890-78-4","455.551","Indicated for the treatment of hypertension either alone or in combination with other antihypertensive agents, including β-adrenoceptor antagonists, diuretics, and ACE-inhibitors .","acidipine is a specific and potent calcium antagonist with a predominant selectivity for calcium channels in the vascular smooth muscle. Its main action is to dilate predominantly peripheral and coronary arteries, reducing peripheral vascular resistance and lowering blood pressure . \r\n\r\nFollowing the oral administration of 4 mg lacidipine to volunteer subjects, a minimal prolongation of QTc interval has been observed (mean QTcF increase between 3.44 and 9.60 ms in young and elderly volunteers) .","By blocking the voltage-dependent L-type calcium channels, it prevents the transmembrane calcium influx . Normally, calcium ions serve as intracellular messengers or activators in exictable cells including vascular smooth muscles. The influx of calcium ultimately causes the excitation and depolarization of the tissues. Lacidipine inhibits the contractile function in the vascular smooth muscle and reduce blood pressure. Due to its high membrane partition coefficient, some studies suggest that lacidipine may reach the receptor via a two-step process; it first binds and accumulates in the membrane lipid bilayer and then diffuses within the membrane to the calcium channel receptor . It is proposed that lacidipine preferentially blocks the inactivated state of the calcium channel .\r\n\r\nThrough its antioxidant properties shared amongst other dihydropyridine calcium channel blockers, lacidipine demonstrates an additional clinical benefit. Its antiatherosclerotic effects are mediated by suppressing the formation of reactive oxygen species (ROS) and subsequent inflammatory actions by chemokines, cytokines and adhesion molecules, thus reducing atherosclerotic lesion formation . Lacidipine may also suppress cell proliferation and migration in smooth muscle cells and suppress the expression of matrix metalloproteinases, which affects the stability of atheromatous plaques .","Voltage-dependent L-type calcium channel antagonist","Therapeutic strategy associated"]
[1259,"DB09237","approved; investigational","small molecule","Levamlodipine","Levamlodipine; Levoamlodipine; S-amlodipine","C20H25ClN2O5","CCOC(=O)C1=C(COCCN)NC(C)=C([C@@H]1C1=CC=CC=C1Cl)C(=O)OC","Levamlodipine, also known as S-amlodipine, is a pharmacologically active enantiomer of , an antihypertensive medication. Levamlodipine belongs to the dihydropyridine group of calcium channel blockers. This medication was first marketed in Russia and India before being granted FDA approval. The names S-amlodipine and levamlodipine may be used interchangeably as both substances are the same, however. As a racemic mixture, amlodipine contains (R) and (S)-amlodipine isomers, but only (S)-amlodipine as the active moiety possesses therapeutic activity.\r\n\r\nLevamlodipine was granted FDA approval on 19 December 2019.","103129-82-4","408.88","Levamlodipine is indicated alone or in combination to treat hypertension in adults and children.","Levamlodipine inhibits L-type calcium channels in vascular smooth muscle, reducing peripheral vascular resistance and blood pressure. It is given once daily in doses of 1.25-2.5mg in children and 2.5-5mg in adults. Patients should be counselled regarding the risk of symptomatic hypotension, worsening angina, and myocardial infarction.","Levamlodipine blocks the transmembrane influx of calcium through L-type calcium channels into the vascular and cardiac smooth muscles resulting in vasodilation and a subsequent decrease in blood pressure. Levamlodipine inhibits calcium influx in vascular smooth muscle to a greater degree than in cardiac muscle, leading to decreased peripheral vascular resistance and lowered blood pressure. In vitro studies have shown a negative inotropic effect but this is unlikely to be clinically relevant.","Voltage-dependent L-type calcium channel subunit alpha-1C antagonist; Voltage-dependent L-type calcium channel subunit alpha-1D antagonist; Nitric oxide synthase, endothelial agonist; Nitric oxide synthase, inducible agonist","Indication associated"]
[1260,"DB09238","approved; investigational","small molecule","Manidipine","Manidipine","C35H38N4O6","COC(=O)C1=C(C)NC(C)=C(C1C1=CC(=CC=C1)N(=O)=O)C(=O)OCCN1CCN(CC1)C(C1=CC=CC=C1)C1=CC=CC=C1","Manidipine (INN) is a calcium channel blocker (dihydropyridine type) that is used clinically as an antihypertensive. It is selective for vasculature and does not produce effects on the heart at clinically relevant dosages.","89226-50-6","610.711","For the treatment of hypertension.","Manidipine produces vasodilation resulting in lower blood pressure .","Contraction of vascular smooth muscle is stimulated by Gq coupled receptors which produce calcium release from the sarcoplasmic reticulum. This is followed by opening of voltage dependent calcium channels and an influx of calcium into the cell ultimately producing contraction. Manidipine binds to and dissociates slowly from L- and T-type voltage dependent calcium channels on smooth muscle cells, blocking the entrance of extracellular calcium into the cell and preventing this contraction . This produces vasodilation which decreases blood pressure. Manidipine produces renal vasodilation and an increase in natriuresis. This likely contributes to the antihypertensive effect by reducing blood volume. Manidipine is selective for the vasculature and does not produce significant effects on the heart or central nervous system at clinically relevant dosages.","Voltage-dependent L-type calcium channel blocker; Voltage-dependent T-type calcium channel blocker","Therapeutic strategy associated"]
[1261,"DB09241","approved; investigational","small molecule","Methylene blue","Basic Blue 9; C.I. basic blue 9; Lowacryl blue 9; Methylene blue; Methylene blue anhydrous; Methylthioninium chloride; Solvent blue 8; Swiss blue","C16H18ClN3S","[Cl-].CN(C)C1=CC2=[S+]C3=C(C=CC(=C3)N(C)C)N=C2C=C1","Methylene blue is an oxidation-reduction agent. The intravenous form of methylene blue is approved by the FDA for the treatment of pediatric and adult patients with acquired methemoglobinemia. Historically, it has been widely used in Africa to treat malaria, but now it disappeared when chloroquine (CQ) and other drugs entered the market. Its use as an urinary tract antiseptic has also been investigated. \r\n\r\nMethylthioninium chloride (INN, or methylene blue, proposed trade name Rember) is an investigational drug being developed by the University of Aberdeen and TauRx Therapeutics that has been shown in early clinical trials to be an inhibitor of Tau protein aggregation. The drug is of potential interest for the treatment of patients with Alzheimer's disease.","61-73-4","319.85","Indicated for the treatment of pediatric and adult patients with acquired methemoglobinemia. \r\n\r\nOther clinical applications of methylene blue include improvement of hypotension associated with various clinical states, an antiseptic in urinary tract infections, treatment of hypoxia and hyperdynamic circulation in cirrhosis of liver and severe hepatopulmonary syndrome, and treatment of ifofosamide induced neurotoxicity.",null,"* Main mechanism of action involves  inhibition of nitric oxide synthase and guanylate cyclase. \r\n* In Alzheimers Disease: a mechanistic study found that methylene blue oxidizes cysteine sulfhydryl groups on tau to keep tau monomeric. One preclinical treatment study in tauopathy mice reported anti-inflammatory or neuroprotective effects mediated by the Nrf2/antioxidant response element (ARE); another reported insoluble tau reduction and a learning and memory benefit when given early. \r\n* In Methemoglobinemia: Methylene Blue acts by reacting within RBC to form leukomethylene blue, which is a reducing agent of oxidized hemoglobin converting the ferric ion (fe+++) back to its oxygen-carrying ferrous state(fe++). \r\n* As antimalarial agent: Methylene Blue, a specific inhibitor of P.falciparum glutathione reductase has the potential to reverse CQ resistance and it prevents the polymerization of haem into haemozoin similar to 4-amino-quinoline antimalarials. \r\n* For ifosfamide induced neurotoxicity: Methylene blue functions as an alternate electron acceptor. It acts to reverse the NADH inhibition caused by gluconeogenesis in the liver while blocking the transformation of chloroethylamine into chloroacetaldehyde. In addition, it inhibits various amine oxidase activities, which also prevents the formation of chloroacetaldehyde. \r","Guanylate cyclase soluble subunit alpha-2 inhibitor; Nitric oxide synthase, brain inhibitor","Therapeutic strategy associated"]
[1262,"DB09243","experimental","small molecule","Hydracarbazine","Hydracarbazine","C5H7N5O","[H]N([H])N([H])C1=NN=C(C=C1)C(=O)N([H])[H]","Hydracarbazine is a pyridazine that has found use as an antihypertensive agent  It was once marketed in France under the tradename Normatensyl.","3614-47-9","153.145","Was used for the treatment of hypertension .","Relaxes vascular smooth muscle .","Likely acts similarly to hydralazine, a related compound, which interferes with calcium release from the sarcoplasmic reticulum in response to inositol .",null,"Indication associated"]
[1263,"DB09244","experimental","small molecule","Pirlindole","2,3,3a,4,5,6-Hexahydro-8-methyl-1H-pyrazino(3,2,1-jk)carbazole; Pirlindole","C15H18N2","CC1=CC=C2N3CCNC4CCCC(=C34)C2=C1","This drug is classified as a reversible inhibitor of monoamine oxidase A enzyme (also known as a RIMA drug). It was developed and is currently used as an antidepressant in Russia. Its chemical structure is similar to metralindole, and it also shares pharmacological properties with this drug.\r\n\r\nPirlindole is a selective, reversible inhibitor of monoamine oxidase (MAO) subtype A (MAO-A) that is approved in several European and non-European countries for the treatment of major depression. The antidepressant efficacy and safety of pirlindole have been demonstrated in numerous studies and, supported by many years of clinical experience in the treatment of depression. Pirlindole's efficacy and safety have also been shown in the treatment of fibromyalgia.","60762-57-4","226.323","For the treatment of major depression.\r\n\r\nIt is being studied in the treatment of fibromyalgia pain syndrome. One study determined that the effect of pirlindole on sensorimotor performance while driving a motor vehicle shows many similarities to that of placebo. The drug appears to stimulate the central nervous system, rather than exhibit a sedative effect, like many antidepressants.  Because of its selective, reversible inhibition of monoamine oxidase (MAO-A) and short half-life, unpleasant \"cheese effects\" are avoided. This refers to the effects of consuming tyramine-rich foods, such as cheese while medicated with monoamine oxidase inhibitors, leading to severe headaches and hypertension .  of The available evidence supports pirlindole as a safe and effective treatment option for the management of depression and fibromyalgia syndrome .\r\n \r\n\r","Pirlindole regulates that metabolism of norepinephrine and catecholamines, leading to relief of depressive symptoms. The prevention of breakdown of these neuromodulators is thought to elevate mood.","This drug is a selective and reversible inhibitor of monoamine oxidase A (also known as MAO-A).  Its main mechanism of action is selective and reversible inhibition of monoamine oxidase A. Its secondary mechanism of action is the inhibition effect of noradrenaline and 5-hydroxytryptamine reuptake .","Amine oxidase [flavin-containing] A antagonist; 5-hydroxytryptamine receptor 1A antagonist; Alpha-2A adrenergic receptor antagonist","Indication associated"]
[1264,"DB09246","withdrawn","small molecule","Benmoxin","Benmoxin; Mebamoxine","C15H16N2O","CC(NNC(=O)C1=CC=CC=C1)C1=CC=CC=C1","Benmoxin is an irreversible and nonselective monoamine oxidase inhibitor (MAOI) of the hydrazine class. It was first synthesized in 1967 and rapidly used in Europe as an antidepressant. However, this agent is no longer marketed.","7654-03-7","240.306","For the treatment of depression.",{"$nulls":3},"Indication associated"]
[1265,"DB09247","withdrawn","small molecule","Iproclozide","Iproclozide","C11H15ClN2O2","CC(C)NNC(=O)COC1=CC=C(Cl)C=C1","Iproclozide is an irreversible and selective hydrazine class based monoamine oxidase inhibitor (MAOI). Although it was employed as an antidepressant for a time, the fact that the agent is capable of causing fulminant hepatitis and that its use has been documented as the cause for at least three reported fatalities has resulted ultimately in the agent being discontinued.","3544-35-2","242.7","For the treatment of depression.",{"$nulls":3},"Indication associated"]
[1266,"DB09248","withdrawn","small molecule","Mebanazine","Mebanazine","C8H12N2","CC(NN)C1=CC=CC=C1","Mebanazine, also known as _Actomol_, is a monoamine oxidase inhibitor (MAOI) belonging to the _hydrazine_ class of chemicals. It was used in the past as an antidepressant in the 1960s, but has since been discontinued because of its hepatotoxic potential.","65-64-5","136.198","For the treatment of depression.",{"$nulls":3},"Indication associated"]
[1267,"DB09249","withdrawn","small molecule","Octamoxin","2-octylhydrazine; Octamoxin","C8H20N2","CCCCCCC(C)NN","Octamoxin, also known as _2-octylhydrazine_, is both an irreversible and nonselective monoamine oxidase enzyme inhibitor (MAOI) of the _hydrazine_ chemical class. This drug was used in the past as an antidepressant agent in the 1960s, however, has since been discontinued.","4684-87-1","144.262","For the treatment of depression.",{"$nulls":3},"Indication associated"]
[1268,"DB09250","withdrawn","small molecule","Pheniprazine","Pheniprazine","C9H14N2","CC(CC1=CC=CC=C1)NN","Pheniprazine is an irreversible and nonselective monoamine oxidase inhibitor (MAOI) of the hydrazine chemical class that was used as an antidepressant in the 1960s. In addition, it was used for the treatment of other conditions, such as angina pectoris and schizophrenia. Pheniprazine was withdrawn by its manufacturer due to its ability to cause toxicity in the liver and its ability to cause optic neuritis.","55-52-7","150.225","For the treatment of depression, schizophrenia, and angina pectoris.",{"$nulls":3},"Indication associated"]
[1269,"DB09251","withdrawn","small molecule","Phenoxypropazine",null,"C9H14N2O","[H]N([H])N([H])C(C)COC1=CC=CC=C1","Phenoxypropazine is a non-selective and irreversible monoamine oxidase enzyme inhibitor (MAOI), belonging to the _hydrazine_ chemical class. It was marketed as an antidepressant in 1961 but was later withdrawn in 1966 because of its hepatotoxic potential.","3818-37-9","166.224","For the treatment of depression.",{"$nulls":3},"Indication associated"]
[1270,"DB09252","withdrawn","small molecule","Pivhydrazine","Pivalylbenzhydrazine; Pivazide","C12H18N2O","[H]N(CC1=CC=CC=C1)N([H])C(=O)C(C)(C)C","Pivhydrazine, also known as pivazide, is a member of the hydrazine family with irreversible and non-selective inhibitory activity against monoamine oxidases. In 1960, it was widely used as an antidepressant agent but it is now discontinued.","306-19-4","206.289","For the treatment of depression.",{"$nulls":3},"Indication associated"]
[1271,"DB09253","withdrawn","small molecule","Safrazine","Safra","C11H16N2O2","CC(CCC1=CC2=C(OCO2)C=C1)NN","Safrazine is a member of the hydrazine family with non-selective and irreversible inhibitor effects against monoamine oxidases. In 1960, it was used as an antidepressant but it is now discontinued.","33419-68-0","208.261","For the treatment of depression.",{"$nulls":3},"Indication associated"]
[1272,"DB09254","withdrawn","small molecule","Caroxazone","Caroxazone","C10H10N2O3","NC(=O)CN1CC2=CC=CC=C2OC1=O","Caroxazone is an antidepressant that has been withdrawn from the market. It is a reversible monoamine oxidase inhibitor (MAOI) of both A and B monoamine oxidase subtypes. However, it presents a five-fold preference for the MAO-B subtype.","18464-39-6","206.201","For the treatment of depression.",{"$nulls":3},"Indication associated"]
[1273,"DB09260","approved; investigational","small molecule","Parnaparin","Parnaparin sodium",null,null,"Parnaparin is an heparin of low molecular weight with antithrombotic effects.","9005-49-6",null,"Used in the prevention and treatment of venous thromboembolism (deep vein thrombosis and pulmonary embolism) and in the treatment of myocardial infarction.",{"$nulls":3},"Indication associated"]
[1274,"DB09261","approved; investigational","small molecule","Certoparin",{"$nulls":3},"Certoparin is part of the heparins of low molecular weight that presents high activity against the coagulation factor Xa. It is normally used to prevent deep venous thrombosis.",null,null,"Used in the prevention and treatment of venous thromboembolism (deep vein thrombosis and pulmonary embolism) and in the treatment of myocardial infarction.",{"$nulls":3},"Indication associated"]
[1275,"DB09265","approved","small molecule","Lixisenatide","des-38-proline-exendine-4 (Heloderma suspectum)-(1-39)-peptidylpenta-L-lysyl-L-lysinamide; DesPro38Exendin-4(1-39)-Lys6-NH2; Lixisenatide","C215H347N61O65S","CC[C@H](C)[C@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC1=CNC=N1)[C@@H](C)O)[C@@H](C)O)C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(N)=O","Lixisenatide is a glucagon-like peptide-1 (GLP-1) receptor agonist used in the treatment of type 2 diabetes mellitus (T2DM). It is sold under the brand name Adlyxin by Sanofi-Aventis. Adlyxin recieved FDA approval July 28, 2016 .","320367-13-3","4858.56","For use as an antihyperglycemic agent in the treatment of T2DM .","Lixisenatide acts as an agonist at the GLP-1 receptor. In the pancreas, this agonism results in increased glucose-stimulated insulin exocytosis by beta islet cells. This produces a reduction in blood glucose due to increased glucose uptake by tissues . GLP-1 receptor activation in the GI tract results in delayed gastric emptying which is thought to mediate the effects of lixisenatide on postprandial blood glucose.","The activation of the GLP-1 receptor by lixisenatide results in the activation of adenylyl cyclase . This increases the concentration of cyclic adenosine monophosphate in the cell leading to the activation of protein kinase A (PKA) as well as Epac1 and Epac2.  PKA, Epac1, and Epac2 are involved the in release of Ca2+ from the endoplasmic reticulum which is known as the \"amplification\" pathway which increases insulin release when the triggering pathway is activated. By activating this amplification pathway lixisenatide increases glucose stimulated insulin secretion.","Glucagon-like peptide 1 receptor agonist","Target associated"]
[1276,"DB09267","approved; withdrawn","small molecule","Strontium ranelate",null,"C12H6N2O8SSr2","[Sr++].[Sr++].[O-]C(=O)CN(CC([O-])=O)C1=C(C#N)C(CC([O-])=O)=C(S1)C([O-])=O","Strontium ranelate, a strontium (II) salt of ranelic acid, is a medication for osteoporosis. Some reports have shown that strontium ranelate can slow down the progression of osteoarthritis of the knee. This agent presents an atypical mechanism of action in which it increases deposition of new bone by osteoblasts and, simultaneously, reduces the resorption of bone by osteoclasts. It is therefore promoted as a \"dual action bone agent\" (DABA) indicated for use in treatment of severe osteoporosis.\r\n\r\nFurthermore, various clinical studies demonstrate the ability of strontium ranelate to improve and strengthen intrinsic bone tissue quality and microarchitecture in osteoporosis by way of a number of cellular and microstructural changes by which anti-fracture efficacy is enhanced.\r\n\r\nAvailable for prescription use for a time in some parts of the world as Protelos (strontium ranelate) 2 g granules for oral suspension by Servier, it was ultimately discontinued in 2016-2017 owing to an increased adverse cardiac effects profile along with increased risk of venous thromboembolism (VTE) and various life threatening allergic reactions.","135459-87-9","513.49","Strontium ranelate is therapeutically indicated for the treatment of severe osteoperosis in: a) postmenopasual women, and b) adult men, who are at high risk of fractures, for whom treatment with other medical products approved for the treatment of osteoperosis is not possible due to, for example, contraindications or intolerance. \r\n\r\nIn postmenopausal women, strontium ranelate can also reduce the risk of vertebral and hip fractures .","In general, it is believed that strontium ranelate is capable of affecting a rebalance in bone turnover in favour of bone formation by: (1) increasing osteoblast differentiation from progenitors, osteoblast activity and survival, as well as regulating osteoblast-induced osteoclastogenesis, and (2) decreasing osteoclast differentiation and activity, as well as increasing osteoclast apoptosis . \r\n\r\nIt has also been shown that strontium ranelate is capable of improving and strengthening various components of overall bone tissue quality like bone mineral density and bone microarchitecture .","The underlying pathogenesis of osteperosis involves an imbalance between bone resorption and bone formation. Osteoclasts are a kind of differentiated or specialized bone cell that breaks down bone tissue while osteoblasts are another set of differentiated bone cells that synthesize and rebuild bone tissue. When osteoclasts degrade bone tissue faster than the osteoblasts are capable of rebuilding the bone tissue, low or inadequate bone mass density and osteoperosis can resula One of the mechanisms with which strontium ranelate is thought to act is its functionality as an agonist of the extracellular calcium sensing receptors (CaSRs)  of osteoblasts and osteoclasts . Ordinary interaction between calcium 2+ divalent cations with mature osteoclast CaSRs is known to induce osteoclast apoptosis. Subsequently, strontium 2+ divalent cations from strontium ranelate use can also bind CaSRs on osteoclasts to induce their apoptosis because of the strontium 2+ cation's close resemeblance to calcium 2+. Contact between extracelluar calcium 2+ and osteoclast CaSRs stimulates the phospholipase C (PLC) dependant breakdown of phosphatidylinositol 4,5-biphosphate (PIP2) into the two secondary messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). Whereas the calcium-CaSRs interaction then performs IP3 Adependent translocation of nuclear factor NF-kB from the cytoplasm to the nucleus in mature osteoclasts, strontium-CaSRs interactions involves a DAG-PKC beta II (protein kinase C beta II) signalling pathway for translocating NF-kB from the cytoplasm to the nucleus in an IP3-independent manner. Although the calcium 2+ and strontium 2+ mediated signalling pathways are different, both CaSR interactions induce osteoclast apoptosis and are in fact capable of potentiating each other, leading to enhanced osteoclast apoptosis and decreased bone tissue degradation .\r\n\r\nAt the same time, given the simiarity between the calcium 2+ and strontium 2+ cations , strontium 2+ cations from strontium ranelate are seemingly also able to act as an agonist and stimulate the CaSRs on osteoblasts, possibly in tandem with various local osteoblast stimulatory growth factors like transforming growth factor β (TGF β) and/or bone morphogenetic proteins (BMPs), to stimulate cyclic D genes and early oncogenes like c-fos and egr-1 that can mediate the mitogenesis and proliferation of new or more osteoblasts . Moreover, although the involvement of the PLC mediated pathway may be a part of the signalling mechanism in osteoblasts following the stimulation of their CaSRs, this has not yet been fully elucidated .\r\n\r\nFurthermore, strontium ranelate is also thought to be capable of stimulating osteoblasts to enhance the expression of osteoprotegerin while also concurrently reducing the expression of receptor activator of nuclear factor kappa-Β ligand (RANKL) in primary human osteoblastic cells. As osteoprotegerin can competitively bind to RANKL as a decoy receptor, which can prevent RANKL from binding to RANK, which is an activity that facilitates the signaling pathway for the differentiation and activaiton of osteoclasts. The subsequent net effect of these actions ultiamtely results in decreased osteoclastogenesis. \r\n\r\nMoreover, bone biopsies obtained from patients treated with stronatium ranelate in clinical study reveal improvements in intrinsic bone tissue quality and microarchitecutre in ostepoerosis as evidenced by increased trabecular number, decreased trabecular separation, lower structure model index, and increased cortical thickness associated with a shift in trabecular structure from rod to plate like configurations compared with control patients .\r\n\r\nAdditionally, strontium from administered strontium ranelate is absorbed onto the crystal surface of treated bones and only slightly substitiutes for calcium in the apatite crystal of newly formed bone. As a result, there is an increased X-ray absorption of strontium as compared to calcium, which can lead to an amplification of bone mineral density (BMD) measurement by dual-proton X-ray absorptiometry. In essence, although strontium ranelate use can increase BMD some of the observations may be overestimations due to skeletal accretion of strontium in strontium ranelate treated patients .\r\n\r\nHaving the ability to both generate more osetoblasts and decrease the number of osteoclasts gives strontium ranelate an apparent dual mechanism of action when used to treat osteoperosis.",null,"Therapeutic strategy associated"]
[1277,"DB09272","approved; investigational","small molecule","Eluxadoline","5-({(4-carbamoyl-2,6-dimethyl-L-phenylalanyl)[(1S)-1-(4-phenyl-1H-imidazol-2-yl)ethyl]amino}methyl)-2-methoxybenzoic acid; Eluxadoline","C32H35N5O5","COC1=CC=C(CN([C@@H](C)C2=NC(=CN2)C2=CC=CC=C2)C(=O)[C@@H](N)CC2=C(C)C=C(C=C2C)C(N)=O)C=C1C(O)=O","Eluxadoline is a mixed mu-opioid receptor agonist, kappa-opioid receptor agonist, and a-delta opioid receptor antagonist indicated for use in diarrhea-predominant irritable bowel syndrome (IBS-D). The mu-, kappa-, and delta-opioid receptors mediate endogenous and exogenous opioid response in the central nervous system and peripherally in the gastrointestinal system. Agonism of peripheral mu-opioid receptors results in reduced colonic motility, while antagonism of central delta-opioid receptors results in improved analgesia, making eluxadoline usable for the symptoms of both pain and diarrhea characteristic of IBS-D. \r\n\r\nMarketed under the tradename Viberzi (FDA), eluxadoline is an antimotility agent that decreases bowel contractions, inhibits colonic transit, and reduces ﬂuid/ion secretion resulting in improved symptoms of abdominal pain and reductions in the Bristol Stool Scale.","864821-90-9","569.662","For the treatment of irritable bowel syndrome with diarrhea (IBS-D).",null,"Eluxadoline is a mu-opioid receptor agonis, kappa opioid receptor agonist and a delta opioid receptor antagonist. Eluxadoline is used for diarrhea predominant IBS because it reduces intestinal contractility and normalizes stress-induced acceleration of upper GI transit. Antagonistic activity at the delta receptor minimizes the constipating effect usually seen by mu-opioid receptor agonists alone. Because of it's limited systemic bioavailability, there may be less side effects associated with the use of eluxadoline in comparison with other therapies used to treat diarrhea predominant IBS.","Mu-type opioid receptor agonist; Delta-type opioid receptor antagonist; Kappa-type opioid receptor agonist","Indication associated"]
[1278,"DB09273","experimental","small molecule","Doxofylline","Doxofylline; Doxophylline","C11H14N4O4","CN1C2=C(N(CC3OCCO3)C=N2)C(=O)N(C)C1=O","Doxofylline is a methylxanthine derivative with the presence of a dioxolane group in position 7. As a drug used in the treatment of asthma, doxofylline has shown similar efficacy to theophylline but with significantly fewer side effects in animal and human studies. In contrast with other xanthine derivatives, doxofylline does not significantly bind to adenosine alpha-1 or alpha-2 receptors and lacks stimulating effects. Decreased affinity for adenosine receptors may account for the better safety profile of doxofylline compared to theophylline . Unlike theophylline, doxofylline does not affect calcium influx and does not antagonize the actions of calcium channel blockers which could explain reduced cardiac adverse reactions associated with the drug . The anti-asthmatic effects of doxophylline are mediated by other mechanisms, primarily through inhibiting the activities of the phosphodiesterase (PDE) enzyme.","69975-86-6","266.257","Indicated for the treatment of chronic obstructive pulmonary disease (COPD), bronchial asthma and pulmonary disease with spastic bronchial component.","Doxofylline is a methylxanthine bronchodilator with potent bronchodilator activity comparable to that of theophylline. In animal studies, doxofylline demonstrated to attenuate bronchoconstriction, inflammatory actions and the release of thromboxane A2 (TXA2) when challenged with platelet-activating factor . \r\n\r\nDoxofylline does not demonstrate direct inhibition of any histone deacetylase (HDAC) enzymes or known PDE enzyme isoforms and did not act as an antagonist at A2 or A2 receptors. The affinity for adenosine A1, A2A and A2B receptors are reported to be all higher than 100 µM . It only displays an inhibitory action against PDE2A1 and antagonism at adenosine A(2A) at high concentrations . A study demonstrated that doxofylline interacts with β2-adrenoceptors to induce blood vessel relaxation and airway smooth muscle relaxation. In dog studies, doxofylline decreased airway responsiveness at a dose that did not affect heart rate and respiratory rate .","The main mechanism of action of doxofylline is unclear. One of the mechanisms of action of is thought to arise from the inhibition of phosphodiesterase activity thus increasing the levels of cAMP and promoting smooth muscle relaxation. \r\n\r\nThe interaction of doxofylline with beta-2 adrenoceptors was demonstrated by a study using nonlinear chromatography, frontal analysis and molecular docking . Serine 169 and serine 173 residues in the receptor are thought to be critical binding sites for doxofylline where hydrogen bonds are formed . Via mediating the actions of beta-2 adrenoceptors, doxofylline induces blood vessel relaxation and airway smooth muscle relaxation. \r\n\r\nThere is also evidence that doxofylline may exert anti-inflammatory actions by reducing the pleurisy induced by the inflammatory mediator platelet activating factor (PAF) according to a rat study . It is suggested that doxofylline may play an important role in attenuating leukocyte diapedesis, supported by mouse preclinical studies where doxofylline administration was associated with inhibited leukocyte migration across vascular endothelial cells in vivo and in vitro .Unlike theophylline, doxofylline does not inhibit tumor necrosis factor-induced interleukin (IL)-8 secretion in ASM cells.","Phosphodiesterase 2A, cGMP-stimulated inhibitor; Adenosine receptor A2a antagonist; Beta-2 adrenergic receptor agonist","Therapeutic strategy associated"]
[1279,"DB09276","approved; investigational","small molecule","Sodium aurothiomalate","Gold sodium thiomalate; Sodium aurothiomalate","C4H3AuNa2O4S","[Na+].[Na+].[O-]C(=O)CC(S[Au])C([O-])=O","Sodium aurothiomalate is a gold compound that is used for its immunosuppressive anti-rheumatic effects. Gold Sodium Thiomalate is supplied as a solution for intramuscular injection containing 50 mg of Gold Sodium Thiomalate per mL. It is most effective in active progressive rheumatoid arthritis and of little or no value in the presence of extensive deformities or in the treatment of other forms of arthritis.","12244-57-4","390.07","A disease-modifying antirheumatic drug (DMARD) indicated for the symptomatic treatment of arthritis.","Unknown, may decrease prostaglandin synthesis or may alter cellular mechanisms by inhibiting sulfhydryl systems.","The precise mechanism of action is unknown. It is known that sodium aurothiomalate inhibits the synthesis of prostaglandins. The predominant action appears to be a suppressive effect on the synovitis of active rheumatoid disease.",null,"Indication associated"]
[1280,"DB09279","investigational","small molecule","Fimasartan","Fimasartan","C27H31N7OS","CCCCC1=NC(C)=C(CC(=S)N(C)C)C(=O)N1CC1=CC=C(C=C1)C1=C(C=CC=C1)C1=NN=NN1","Fimasartan is an angiotensin II receptor antagonist (ARB) drug employed in the treatment of both hypertension and heart failure. It has been found to be safe when administered with hydrochlorothiazide (a diuretic) in clinical trials. Fimasartan was initially approved September 9th, 2010 in South Korea and is marketed under the brand name _Kanarb_ by Boryung Pharmaceuticals.","247257-48-3","501.65","Used for the treatment of hypertension and heart failure .","Fimasartan is a selective angiotensin receptor 1 (AR1) inhibitor . It acts to lower blood pressure by inhibiting vasoconstriction","Angiotensin II activates AR1 leading to vasoconstriction and increased noradrenaline release which further increases vasoconstriction via action at α1-adrenergic receptors . It also stimulates secretion of aldosterone which acts to increase sodium and water reabsorption in the renal tubules . Fimasartan bind to and antagonizes AR1 preventing vasoconstriction and reducing aldosterone secretion to increase natriuresis leading to a reduction in blood volume. Together these effects produce an anti-hypertensive effect.","Type-1 angiotensin II receptor antagonist","Therapeutic strategy associated"]
[1281,"DB09282","approved; investigational","small molecule","Molsidomine","Molsidomine","C9H14N4O4","CCOC(=O)[N-]C1=C[N+](=NO1)N1CCOCC1","Molsidomine is an orally active, long-acting vasodilator, which belongs to the class of medications known as syndnones. Interestingly, it is being studied as being a preventive measure in cerebral infarction .","25717-80-0","242.235","The indications for use of molsidomine include ischemic heart disease, angina, chronic heart failure, and pulmonary hypertension .","Molsidomine leads to smooth muscle relaxation in the coronary blood vessels, relieving symptoms of angina and increasing blood flow to the coronary arteries.","Molsidomine, a cardiovascular drug, acts in a similar fashion to organic nitrates.  The SIN-1A metabolite of molsidomine has a pharmacologically active group of nitric oxide, which increases levels of cyclic GMP, and decreases intracellular calcium ions in smooth muscle cells. This leads to relaxation of smooth muscle in the blood vessels, and inhibits platelet aggregation.\r\n\r","Guanylate cyclase soluble subunit alpha-2 agonist","Therapeutic strategy associated"]
[1282,"DB09284","investigational","small molecule","Imolamine","3-Phenyl-4-diethylaminoethyl-5-imino-1,2,4-oxadiazol; Imolamine","C14H20N4O","CCN(CC)CCN1C(=N)ON=C1C1=CC=CC=C1","Imolamine is a compound with a molecular weight of 260.33 g/mol with the formula diethylamine. It is developed under the brand name Coremax by Novartis consumer health SA.","318-23-0","260.341","Imolamine is indicated for the treatment of angina pectoris. The hydrochloride form is used as a local anesthetic.",{"$nulls":3},"Indication associated"]
[1283,"DB09285","experimental","small molecule","Morniflumate","Morniflumate","C19H20F3N3O3","FC(F)(F)C1=CC(NC2=C(C=CC=N2)C(=O)OCCN2CCOCC2)=CC=C1","Morniflumate is a non-steroidal anti-inflammatory drug with antipyretic properties.  It is the morpholinoethyl ester of niflumic acid .  In one study, post morniflumate ingestion, physical examination and clinical symptoms of those with bronchitis showed improvement .","65847-85-0","395.382","\r\nMorniflumate is indicated for the treatment of inflammatory conditions affecting the airways, ENT system, urogenital tract and bone and joint systems in adults. In Italy, morniflumate is also indicated for the treatment of pain associated with ear, nose, throat (ENT) and gastrointestinal inflammatory conditions in children.  Morniflumate is a well established NSAID that has been in use for over three decades in Italy (particularly for the treatment of upper respiratory tract infections in children), France, Belgium, Austria, Switzerland, Spain and Portugal; it has a generally favorable tolerability profile.","Morniflumate, given at therapeutic dosages to healthy human volunteers, on leukotriene B4 (LTB4) and thromboxane (TXB2) synthesis, both in purified PMNs (polymorphnuclear neutrophils)  and in whole blood .\r\n\r\nIn whole blood experiments, morniflumate reduced blood leukotriene B4 (LTB4) synthesis induced by Ca-ionophore A23187 Bx approximately 50%, both after a single dose and at steady state; the level of inhibition showed a pattern similar to the plasma levels of the bioactive metabolite of morniflumate (M1). The inhibition of serum thromboxane B2 (TXB2) levels was higher than 85%. Hence, morniflumate is demonstrated to reduce arachidonic acid metabolism, by exerting its effects on cyclooxygenase and 5-lipoxygenase. This characteristic might provide a better approach for anti-inflammatory therapy .\r\n\r\nIn several animal models orally administered morniflumate, the beta-morpholinoethyl ester of niflumic acid, proved almost equal to the parent compound in anti-inflammatory, analgesic and antipyretic activity with the absence of gastric irritating/ulcerogenic effects of its acidic parent compound .","The primary mechanism of niflumic acid and its ester is action is inhibition of enzymes involved in the synthesis of inflammatory prostaglandins . This medication inhibits cyclooxygenase and 5-lipoxygenase pathways, which lead to fever and inflammation .  \r\n\r\nNiflumic acid, a calcium-activated Cl- channel blocker, is an analgesic and anti-inflammatory agent used in the treatment of inflammatory conditions.  Niflumic acid does directly inhibit calcium channels or activate potassium channels. Niflumic acid selectively reduces noradrenaline- and 5-HT-induced pressor responses by inhibiting a mechanism which leads to the opening of voltage-gated calcium channels .  Niflumic acid (NFA) produces biphasic behavior on human CLC-K channels that suggests the presence of two functionally different binding sites: an activating site and a blocking site .","Arachidonate 5-lipoxygenase antagonist; Prostaglandin G/H synthase 2; Leukotriene B4 receptor 1 antagonist; Thromboxane A2 receptor","Therapeutic strategy associated"]
[1284,"DB09287","approved; vet_approved","small molecule","Polyethylene glycol","Macrogol; Macrogol 3350; Macrogol 4000; Macrogol 6000; PEG; Polyethylene glycol 3350; Polyethylene glycol 4000; Polyethylene glycol 6000",null,null,"Polyethylene glycol (PEG) is a synthetic polymer produced via polymerization of ethylene oxide molecules to make joining units of ethylene glycol by an ether linkage. PEGs are water-soluble polymers that can form hydrogen bonds in a ratio of 100 water molecules per one PEG molecule. Molecular weights of PEGs vary by time of the polymerization process and the molecular weight represents the weighted average of the individual PEG molecules. PEGs differ in their physical and chemical properties depending on their molecular weight: PEGs are liquids when molecular weights are <1000 and the molecule turns to waxy solids with increasing molecular weights. The most common preparations of PEGs include PEG 3350 and PEG 400. PEGs have various applications in many fields, ranging from medical to industrial areas. PEGs have a long history of gastroenterology: PEG 3350 is a common over-the-counter osmotic laxative used to relieve occasional constipation. PEG 3350 is also used for cleansing of the colon in preparation for colonoscopy in adults.\r\n\r\nThe rationale of using PEG in gastroenterology is due to the physical properties of the compound: its potent water-binding capacity, negligible intestinal absorption with increasing molecular mass, lack of significant toxicity, and limited intestinal enzymatic degradation or bacterial metabolism all make PEG a useful therapeutic agent for the treatment of occasional constipation and bowel cleansing for preparation in colonoscopy.","25322-68-3",null,"Polyethylene glycol is indicated for use as an over-the-counter osmotic laxative to relieve occasional constipation. When used in combination with sodium ascorbate, sodium sulfate, ascorbic acid, sodium chloride and potassium chloride, it is used for cleansing of the colon in preparation for colonoscopy in adults.","The osmotic effect of PEG produces a copious watery diarrhea. The onset of action of PEG 3350 is about 1 to 2 hours after oral ingestion. The colonic transit of polyethylene glycol occurs in a dose-dependent manner. When used for bowel preparation before colonscopy, electrolytes are typically added in the oral solution to prevent dehydration and electrolyte disturbances. As an over-the-counter laxative, the OTC product does not contain any salts that can be absorbed. In a study involving healthy subjects, PEG 3350 had negligible effects on colonic fluid absorption or with the ability of the colonic mucosa to generate and sustain steep electrochemical gradients.","Osmotic laxatives contain substances that are poorly absorbable and draw water into the lumen of the bowel. Polyethylene glycol functions is an osmotic laxative that causes increased water retention in the lumen of the colon by binding to water molecules, thereby producing loose stools.",null,"Indication associated"]
[1285,"DB09288","experimental","small molecule","Propacetamol","Propacetamol","C14H20N2O3","CCN(CC)CC(=O)OC1=CC=C(NC(C)=O)C=C1","Propacetamol is a non-opioid analgesic devoid of the major contraindications. It is a derivative of , or paracetamol, with the molecular formula glycine, N, N-diethyl-,4-(acetylamino)phenyl ester. Propacetamol is a parenteral formulation of paracetamol and thus, it is a prodrug that is completely hydrolyzed to paracetamol. It is not available in the United States but this prodrug has been widely used in other countries such as France since 1985.","66532-85-2","264.325","Propacetamol is a paracetamol prodrug of intravenous administration used to control fever and pain of perioperative period in multimodal analgesia therapy.","Propacetamol is hydrolyzed to paracetamol and then it presents a weak inhibition of COX-1 and COX-2 which is translated into a low anti-inflammatory activity. Therefore, in high inflammatory conditions, such as rheumatoid arthritis, these agents show limited in vivo suppression of inflammation and platelet activity. The formation of N-arachidonoylphenolamine, donates paracetamol with analgesic and antipyretic properties.","As propacetamol is a prodrug, its mechanism of action is directly linked to the activity of paracetamol. The mechanism of action of paracetamol is described by the inhibition of prostaglandin synthesis. This inhibition is attained by inhibition of COX-1 and COX-2 in an environment where arachidonic acid and peroxides are kept low. It is considered that paracetamol presents a very complex mechanism of action involving effects in the peripheral system, described by direct COX inhibition; the central system, characterized by inhibition of COX, serotonergic descending neuronal pathway, L-arginine/NO pathway and cannabinoid system; and a redox mechanism. In the brain and spinal cord, paracetamol can combine with arachidonic acid to form N-arachidonoylphenolamine. This metabolite is an activator of capsaicin receptor (TRPV1) and cannabinoid CB1.","Prostaglandin G/H synthase 1 antagonist; Prostaglandin G/H synthase 2 antagonist; Transient receptor potential cation channel subfamily V member 1 antagonist; Cannabinoid receptor 1 antagonist","Therapeutic strategy associated"]
[1286,"DB09290","investigational","small molecule","Ramosetron","Ramosetron","C17H17N3O","CN1C=C(C(=O)[C@@H]2CCC3=C(C2)N=CN3)C2=C1C=CC=C2","Ramosetron is a _serotonin 5-HT3 receptor antagonist_ commonly employed to treat nausea and vomiting, in addition to certain diarrheal conditions. It is believed to have higher potency and longer antiemetic action than other 1st generation 5-HT3 antagonists such as ondansetron. Currently, ramosetron is only approved for use Japan and in certain Southeast Asian countries.","132036-88-5","279.343","For the treatment of nausea and vomiting and diarrhea-predominant irritable bowel syndrome in males.",null,null,"5-hydroxytryptamine receptor 3A antagonist","Indication associated"]
[1287,"DB09291","approved; investigational","small molecule","Rolapitant","Rolapitant","C25H26F6N2O2","C[C@@H](OC[C@]1(CC[C@]2(CCC(=O)N2)CN1)C1=CC=CC=C1)C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F","Rolapitant is a potent, highly selective, long-acting Neurokinin-1 (NK-1) receptor antagonist approved for the prevention of delayed chemotherapy-induced nausea and vomiting (CINV) in adults. Delayed-phase CINV typically occurs >24 hours after chemotherapy treatment and is principally mediated by Neurokinin-1 and its ligand Substance P, which is released in the gut following chemotherapy administration. Neurokinin-1 is also known as Tachykinin Receptor 1 (TACR1), Neurokinin 1 Receptor (NK1R), and Substance P Receptor (SPR). \r\nBy blocking Substance P from interacting with NK-1 receptors in the gut and the central nervous system, rolapitant prevents late-phase CINV. Unlike other available NK-1 receptor antagonists, rolapitant is not an inhibitor of Cytochrome P450 enzyme CYP3A4 and has a long elimination half-life, allowing a single dose to prevent both acute and late-phase CINV during the first 120 hours post-chemotherapy.","552292-08-7","500.485","This drug is indicated in adults in combination with other antiemetics for the prevention of delayed nausea and vomiting associated with emetogenic chemotherapy.",null,"Rolapitant is an orally active, highly selective Neurokinin-1 Receptor (NK1R) antagonist. NK1 receptors are located primarily in the gut and central nervous system and are activated by Substance P following chemotherapy administration. By binding to the NK1 receptor, rolapitant prevents binding of its ligand Substance P, which is released in the gut following chemotherapy administration.","Neurokinin 1 receptor antagonist","Therapeutic strategy associated"]
[1288,"DB09292","approved","small molecule","Sacubitril","Sacubitril","C24H29NO5","CCOC(=O)[C@H](C)C[C@@H](CC1=CC=C(C=C1)C1=CC=CC=C1)NC(=O)CCC(O)=O","Sacubitril is a prodrug neprilysin inhibitor used in combination with valsartan to reduce the risk of cardiovascular events in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction. It was approved by the FDA after being given the status of priority review for on July 7, 2015.\r\n\r\nSacubitril's active metabolite, LBQ657 inhibits neprilysin, a neutral endopeptidase that would typically cleave natiuretic peptides such as atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and c-type natriuretic peptide (CNP). ANP and BNP are released under atrial and ventricle stress, which activate downstream receptors leading to vasodilation, natriuresis and diuresis. Under normal conditions, neprilysin breaks down other vasodilating peptides and also vasoconstrictors such as angiotensin I and II, endothelin-1 and peptide amyloid beta-protein. Inhibition of neprilysin therefore leads to reduced breakdown and increased concentration of endogenous natriuretic peptides in addition to increased levels of vasoconstricting hormones such as angiotensin II.","149709-62-6","411.498","Used in combination with valsartan to reduce the risk of cardiovascular events in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.  It is usually administered in conjunction with other heart failure therapies, in place of an ACE inhibitor or other ARB.","n a 7-day valsartan-controlled study in patients with reduced ejection fraction (HFrEF), administration of sacubitril + valsartan (Entresto) resulted in a significant non-sustained increase in natriuresis, increased urine cGMP, and decreased plasma MR-proANP and NT-proBNP compared to valsartan. In a 21-day study in HFrEF patients, it significantly increased urine ANP and cGMP and plasma cGMP, and decreased plasma NT-proBNP, aldosterone and endothelin-1. In clinical studies, this combination had no effect on QTc interval.","Sacubitril's active metabolite, LBQ657 inhibits neprilysin, a neutral endopeptidase that would typically cleave natiuretic peptides, which includes: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and c-type natriuretic peptide (CNP). ANP and BNP are released under atrial and ventricle stress, which activate downstream receptors leading to vasodilation, natriuresis and diuresis. Under normal conditions, neprilysin breaks down other vasodilating peptides and also vasoconstrictors such as angiotensin I and II, endothelin-1 and peptide amyloid beta-protein. Therefore, the inhibition of neprilysin leads to reduced breakdown and increased concentration of endogenous natriuretic peptides in addition to increased levels of vasoconstricting hormones such as angiotensin II. (However, when combined with valsartan, would result in  blocking of angiotensin II to its receptor, preventing the vasoconstrictive effects and resulting in a decrease in vascular resistance and blood pressure.)  Cardiovascular and renal effects of sacubitril is a result of the increased levels of peptides that are normally degraded by neprilysin.","Neprilysin antagonist&inhibitor","Indication associated"]
[1289,"DB09295","experimental","small molecule","Talniflumate","Talniflumate","C21H13F3N2O4","FC(F)(F)C1=CC(NC2=C(C=CC=N2)C(=O)OC2OC(=O)C3=CC=CC=C23)=CC=C1","Talniflumate, is an anti-inflammatory molecule studied and used as a mucin regulator in the treatment of cystic fibrosis, chronic obstructive pulmonary disease (COPD) and asthma . In addition, it is used in inflammatory conditions such as rheumatoid arthritis. Phase I trials with talniflumate for the treatment of cystic fibrosis and COPD were completed in August 2001, and phase II trials were performed in Ireland for the treatment of cystic fibrosis but this research has now been discontinued . Talniflumate has been approved for approximately 20 years in Argentina other countries (excluding the United States, Europe, and Japan) .","66898-62-2","414.34","Talnifumate is a phthalidyl ester of nifumic acid, which has potent analgesic and anti-inflammatory effects and is widely used to treat inflammatory disorders, such as rheumatoid arthritis and osteoarthritis , and has also been studied for the management of cystic fibrosis .","Talniflumate is metabolized to its prodrug, niflumic acid, which has several pharmacodynamic effects. Firstly, it blocks synthesis of mucin. Secondly, talniflumate blocks prostaglandin synthesis by cyclooxygenases, which aids in pain and inflammation management.","Talniflumate is a strong and selective inhibitor of core mucin-synthesizing enzyme GCNT3 (core 2 b-1,6 N-acetylglucosaminyltransferase). Talniflumate decreases gene expression of GCNT3 and production of mucins in vivo and in vitro. Talniflumate improves response of pancreatic tumors to gefitinib (chemotherapy drug). Talniflumate is a strong calcium-activated chloride channel (CaCC) blocker.","Prostaglandin G/H synthase 1 antagonist; Prostaglandin G/H synthase 2 antagonist; Chloride channel protein ClC-Ka antagonist","Indication associated"]
[1290,"DB09301","approved; investigational; nutraceutical","small molecule","Chondroitin sulfate","Chondroitin sulfates",null,null,"Chondroitin sulfate is a glycosaminoglycan considered as a symptomatic slow-acting drug for osteoarthritis (SYSADOA). The SYSADOA status suggested a pain relief and increased joint mobility after a relative long regular administration, as well as a long-lasting effect after the end of the treatment. Chondroitin sulfate is composed of alternating 1,3-N-acetyl-β-d-galactosamine and 1,4-β-d-glucuronic acid units which bear 4-O- and/or 6-O-sulfations at the N-acetylgalactosamine units disposed of in specific patterns. Depending on the predominating disaccharide unit, it will present different biological activities. Chondroitin sulfate is sold as an OTC dietary supplement in North America and it is a prescription drug under the EMA in Europe.","24967-93-9",null,"Chondroitin sulfate, used with glucosamine, is indicated to alleviate pain and inflammation from primary osteoarthritis. This supplement is reported to improve joint function and slow disease progression. Osteoarthritis is characterized by progressive structural and metabolic changes in joint tissues, mainly cartilage degradation, subchondral bone sclerosis and inflammation of synovial membrane.\r\n\r\nStudies have proposed the potential use of chondroitin sulfate as a nutraceutical in dietary supplements.\r\n\r","In clinical trials, chondroitin sulfate has been reported a significant pain relief. Some reports have shown no slow in joint damage. The effects of chondroitin sulfate have been very controversial. One of the characteristics of chondroitin is a slow onset of action with a maximal effect attained after several months. Chondroitin sulfate has been reported to have anti-inflammatory properties by reducing the synovitis and prevent proinflammatory cytokine up-regulation in arthritis models.\r\n\r\nIt is also registered an anabolic effect of chondroitin sulfate in which it induces the synthesis of hyaluronate in synovial cells, it increases type II collagen and proteoglycan synthesis.\r\n\r","Chondroitin sulfate functions as a major component of the intricate extracellular matrix. It is proposed that chondroitin sulfate supply can provide new building blocks for the synthesis of new matrix components.\r\n\r\nThe anti-inflammatory effect of chondroitin sulfate is thought to be caused by the inhibition of the synthesis of inflammatory intermediates such as the inhibition of nitric oxide synthase, COX-2, microsomal prostaglandin synthase 1 and prostaglandin E2. It is reported also an inhibitory activity in the toll-like receptor 4 which will later inhibit inflammatory cytokines, NFkB and MyD88. This activity suggests a modulation of the MAP kinase pathway. On the other hand, some reports have pointed out an induction on the PKC/PI3K/Akt pathway in neuroblastoma.\r\n\r\nThe anabolic effect of chondroitin sulfate is suggested to be caused by the inhibition of metalloproteinases such as MMP-1, -3 and -13 as well as ADAMTS-4 and -5.","Brain-derived neurotrophic factor; Glial cell line-derived neurotrophic factor; Vascular endothelial growth factor A; C-C motif chemokine 2","Therapeutic strategy associated"]
[1291,"DB09302","approved","biotech","Alirocumab","Alirocumab",null,null,"Alirocumab is a biopharmaceutical that obtained FDA approval in July 2015 as a second line treatment for high cholesterol in adults whose LDL-cholesterol (LDL-C) is not controlled by the combination of diet and statin treatment. It is a human monoclonal antibody part of the family of the PCSK9 inhibitors which are a novel class of anticholesterol therapeutics. From this family, it was the first agent to receive FDA approval. The FDA approval was contingent on the completion of further clinical trials to better determine efficacy and safety. PCSK9 inhibition facilitates more LDL-C clearance from the blood.","1245916-14-6",null,"Alirocumab is an antibody eliciting proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor activity that is indicated for:\r\n\r\n(i) use in reducing the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease , and/or\r\n\r\n(ii) use as an adjunct to diet or use alone or in combination with other lipid-lowering therapies (statins, ezetimibe, for example) for the treatment of adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) to reduce low-density lipoprotein cholesterol (LDL-C) levels in the body .","Alirocumab reduces levels of PCSK9 in a concentration-dependent manner.","Alirocumab is a fully human IgG1 monoclonal antibody that binds and inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), an enzyme found to have \"gain of function\" mutations in autosomal dominant hypercholesterolemia. PCSK9 is secreted by the liver and typically binds to the LDL receptors in serum and marks them for lysosomal degradation. In result, the LDL receptors are not able to recycle to the plasma membrane, reducing their binding to LDL-C and therefore reducing the clearance of LDL-C from plasma. Therefore by inhibiting PCSK9's actions, alirocumab allows for more LDL-C reuptake by the liver and facilitates a higher rate of clearance. Lower LDL cholesterol concentrations are associated with a reduced risk of coronary heart disease.","Proprotein convertase subtilisin/kexin type 9 inhibitor","Indication associated"]
[1292,"DB09303","approved","biotech","Evolocumab","Evolocumab",null,null,"Evolocumab is a monoclonal antibody designed for the treatment of hyperlipidemia by Amgen. It is a subcutaneous injection approved by the FDA for individuals on maximum statin therapy who still require additional LDL-cholesterol lowering. It is approved for both homozygous and heterozygous familial cholesterolemia as an adjunct to other first-line therapies. Evolocumab is a human IgG2 monoclonal antibody that targets the proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 is a protein that targets LDL receptors for degradation, therefore reducing the liver's ability to remove LDL-cholesterol (LDL-C), or \"bad\" cholesterol, from the blood. Evolocumab is designed to bind to PCSK9 and inhibit PCSK9 from binding to LDL receptors on the liver surface, resulting in more LDL receptors on the surface of the liver to remove LDL-C from the blood. Evolocumab is the second PCSK9 inhibitor on the market, first being alirocumab.","1256937-27-5",null,"For the treatment of heterozygous/homozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease in patients on maximum tolerated statin therapy requiring additional LDL-cholesterol lowering.",null,"Evolocumab is a human IgG monoclonal antibody which targets PCSK9 (proprotein convertase subtilisin/kexin type 9). PCSK9 is a serine protease produced by the liver which binds LDL receptors and creates a complex to be targeted for lysosomal degradation. LDL receptors typically bind LDL-cholesterol (\"bad\" cholesterol) for cellular reuptake, therefore the formation of these complexes with PCSK9 inhibits LDL receptor recycling to the cell surface, resulting in decreased cellular reuptake of LDL-C and increased levels of free LDL-C in the plasma. Individuals with familial hypercholesterolemia often may have \"gain of function\" mutations in the PCSK9 molecules in their body, resulting in increased LDL-C plasma levels and a consequent cardiovascular risk. Evolocumab is able to bind both the normal PCSK9 and the \"gain of function\" mutant, D374Y. The exact mechanism of the binding has not been published, however the precursor molecule, mAb1, is indicative of the interaction. The mAb1 molecule binds on the catalytic site of PCSK9 next to the binding site for the LDL receptor and creates hydrogen bonds and hydrophobic interactions, resulting in the steric inhibition of binding between PCSK9 and the LDL receptor. Because the formation of complexes between LDL receptor and PCSK9 are prevented, the internalized LDL receptors are less likely to be degrated by lysosomes and may recycle to the surface of the cell to serve their function of removing LDL from the blood.","Proprotein convertase subtilisin/kexin type 9 inhibitor","Indication associated"]
[1293,"DB09304","experimental","small molecule","Setiptiline","Setiptiline","C19H19N","CN1CCC2=C(C1)C1=CC=CC=C1CC1=CC=CC=C21","Setiptiline is a tetracyclic antidepressant (TeCA) which acts as a noradrenergic and specific serotonergic antidepressant (NaSSA). In Japan, the company Mochida started its commercialization for the treatment of depression started in 1989.","57262-94-9","261.368","For the treatment of depression .","Setiptiline is a tertacyclic antidepressant . It acts to reduce the symptoms of major depressive disorder.","Setiptiline is an antagonist at the α2 adrenergic receptor and at serotonin receptors . The antagonism of the α2 receptors likely relieves presynaptic inhibition of adrenergic neurotransmission, allowing for greater and longer sustained release of noradrenaline into the synapse. The antagonism of serotonin receptors may produce an upregulation of the receptors leading to an eventual increase in serotonergic signalling. The actual physiological mechanisms behind the antidepressant effect of setiptiline is unknown but the listed possibilities exist as likely explanations.","Alpha-2 adrenergic receptors antagonist; Serotonin Receptors antagonist","Indication associated"]
[1294,"DB09305","experimental","small molecule","Aptazapine","Aptazapine","C16H19N3","CN1CCN2C(C1)C1=CC=CN1CC1=C2C=CC=C1","Aptazapine (CGS-7525A) was a tetracyclic antidepressant developed in the 1980s. Aptazapine had noradrenergic and specific serotonergic activity. It antagonised α2 adrenergic receptors approximately 10 times more effectively than mianserin, antagonised 5-HT2 receptors, agonised H1 receptors, and did not affect reuptake of serotonin or norepinephrine. Although Aptazapine reached clinical trials, it was never marketed.","71576-40-4","253.349","Investigated for the treatment of depression.",{"$nulls":3},"Indication associated"]
[1295,"DB09306","experimental","small molecule","Metralindole","Incasan; Inkazan; Metralindole","C15H17N3O","COC1=CC2=C(C=C1)N1CCN(C)C3=NCCC2=C13","Metralindole, also known as Inkazan, is similar in structure and pharmacology to pirlindole. It functions as a reversible inhibitor of monoamine oxidase A. In Russia, this drug was investigated for potential antidepressant activity.","54188-38-4","255.321","Investigated for the treatment of depression.",{"$nulls":3},"Indication associated"]
[1296,"DB09307","experimental","small molecule","Oxaprotiline","Hydroxymaprotiline; Oxaprotiline","C20H23NO","CNCC(O)CC12CCC(C3=CC=CC=C13)C1=CC=CC=C21","Oxaprotiline is a norepinephrine reuptake inhibitor of the tetracyclic antidepressant family that is related to maprotiline. This drug was never marketed. Oxaprotiline is a racemic mixture of the isomers levoprotiline and dextroprotiline. Levoprotiline is the R or levo isomer of oxaprotiline (CGP-12,103-A). Dextroprotiline is the S or dextro isomer of oxaprotiline (CGP-12,104-A). Both enantiomers have antidepressant effects but levoprotiline also is an antihistamine and dextroprotiline has many other pharmacological actions.","56433-44-4","293.41","Investigated for the treatment of depression.",{"$nulls":3},"Indication associated"]
[1297,"DB09311","experimental","small molecule","Polycarbophil","Polycarbofil; Polycarbophil",null,null,"Polycarbophil calcium is a synthetic polymer manufactured from the cross-linking of polyacrylic acid with divinyl glycol and a calcium counter-ion.\r\nPolycarbophil calcium is a stool stabilizer used to treat constipation. This drug may also be used to help relieve the symptoms of irritable bowel syndrome or diarrhea.\r\nLess gas and bloating compared to psyllium laxative products, but can cause heartburn, and belly cramps. It is insoluble in water, dilute acids, and dilute alkali. The material possesses exceptionally high water-binding capacity. is not absorbed, does not interfere with the activity of digestive enzymes or intestinal absorption, possesses satisfactory stability, is physiologically inert, and does not cause gastrointestinal irritation.","9003-97-8",null,"Polycarbophil is used to treat constipation and to help maintain regular bowel movements.","Relieves constipation or diarrhea associated with bowel disorders and acute nonspecific diarrhea.","It is known as a bulk-forming laxative. It increases the bulk in the stool, an effect that helps to cause movement of the intestines. It also works by increasing the amount of water in the stool, making the stool softer and easier to pass.",null,"Indication associated"]
[1298,"DB09320","approved; vet_approved","small molecule","Procaine benzylpenicillin","Penicillin G procaine","C29H38N4O6S","CCN(CC)CCOC(=O)C1=CC=C(N)C=C1.[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)CC1=CC=CC=C1)C(O)=O","Procaine benzylpenicillin (INN), also known as procaine G penicillin, is an injectable antiobiotic. It is a poorly soluble salt form of penicillin which is a combination of naturally occuring benzylpenicillin (penicillin G) and the local anaesthetic agent procaine in equimolar amounts. Procaine benzylpenicillin is administered by deep intramuscular injection. It is slowly absorbed and hydrolyzed to benzylpenicillin. This drug is used where prolonged exposure to benzylpenicillin at a low concentration is required. This combination is aimed at reducing the pain and discomfort associated with a large intramuscular injection of penicillin. It is widely used in veterinary settings. Benzylpenicillin is active against a wide range of organisms and is the drug of first choice for many infections.","54-35-3","570.71","For the treatment of a number of bacterial infections such as syphilis, anthrax, mouth infections, pneumonia and diphtheria.","It is an antibiotic against penicillin-susceptible microorganisms with bactericidal effect. Like all penicillins, procaine benzylpenicillin interferes with the synthesis of the bacterial cell wall peptidoglycan. It acts through the inhibition of biosynthesis of cell-wall peptidoglycan, rendering the cell wall osmotically unstable. It is part of the penicillin and beta lactam family of antibacterial drugs.","Procaine benzylpenicillin is hydrolyzed into penicillin G once it is released from the injection site. Penicillin G attaches to the penicillin-binding proteins on bacterial cell wall and inhibit the transpeptidation enzyme that crosslinks the peptide chains attached to the backbone of the peptidoglycan. The final bactericidal event involves the inactivation of an inhibitor of autolytic enzymes in the cell wall, leading to lysis of the bacterium .",null,"Indication associated"]
[1299,"DB09324","approved","small molecule","Sulbactam","(2S,5R)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid 4,4-dioxide; (2S,5R)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid 4,4-dioxide; Penicillanic acid 1,1-dioxide; Penicillanic acid sulfone; Sulbactam","C8H11NO5S","[H][C@@]12CC(=O)N1[C@@]([H])(C(O)=O)C(C)(C)S2(=O)=O","Sulbactam is a β-lactamase inhibitor given in combination with β-lactam antibiotics to inhibit β-lactamase, an enzyme produced by bacteria that destroys antibiotic activity.","68373-14-8","233.242","Sulbactam is currently available in combination products with ampicillin. Within this formulation it is indicated  for the treatment of infections due to susceptible strains of the designated microorganisms in the conditions listed below.\r\nSkin and Skin Structure Infections caused by beta-lactamase producing strains of Staphylococcus aureus, Escherichia coli, Klebsiella spp. (including K. pneumoniae), Proteus mirabilis, Bacteroides fragilis, Enterobacter spp., and Acinetobacter calcoaceticus.\r\nIntra-Abdominal Infections caused by beta-lactamase producing strains of Escherichia coli, Klebsiella spp. (including K. pneumoniae), Bacteroides spp. (including B. fragilis), and Enterobacter spp.\r\nGynecological Infections caused by beta-lactamase producing strains of Escherichia coli, and Bacteroides spp. (including B. fragilis).",null,"Sulbactam is an irreversible inhibitor of β-lactamase; by binding and inhibiting β-lactamase produced by bacterial cells, sulbactam is thereby able to prevent it from reducing antibiotic activity.  Although sulbactam alone possesses little useful antibacterial activity, except against the Neisseriaceae, whole organism studies have shown that sulbactam restores ampicillin activity against beta-lactamase producing strains. In particular, sulbactam has good inhibitory activity against the clinically important plasmid mediated beta-lactamases most frequently responsible for transferred drug resistance. The presence of sulbactam in formulations with ampicillin effectively extends the antibacterial spectrum of ampicillin to include many bacteria normally resistant to it and to other beta-lactam antibacterials. Thus, products with ampicillin + sulbactam possess the properties of a broad-spectrum antibacterial and a beta-lactamase inhibitor.","Beta-lactamase inhibitor","Indication associated"]
[1300,"DB09328","approved; investigational","biotech","Vayarin","Phosphatidylserine, DHA, and EPA",null,null,"Vayarin is a prescription medical food for the clinical dietary management of certain lipid imbalances blamed to be associated with attention deficit hyperactivity disorder (ADHD) in children. Vayarin contains _Lipirinen_, a proprietary composition containing phosphatidylserine-omega 3, EPA (eicosapentaenoic acid), and docosahexaenoic acid (DHA) . Vayarin is currently available only by prescription in the USA .  This drug has also been used for management of hypertriglyceridemia .\r\n\r\nVayarin is an orally administered prescription medical food for the clinical dietary management of complex lipid imbalances thought to be associated with ADHD. Vayarin is a specially formulated and designed to address the distinct, previously determined lipid nutritional requirements of children with ADHD, the dietary management of which cannot be achieved with lifestyle modification .\r\n\r\nVayarin is a novel therapy for ADHD that appears to be effective in several studies . Approximately 60% of the users who completed 12 weeks of therapy reported subjective benefits from treatment. A slow response time of 12 weeks is an impediment to successful management of ADHD as only 41.6% of subjects prescribed Vayarin remained compliant for the duration of the study. Cost of the drug and patient aversion to the taste of Vayarin were significant reasons for therapy failure .",null,null,"ADHD in children,  hypertriglyceridemia .","Compared to healthy children of the same age, children with ADHD have lower circulating concentrations of omega-3 long-chain polyunsaturated fatty acid. These lipids, found in the brain, play an essential role in central nervous system development and function. It has been reported that omega-3 fatty acid deficiency is directly associated with decreased brain phosphatidylserine, which is mainly in the form of phosphatidylserine-Omega-3 (Ps-Omega-3) .\r\n\r\nPS-Omega-3 such as Vayarin, are believed to be essential in the functioning of neuronal cell membranes, in activities such as signal transduction, secretory vesicle release, cell-to-cell communication, and cell growth regulation. Reduced levels of PS-Omega-3 and omega-3 fatty acids may play an important role in the pathogenesis of ADHD and other neuronal disorders. Vayarin is a proprietary lipid composition of phosphatidylserine-Omega-3 (PS-Omega-3), enriched with eicosapentaenoic acid. This formula has been designed to provide the essential lipids to brain tissues in order to support and maintain proper brain function. Additionally, the enrichment of EPA in the Vayarin medical food allows for better regulation of lipids and acts on the specific imbalances that are thought to be associated with ADHD .\r\n\r\nCurrent studies are underway for the efficacy of Vayarin in ADHD and autism spectrum disorder co-morbidity .  In addition, studies of Vayarin in adults using MRI to study alterations in radiographic findings are currently underway, allowing for other possible benefits of this medication .\r\n\r","Phosphatidylserine (PS) in the mammalian nervous system, containing high levels of omega-3 fatty acids, has been implicated in numerous membrane-associated functions, such as maintaining the integrity of cell membranes, cell excitability and cell-to-cell recognition and communication. While the exact mechanism by which this medical food exerts its effects is not fully understood, PS has been found to regulate important proteins in neuronal cell membranes, including sodium/calcium ATPase and protein kinase C, which perform crucial functions in many signal transduction pathways. Similarly, PS interacts with Raf-1 protein kinase  to promote a cascade of reactions that are believed to be involved in the survival of cells . Additionally, PS has been found to influence neurotransmitter activity, such as the release of acetylcholine (Ach), dopamine, and noradrenaline. In addition, it is also thought to increase brain glucose concentrations . Administration of specially processed formulations consisting of PS conjugated to omega-3 fatty acids was found to significantly increase DHA levels in the brain tissue of rats .",null,"Indication associated"]
[1301,"DB09331","approved","biotech","Daratumumab","Daratumumab",null,null,"Daratumumab is an immunoglobulin G1 kappa monoclonal antibody developed by Janssen and Genmab. It was first described in the literature in 2010 as a monoclonal antibody that targets CD38+ multiple myeloma cells; the first of its kind.\r\n\r\nDaratumumab was granted FDA approval on 16 November 2015. It is approved for the treatment of multiple myeloma as monotherapy or combination therapy and light chain (AL) amyloidosis in combination with other drugs.","945721-28-8",null,"Daratumumab is indicated as an intravenous injection alone or in combination with other medications for the treatment of multiple myeloma. It is available as a combination product with  for the treatment of adults with multiple myeloma as monotherapy or combination therapy and light chain amyloidosis in combination with other drugs.","Daratumumab is a monoclonal antibody that targets and induces apoptosis in cells that highly express CD38, including multiple myeloma cells. It has a long duration of action as it is given every 1-4 weeks. Patients should be counselled regarding the risk of hypersensitivity, neutropenia, thrombocytopenia, embryo-fetal toxicity, and interferences with cross-matching and red blood cell antibody screening.","CD38 is a glycoprotein present on the surface of hematopoietic cells and is responsible for a number of cell signalling functions. Daratumumab is an immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that targets CD38. Cancers like multiple myeloma overexpress CD38, allowing daratumumab to have higher affinity for these cells. This binding allows daratumumab to induce apoptosis, antibody dependent cellular phagocytosis, and antibody and complement-dependent cytotoxicity. Antibody dependent cellular phagocytosis is mediated by the FC region of the antibody inducing phagocytes such as macrophages, antibody dependent cellular cytotoxicity is mediated by the FC region of the antibody inducing effector cells such as natural killer cells, and complement dependent cytotoxicity is mediated by the FC region of the antibody binding to and inducing complement protein activity.","ADP-ribosyl cyclase 1 antibody","Therapeutic strategy associated"]
[1302,"DB09338","experimental","small molecule","Mersalyl","Mersal","C13H17HgNO6","COC(CNC(=O)C1=CC=CC=C1OCC(O)=O)C[Hg]O","Mersalyl is the sodium salt form of mersalyl acid, a mercurial diuretic. It is an outdated drug, and its approval has been discontinued by the FDA. Mersalyl acid is currently replaced by less toxic non-mercury containing diuretics . The sodium salt of a mercury-containing derivative of salicylamide, was formerly used (often in combination with theophylline) to treat edema, due to its powerful diuretic properties .  Interestingly, it has been found to have antiviral properties in mice .","486-67-9","483.87","Elevated blood pressure, edema .","Mersalyl acid is an organomercuric compound. It is used as a diuretic. Mercury is a heavy, silvery d-block metal and one of six elements that are liquid at or near room temperature and pressure. It is a naturally occuring substance, and combines with other elements such as chlorine, sulfur, or oxygen to form inorganic mercury compounds (salts). Mercury also combines with carbon to make organic mercury compounds .","Mersalyl is a mercurial diuretic which acts on the renal tubules, increasing the excretion of sodium and chloride, in approximately equal amounts, and of water .  As a result, blood pressure and edema is markedly decreased.  \r\n\r\nHigh-affinity binding of the divalent mercuric ion to thiol or sulfhydryl groups of proteins is believed to be the major mechanism for the activity of mercury. Through alterations in intracellular thiol status, mercury can promote oxidative stress, lipid peroxidation, mitochondrial dysfunction, and changes in heme metabolism. Mercury is known to bind to microsomal and mitochondrial enzymes, resulting in cell injury and death. For example, mercury is known to inhibit aquaporins, halting water flow across the cell membrane. It also inhibits the protein LCK, which causes decreased T-cell signaling and immune system depression. Mercury is also believed to inhibit neuronal excitability by acting on the postsynaptic neuronal membrane. It also affects the nervous system by inhibiting protein kinase C and alkaline phosphatase, which impairs brain microvascular formation and function, as well as alters the blood-brain barrier. Organic mercury exhibits developmental effects by binding to tubulin, which prevents microtubule assembly and causes mitotic inhibition. In addition, mercury produces an autoimmune response, likely by modification of major histocompatibility complex (MHC) class II molecules, self-peptides, T-cell receptors, or cell-surface adhesion molecules .","Alkaline phosphatase, tissue-nonspecific isozyme antagonist; Aquaporin-1; Monocarboxylate transporter 1 antagonist","Therapeutic strategy associated"]
[1303,"DB09351","approved; investigational","small molecule","Levobetaxolol","(S)-betaxolol","C18H29NO3","CC(C)NC[C@H](O)COC1=CC=C(CCOCC2CC2)C=C1","Levobetaxolol is a beta-blocker used to lower the pressure in the eye to treat conditions such as glaucoma. It was marketed as a 0.5% ophthalmic solution of levobetaxolol hydrochloride under the trade name Betaxon but has been discontinued.","93221-48-8","307.434","Used in the treatment of open-angle glaucoma and ocular hypertension .","Levobetaxolol is a selective β1 adrenergic receptor antagonist . It acts to lower intraocular pressure. Levobataxolol is condsidered to be the more active component of the betaxolol racemate.","The exact mechanism by which levobetaxolol lowers intraocular pressure is not known. It it thought that antagonism of β-adrenergic receptors may reduce the production of aqueous humour stimulated via the cyclic adenosine monophosphate-protein kinase A pathway . It is also thought that the vasoconstriction produced by antagonism of β adrenergic receptors reduces blood flow to the eye and therefore the ultrafiltration responsible for aqueous humour production. β1 selective antagonists are less effective than non-selective β adrenergic receptor antagonists because β2 receptors make up the bulk of the population in the eye. They do, however, come with the benefit of reduced respiratory complications.","Beta-1 adrenergic receptor antagonist","Indication associated"]
[1304,"DB09357","approved","small molecule","Dexpanthenol","(+)-Panthenol; (2R)-2,4-dihydroxy-N-(3-hydroxypropyl)-3,3-dimethylbutanamide; Bepanthen; Bepanthene; Bepantol; D-panthenol; D-panthenol 50; D-Pantothenol; D-Pantothenyl alcohol; D(+)-Panthenol; Dexpanthenol; Pantol; Pantothenyl alcohol; Provitamin B","C9H19NO4","CC(C)(CO)[C@@H](O)C(=O)NCCCO","Dexpanthenol is an alcohol derivative of pantothenic acid, a component of the B complex vitamins and an essential component of a normally functioning epithelium. Dexpanthenol is enzymatically cleaved to form pantothenic acid, which is an essential component of Coenzyme A, which acts as a cofactor in many enzymatic reactions that are important for protein metabolism in the epithelium. \r\n\r\nDue to its good penetration and high local concentrations, dexpanthanol is used in many topical products, such as ointments and lotions for treatment of dermatological conditions to relieve itching or promote healing. Dermatological effects of the topical use of dexpanthenol include increased fibroblast proliferation and accelerated re-epithelialization in wound healing. Furthermore, it acts as a topical protectant, moisturizer, and has demonstrated anti-inflammatory properties .\r\n\r\nDexpanthenol is also available as a racemic mixture containing both the dextrorotatory form (dexpanthenol) and the levorotatory form (levopanthenol) as . While pantothenic acid is optically active, only the dextrorotatory form (dexpanthenol) is biologically active.","81-13-0","205.2515","Injection: Prophylactic use immediately after major abdominal surgery to minimize the possibility of paralytic ileus. Intestinal atony causing abdominal distention; postoperative or postpartum retention of flatus, or postoperative delay in resumption of intestinal motility; paralytic ileus.\r\n\r\nTopical: This medication is used as a moisturizer to treat or prevent dry, rough, scaly, itchy skin and minor skin irritations (e.g., diaper rash, skin burns from radiation therapy).","Pantothenic acid is a precursor of coenzyme A, which serves as a cofactor for a variety of enzyme-catalyzed reactions involving transfer of acetyl groups. The final step in the synthesis of acetylcholine consists of the choline acetylase transfer of acetyl group from acetylcoenzyme A to choline. Acetylcholine is the neurohumoral transmitter in the parasympathetic system and as such maintains the normal functions of the intestine. Decrease in acetylcholine content would result in decreased peristalsis and in extreme cases adynamic ileus.","Dexpanthenol is an alcohol derivative of pantothenic acid, a component of the B complex vitamins and an essential component of a normally functioning epithelium. Dexpanthenol is enzymatically cleaved to form pantothenic acid, which is an essential component of Coenzyme A, which acts as a cofactor in many enzymatic reactions that are important for protein metabolism in the epithelium.  \r\n\r\nDermatological effects of the topical use of dexpanthenol include increased fibroblast proliferation and accelerated re-epithelialization in wound healing. Furthermore, it acts as a topical protectant, moisturizer, and has demonstrated anti-inflammatory properties .\r",null,"Therapeutic strategy associated"]
[1305,"DB09363","investigational","small molecule","Rauwolfia serpentina root","Alkaloids, rauwolfia; Alseroxylon; Rauvolfia serpentina root; Rauwolfia; Rauwolfia alkaloids; Rauwolfia root; Rauwolfia serpentina; Rauwolfia serpentina alseroxylon; Snakeroot",null,null,"Rauwolfia (Rauwolfia serpentina), also spelled _ravolphia_, is a medicinal plant in the milkweed family. The root of the plant is ground into a powder or sold in tablets or capsules. It is a compound commonly used in Asian medicine, which includes traditional Ayurvedic medicine native to India. The active ingredients in this drug are alkaloids and about 50 have been identified through various studies, although the primary psychoactive components appear to be reserpine, rescinnamine, and deserpidine .\r\n\r\nThis product was approved prior to Jan 1, 1982, but since, has been discontinued due to its propensity for leading to depression .  Reserpine is derived from Rauwolfia serpentina, and was commonly used as an antihypertensive agent in the 1950s .  Rauwolfia serpentina is also commonly referred to as _Sarpaghanda_ . Interestingly, the hairy root component of this plant has shown a remarkable capacity to regenerate into complete Rauwolfia plants and shows survival and unaltered biosynthetic potential during storage at decreased temperatures.   For this reason, various studies into biotechnological applications of this plant have been performed. Multiple studies have been done on their biosynthetic potential and numerous biotechnological methods used to study the production of pharmaceutically important alkaloids .","8063-17-0",null,"Rauwolfia alkaloids are indicated in the treatment of hypertension . Rauwolfia alkaloids have been used for relief of symptoms in agitated psychotic states such as schizophrenia; however, use as antipsychotics and sedatives have been replaced with the use of more effective, safer agents .\r","Reserpine is used to treat high blood pressure. It also is used to treat severe agitation in patients with mental disorders. Reserpine is in a class of medications called rauwolfia alkaloids. It works by slowing the activity of the nervous system, causing the heart rate to slow and the blood vessels to dilate .","\r\nReserpine is an adrenergic blocking agent used to treat mild to moderate hypertension via the disruption of norepinephrine vesicular storage. The antihypertensive actions of Reserpine are a result of its ability to deplete catecholamines from peripheral sympathetic nerve endings. These substances are normally involved in controlling heart rate, the work of cardiac contraction and peripheral resistance . Reserpine depletes brain (depression) and peripheral (PPH) noradrenaline (NA) storage sites, guanethidine depleted NA storage via blockade of reuptake .\r\n  \r\nThis agent binds and inhibits catecholamine pump on the storage vesicles in central and peripheral adrenergic neurons, thereby inhibiting the uptake of norepinephrine, dopamine serotonin into presynaptic storage vesicles. This results in catecholamines and serotonin lingering in the cytoplasm where they are destroyed by intraneuronal monoamine oxidase, thereby causing the depletion of catecholamine and serotonin stores in central and peripheral nerve terminals. Depletion results in a lack of active transmitter discharge from nerve endings upon nerve depolarization, and consequently leads to a decreased heart rate and decreased arterial blood pressure as well as sedative effects .","Synaptic vesicular amine transporter inhibitor","Therapeutic strategy associated"]
[1306,"DB09394","approved","small molecule","Phosphoric acid",null,"H3O4P","OP(O)(O)=O","Phosphoric Acid is a colorless, odorless phosphorus-containing inorganic acid. Phosphoric acid is a sequestering agent which binds many divalent cations, including Fe++, Cu++, Ca++, and Mg++.","7664-38-2","97.9952","Phosphoric acid is used in dentistry and orthodontics as an etching solution, to clean and roughen the surfaces of teeth where dental appliances or fillings will be placed.","Transport of phosphate from the gut lumen is an active, energy-dependent process that is modified by several factors. ... Vitamin D stimulates phosphate absorption, an effect reported to precede its action on calcium ion transport.","Phosphate supplementation of the diet of rodents has been shown to lead to reduction in the incidence of dental caries and different phosphates have different powers in reducing the cariogenic potential of the carbohydrates in a diet. Phosphate supplements seem to exert their cariostatic effect on the tooth surface either directly during eating or by excretion in the saliva.",null,"Therapeutic strategy associated"]
[1307,"DB09398","approved","small molecule","Fluoride ion F-18","(18F)-Fluoride; 18F-Fluoride; Fluoride-18 anion","F","[18F-]","Sodium Fluoride F 18 Injection is a positron emitting radiopharmaceutical, no-carrier added. It contains radioactive fluoride F 18 that is used for diagnostic purposes in conjunction with positron emission tomography (PET) imaging and is administered by intravenous injection. Its primary indication is for bone imaging. Increased deposition around joints can occur in arthritis and following trauma and increased deposition in bone has been noted around fracture sites, in osteomyelitis, fibrous dysplasia, spondylitis tuberculosa, and Paget's disease. No adverse reactions have been reported.","67862-54-8","18.0015","18F is used as a bone imaging agent to define areas of altered osteogenic activity.  It has been indicated for back pain  and otherwise unexplained bone pain, child abuse, abnormal radiographic or laboratory findings, osteomyelitis, trauma, inflammatory and degenerative arthritis, avascular necrosis. Osteonecrosis of the mandible, condylar hyperplasia, and metabolic bone disease are also among the indications for fluoride imaging.","Deposition of 18F fluoride in bone appears to be primarily a function of blood flow to the bone and the efficiency of the bone in extracting the 18F from the blood perfusing the bone. Increased fluorine F 18 ion deposition around joints can occur in arthritis or following trauma; increased deposition has also been documented in bone around fracture sites, in osteomyelities, fibrous dysplasia, spondylitis tuberculosa, Paget's disease, hyperstosis frontalis interna, myositis, ossificans, and in rapidly growing epiphyses. The tendency for fluorine F 18 ions to accumulate in the vicinity of primary and metastatic malignancy in bone has proven clinically useful in detection of such lesions","18F-fluoride is a highly sensitive bone-seeking PET tracer used for detection of skeletal abnormalities. The uptake mechanism of 18F-fluoride has  better pharmacokinetic characteristics (compared to other elements) including faster blood clearance and 2-fold higher uptake in bone. Uptake of 18F-fluoride reflects blood flow and bone remodeling.",null,"Indication associated"]
[1308,"DB09409","approved","small molecule","Magnesium acetate tetrahydrate","Acetic acid, magnesium salt, tetrahydrate; Magnesium diacetate tetrahydrate","C4H14MgO8","O.O.O.O.[Mg++].CC([O-])=O.CC([O-])=O","Magnesium acetate tetrahydrate is a hydrated form of anhydrous magnesium acetate salt with the chemical formula of Mg(CH3COO)2 • 4H2O. As a salt form of magnesium, magnesium acetate is one of the bioavailable forms of magnesium and forms a very water soluble compound. Magnesium is an essential element and second most abundant cation in the body that plays a key role in maintaining normal cellular function such as production of ATP and efficient enzyme activity. Magnesium acetate tetrahydrate can be used as an electrolyte supplementation or a reagent in molecular biology experiments.","16674-78-5","214.453","Used as magnesium salf-containing laxatives to prevent constipation. It can bring synergistic effect to restore normal bowel function when using in combination with aluminum salts that induce bowel retention . Magnesium acetate tetrahydrate is used as a source of water and electrolytes when combined with dextrose and other salts to form intravenous infusions. This injection can be used for patients with carbohydrate or magnesium deficiency, insulin hypoglycemia, constipation or hypertension during pregnancy.","Magnesium is an essential cofactor for many enzymatic reactions such as protein synthesis and ATP production. It also participates in adenylyl cyclase pathway and tyrosine kinase signalling pathways. Magnesium may also play a role in regulating glucose metabolism. It serves as an essential cation for a number of biochemical processes involved in nerve signaling, bone mineralization and muscle contractions.","Magnesium ions electrostatically stabilize the adenylyl cyclase complex and enhance its catalytic actions and production of cAMP. They also regulate the level of phosphorylation in various pathways by formation of transition state of phosphoryl transfer reaction by protein kinases and stabilize ATP binding to protein kinases via electrostatic interactions . Many metabolic enzymes involved in glycolysis and Krebs cycle are magnesium-dependent. Magnesium-containing laxatives cause diarrhea through water retention and increased fecal mass that stimulates peristalsis. When used as an electrolyte supplementation, magnesium acetate tetrahydrate induces diuresis and metabolic alkalinizing effect. Magnesium ions enhance reactivity of arteries to vasoconstrictors, promotes vasoconstriction, and increases peripheral resistance, leading to increased blood pressure  through potential competition with calcium ions in the vascular system. Magnesium ions also regulate other ions entering and exiting the cell membrane by acting as a ligand in N-methyl-D-aspartate receptor.","Glutamate (NMDA) receptor ligand","Indication associated"]
[1309,"DB09422","approved","biotech","Soybean oil","Dolichos soja seed oil; Glycine angustifolia seed oil; Glycine gracilis seed oil; Glycine hispida seed oil; Oils, soybean; Phalseolus max seed oil; Phaseolus max seed oil; Soja angustifolia seed oil; Soja hispida seed oil; Soja japonica seed oil; Soja max seed oil; Soja soja seed oil; Soja viridis seed oil; Soya bean seed oil; Soya oil; Soybean oil; Soybean seed oil",null,null,"Derived from soybeans, soybean oil is a common vegetable oil and a source of polyunsaturated and saturated fatty acids. It is a complex mixture of triglycerides where per 100 g, soybean oil has 16 g of saturated fat, 23 g of monounsaturated fat, and 58 g of polyunsaturated fat. The major component fatty acids are linoleic (48% - 58%), oleic (17% - 30%), palmitic (9% -13%), linolenic (4% - 11%), and stearic (2.5% - 5.0%). It is used as a cooking oil and lipid emulsion for parenteral nutrition in clinical settings. Soybean oil-based lipid emulsion is the only FDA-approved lipid formulation for clinical use.","8001-22-7",null,"Indicated for parenteral nutrition as a source of calories and essential fatty acids when oral or enteral nutrition is not possible, insufficient, or contraindicated.","Soybean oil is a nutrition source that provides a biologically utilizable source of calories and essential fatty acids. It prevents the biochemical lesions of essential fatty acid deficiency (EFAD), and correct the clinical manifestations of the EFAD syndrome  by supplying energy and nutrients.","Fatty acids serve as an important substrate for energy production. The most common mechanism of action for energy production derived from fatty acid metabolism is beta oxidation. Fatty acids are also important for membrane structure and function, precursors for bioactive molecules (such as prostaglandins), and as regulators of gene expression. Soybean oil-based lipid emulsion may also cause an increase in heat production, decrease in respiratory quotient, and increase in oxygen consumption following its administration . Soybean oil contents prevent abnormally high triacylglycerol synthesis and its accumulation as lipid droplets in the liver by regulating hepatic lipogenesis and lipolysis. In vitro, soybean oil is shown to prevent downregulation of CYP2C2, CYP2C11 and CYP3A2 mRNA thus maintaining hepatic drug oxidation capabilities. Soybean oil is broken down into free fatty acids that activate PPAR-alpha, which regulate hepatic CYP4A1 that hydroxylate saturated and unsaturated fatty acids. Soybean oil is also shown to prevent up/downregulation of efflux transporters and maintain mRNA levels of hepatic antioxidant enzymes in vitro rat studies .","Peroxisome proliferator-activated receptor alpha activator","Therapeutic strategy associated"]
[1310,"DB09446","approved; investigational","biotech","Safflower oil","Carthamus tinctorius seed oil; Safflower oil",null,null,"Safflower (_Carthamus tinctorius_ L) is a herbaceous plant in the Asteraceae family. Extracted from the seeds of safflowers, safflower oil is a rich source of various saturated fatty acids, monounsaturated fatty acid (oleic acid) or essential n-6 polyunsaturated fatty acid (PUFA) linoleic acid , depending on the flower type. Safflower oil with a higher content of polyunsaturated fatty acids is more commonly used as an edible oil. The constituents of safflower oil also include alpha-tocopherol, gamma-tocopherol, and mixed  .  Safflower oil is approved for use as an indirect additive in food contact substances and is readily available as a food ingredient. Gamma linolenic acid (GLA) safflower oil is marketed as an over-the-counter dietary supplement.","8001-23-8",null,"No approved therapeutic indications.","Safflower oil contains n-6 polyunsaturated fatty acids (PUFAs) such as conjugated linoleic acid (CLA) which may have lipid-lowering and anti-inflammatory actions, as well as tocopherols. In a study of post-menopausal, obese women with type 2 diabetes, safflower oil supplementation was associated with improved metabolic endpoints including HbA1c, fasting glucose, insulin sensitivity estimated by QUICKI, HDL cholesterol, CRP, and adiponectin .","Linoleic acid in safflower oil may decrease serum cholesterol levels by activating hepatic uptake and biliary excretion of serum cholesterol . Tocopherol in safflower oil is a radical scavenger with antioxidant properties.",null,"Therapeutic strategy associated"]
[1311,"DB09449","approved","small molecule","Sodium phosphate, monobasic","Disodium hydrogen phosphate anhydrous; Monosodium dihydrogen monophosphate; Monosodium dihydrogen orthophosphate; Monosodium monophosphate; Monosodium phosphate, anhydrous; Phosphoric acid, monosodium salt, anhydrous; Sodium acid phosphate; Sodium biphosphate, anhydrous; Sodium dihydrogen phosphate; Sodium dihydrogen phosphate, anhydrous; Sodium orthophosphate; Sodium orthophosphate monobasic; Sodium phosphate monobasic; Sodium phosphate monobasic (anhydrate); Sodium phosphate monobasic (anhydrous); Sodium phosphate, monobasic; Sodium phosphate, monobasic anhydrous; Sodium phosphate,monobasic; Sodium primary phosphate","H2NaO4P","[Na+].OP(O)([O-])=O","Sodium phosphate is a saline laxative that is thought to work by increasing fluid in the small intestine. It usually results in a bowel movement after 30 minutes to 6 hours.","7558-80-7","119.977","Used to treat constipation or to clean the bowel before a colonoscopy .","Sodium phosphate inceases fecal water content to increase mobility through the large intestine .","Sodium phosphate is thought to work by increasing the amount of solute present in the intestinal lumen thereby creating an osmotic gradient which draws water into the lumen .",null,"Indication associated"]
[1312,"DB09462","approved; investigational","small molecule","Glycerin","1,2,3-propanetriol; 1,2,3-trihydroxypropane; Glycerin; Glycerin, anhydrous; Glycerin,anhydrous; Glycerine; Glycerol; Monoctanoin component D; Propanetriol; Trihydroxypropane","C3H8O3","OCC(O)CO","A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism.","56-81-5","92.0938","It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent.","Glycerin is commonly classified as an osmotic laxative but may act additionally or alternatively through its local irritant effects; it may also have lubricating and fecal softening actions. Glycerin suppositories usually work within 15 to 30 minutes.","When administered rectally, glycerin exerts a hygroscopic and/or local irritant action, drawing water from the tissues into the feces and reflexively stimulating evacuation. \r\nGlycerin decreases intraocular pressure by creating an osmotic gradient between the blood and intraocular fluid, causing fluid to move out of the aqueous and vitreous humors into the bloodstream.","Peroxisome proliferator-activated receptor delta agonist; Group IIE secretory phospholipase A2; Inositol-3-phosphate synthase 1; Alcohol dehydrogenase 1B; Inositol 1,4,5-trisphosphate receptor type 1; Glycodelin; Alpha-N-acetylgalactosaminidase; ADP-ribosylation factor 1; Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 1; DNA mismatch repair protein MutL; Ribonucleoside-diphosphate reductase 1 subunit beta; A/G-specific adenine glycosylase; tRNA (cytosine(38)-C(5))-methyltransferase; Maleylacetoacetate isomerase","Target associated"]
[1313,"DB09477","approved","small molecule","Enalaprilat","Enalaprilat; Enalaprilat anhydrous","C18H24N2O5","[H][C@@](C)(N[C@@]([H])(CCC1=CC=CC=C1)C(O)=O)C(=O)N1CCC[C@@]1([H])C(O)=O","Enalaprilat is the active metabolite of the orally available pro-drug, . Used in the treatment of hypertension, enalapril is an ACE inhibitor that prevents Angiotensin Converting Enzyme (ACE) from transforming angiotensin I into angiotensin II. As angiotensin II is responsible for vasoconstriction and sodium reabsorption in the proximal tubule of the kidney, down-regulation of this protein results in reduced blood pressure and blood fluid volume. Enalaprilat was originally created to overcome the limitations of the first ACE inhibitor, captopril, which had numerous side effects and left a metallic taste in the mouth. Removal of the problematic thiol group from captopril resulted in enalaprilat, which was then modified further with an ester to create the orally available pro-drug enalapril.\r\n\r\nEnalaprilat is poorly orally available and is therefore only available as an intravenous injection for the treatment of hypertension when oral therapy is not possible.","76420-72-9","348.3936","Enalaprilat injection is indicated for the treatment of hypertension when oral therapy is not practical.","Enalaprilat injection results in the reduction of both supine and standing systolic and diastolic blood pressure, usually with no orthostatic component. Symptomatic postural hypotension is therefore infrequent, although it might be anticipated in volume-depleted patients. The onset of action usually occurs within fifteen minutes of administration with the maximum effect occurring within one to four hours. The abrupt withdrawal of enalaprilat has not been associated with a rapid increase in blood pressure.\r\nThe duration of hemodynamic effects appears to be dose-related. However, for the recommended dose, the duration of action in most patients is approximately six hours.\r\nFollowing administration of enalapril, there is an increase in renal blood flow; glomerular filtration rate is usually unchanged. The effects appear to be similar in patients with renovascular hypertension.","Enalaprilat is the active metabolite of the orally available pro-drug, enalapril. Used in the treatment of hypertension, enalapril is an ACE inhibitor that prevents Angiotensin Converting Enzyme (ACE) from transforming angiotensin I into angiotensin II. As angiotensin II is responsible for vasoconstriction and sodium reabsorption in the proximal tubule of the kidney, down-regulation of this protein results in reduced blood pressure and blood fluid volume","Angiotensin-converting enzyme inhibitor; B1 bradykinin receptor","Indication associated"]
[1314,"DB09496","approved; investigational","small molecule","Octinoxate","ethylhexyl methoxycinnamate; ethylhexyl p-methoxycinnamate; Octinoxate; octyl methoxycinnamate; parsol","C18H26O3","[H]\\C(=C(\\[H])C1=CC=C(OC)C=C1)C(=O)OCC(CC)CCCC","Octinoxate is a cinnamate ester and common ingredient in sunscreen and other skin care products to minimize DNA photodamage. It was originally developed in 1950's as an organic UV-B filter that absorbs UV-B rays from sun. It is often combined with nanoparticles or other water-resistant liposomes in formulations to increase the localization at the epidermis and decrease the risk of percutaneous absorption. Its use in pharmaceutical and cosmetic formulations is approved by FDA.","5466-77-3","290.3972","As an active ingredient in sunscreens and lip balms. Used for protection against damaging effects of sun rays.","Acts as a photoprotective agent that protects the skin by preventing and minimizing the damaging effects of ultraviolet (UV) rays of natural light. The cellular effects of UV irradiation include DNA damage, cell cycle arrest, immunological depression, apoptosis, and transcriptional changes .","Absorbs UV-B (predominantly) and UV-A rays while accumulating in the outermost layer of the epidermis. Like any other photoprotective agents, octinoxate prevents the damage to cells and deoxyribonucleic acid (DNA) by reducing the p53 protein expression following UV exposure  and also increases the skin's tolerability to UV rays .",null,"Therapeutic strategy associated"]
[1315,"DB09502","approved; investigational","small molecule","Fludeoxyglucose (18F)","(18F)-FDG; 18-F FDG; 18F-FDG; Fludeoxyglucose (18F); Fludeoxyglucose F 18; Fludeoxyglucose F-18; Fludeoxyglucose, F-18; Fluorine (18F) fludeoxyglucose","C6H11FO5","[H]C(=O)[C@H]([18F])[C@@H](O)[C@H](O)[C@H](O)CO","Fludeoxyglucose F 18 Injection is a positron emitting radiopharmaceutical containing no-carrier added radioactive 2-deoxy-2-fluoro-D-g1ucose, which is used for diagnostic purposes in conjunction with Positron Emission Tomography (PET). It is administered by intravenous injection.","63503-12-8","181.15","The uptake of 18F-FDG by tissues is a marker for the tissue uptake of glucose, which in turn is closely correlated with certain types of tissue metabolism.\r\nFludeoxyglucose F 18 Injection is indicated in positron emission tomography (PET) imaging for assessment of abnormal glucose metabolism to assist in the evaluation of malignancy in patients with known or suspected abnormalities found by other testing modalities, or in patients with an existing diagnoses of cancer.","Fludeoxyglucose F 18 Injection is rapidly distributed to all organs of the body after intravenous administration. After background clearance of Fludeoxyglucose F 18 Injection, optimal PET imaging is generally achieved between 30 to 40 minutes after administration.\r\nIn cancer, the cells are generally characterized by enhanced glucose metabolism partially due to (1) an increase in the activity of glucose transporters, (2) an increased rate of phosphorylation activity, (3) a reduction of phosphatase activity or, (4) a dynamic alteration in the balance among all these\r\nprocesses. However, glucose metabolism of cancer as reflected by Fludeoxyglucose F 18 accumulation shows considerable variability. Depending on tumor type, stage, and location, Fludeoxyglucose F 18 accumulation may be increased, normal, or decreased. Also, inflammatory cells can have the same variability of uptake of Fludeoxyglucose F 18.\r\nIn the heart, under normal aerobic conditions, the myocardium meets the bulk of its energy requirements by oxidizing free fatty acids. Most of the exogenous glucose taken up by the myocyte is converted into glycogen. However, under ischemic conditions, the oxidation of free fatty acids decreases, exogenous glucose becomes the preferred myocardial substrate, glycolysis is stimulated, and glucose taken up by the myocyte is metabolized immediately instead of being converted into glycogen. Under these conditions, phosphorylated Fludeoxyglucose F 18 accumulates in the myocyte and can be detected with PET imaging.\r\nNormally, the brain relies on anaerobic metabolism. In epilepsy, the glucose metabolism varies. Generally, during a seizure glucose metabolism increases. Interictally, the seizure focus tends to be hypometabolic.","Fludeoxyglucose F 18 is a glucose analog that concentrates in cells that rely upon glucose as an energy source, or in cells whose dependence on glucose increases under pathophysiological conditions. Fludeoxyglucose F 18 is transported through the cell membrane by facilitative glucose transporter proteins and is phosphorylated within the cell to  FDG-6- phosphate by the enzyme hexokinase. Once phosphorylated it cannot exit until it is dephosphorylated by glucose-6-phosphatase. Therefore, within a given tissue or pathophysiological process, the retention and clearance of Fludeoxyglucose F 18 reflect a balance involving glucose transporter, hexokinase and glucose-6- phosphatase activities. When allowance is made for the kinetic differences between glucose and Fludeoxyglucose F 18 transport and phosphorylation (expressed as the “lumped constant” ratio), Fludeoxyglucose F 18 is used to assess glucose metabolism.\r\nIn comparison to background activity of the specific organ or tissue type, regions of decreased or absent uptake of Fludeoxyglucose F 18 reflect the decrease or absence of glucose metabolism. Regions of increased uptake of Fludeoxyglucose F 18 reflect greater than normal rates of glucose metabolism.",null,"Therapeutic strategy associated"]
[1316,"DB09532","approved","biotech","Secretin human","Human secretin; Secretin; Secretin (human); Secretin human; Secretin synthetic human; Synthetic human secretin",null,null,"Human secretin is a gastrointestinal peptide hormone that regulates secretions in the stomach, pancreas, and liver. The hormone is produced from the enterochromaffin cells in the duodenum in response to the duodenal content with the pH less than 4.5 . The main action of secretin is to stimulate the pancreas to secrete pancreatic juice for pH regulation in the small intestines. Secretin is also responsible in body fluid homeostasis  and bile production. Although it is a gastrointestinal hormone, secretin is also considered as a neuropeptide hormone since it is also expressed in the central nervous system .\r\n\r\nPurified synthetic human secretin, also referred to as RG1068, is available as an intravenous injection under the market name ChiRhoStim ® in the U.S.. It contains an amino acid sequence identical to the naturally occurring hormone consisting of 27 amino acids  that supports α-helical formation .  The carboxyl-terminal amino acid, valine, is amidated. Synthetic human secretin displays equivalent biological activity and properties as naturally-occurring secretin . It is indicated for the stimulation of the pancreatic and gastric secretions to aid in the diagnosis of pancreatic exocrine dysfunction and the diagnosis of gastrinoma, and facilitate the identification of the ampulla of Vater and accessory papilla during endoscopic retrograde cholangiopancreatography (ERCP).","108153-74-8",null,"Indicated for the stimulation of:\r\n\r\n- pancreatic secretions, including bicarbonate, to aid in the diagnosis of pancreatic exocrine dysfunction .\r\n\r\n- gastrin secretion to aid in the diagnosis of gastrinoma .\r\n\r\n- pancreatic secretions to facilitate the identification of the ampulla of Vater and accessory papilla during endoscopic retrograde cholangiopancreatography (ERCP) .","In clinical trials, intravenous administration of synthetic human secretin stimulated the exocrine pancreas to promote juice and bicarbonate secretion, with variable responses depending on the pancreatic function of the individual . Having an identical amino acid sequence to the biologically-derived secretin, synthetic human secretin exhibits an equivalent biological activity as the natural hormone. The biological activity of synthetic human secretin was approximately 5.0 CU per mcg . In patients with suspected or known exocrine pancreatic dysfunction, a volume response of less than 2 mL/kg/hr, peak bicarbonate concentration of less than 80 mEq/L, and a bicarbonate output of less than 0.2 mEq/kg/hr following intravenous synthetic human secretin . Administration in healthy subjects in three crossover studies led to overall pancreatic secretory response of a mean peak bicarbonate concentration of 100 mEq/L, a mean total volume over one hour of 260.7 mL, and a peak bicarbonate concentrations ≥ 80 mEq/L . \r\n\r\nIn a baseline-controlled study of patients with acute and acute recurrent pancreatitis undergoing magnetic resonance cholangiopancreatography (MRCP), administration of synthetic human secretin resulted in higher levels of sensitivity with minimal loss in specificity. This indicates that the stimulation of pancreatic secretions by synthetic secretin facilitates the diagnosis and clinical decision making of patients acute, acute recurrent, or chronic pancreatitis .","Synthetic human secretin mediates the same biological effects as the naturally-occurring gastrointestinal peptide hormone. Secretin is normally released from enterochromaffin cells and S cells in the intestinal mucosa of duodenum upon exposure of proximal intestinal lumen to the acidic gastric content, or fatty acids and amino acids . Secretin mediates an inhibitory effect on acid secretion by parietal cells of the stomach, and causes alkalinazation of the duodenal content by stimulating the release of pancreatic juice, which has high amounts of water and bicarbonate ions . Bicarbonate ions are released into the duodenum from the centroacinar cells, and epithelia lining the pancreatic and biliary ducts . Human secretin is a ligand at G-protein coupled secretin receptors which are expressed in the basolateral domain of several tissue cell types , including pancreas, stomach, liver, colon and other tissues . Upon interaction, levels of cAMP increase and initiates the cAMP-mediated signalling cascade that results in phosphorylation of protein kinase A (PKA) and activation of cystic fibrosis transmembrane conductance regulator (CFTR) . Activation of CFTR activates Cl-/HCO3- anion exchanger 2 and leads to secretion of bicarbonate-rich-pancreatic fluid . Via the same cAMP signalling pathway, secretin promotes the secretion of water and electrolytes in cholangiocytes . Secretin may work through vagal-vagal neural pathways since stimulation of the efferent vagus nerve stimulates bicarbonate secretion and atropine blocks secretin-stimulated pancreatic secretion . Additionally, secretin acts as a diuretic to increase urinary volume and bicarbonate excretion .","Secretin receptor ligand","Therapeutic strategy associated"]
[1317,"DB09543","approved; vet_approved","small molecule","Methyl salicylate","2-(Methoxycarbonyl)phenol; 2-Carbomethoxyphenol; 2-Hydroxybenzoic acid methyl ester; Betula oil; Gaultheria oil; Methyl 2-hydroxybenzoate; Methyl o-hydroxybenzoate; Methyl salicylate; Natural wintergreen oil; Oil of wintergreen; Spicewood Oil; Sweet birch oil; Teaberry oil","C8H8O3","COC(=O)C1=CC=CC=C1O","Methyl salicylate (oil of wintergreen or wintergreen oil) is an organic ester naturally produced by many species of plants, particularly wintergreens. The compound was first extracted and isolated from plant species Gaultheria procumbens in 1843. It can be manufactured synthetically and it used as a fragrance, in foods, beverages, and liniments. It forms a colorless to yellow or reddish liquid and exhibits a characteristic odor and taste of wintergreen. For acute joint and muscular pain, methyl salicylate is used as a rubefacient and analgesic in deep heating liniments. It is used as a flavoring agent in chewing gums and mints in small concentrations and added as antiseptic in mouthwash solutions.","119-36-8","152.1473","Ointments or liniments containing methyl salicylate are applied topically as counter irritant for relief of acute pain associated with lumbago,sciatica and rheumatic conditions. Local analgesics for human and veterinary medicine.","Methyl salicylate relieve musculoskeletal pain in the muscles, joints, and tendons by causing irritation and reddening of the skin due to dilated capillaries and increased blood flow. It is pharmacologically similar to aspirin and other NSAIDs but as a topical agent it primarily acts as a rubefacient and skin irritant. Counter-irritation is believed to cause a soothing sensation of warmth.","Counter-irritation is thought to be effective at alleviating musculoskeletal pain as the irritation of the sensory nerve endings is thought to alter or offset pain in the underlying muscle or joints that are served by the same nerves . This is thought to mask the underlying musculoskeletal pain and discomfort. When applied topically, methyl salicylate is thought to penetrate the skin and underlying tissues where it reversibly inhibits cyclooxygenase enzyme and locally and peripherally prevents the production of inflammatory mediators such as prostaglandin and thromboxane A2.",null,"Therapeutic strategy associated"]
[1318,"DB09564","approved","biotech","Insulin degludec","Insulin degludec",null,null,"Insulin degludec is an ultra-long-acting form of insulin used for the treatment of hyperglycemia caused by Type 1 and Type 2 Diabetes. Insulin is typically prescribed for the management of diabetes mellitus to mimic the activity of endogenously produced human insulin, a peptide hormone produced by beta cells of the pancreas that promotes glucose metabolism. Insulin is released from the pancreas following a meal to promote the uptake of glucose from the blood into internal organs and tissues such as the liver, fat cells, and skeletal muscle. Absorption of glucose into cells allows for its transformation into glycogen or fat for storage. Insulin also inhibits hepatic glucose production, enhances protein synthesis, and inhibits lipolysis and proteolysis among many other functions.\r\n\r\nInsulin is an important treatment in the management of Type 1 Diabetes (T1D) which is caused by an autoimmune reaction that destroys the beta cells of the pancreas, resulting in the body not being able to produce or synthesize the insulin needed to manage circulating blood sugar levels. As a result, people with T1D rely primarily on exogenous forms of insulin, such as insulin degludec, to lower glucose levels in the blood. Insulin is also used in the treatment of Type 2 Diabetes (T2D), another form of diabetes mellitus that is a slowly progressing metabolic disorder caused by a combination of genetic and lifestyle factors that promote chronically elevated blood sugar levels. Without treatment or improvement in non-pharmacological measures such as diet and exercise to lower blood glucose, high blood sugar eventually causes cellular resistance to endogenous insulin, and in the long term, damage to pancreatic islet cells. Insulin is typically prescribed later in the course of T2D, after several oral medications such as , , or  have been tried, when sufficient damage has been caused to pancreatic cells that the body is no longer able to produce insulin on its own. \r\n\r\nMarketed as the brand name product Tresiba, insulin degludec has a duration of action up to 42 hours allowing for once-daily dosing, typically at bedtime. Due to its duration of action, Tresiba is considered \"basal insulin\" as it provides low concentrations of background insulin that can keep blood sugar stable between meals or overnight. Basal insulin is often combined with short-acting \"bolus insulin\" such as , , or  to provide higher doses of insulin required following meals. Use of basal and bolus insulin together is intended to mimic the pancreas' production of endogenous insulin, with a goal of avoiding any periods of hypoglycemia.\r\n\r\nCompared to endogenous insulin, insulin degludec has an added hexadecanedioic acid on lysine at the B29 position which allows for the formation of multi-hexamers. When injected subcutaneously, these multi-hexamers form a drug depot store from which monomers are slowly and continuously absorbed into the circulation. As a result, Insulin Degludec has a protracted time action profile due to the delayed absorption from subcutaneous tissue depots into the systemic circulation. Compared to available long-acting analogues such as  and , which have a duration of action of 20-24 hours, insulin degludec provides a consistent level of basal insulin over 42 hours with a low peak:trough ratio. Limitations of shorter acting analogues include more frequent dosing and less stable pharmacokinetics, which may negatively impact patient adherence and glucose control, particularly nocturnal control.\r\n\r\nWithout an adequate supply of insulin to promote absorption of glucose from the bloodstream, blood sugar levels can climb to dangerously high levels and can result in symptoms such as fatigue, headache, blurred vision, and increased thirst. If left untreated, the body starts to break down fat, instead of glucose, for energy which results in a build-up of ketone acids in the blood and a syndrome called ketoacidosis, which is a life-threatening medical emergency. In the long term, elevated blood sugar levels increase the risk of heart attack, stroke, and diabetic neuropathy.\r\n\r\nInsulin Degludec was approved by the FDA in September 2015 as the product Tresiba, for use in providing glycemic control to adults with diabetes mellitus.","844439-96-9",null,"Insulin degludec is indicated to improve glycemic control in patients 1 year of age and older with diabetes mellitus.","Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, the pancreas produces a continuous supply of low levels of basal insulin along with spikes of insulin following meals. Increased insulin secretion following meals is responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by the liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin detemir is a long-acting insulin analogue with a flat and predictable action profile. It is used to mimic the basal levels of insulin in diabetic individuals. The onset of action of insulin detemir is 1 to 2 hours and its duration of action is up to 24 hours. Interestingly, it has a lower affinity (30%) for the insulin receptor than human insulin.","Insulin detemir binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signalling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism and catabolism.","Insulin receptor agonist; Insulin-like growth factor 1 receptor activator","Indication associated"]
[1319,"DB09568","approved; investigational","small molecule","Omega-3-carboxylic acids","Omega-3-carboxylic acids",null,null,"The omega-3 carboxylic acid (OM3-CA) is a new formulation of omega-3 fatty acids that present an enhanced bioavailability in the treatment of dyslipidemia.  The increased bioavailability is explained because OM3-CA is found in a form of polyunsaturated free fatty acids as opposed to other products whose form is as ethyl esters. It is a complex mixture of the free fatty acids form containing eicosapentaenoic acid and docosahexaenoic acid as the most abundant species found in a proportion of 55% and 20% respectively. The rest of the concentration is represented by docosapentaenoic acid and traces of some other components such as alpha-tocopherol, gelatin, glycerol, sorbitol and purified water. It was developed by AstraZeneca Pharmaceuticals and firstly approved by the FDA on May 05, 2014.",null,null,"OM3-CA is indicated as an adjunct to diet to reduce triglycerides levels in adults patients with severe hypertriglyceridemia (>500 mg/dL). The patients involved in this treatment should be laced with an appropriate lipid-lowering diet.\r\n\r\nHypertriglyceridemia is defined as an elevated plasma triglyceride concentration. It is usually correlated to other secondary conditions such as poor diet, alcohol use, obesity, metabolic syndrome and type 2 diabetes.","OM3-CA is very effective in reducing triglyceride levels. After 14 days of treatment, it is possible to observe even a 21% reduction. The reduction of the triglycerides could reach even to 25% in cases with the maximal used concentration of 4 g.","The reduction of the synthesis of triglycerides in the liver may be caused because the main components of OM3-CA, eicosapentaenoic acid, and docosahexaenoic acid, are poor substrates for the enzymes responsible for the synthesis of triglycerides. These two major components inhibit the esterification of other fatty acids. OM3-CA is also thought to enhance the clearance of triglycerides from the circulating very low-density lipoprotein particles by different potential effects such as inhibition of acyl-CoA:1,2-diacylglycerol acyltransferase, increase in mitochondrial and peroxisomal beta-oxidation in the liver, decrease lipogenesis in the liver and increase lipoprotein lipase activity.","Diacylglycerol O-acyltransferase 2 antagonist; 3-hydroxyacyl-CoA dehydrogenase type-2 potentiator; Enoyl-CoA hydratase, mitochondrial potentiator; Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial potentiator; Elongation of very long chain fatty acids protein 4 potentiator; Lipoprotein lipase stimulator","Therapeutic strategy associated"]
[1320,"DB09570","approved; investigational","small molecule","Ixazomib","Ixazomib","C14H19BCl2N2O4","CC(C)C[C@H](NC(=O)CNC(=O)C1=CC(Cl)=CC=C1Cl)B(O)O","Ixazomib a second generation proteasome inhibitor (PI) and the first oral PI approved by the FDA in November 2015 for multiple myeloma treatment in combination with 2 other therapies (lenalidomide and dexamethasone) for patients who have received at least 1 prior therapy. It was found to have similar efficacy to bortezomib (the first PI approved for multiple myeloma therapy) in the control of myeloma growth and prevention of bone loss. Ixazomib citrate is marketed by Takeda Pharmaceuticals under the brand name Ninlaro, which is a prodrug that becomes quickly converted to its active metabolite, ixazomib, after administration.","1072833-77-2","361.03","Ixazomib is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy.","In vitro studies have shown ixazomib to induce apoptosis in multiple myeloma cells sensitive or resistant to other conventional therapies. In mouse xenograft models, ixazomib induced tumor growth inhibition.","Ixazomib is an N-capped dipeptidyl leucine boronic acid which reversibly inhibits the CT-L proteolytic (β5) site of the 20S proteasome. At higher concentrations, ixazomib also seems to inhibit the proteolytic β1 and β2 subunits and to induce accumulation of ubiquitinated proteins.",null,"Therapeutic strategy associated"]
[1321,"DB10552","approved","biotech","Peach","PEACH ALLERGENIC EXTRACT",null,null,"Peach allergenic extract is used in allergenic testing.",null,null,"For the treatment of Pneumococcal pneumonia due to susceptible strains and group A beta-hemolytic streptococcal infections of the upper respiratory tract.","Troleandomycin is a macrolide antibiotic that is similar to erythromycin. It is active in vitro against the following gram-positive organisms: *Streptococcus pyogenes* and *Diplococcus pneumoniae*.","Troleandomycin acts by penetrating the bacterial cell membrane and reversibly binding to the 50 S subunit of bacterial ribosomes or near the \"P\" or donor site so that binding of tRNA (transfer RNA) to the donor site is blocked. Translocation of peptides from the \"A\" or acceptor site to the \"P\" or donor site is prevented, and subsequent protein synthesis is inhibited.",null,"Indication associated"]
[1322,"DB10770","approved","biotech","Foreskin fibroblast (neonatal)","foreskin fibroblast, neonatal",null,null,"Foreskin fibroblast-like stromal cells (FDSCs) are progenitors isolated from human tissue that can differentiate into various cell types .\r\n\r\nAlso known as Dermagraft, this device is a cryopreserved human fibroblast-derived dermal substitute. Composed of fibroblasts, extracellular matrix, and a bioabsorbable scaffold, it effectively supports wound healing .\r\n\r\nDermagraft has only been available in the United States as an investigational device (IDE). Dermagraft for the treatment of diabetic foot ulcers was approved for sale in Canada in 1997. Dermagraft was introduced in the United Kingdom in October 1997, and several other European countries, as well as New Zealand and Australia. The device is available for commercial distribution in Australia, Canada, Finland, France, Hong Kong, Ireland, The Netherlands, New Zealand, Singapore, and The United Kingdom .\r\n\r\nThe impact of diabetic foot ulcers (DFU) on individuals and society is devastating. Failure to observe proper wound care in this condition often results in amputation. If wound closure is achieved, it is likely to delay the need for surgical intervention and provide other benefits such as improvements in productivity, mental outlook, social interactions, and time at work, in addition to decreased mortality .\r\n\r\nInterestingly, it has been shown that human foreskin cells possess immunosuppressive properties, which are mediated by other processes than that reported for bone marrow/stromal stem cells .  Dermagraft has been combined with  to create a drug beneficial to patients with open burn wounds .",null,null,"This device is indicated for use for the treatment of full-thickness,  diabetic foot ulcers greater than six weeks duration which extends through the dermis, but without tendon, muscle, joint capsule or bone exposure. This drug should be used in conjunction with standard wound care regimens and in patients with an adequate blood supply to the involved foot .\r\n\r","This physiologically active dermal substitute is a scaffold upon which tissue can grow, allowing for effective healing of wounds .\r\n\r\nDermagraft is made from human fibroblast cells obtained from newborn foreskin tissue. During the manufacturing process, the human fibroblasts are placed onto a bioabsorbable polyglactin mesh scaffold. The fibroblasts grow to fill the interstices of this scaffold and secrete human dermal collagen, matrix proteins, and growth factors, as well as cytokines. This creates a three-dimensional human dermal substitute containing active, living cells. Dermagraft does not contain macrophages, lymphocytes, blood vessels, or hair follicles .\r\n\r\nAmong other cytokines, this device induces the production of interleukin 6 (IL-6). This gene encodes a cytokine that functions in inflammation and the maturation of B type immune cells. In addition the above, the encoded protein has been shown to be an endogenous pyrogen capable of inducing fever in people with autoimmune diseases or infections. The protein is mainly produced at sites of acute and chronic inflammation, where it is secreted into the serum and induces a transcriptional inflammatory response through interleukin 6 receptor, alpha. The function this gene is involved in a wide variety of inflammation-associated disease states, including susceptibility to diabetes mellitus and systemic juvenile rheumatoid arthritis .\r","Dermagraft is a cryopreserved, human fibroblast-derived dermal substitute that contains fibroblasts, extracellular matrix, and a bioabsorbable polyglactin mesh scaffold . The fibroblasts are obtained from human newborn foreskin tissue. The fibroblasts are then placed on a scaffold and progress to proliferate and produce human dermal collagen, matrix proteins, growth factors, and cytokines. The above steps create a three-dimensional human dermal substitute with active human cells. Dermagraft does not contain macrophages, lymphocytes, blood vessels, nor hair follicles. It is available frozen as a single sheet (2 by 3 inches) for a single application .","Interleukin-6 agonist; Vascular endothelial growth factor receptor 1 agonist; Interleukin-1 receptor type 1 agonist; TGF-beta receptor type-2 agonist; Fibroblast growth factor 1 agonist; Interferon gamma agonist; Fibroblast growth factor receptor 2 agonist; Granulocyte-macrophage colony-stimulating factor receptor subunit alpha agonist; Platelet-derived growth factor receptor beta agonist; Transforming growth factor beta-1 agonist; Tumor necrosis factor agonist","Target associated"]
[1323,"DB10771","approved","biotech","Bovine type I collagen","Collagen Type I, Bovine",null,null,"Bovine collagen alpha-1 is a naturally occurring extracellular matrix protein which is found in tendons and other connective tissues. It plays a vital role in cell growth, differentiation, attachment, and migration .  Often combined with other ingredients, such as fibroblasts and keratinocytes, it allows for accelerated and effective wound healing , . \r\n\r\nExcellagen, a topical gel of bovine type I collagen, is used in the management of wounds including: partial and full- thickness wounds, pressure ulcers, venous ulcers, diabetic ulcers, chronic vascular ulcers, tunneled/undermined wounds, surgical wounds (donor sites/graft, post-Moh’s surgery, post-laser surgery, podiatric, wound dehiscence), trauma wounds (abrasions, lacerations, second-degree burns and skin tears) and draining wounds . \r\n\r\nBovine type I collagen is also used as a health supplement for bones and joints .\r\n\r\nInterestingly, bovine type I collagen has been studied as a possible endovascular stent material, and has demonstrated promising results in rabbits .","9050-08-2",null,"For the management of wounds including: partial and full- thickness wounds, pressure ulcers, venous ulcers, diabetic ulcers, chronic vascular ulcers, tunneled/undermined wounds, surgical wounds (donor sites/graft, post-Moh’s dermatological surgery, post-laser surgery, podiatric, wound dehiscence), trauma wounds (abrasions, lacerations, second-degree burns and skin tears) and draining wounds .\r\n\r\nGintuit (Allogeneic Cultured Keratinocytes and Fibroblasts in Bovine Collagen) is an allogeneic cellularized scaffold product indicated for topical (non-submerged) application to a surgically created vascular wound bed in the treatment of mucogingival conditions in adults. It uses bovine collagen as a matrix to support the growth of keratinocytes and fibroblasts in wound healing . Other products using bovine type 1 collagen include PriMatrix, Integra, Orcel and Matriderm .\r\n\r\nOrcel is a bilayered cellular matrix in which normal human allogeneic skin cells (both epidermal keratinocytes and dermal fibroblasts) are cultured in two separate layers into a Type I bovine collagen sponge, indicated in venous leg ulcers and diabetic foot. Type I bovine collagen acts as a matrix for the growth and proliferation of fibroblasts and keratinocytes, offering structure and support .\r\n\r\nIn the laboratory, bovine Collagen Type I purified protein standard is used as a control for SDS-PAGE, Western Blot, ELISA, immunoprecipitation, and for other immunological assays .","Collagen-based ingredients are very important for tissue engineering and regenerative medicine because of its superior human biocompatibility and low immunogenicity .\r\n\r\nBovine Collagen Type I belongs to a family of proteins found particularly in the flesh and connective tissues of mammals (approximately 1/3 of the body's total protein). More than two dozen types of collagen have been discovered; Type I is the most abundant form in the body. This type of collagen is found in scar tissue, tendons, the skin, arterial wall, the cornea, muscles, cartilage, and in certain parts of bones and teeth. Bovine Collagen Type I is ideal for investigators studying in extracellular matrix proteins and osteoporosis .\r\n\r\nType I collagen is the primary organic component of the extracellular matrix in the bone and can play an imperative role in bone tissue engineering. Type I collagen (bovine) is the basis of several laboratory and pharmaceutical products including Collapat II, Healos, Collagraft, and Biostite, among others .","Collagen is a fibrillar protein that forms the conjunctive and connective tissues in the human body, including the skin, joints, and bones. This molecule is one of the most predominant in many living organisms, owing to its connective role in biological structures .  \r\n\r\nCollagen as a general substance is the most abundant structural protein in the human body that provides support to numerous tissues such as tendons, skin, and teeth (collagen joined to mineral crystals). All proteins that have a structure based on three helix structured polypeptidic chains . Bovine collagen is used most frequently out of naturally-sourced collagen, due to its biocompatibility with human beings .\r\n\r\nWhen applied to a wound surface, bovine type I collagen absorbs wound fluid and maintains a moist wound environment, which is optimal for healing .\r\n\r\nNumerous studies have demonstrated that the use of type I collagen matrices is capable of promoting osteogenic differentiation and mineralization of marrow stromal cells as well as human adipose stem cells. Another study demonstrated that a collagen scaffold (Gingistat) is appropriate for supporting the distribution of cells to form bone tissue .\r",null,"Indication associated"]
[1324,"DB10772","approved","biotech","Foreskin keratinocyte (neonatal)","foreskin keratinocyte, neonatal",null,null,"Skin, the largest organ of the human body, plays the main role in protecting the body from mechanical damage. It is composed of epidermal, dermal and hypodermal layers. The barrier function of the skin owed to its avascular epidermal layer, which is made mainly of keratinocytes. The keratinocytes form a stratified epithelium, with growing basal cells at the innermost layer and the keratinized, and mostly impermeable outer stratum corneum layer on the surface .\r\n\r\nForeskin keratinocytes are a form of skin cells that are cultured as a skin cell replacement for wounds, to accelerate wound closure and healing , . \r\n\r\nThe defining moment in skin culture was in 1975 when Rheinwald and Green successfully grew human keratinocytes on lethally irradiated murine fibroblasts. In 1981, O’Conner and his group utilized cultured autologous epithelium to coat burn defects for the first time. To construct a \"living\" alternative, a dermal substitute based on collagen I gel was created with mesenchymal cells such as fibroblasts. When an epidermal layer was added, this approach became known as \"skin equivalent\", \"composite culture\" or \"organotypical culture\" .\r\n\r\nForeskin keratinocytes are an important ingredient in several skin substitutes , used for various indications. \r\nKeratinocytes are derived from neonatal foreskins and used to create a drug called _Apligraf_, a mixture of  and keratinocytes. A gel made of bovine collagen is used as the matrix for cell growth and differentiation. Apligraf has been useful in the treatment of venous leg ulcers and diabetic foot ulcers, by increasing rates of wound healing and decreasing the time required for closure of wounds .\r\n\r\nOrcel, another skin substitute,  is similar to Apligraf since it contains both fibroblasts and keratinocytes derived from neonatal foreskin, but in addition, utilizes a type I collagen sponge as its matrix. It is used for grafting onto partial-thickness wounds, where it offers a favorable matrix for host cell migration .",null,null,"For chronic leg ulcers and diabetic foot .  \r\n\r\nOrcel is indicated for use with standard therapeutic compression for the treatment of non-infected partial and full-thickness skin ulcers due to venous insufficiency of greater than 1 month in duration and which have not effectively responded to conventional ulcer therapy. Orcel is also for use with standard diabetic foot ulcer care for the treatment of full-thickness neuropathic diabetic foot ulcers of greater than 3 weeks in duration which have not effectively responded to conventional ulcer therapy, and which extend through the dermis but without tendon, muscle, capsule or bone involvement .\r\n\r\n\r\n\r","Foreskin keratinocyte grafts lead to the re‐epithelialization of partial deep severe burns, thus allowing complete wound closure, and improves the condition of scars .","Foreskin keratinocytes promote the proliferation of epithelial (skin) cells. \r\nEpidermal keratinocytes (skin cells) are very specialized epithelial cells designed for a very specific function, which is the separation of the organism from its outside environment. To provide this protection, the cells synthesize precursors and assemble them into two distinct structures, the cornified envelope and keratin intermediate filaments. The intermediate filaments are formed by keratin monomers and the cornified envelope is assembled from a protein called _involucrin_ and several other proteins .\r\n\r\nThe following is a description of the mechanism of action of foreskin keratinocytes in various devices, while combined with other types of cells:\r\n\r\nOrcel (epidermal keratinocytes and dermal fibroblasts) are cultured in two separate layers into a Type I bovine collagen sponge. Donor dermal fibroblasts are cultured on and within the porous sponge side of the collagen matrix while keratinocytes, from the same donor, are also cultured on the covered, non-porous side of the collagen matrix. Orcel acts as an absorbable matrix, providing a fertile environment for host cell migration and has been shown to contain the following cell-expressed cytokines with growth factors: FGF-1 (bFGF), NGF, GM-CSF, IL-1α, IL-1β, IL-6, HGF, KGF-1 (FGF- 7), M-CSF, PDGF-AB, TGF-α, TGF-β1, TGF-β2, and VEGF. DNA analysis performed on two Orcel treated donor site patient tissue samples demonstrated no trace of allogeneic cell DNA after 2-3 weeks post-treatment. Orcel is manufactured under aseptic conditions from human neonatal foreskin tissue .\r\n\r\nApligraf is supplied as a living, bi-layered skin substitute: the epidermal layer is formed by human keratinocytes and has a well-differentiated stratum corneum; the dermal layer is composed of human fibroblasts in a bovine Type I collagen lattice. While matrix proteins and cytokines found in human skin are present in Apligraf, Apligraf does not contain Langerhans cells, melanocytes, macrophages, lymphocytes, blood vessels or hair follicles. In a 10 patient venous leg ulcer study to determine the longevity of Apligraf cells, 2 of 8 patients evaluated at 4 weeks demonstrated Apligraf DNA. Neither of these patients showed Apligraf DNA at 8 weeks .\r\n\r\nFor dental applications, Gintuit (Allogeneic Cultured Keratinocytes and Fibroblasts in Bovine Collagen) is an allogeneic cellularized scaffold product indicated for topical application to a surgically created vascular wound bed in the treatment of mucogingival conditions in adults .","Fibroblast growth factor 1 agonist; Epidermal growth factor receptor agonist; Granulocyte-macrophage colony-stimulating factor receptor subunit alpha agonist; Interleukin-1 beta agonist; Interleukin-6 agonist; Interferon gamma agonist; Fibroblast growth factor receptor 2 agonist; Platelet-derived growth factor receptor alpha agonist; TGF-beta receptor type-2 agonist; Transforming growth factor beta-1 agonist; Tumor necrosis factor agonist; Vascular endothelial growth factor A agonist","Target associated"]
[1325,"DB10989","approved","biotech","Hepatitis A Vaccine","Hepatitis A vaccine, inactivated",null,null,"Hepatitis A viral infection can lead to significant morbidity and mortality, with signs and symptoms that include anorexia, nausea, vomiting, and liver failure. Known by several trade names, such as Havrix and Twinrix, the Hepatitis A vaccine has been formulated for immunization against hepatitis A virus (HAV) infection and safely confers strong protection against the disease caused by infection with this virus. In the US, the approved vaccine is inactivated while live Hepatitis A vaccines are currently available in other countries.",null,null,"Hepatitis A vaccine is indicated for immunization against hepatitis A virus (HAV) infection in patients aged 12 months and older, and the first dose should be administered at least 2 weeks before expected exposure to the Hepatitis A virus.\r","Hepatitis A vaccine stimulates the immune-mediated production of anti-Hepatitis A antibodies, allowing for protection against Hepatitis A infection via the production of specific antibodies against the virus and other immune cells that prevent infection with Hepatitis A virus.","The administration of the hepatitis A vaccine leads to immune activation of lymphocytes, which proceed to engulf the hepatitis A antigen, leading to the release of inflammatory mediators that stimulate  B and T cells to attack the viral antigen. Following this stimulation, the B cells and T cells then differentiate into memory cells, antibody-producing B cells, cytotoxic T cells, and helper T cells to provide immunity against infection with Hepatitis A.","B-lymphocytes inducer","Therapeutic strategy associated"]
[1326,"DB11051","approved; investigational","biotech","Azficel-T","Autologous cultured fibroblasts; Azficel-T",null,null,"Azficel-T is an autologous cellular product composed of fibroblasts indicated for improvement of the appearance of moderate to severe nasolabial fold wrinkles in adults. Dermal fibroblasts are collected from the post-auricular biopsy tissue and aseptically expanded using standard tissue-culture procedures until sufficient cells for three doses are obtained . Expanded cells are then suspended in a cell medium. As a replacement for lost dermal constituents in the aging or skin deformation process, treatment with autologous fibroblasts has shown to improve wrinkle and acne scar appearance than with placebo treatment . Intradermal administration of autologous dermal fibroblasts into irradiated skin following surgical procedures was associated with an improved healing process of subsequent surgical wounds . Azficel-T is marketed in the US as Laviv for intradermal injection.",null,null,"Indicated for improvement of the appearance of moderate to severe nasolabial fold wrinkles in adults .","In clinical studies involving patients with moderate to severe bilateral nasolabial fold wrinkles, there was a substantial improvement in the wrinkle appearance . In a randomized multicenter, double-blind, placebo-controlled trial in subjects with bilateral moderate to severe acne scarring, treatment of autologous fibroblast treatment was associated with a significant improvement in the appearance of acne scars without permanent adverse reactions .","The mechanism of action of azficel-T, or autologous human fibroblasts, is not fully elucidated. Autologous fibroblasts correct dermal defects such as acne or other dermal conditions associated with aging, such as reduced elasticity. The importance of collagen matrix production by fibroblasts in maintaining skin integrity and reducing the appearance of scars has been highlighted. The appearance of acne scars is also associated with the loss of collagen at the site of inflammation following resolution of localized intense inflammation and wound healing associated with inflammatory acne . Fragmentation of the dermal collagen matrix occurs in the natural aging process; due to UV-induced photodamage and the actions of collagen-degrading enzymes (matrix metalloproteinases, MMPs) overtime, the structural integrity of the dermis and function of fibroblasts may be impaired . While fibroblasts are responsible in the synthesis, organization, regulation and the maintenance of collagen network, the function of fibroblasts are strongly dependent on the physical properties of collagen fibres, and vice versa . The aging process is associated with a reduced rate of collagen turnover and formation of modified crosslinks that normally give structural support for collagen fibres. These crosslinks prevent the removal of degraded collagen, leading to accumulation of collagen fragments within the extracellular matrix, and compromised structural and mechanical integrity of the dermis . Integrins that are expressed by the fibroblasts allow the cell to bind to collagen matrix and allow mechanical tension within fibroblasts and the collagenous matrix. In the presence of fragmented collagen, the fibroblasts lose attachment to the collagen matrix and collapse within the dermis and subsequently leads to reduced collagen production and increased production of MMPs . Autologous human fibroblasts have the ability to increase the formation of human collagen _in vivo_ and promote remodelling of pre-existing extracellular matrix in the scarred tissue . They may also decrease the degradation of collagen .",null,"Therapeutic strategy associated"]
[1327,"DB11068","approved","small molecule","Selenic acid",null,"H2O4Se","O[Se](O)(=O)=O","Selenic acid is an organic compound with the chemical formula H2SeO4. It may be found in over-the-counter daily dietary supplements as a source of , an essential trace mineral for human health.","7783-08-6","144.97","Indicated for use as a nutritional supplement.","is an essential trace mineral that plays a critical role in antioxidant actions, anti-inflammatory effects, immune function, and the production of active thyroid hormone .","is a constituent of selenoproteins thus has structural and enzymatic roles. It acts as an antioxidant via the actions of selenoproteins for protection against oxidative stress, and acts as a catayst for the production of active thyroid hormone . It may also play a role in sperm motility .",null,"Therapeutic strategy associated"]
[1328,"DB11073","approved","small molecule","Cetylpyridinium","1-hexadecylpyridinium","C21H38N","CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1","Cetylpyridinium is a quaternary ammonium with broad-spectrum antiseptic properties. Its salt form, cetylpyridinium chloride, is typically found as an active ingredient in mouthwashes, toothpastes, lozenges, throat sprays, breath sprays, and nasal sprays. In these products, it generally mediates an antiseptic activity and protective action against dental plaque and reducing gingivitis.","7773-52-6","304.541","Typically employed as the cetylpyridinium chloride salt, this compound is commonly used as an active ingredient in various over-the-counter mouthwashes, toothpastes, lozenges, and mouth sprays where it is generally indicated for antiseptic actions, gingivitis and plaque prevention, as well as action or prevention against some other oropharyngeal bacterial infections .","Cetylpyridinium chloride is considered a cationic disinfectant with properties and uses similar to other such cationic surfactants . In particular, cetylpyridinium chloride has demonstrated a rapid bactericidal and fungicide effect on gram-positive pathogens and yeasts, respectively . Cetylpyridinium chloride is subsequently utilized in a variety of preparations for the local treatment of minor infections . Despite the variety of formulations in which cetylpyridinium chloride may appear as an active ingredient, it is generally accepted that it only elicits a local effect  owing to the compound's relatively poor absorption by route of exposure .","When incorporated into mouthwashes, toothpastes, lozenges, or mouth sprays, cetylpyridinium chloride is expected to elicit a mechanism of action that decreases new dental plaque growth, decreases or removes existing dental plaque, diminishes the growth of pathogenic bacteria, and inhibits the production of virulence factors . Cetylpyridinium chloride is a quaternary ammonium compound that demonstrates a broad spectrum anti-bacterial activity . It possesses a cationic surface active agent surfactant which can absorb readily to oral surfaces . The molecules of this agent have both hydrophilic and hydrophobic groups . In action, the positively charged hydrophilic region of cetylpyridinium chloride molecules enables the compound to interact with microbial cell surfaces and even integrate into the bacterial cytoplasmic membrane . Consequently, there is a resultant disruption of bacterial membrane integrity causing a leakage of bacterial cytoplasmic components, interference with cellular metabolism, inhibition of cell growth, and ultimately - cell death . Moreover, cetylpyridinium chloride can also inhibit the synthesis of insoluble glucan by streptococcal glucosyltransferase, adsorb to pellicle-covered enamel, and inhibit co-adhesion of bacteria, and bind streptococcus mutans biofilms . This ability of cetylpyridinium chloride to be able to adsorb to pellicle covered enamel imparts substantivity to the compound molecules - that is retention in the mouth and continued antimicrobial activity for a period of time after rinsing . Taking these mechanisms into consideration, cetylpyridinium chloride may be considered an active ingredient that is effective in the treatment and prevention of bacterial or fungal disorders of the oropharyngeal cavity .",null,"Indication associated"]
[1329,"DB11079","approved","small molecule","Trolamine salicylate","Trolamine salicylate","C13H21NO6","OCCN(CCO)CCO.OC(=O)C1=CC=CC=C1O","Trolamine salicylate is an organic compound or a salt formed between triethanolamine and salicylic acid. Triethanolamine neutralizes the acidity of the salicylic acid. It is a topical analgesic used for temporary relief of minor pain associated with arthritis, simple backache, muscle strains, sprains, and bruises. Unlike other topical analgesics, trolamine salicylate has no distinct odor which improves patient acceptability . It also displays low systemic absorption upon dermal or topical administration  and has low skin irritant properties . As with other salicylates, trolamine salicylate is an inhibitor of cyclo-oxygenase (COX) enzymes with no reported selectivity towards a specific enzyme isoform. Trolamine salicylate serves as an active ingredient in topical over-the-counter products for temporary management of mild to moderate muscular and joint pains.","2174-16-5","287.312","Indicated for the temporary relief of aches, and pains of muscles and joints associated with backache, lumbago, strains, bruises, sprains and arthritic or rheumatic pain, pain of tendons and ligaments .","Trolamine salicylate is a salicylate that inhibits cyclo-oxygenase (COX) enzymes responsible for generating pro-inflammatory factors such as to induce pain and inflammation. It is thought to mediate its analgesic effect through inhibition of COX-2 enzyme, which is an induced enzyme responsible for inflammatory responses and pain in muscle and joint disorders. By inhibiting fatty acid COX enzyme, trolamine salicylate inhibits the production of prostaglandins and thromboxanes in inflammatory cells involved in generating pain and inflammation . It thereby works to temporarily reduce mild to moderate pain. In subjects with muscle soreness from exercise, administration of topical trolamine salicylate was associated with reduced duration and severity of muscule soreness compared to placebo . In subjects with osteoarthritis in hands, trolamine salicylate cream was shown to be effective in achieving temporary relief of minor pain and stiffness .","Inflammation and tissue damage in different conditions including arthritis, bursitis, joint disorder, bruises, and strains or sprains of muscle origin, induce mild to moderate pain and are associated with increase prostaglandin synthesis . This is thought to be a result of COX-2 enzyme induction. COX-2 is induced in inflammatory cells in case of cell injury, infection or activation from inflammatory cytokines such as interleukin (IL)-1 and tumor necrosis factor (TNF)-α. Upon activation, COX-2 produces prostanoid mediators of inflammation such as prostaglandins and thromboxanes . Trolamine salicylate mediates its analgesic effect by inhibiting the production of inflammatory mediators that sensitize nociceptive nerve endings and generate pain .","Prostaglandin G/H synthase 1 inhibitor; Prostaglandin G/H synthase 2 inhibitor","Therapeutic strategy associated"]
[1330,"DB11086","approved","biotech","Cocoa butter","Cacao butter; Cacao seed oil, fermented; Oil, cocoa butter; Oil,cocoa butter; Theobroma cacao (cocoa) seed butter; Theobroma cacao oil; Theobroma oil",null,null,"Cocoa butter is an edible natural fat obtained from the _Theobroma cocoa_ seeds that is predominantly found in dark chocolate . It is a rich source of monounsaturated and saturated fatty acids  that mainly contains approximately 33% , 25% , and 33%   but does not contain caffeine or theobromine. Fat cocoa solids, including cocoa butter, have lower phenolic content than non-fat cocoa solids but may contain some polyphenols of different structures of flavonoids with antioxidant properties .\r\n\r\nCocoa butter is included in chocolate and other food products, and can also be found in over-the-counter skin products such as lotions, creams, and bars intended to maintain skin softness. While cocoa butter has skin moisturizing properties, it was not shown to reduce the likelihood of developing of striae gravidarum, or stretch marks, in a double-blind, randomized clinical trial of women in the first trimester . Still, it is a common active ingredient for prevention of skin dryness in cosmetic and skincare products. Oftentimes cocoa butter is used in over-the-counter pharmaceutical products and suppositories. The lipid-lowering effects of cocoa butter have been studied and investigated, as fatty acid constituents of cocoa butter are known to exhibit lipid-lowering properties. Dyslipidemia is characterized by elevated levels of plasma triglyceride and very-low-density lipoprotein (VLDL) cholesterol due to overproduction of large triglyceride-enriched VLDL cholesterol particles . Cocoa butter has shown to reduce VLDL cholesterol levels in animal studies, suggesting its potential use in lipid disorders.","8002-31-1",null,"Indicated for topical use in over-the-counter skin products for the treatment of skin dryness and reduction of striae gravidarum (stretch marks).","In a rat study, treatment with 10% cocoa butter has been shown to lower liver cholesterol and triglyceride levels without affecting the serum cholesterol levels . Supplementation of cocoa butter reduced the level of creatinine _in vitro_, suggesting that cocoa butter may also beneficial to renal function via antioxidant effects .","Cocoa butter is comprised of saturated fatty acids that exert a neutral cholesterolemic response in humans .  is one of the major constituent in cocoa butter that is a non-atherogenic type of dietary saturated fat . Although it is a saturated fatty acid known to elevate plasma lipids and lipoproteins, stearic acid from plant sources differs from animal-derived sources of stearic acid . Possible explanations for this unique property may include chain length, inefficient absorption, metabolism kinetics, and hepatic desaturation of stearic into oleic acid . Apart from its lipid-lowering actions, stearic acid may also mediate actions on hemostasis and thrombosis which still remain inconclusive . _In vitro_, stearic acid was demonstrated to promote platelet aggregation and factor VII coagulant activity; however _in vivo_ preliminary studies mixed results . \r\n\r\nCocoa butter may contain flavonoids that elicit antioxidant, anti-platelet, anti-inflammatory effects, as well as possibly increasing HDL, lowering blood pressure, and improving endothelial function . They inhibit lipid peroxidation, scavenge reactive oxygen species, and attenuate photochemical overproduction of ROS thus minimize UV-induced photodamage and signs of aging on the skin .",null,"Therapeutic strategy associated"]
[1331,"DB11089","approved","small molecule","Docusate","Dioctyl sulfosuccinate; Docusate hydrogen","C20H38O7S","CCCCC(CC)COC(=O)CC(C(=O)OCC(CC)CCCC)S(O)(=O)=O","Docusate, or dioctyl sulfosuccinate, is a stool softener indicated for the treatment of constipation. Docusate acts by increasing the amount of water the stool absorbs in the gut, making the stool softer and easier to pass . Docusate can be orally or rectally administered. Docusate is on the World Health Organization's List of Essential Medicines. However the effectiveness of docusate in treating constipation remains unclear, as several studies report docusate to be no more effective than placebo for increasing the frequency of stool or stool softening . Recently there has been pressure to stop prescribing docusate as it has been identified as an ineffective medicine. Additionally, it does not appear to lessen symptoms associated with constipation such as abdominal cramps. Still docusate is available in over-the-counter products as a common laxative.","10041-19-7","422.577","Indicated for the treatment of constipation associated with dry, hard stools or opioid induced constipation. Though recently, pressure has been building to end the use of docusate over concerns of efficacy.","Docusate sodium is a laxative and an anionic detergent that supposedly promotes incorporation of water and fats into stool through a reduction in surface tension, resulting in softer fecal mass . Docusate's onset of action is 6-72 hours orally and 2-15 minutes rectally . The effects of docusate are thought to be exerted locally in the jejunum.","Recent studies suggest that docusate's mechanism of action is due largely to it's surfactant effect in the intestines, which allow fat and water into the feces to soften the stool.\r\n\r\nDocusate’s mechanism of action was investigated in 1985 on healthy patients. Docusate was added directly to the jejunum based on calculated concentrations of docusate in the jejunum. At this concentration, there was an increase in secretion of water, sodium, chloride, and potassium as well as a decrease in absorption of glucose and bicarbonate. Based on in vitro data, the authors suggested this effect was due to an increase in intracellular cyclic AMP either directly through docusate or E series prostaglandins.",null,"Indication associated"]
[1332,"DB11095","approved","biotech","Desirudin","63-Desulfohirudin; 63-Desulfohirudin (Hirudo Medicinalis Isoform HV1); 63-Desulfohirudin (recombinant); Desirudin; Desirudin recombinant; Hirudin desirudin",null,null,"Desirudin is a direct inhibitor of human thrombin. It has a protein structure that is similar to that of hirudin, the naturally occurring anticoagulant present in the peripharyngeal glands in the medicinal leech, Hirudo medicinalis. Hirudin is a single polypeptide chain of 65 amino acids residues and contains three disulfide bridges. Desirudin has a chemical formula of C287H440N80O110S6 with a molecular weight of 6963.52.\r\n\r\nIt is mainly indicated for the prevention of deep vein thrombosis in hip replacement surgery patients. \r\nCommon side effects include: Bleeding gums, collection of blood under the skin, coughing up blood, deep, dark purple bruise and difficulty with breathing or swallowing.","120993-53-5",null,"Indicated as prophylaxis of deep vein thrombosis for patients undergoing hip replacement surgery.","Desirudin results in dose-dependent prolongation of the activated partial thromboplastin time (aPTT).","Desirudin is a direct, highly selective thrombin inhibitor. Reversibly binds to the active thrombin site of free and clot-associated thrombin. Inhibits fibrin formation, activation of coagulation factors V, VII, and XIII, and thrombin-induced platelet aggregation resulting in a dose-dependent prolongation of the activated partial thromboplastin time (aPTT).",null,"Therapeutic strategy associated"]
[1333,"DB11100","approved","small molecule","Allantoin","(2,5-Dioxo-4-imidazolidinyl)urea; 2,5-Dioxo-4-imidazolidinyl-urea; 4-ureido-2,5-imidazolidinedione; 5-Ureido-2,4-imidazolidindione; 5-Ureidohydantoin; Allantoin; Glyoxyldiureide; N-(2,5-Dioxo-4-imidazolidinyl)urea","C4H6N4O3","NC(=O)NC1NC(=O)NC1=O","Allantoin is a substance that is endogenous to the human body and also found as a normal component of human diets . In healthy human volunteers, the mean plasma concentration of allantoin is about 2-3 mg/l. During exercise, the plasma allantoin concentration rapidly increases about two fold and remains elevated . In human muscle, urate is oxidized to allantoin during such exercise . The concentration of allantoin in muscles increases from a resting value of about 5000 ug/kg to about 16000 ug/kg immediately after short-term exhaustive cycling exercise . \r\n\r\nMore specifically, allantoin is a diureide of glyoxylic acid that is produced from uric acid. It is a major metabolic intermediate in most organisms. Allantoin is found in OTC cosmetic products and other commercial products such as oral hygiene products, in shampoos, lipsticks, anti-acne products, sun care products, and clarifying lotions . Allantoin has also demonstrated to ameliorate the wound healing process in some studies .","97-59-6","158.1154","Allantoin is commonly applied in a variety of topical vehicles or applications such as cosmetic creams, toothpastes, mouthwashes, shampoos, lipsticks, anti-acne products, and lotions  for the purpose of moisturizing skin, enhancing the smoothness of skin, stimulating the healing of wounds, and soothing irritated skin .","There is no well controlled and appropriate data that can formally substantiate the pharmacodynamic properties of allantoin . Nevertheless, ongoing studies suggest that allantoin possesses moisturizing and keratolytic effects, as well as abilities to increase the water content of the extracellular matrix and enhance the desquamation of upper layers of dead skin cells, all of which are activities that can promote cell proliferation and facilitate wound healing .","There is no well controlled data that can formally substantiate the method of action . However, ongoing studies suggest that there may exist a histological wound healing profile induced by allantoin in rats that leads to the amelioration and fastening of the reestablishment of normal skin . This facilitation of wound healing is supported by observations that wounds inflicted to rat subjects to which topical allantoin preparations were applied histologically demonstrated increased vasodilation, presence of inflammatory exudates, number of inflammatory cells, angiogenesis, fibroblast proliferation, and increased collagen deposition when compared to rat subjects with wounds that did not receive any allantoin administration .",null,"Therapeutic strategy associated"]
[1334,"DB11107","experimental","small molecule","Potassium bitartrate","Potassium bitartrate; potassium hydrogen tartrate","C4H5KO6","[K+].O[C@H]([C@@H](O)C([O-])=O)C(O)=O","Potassium bitartate, also referred to as potassium acid tartrate or cream of tartar, is the potassium acid salt of l-( + )-tartaric acid. It is obtained as a byproduct of wine manufacture during the fermentation process. Approved by the FDA as a direct food substance, potassium bitartrate is used as an additive, stabilizer, pH control agent, antimicrobial agent, processing aid, or thickener in various food products . Potassium bitartrate has a long history of medical use as a laxative administered as a rectal suppository and is an approved third-class OTC drug in Japan.\r\n\r\nPotassium bitartrate was one of active ingredients in Phexxi, a non-hormonal contraceptive agent that was approved by the FDA on May 2020.","868-14-4","188.176","Indicated for the treatment of constipation.","Potassium bitartrate potentiates bowel movements. In medical studies, it was shown to be an effective treatment for chronic constipationwhen combined with sodium bicarbonate in a polyethylene glycol-based suppository .","Potassium bitartrate is a carbon dioxide-releasing laxative that works by forming carbon dioxide gas, which creates a mechanical distension against the intestinal wall and induces bowel contractions. Rectal suppositories of carbon dioxide-releasing type of laxative were demonstrated to be useful and safe in the treatment of patients at risk for electrolyte disorders such as the elderly or patients with renal or cardiovascular disorders .",null,"Indication associated"]
[1335,"DB11110","approved","small molecule","Magnesium citrate","Magnesium citrate; Magnesium dicitrate; Trimagnesium citrate; Trimagnesium dicitrate","C12H10Mg3O14","[Mg++].[Mg++].[Mg++].OC(CC([O-])=O)(CC([O-])=O)C([O-])=O.OC(CC([O-])=O)(CC([O-])=O)C([O-])=O","Magnesium citrate is a low volume and osmotic cathartic agent. The cathartic action works primarily through the high osmolarity of the solution which draws large amounts of fluid into space where is used. Magnesium citrate is considered by the FDA as an approved inactive ingredient for approved drug products under the specifications of oral administration of a maximum concentration of 237 mg. It is also considered as an active ingredient in over-the-counter products.","3344-18-1","451.113","Magnesium citrate has been used in bowel preparations prior to a colonoscopy as a cathartic agent. \r\n\r\nIt is also used in over-the-counter products to relieve occasional constipation.\r\n\r\nMagnesium citrate can be one of the forms used for the administration of dietary supplements.","The onset of action can be as early as 30 minutes after administration with a mean onset time of approximately 2 hours and a maximum action of 4 hours. The effect of magnesium citrate is highly dependent on the individual's hydration status.","It mainly works through its property of high osmolality which will draw large amounts of fluid into the colonic lumen. There is also a possible stimulation of fluid excretion by cholecystokinin release and activation of muscle peristalsis.",null,"Indication associated"]
[1336,"DB11113","approved; investigational; nutraceutical; vet_approved","biotech","Castor oil","Agaliya oil; Bimayou; Castor oil; Castorbean oil; Cataputia major oil; Cataputia minor oil; Croton spinosus oil; Lama palagi oil; Maskerekur oil; Oleum ricini; Ricinus africanus oil; Ricinus angulatus oil; Ricinus armatus oil; Ricinus atropurpureus oil; Ricinus badius oil; Ricinus borboniensis oil; Ricinus cambodgensis oil; Ricinus communis (castor) seed oil; Ricinus communis castor seed oil; Ricinus communis fibre oil; Ricinus communis oil; Ricinus communis seed oil; Ricinus compactus oil; Ricinus digitatus oil; Ricinus europaeus oil; Ricinus gibsonii oil; Ricinus giganteus oil; Ricinus glaucus oil; Ricinus hybridus oil; Ricinus inermis oil; Ricinus japonicus oil; Ricinus krappa oil; Ricinus laevis oil; Ricinus lividus oil; Ricinus macrocarpus oil; Ricinus macrophyllus oil; Ricinus medicus oil; Ricinus medius oil; Ricinus messeniacus oil; Ricinus metallicus oil; Ricinus microcarpus oil; Ricinus minor oil; Ricinus nanus oil; Ricinus obermannii oil; Ricinus oil; Ricinus peltatus oil; Ricinus perennis oil; Ricinus persicus oil; Ricinus purpurascens oil; Ricinus ruber oil; Ricinus rugosus oil; Ricinus rutilans oil; Ricinus sanguineus oil; Ricinus scaber oil; Ricinus speciosus oil; Ricinus spectabilis oil; Ricinus tunisensis oil; Ricinus undulatus oil; Ricinus urens oil; Ricinus viridis oil; Ricinus vulgaris oil; Ricinus zanzibarensis oil; Ricinus zanzibarinus; Toto ni vavalagi oil; Uluchula skoki oil",null,null,"Castor oil is a vegetable oil obtained by pressing the seeds of the castor oil plant (_Ricinus communis_ L.) mainly cultivated in India, South America, Africa, and China. Castor oil is a rich source of , which represents up to 90% of the total castor oil content. It also consists up to 4% linoleic, 3% oleic, 1% stearic, and less than 1% linolenic fatty acids .  has a hydroxyl group that provides a functional group location for various chemical reactions, making it a favourable substance in industrial applications . Castor oil does not contain ricin, which is a natural poison found in the castor oil plant; the toxic lectin remains in the bean pulp following oil isolation . Due to its renewability and high versatility in addition to being the only commercial source of a hydroxylated fatty acid , castor oil has been used as a vital raw material for the chemical industry . Castor oil was mainly used in the manufacturing of soaps, lubricants, and coatings . It is an FDA-approved food additive directly added to food products for human consumption. It can also be found in hard candies as a release agent and anti-sticking agent, or supplementary vitamins and mineral oral tablets as an ingredient for protective coatings. Castor oil is found in over-the-counter oral liquids as a stimulant laxative, and is also added in commercial cosmetic, hair, and skincare products.","8001-79-4",null,"Indicated for over-the-counter use as a laxative for oral use and as a soothing agent for topical use on skin and hair.","Castor oil is a potent laxative that was shown to be effective for short-term constipation. In a prospective study, the group receiving oral castor oil was associated with a higher likelihood of initiation of labour compared to the placebo group . Castor oil is known to induce diarrhea, and has been used in studies to assess anti-diarrheal effect of some compounds .","Castor oil is a mix of triglycerides consisting of mainly ricinolein, linoleic acid, oleic acid, palmitic acid, stearic acid, dihydroxystearic acid, and traces of other fatty acids . The main pharmacodynamic effects of castor oil are mediated by ricinoleic acid, a hydroxylated fatty acid released from castor oil by intestinal lipases . It was believed that ricinoleic acid acts as an anionic surfactant that reduces net absorption of fluid and electrolytes, and stimulates intestinal peristalsis . However, a recent study suggests that ricinoleic acid interacts with EP3 prostanoid receptors expressed on intestinal and uterine smooth muscles. Via activating EP3 prostanoid receptors on intestinal and uterine smooth muscle cells, ricinoleic acid promotes laxation and uterus contraction, respectively . EP3 receptor act as the major prostanoid receptor in the intestine mediating propulsive effects on gut motility, and activation of EP3 receptors has been demonstrated to evoke contraction of uterine smooth muscle .","Prostaglandin E2 receptor EP3 subtype agonist&activator; Prostaglandin E2 receptor EP4 subtype agonist","Therapeutic strategy associated"]
[1337,"DB11114","approved","biotech","Eucalyptus oil","Blue gum leaf oil; Dinkum oil; Eucalyptus essential oil; Eucalyptus globulus leaf essential oil; Eucalyptus globulus leaf oil; Eucalyptus globulus leaf water; Eucalyptus globulus leaf/twig oil; Eucalyptus globulus oil; Eucalyptus globulus oil burundia; Eucalyptus globulus oil pakistan; Eucalyptus globulus oil rwanda; Eucalyptus globulus oil zambia; Eucalyptus leaf oil; Eucalyptus oil; Eucalyptus terpene oil; Eucalyptus volatile oil; Oil of eucalyptus; Southern blue gum leaf oil; Tasmanian blue gum leaf oil",null,null,"Eucalyptus oil is a distilled oil derived from the leaves of the tree Eucalyptus. It is shown to be effective in reducing pain, swelling, and inflammation via its modulatory effect on the immune response. It is also shown to exhibit antibacterial activity against some bacterial species and cough suppressant actions. Eucalyptus oil can be applied directly to the skin for pain and swelling of respiratory tract mucous membranes, joint pain, genital herpes, and nasal stuffiness.","8000-48-4",null,"As an active agent, eucalyptus oil has been indicated for relief of the symptoms of catarrhal colds, and/or the relief of the symptoms of minor muscular sprains and cramps .","Lipophilic monoterpene formulations of eucalyptus oil appear to be readily absorbed orally, with a primarily oxidative metabolism that might necessitate induction of the cytochrome P450 enzyme system and subsequent urinary excretion . Gastrointestinal absorption of eucalyptus appears to be rapid and may be enhanced by the intake of lipids and milk. 1,8-cineole (which makes up to as much as 90% of most commonly used cineole-based eucalyptus oils)  has also been found in vitro and in animals to possess cytochrome P450 inducing activity .","The general consensus is that the exact mechanism of action of eucalyptus oil is largely unknown at this time but comprises various hypotheses from various studies.\r\n\r\nCineol containing preparations of eucalyptus oil may contain up to 80% (or more) 1,8-cineole  and is one of the most common types of eucalyptus oil formulations used. As an active agent indicated for relieving certain cold symptoms and/or certain muscular sprains and cramps, it is believed that eucalyptus oil may possess some antimicrobial and anti-inflammatory activities.\r\n\r\nSome in vitro studies of human blood monocytes suggest a dose-dependent effect of eucalyptus oil to elicit significant inhibition of multiple cytokines, perhaps in the treatment of airway inflammation . Moreover, other studies in animal models discuss the possibility of eucalyptus oil demonstrating anti-inflammatory and anti-nociceptive effects that potentially account for inhibiting the formation of prostaglandins and cytokines by stimulated monocytes in vitro .\r\n\r\nFurthermore, additional studies have observed eucalyptus oil anti-viral activity against herpes simplex virus (HSV-1, HSV-2) in cell cultures as well as the demonstration of broad antimicrobial activity of eucalyptus medicinal plant extracts against Alicyclobacillus acidoterretris, Bacillus cereus, E. coli, Enterococcus faecalis, MRSA, Propionibacterium acnes, S. aureus, fungus including C. albicans isolates, Trichophyton mentagrophytes, and other Gram-positive bacteria. Specific activity against periodontopathic bacteria, such as Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, Streptococcus mutans, and Streptococcus sobrinus has also been observed .",null,"Therapeutic strategy associated"]
[1338,"DB11117","approved; investigational","small molecule","Undecylenic acid","10-undecenoic acid; Undecenoic acid; Undecylenate; Undecylenic acid","C11H20O2","OC(=O)CCCCCCCCC=C","Undecylenate, or undecylenic acid, is an unsaturated fatty acid with a terminal double bond that is derived from castor oil. Undecylenic acid is also found naturally in the human sweat. It is used as a precursor in the manufacture of aromatic chemicals, polymers or modified silicones . Undecylenic acid was first isolated from the products of distillation of castor oil in 1877 via pyrolysis of ricinoleic acid, and has been polymerized for vinyl production . It it suggested that many organic fatty acids exert fungicidal or fungistatic actions. Undecylenic acid also possesses antifungal properties, but is never used on its own for antifungal purposes. Salts of undecylenate are found in topical over-the-counter or mixture products as antifungal agents. Zinc undecylenate is an example of a topical antifungal agent that treats skin infections such as athlete’s foot and relieves itching, burning, and irritation associated with the skin condition. Due to its bifunctional properties, undecylenate is also used as a linking molecule to conjugate other biomolecules such as proteins. It serves as an acid moiety for anabolic steroid boldenone.","112-38-9","184.2753","Indicated for the treatment of fungal infections as a salt form. No therapeutic indications on its own.","Zinc undecylendate acts as a fungistatic agent but fungicidal activity may be observed with chronic exposure in high concentrations . It is effective against _Candida albicans_ . It is proposed that undecylenic acid exerts antimicrobial actions via interacting with nonspecific components in the cell membrane .","Undecylenic acid demonstrated effectiveness against _Candida albicans_, which is an opportunistic pathogenic yeast with two cellular morphologies: the round yeast form and the filamentous form with elongated hyphae. Hyphae formation is associated with active infections and virulence . A study proposed that undecylenic acid inhibits biofilm formation of _Candida albicans_ with optimal concentration above 3 mM and disrupts hyphal growth, which is the morphological transition from yeast to filamentous phase, at concentration above 4 mM . Under the drug treatment, hyphal formation related genes, like HWP1, were significantly reduced in transcriptional level leading to poor biofilm formation . Both biofilm and hyphae formation are critical virulence factors for the initiation of skin infection and late development of disseminated infection . Undecylenic acid may also inhibit enzyme involved in lipid metabolism and abolish germ tube formation by carrying protons across the plasma membrane, thus altering cytoplasmic pH .",null,"Therapeutic strategy associated"]
[1339,"DB11120","approved; experimental","small molecule","Turpentine","Gum turpentine; Spirits of gum turpentine; Turpentine (gum); Turpentine gum",null,null,"Turpentine, also known as spirit of turpentine, oil of turpentine, and wood turpentine, is a liquid extracted from live trees, mainly pine, through distillation of resin. It is used as a solvent and base material in organic synthesis reactions. Turpentine is composed of terpenes, mainly the monoterpenes alpha-pinene and beta-pinene with lesser amounts of carene, camphene, dipentene, and terpinolene.","9005-90-7",null,"Turpentine has been used experimentally in a bath for the treatment of disseminated sclerosis and sexual dysfunction. It also has been studied for its antibacterial activity and inhibition of osteoclast activity. Turpentine is utilized in experimental models of inflammation to induce a systemic inflammatory immune response in animals.","Turpentine oil, when inhaled, may help reduce congestion. When used on the skin, turpentine oil may cause warmth and redness that can help relieve pain in the tissue underneath.\r","Binding of turpentine oil or inflammatory cytokines e.g. interleukin-1 (IL-1) activate signalling through the IL-1 Type 1 receptor (IL-1 R1). Initiation occurs by binding of Toll-interleukin 1 receptor adaptor protein (TIRAP) and Myeloid differentiation primary response gene 88 (mD88) which then dissociates and interacts with IRAK (Interleukin 1 receptor associated kinase) and the tumour necrosis factor receptor associated factor 6 (TRAF6). This activates the MAPK pathway leading to transcription of the nuclear factor κB transcription factor and production of inflammatory mediators.","Mitogen-activated protein kinase 1","Therapeutic strategy associated"]
[1340,"DB11125","approved","small molecule","Benzethonium",null,"C27H42NO2","CC(C)(C)CC(C)(C)C1=CC=C(OCCOCC[N+](C)(C)CC2=CC=CC=C2)C=C1","Benzethonium is a synthetic quaternary ammonium salt with surfactant, antiseptic, and broad spectrum antimicrobial properties. Its salt form, benzethonium chloride, is primarily used as a skin disinfectant at concentrations of 0.1-0.2 %, which are safe and effective concentrations for the compound specified by the U.S. Food and Drug Administration (FDA). It is additionally found in cosmetics and toiletries such as mouthwashes and anti-itch ointments. It is shown to be effective in mediating its antimicrobial action against bacteria, fungi, mold and viruses. There is evidence that benzethonium acts as a spermatocide but may cause vaginal irritation . Benzethonium was identified as a novel cancer-specific compound by cell-based small-molecule screen .","10172-60-8","412.637","Indicated as an antiseptic agent. No therapeutic indications for clinical use.","Benzethonium belongs to the family of compounds known as cationic detergents that act by disrupting lipid bilayers. It demonstrated antitumor activity against cancer cell lines in vitro. The effective dose required to decrease cell viability by 50% after 48 hours (ED50) of benzethonium for FaDu (hypopharyngeal squamous cancer) and C666-1 (nasopharyngeal cancer) cell lines were approximately 3.8 and 5.3 μmol/L, respectively .","While exact mechanism of benzethonium is not fully understood, it is proposed that benzethonium acts similarly to other structurally-related quaternary ammonium compounds in disrupting cytoplasmic and outer membrane lipid bilayers of microorganisms . The positively charged quaternary nitrogen associates with the polar head groups of acidic membrane phospholipids, followed by the hydrophobic tail interacting with the hydrophobic membrane core. Benzethonium is thought to form mixed-micelle aggregates with hydrophobic membrane components that solubilize membrane and lyse the cells, leading to leakage of cytoplasmic contents . Based on findings in vitro cell assays, its mode of action on cancer cells may involve cancer cell apoptosis via dysregulating mitochondria or rough endoplasmic reticulum (rER) . It is proposed that intracellular cationic molecules such as benzethonium will create swelling of the rER and damage the organelle. Ultimately, there is a loss in cell membrane integrity and cytosolic Ca2+ levels increase. Dysregulation of mitochondria and rER leads to the activation of caspase-2, caspase-8, caspase-9, and caspase-3 .",null,"Therapeutic strategy associated"]
[1341,"DB11127","approved; investigational","small molecule","Selenious acid","Selenious acid; Selenous acid","H2O3Se","O[Se](O)=O","Selenious acid is the acid form of sodium selenite, a form of selenium .\r\n\r\nSelenium is an essential trace element and antioxidant. It is a cofactor metabolic enzyme regulation. It also plays an important role in maintaining the general health of tissue and muscle and has antioxidant properties. Selenium is a component of glutathione peroxidase enzyme, which protects cell components from oxidative damage due to peroxides produced during cellular metabolism .\r\n\r\nSelenium (Se) has been demonstrated to prevent cancer in numerous animal models when administered selenium at levels exceeding the nutritional requirements. One study showed efficacy in the prevention of malignancy while utilizing a selenium supplement in humans. The reports from such studies have heightened the interest in additional human selenium supplementation studies to validate the results in larger populations .\r\n\r\nInterestingly, selenium is being studied as a potential therapy in the prevention or management of atherosclerosis .","7783-00-8","128.97","\r\nSelenium injection is indicated for use as a supplement to intravenous solutions given for total parenteral nutrition (TPN). Administration of selenious acid in TPN formulas helps to maintain plasma selenium levels and also to maintain endogenous stores to prevent deficiency .\r\n\r\nSelenium compounds, such as selenium sulfide, are used topically in anti-dandruff shampoos and in cases of seborrhea . \r\n \r\nFor the purpose of brevity, selenite will the focus of discussion, and more information about selenium can be obtained at .","Selenium is a component glutathione peroxidase, which protects cells from oxidative damage caused by peroxidases produced during cellular metabolism .\r\n\r\nSelenium is needed to maintain the circulatory system. It also keeps the heart muscle and skin tissue healthy. It may also help in the prevention of cancer due to its stimulation of antioxidant activity and protection of cell membranes , .\r\n\r\nSelenious acid preserves vitamin E, which improves the cell's antioxidant defense, and plays an important role in the structure of teeth .\r\n\r\nProlonged TPN (total parenteral nutrition) support in humans has resulted in selenium deficiency symptoms which include muscle pain and tenderness. The symptoms have been reported to respond to supplementation of TPN solutions with selenium , .\r\n\r\nPediatric conditions, Keshan disease, and Kwashiorkor have been associated with low dietary intake of selenium. The conditions are endemic to geographical areas marked by low selenium content in the soil. Dietary supplementation with selenium salts has been reported to reduce the incidence of the conditions among affected children .","\r\n\r\nSodium selenite likely has the same mechanism of action as .\r\n\r\nThe most important physiological role of sodium selenite is associated with its presence as an active component of many enzymes and proteins, in addition to its antioxidative role. Selenium has been shown to activate anticancer agents, prevent heart and vascular diseases, exhibit anti-proliferative and anti-inflammatory properties, and to stimulate the immune system .\r\n\r\nIts anticancer properties may be explained by the oxidation of free sulfhydryl groups. Tumor cells express free sulfhydryl groups (–SH) on the surface of their cell membranes and contribute to uncontrolled cell division. Only those compounds that can oxidize these groups to disulfides (S–S) may inhibit this process. Some organic forms of selenium, including selenocysteine, methylseleninic acid, and Se-methylselenocysteine have been established to be antioxidants. However, their anticancer mechanism is still not well understood .\r\n\r\nSelenious acid, during an in vitro study, was found to stimulate hemoglobin synthesis in three different malignant erythroleukemia cell lines (MEL) . It has also been shown to increase the release of interleukin 2 in a dose-dependent manner . Interleukin-2 is made by a type of T lymphocyte (white blood cell). It increases the growth and activity of other T-lymphocytes and B-lymphocytes and this contributes to the development of the immune system .",null,"Therapeutic strategy associated"]
[1342,"DB11131","approved","biotech","Capsicum oleoresin","Capsaicin oleoresin; Capsicum annuum resin; Capsicum capsicum resin; Capsicum longum resin; Capsicum oleoresin; Cayenne pepper resin; Chili oleoresin; Oleoresin capsicum; Oleoresins of capsicum",null,null,"Capsicum oleoresin is an oily organic resin derived from the fruit of plants in the Capsicum genus, such as chilli peppers. When the plants are finely ground, capsicum oleoresin is formed after the extraction process of capsaicin using oragnic solvents such as ethanol. It is commonly used as a culinary spice. The intensity of biological actions and toxicological effects of capsicum oleoresin are a direct function of the amount of capsaicinoids, or capsaicin, present in the compound . Capsaicinoids comprise of a group of fat-soluble pungent chemical phenols and include , dihydrocapsaicin, nordihydrocapsaicin, homocapsaicin, and homodihydrocapsaicin .  and dihydrocapsaicin are the most pungent capsaicinoid analogues .\r\n\r\nCapsicum oleoresin is contained in pepper sprays when suspended in water, and acts an active lachrymatory agent that induces irritation, lacrimation, pain, and temporary blindness when in contact with eyes. Due to its analgesic properties, capsicum oleoresin is used to temporarily relieve of minor aches and pains of muscles and joints as an active ingredient in topical OTC preparations and has been studied for management of different models of neuropathic pain . It is suggested that capsicum oleoresin is a rich source of phytochemicals that consist of phenolic compounds with antioxidant and antidiabetic activities .","8023-77-6",null,"Indicated for the temporary relief of minor aches and pains of muscles and joints associated with simple backache, arthritis, strains and sprains.","Capsicum oleoresin is a topical analgesic and inflammatory agent. Capsaicin, an active ingredient in capsicum oleoresin, causes pain and sensitization of both peripheral and central nerves. It induces primary and secondary hyperalgesia and mimics the symptoms associated with neuropathic pain, such as allodynia, secondary hyperalgesia, referred pain area, and viscerovisceral hyperalgesia . In opposition, capsaicin also mediates analgesic actions via desensitization and withdrawal of epidermal nerve fibers . Systemic reviews of capsaicin-containing topical formulations demonstrate clinical effectiveness for pain reduction in postherpetic neuralgia, postsurgical neuropathies, and diabetic neuropathy, compared to placebo .","Capsaicin is the active ingredient in capsicum oleoresin that confers the molecule its biological actions. It induces central sensitization to cause pain and depolarizes nociceptors to increases their cytosolic free Ca2+ concentration . It is a highly selective agonist and activator at the transient receptor potential vanilloid subfamily member 1 (TRPV1) receptors expressed in afferent neuronal C fibers and some Aδ fibers . The aliphatic tail of capsaicin interacts with the channel via nonspecific Van der Waals forces, while hydrogen bonds between its vanillyl “head” and amide “neck” with residues of glutamic acid E571 and T551 of the channel, respectively, confers specificity for ligand binding . Binding and local activation of these receptors lead to increased influx of calcium ions and nerve depolarization. Signal propagation to the central nervous system causes local heat, stinging, and/or itching sensations . Prolonged activation of TRPV1 receptors results in loss of receptor functionality, causing impaired local nociception for extended periods due to desensitization and inactivation of sensory neurons. It is thought that the activation of TRPV1 receptors is the main mechanism of action of capsaicin. Capsaicin also induces a local depletion of substance P, which is a neuropeptide involved in visceral pain signalling ; however this effect in the relief of pain remains controversial .","Transient receptor potential cation channel subfamily V member 1 agonist&activator","Therapeutic strategy associated"]
[1343,"DB11134","approved","small molecule","Cupric oxide","Cuprous Oxide; Cuprum oxydatum nigrum","CuO","[O--].[Cu++]","Cupric oxide, or copper (II) oxide, is an inorganic compound with the chemical formula CuO. Cupric oxide is used as a precursor in many copper-containing products such as wood preservatives and ceramics. Cupric oxide may be found in over-the-counter vitamin-mineral supplements as a source of . The mean daily dietary intake of copper in adults ranges between 0.9 and 2.2 mg . Common routes of cupric oxide exposure include ingestion, dermal exposure and inhalation. Copper(II) oxide nanoparticles (NPCuO) have industrial applications as antimicrobial agents in textiles and paints, and catalysts in organic synthesis . They may also be produced from electronic wastes. Cupric oxide poses potential health and environmental concern due to toxic and mutagenic particles generating reactive oxygen species .","1317-38-0","79.545","No FDA- or EMA-approved therapeutic indications.","For pharmacodynamic information of copper, refer to drug entry for . Copper(II) oxide nanoparticles are known to generate reactive oxygen species (ROS), leading to cytotoxicity . In a comparative toxicity assay, nanoparticles caused significant mitochondrial depolarization leading to DNA damage . In the human skin organ culture study, topical application of copper oxide (CuO) nanoparticles induced inflammatory cytokine secretion and necrosis _in vitro_, indicating that the nanoparticles may adhere to the skin surface and react with the local acidic environment .","For pharmacodynamic information of copper, refer to drug entry for . Copper(II) oxide nanoparticles generate DNA-damaging reactive oxygen species at the nanoparticle surface or in solution by copper dissolved from the nanoparticle surface via Fenton-like reactions . In presence of H2O2, ascorbate, or both, copper (II) oxide generates hydroxyl radical, ascorbyl radical, and superoxide anion that interact with DNA, proteins, and lipids cause oxidative damage and cell death .",null,"Therapeutic strategy associated"]
[1344,"DB11157","approved","small molecule","Anthralin","Anthralin; Dithranol","C14H10O3","OC1=CC=CC2=C1C(=O)C1=C(O)C=CC=C1C2","Anthralin (1,8‐dihydroxy‐9anthrone, dithranol) is an older anti-psoriatic agent that was first synthesized as a derivative of chrysarobin, obtained from the araroba tree in Brazil over 100 years ago. Adverse effects of anthralin include irritation and discoloration of the skin .\r\n\r\nThis specific property of the molecule inspired workers to study details of its pharmacology. It is important to consider that the drug is relatively innocuous, yet effective, and systemic side effects have not been observed with this anthralin, in contrast to a wide variety of systemic and topical therapies for psoriasis . \r\n\r\nAnthralin is also known as dithranol.  It is a main active ingredient in topical skin formulations for the treatment of psoriasis. Various formulations of the drug are available, including solutions, foams, and shampoos . The chemical structure of anthralin allows for dual solubility, permitting the compound to be absorbed well through the epidermis . \r\n\r\nAnthralin has also been studied in the treatment of warts, showing promising results . Salicylic acid is frequently added to anthralin to augment the stability of anthralin and to increase its penetration and efficacy .","1143-38-0","226.231","Stable plaque psoriasis of the skin and scalp .\r\n\r\nIt is also used topically in the management of psoriasis, dermatoses, and alopecia areata. Anthralin is also used in biomedical research due to its effect on EGFR autophosphorylation .","\r\nAnthralin is a natural anthraquinone derivative, anti-psoriatic and anti-inflammatory agent.  It controls skin growth by reducing the synthesis of DNA and the mitotic activity in the hyperplastic epidermis, normalizing the rate of cell proliferation and keratinization .","\r\nAnthralin inhibits the proliferation of keratinocytes (epidermal skin cells), prevents the action of T-cells, and promotes cell differentiation, likely through mitochondrial dysfunction. In addition, the production of free radicals may contribute to its anti-psoriatic effect . In vitro studies demonstrate that anthralin prolongs the prophase component of mitosis for keratinocytes and leukocytes .  Prophase is the first step of mitosis, the process separating the duplicated genetic material carried in the nucleus of a parent cell into two identical daughter cells . In vivo studies demonstrate that anthralin blocks DNA synthesis and can increase the release of reactive oxygen species .\r\n\r\nAnthralin is believed to normalize the rate of epidermal cell proliferation and keratinization by reducing the mitotic activity of the epidermal hyperplasia in psoriasis .\r\n\r\n\r\nAnti-proliferative and anti-inflammatory effects of anthralin have been demonstrated on both psoriatic and healthy skin. The anti-proliferative effects of anthralin are thought to be due to a combination of inhibition of DNA synthesis and its strong reducing properties. The effectiveness of anthralin as an anti-psoriatic agent is partly owed to its ability to promote lipid peroxidation and reduce the concentration of endothelial adhesion molecules, which are found to be elevated in psoriatic patients , .\r\n\r\nRecent studies suggest that its ability to prevent T-lymphocyte activation and normalize keratinocyte differentiation may occur by a direct effect on mitochondria .","Keratin, type II cytoskeletal 2 epidermal antagonist; C-Jun-amino-terminal kinase-interacting protein 1 agonist; Keratin, type I cytoskeletal 12 antagonist","Therapeutic strategy associated"]
[1345,"DB11160","approved","small molecule","Phenyltoloxamine","Phenyltoloxamine","C17H21NO","CN(C)CCOC1=CC=CC=C1CC1=CC=CC=C1","Phenyltoloxamine is an antihistamine drug with sedative and analgesic effects. It is a H1 receptor blocker and a member of the ethanolamine class of antihistaminergic drugs. It is available in combination products that also contain other analgesics and antitussives such as acetaminophen. Phenyltoloxamine citrate is the more common salt form that acts as an active ingredient in pharmaceutical products and promotes hay fever relief via reversing the effects of histamine. Phenyltoloxamine acts as an adjuvant analgesic, which augments the analgesic effect of acetaminophen. It also potentiates the effects of other drugs, such as codeine and codeine derivatives.\r\n\r\nAlthough phenyltoloxamine's ability to potentiate the effects of analgesics may be explained in part by its chemical nature as a first-generation H1 antihistamine that is capable of crossing the blood-brain barrier and causing tranquilizing effects at CNS histamine receptors, many of the drug's specific pharmacokinetics are not readily available - perhaps also because many early (phenyltoloxamine was involved in studies as early as the 1950s) first-generation antihistamines were not optimally investigated . Nevertheless, phenyltoloxamine is used to a fairly limited extent in contemporary medicine, with only very few products involving it as an active ingredient.","92-12-6","255.361","The primary therapeutic use for which phenyltoloxamine is currently indicated is as an adjuvant therapy in various combination products containing an analgesic(s) (either narcotic or non-narcotic), where it is expected to potentiate the pain relieving, anti-tussive, etc. effect(s) of the analgesic component of the product.\r\n\r\nIn that regard, some of these aforementioned combination products are typically indicated for the temporary relief of minor aches and pains like headache, muscular aches, backaches, minor arthritis pain, common cold, toothaches, menstrual cramps, etc ; or perhaps for the treatment of exhausting or non-productive cough, associated with cold or with upper respiratory allergic condition that does not respond to non-narcotic antitussives .","As a member of the first generation H1 antihistamines, it is known that phenyltoloxamine - like virtually all first generation H1 antihistamines - has a propensity for crossing the blood-brain barrier and acting on H1 histamine receptors there to interfere with neurotransmission . The most common results of this kind of first generation H1 antihistamine CNS neurotransmission interference are adverse effects like drowsiness, sedation, somnolence, and fatigue . Given these effects, under specific circumstances like a patient experiencing a pain or a cough that may be preoccupying all of their waking energy and attention, it is perhaps possible that the sedative and tranquilizing characteristics of phenyltoloxamine may be the factors that contribute to its apparent adjunctive analgesic  and antitussive actions .","As a first-generation H1 antihistamine, phenyltoloxamine interferes with the agonist activity of histamine at the H1 receptor and are ostensibly used to attenuate inflammatory processes as a means to treat conditions like allergic rhinitis, allergic conjunctivitis, and urticaria . Reduction of the activity of the NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) immune response transcription factor via the phospholipase C and phosphatidylinositol (PIP2) signaling pathways also serves to decrease antigen presentation and the expression of pro-inflammatory cytokines, cell adhesion molecules, and chemotactic factors . Moreover, lowering calcium ion concentration leads to increased mast cell stability which reduces further histamine release .\r\n\r\nAdditionally, first-generation antihistamines like phenyltoloxamine readily cross the blood-brain barrier and cause sedation and other adverse central nervous system (CNS) effects, like nervousness and insomnia . By comparison, second-generation antihistamines are more selective for H1 receptors in the peripheral nervous system and do not cross the blood-brain barrier, resulting in fewer adverse drug effects overall .\r\n\r\nFurthermore, although some studies propose that phenyltoloxamine may possess some intrinsic antispasmodic and distinct local anesthetic properties , the specific mechanisms of action for these effects have not been formalized. Also, even though the combination of phenyltoloxamine's ability to cross the blood-brain barrier and cause various tranquilizing effects may explain to some extent how it may be able to potentiate analgesic effects , there are also studies that observed no potentiating effects associated with phenyltoloxamine use either .","Histamine H1 receptor inverse agonist","Therapeutic strategy associated"]
[1346,"DB11164","approved; investigational","small molecule","Bicisate",null,"C12H24N2O4S2","CCOC(=O)[C@H](CS)NCCN[C@@H](CS)C(=O)OCC","Bicisate, also known as ethyl cysteinate dimer (ECD), is a N,N'-1,2-ethylene-di-yl-bis-L-cysteinate diethyl ester. It is used in conjunction with technetium Tc99m as a tracer to measure cerebral blood flow with single-photon emission computed tomography (SPECT). The complex of bicisate and technetium Tc99m as a kit was developed by Lantheus Medcl and FDA-approved on November 23, 1994.","121251-02-3","324.45","Bicisate as a complex with technetium Tc-99m is used in single photon emission computerized tomography (SPECT) as an adjunct to conventional CT or MRI in the localization of stroke in patients whom the presence of a stroke has already been diagnosed. It is not indicated to assess the functional viability of brain tissue or to distinguish between a stroke and other brain lesions.\r\n\r\nA stroke is defined as a condition in which the blood stops flowing to any part of the brain causing a damage to brain cells. The potential effect of a stroke depends on the part of the brain that was affected by it as well as the extension of the damage.","The neutral and lipophilic nature of bicisate provides it with high stability. This property is given by its N2S2 core. This characteristic has been proven to allow bicisate to be used even several hours after preparation and to present an easy passage through the blood-brain barrier.","Bicisate is rapidly uptaken by the brain. The retention of bicisate in the brain is associated with stereospecific de-esterification to hydrophilic acid derivatives. Even though both DD and LL isomers demonstrate brain uptake, only the LL presents brain retention. Bicisate brain localization is performed by passive diffusion and the presence of slow hydrolysis in the blood and rapid hydrolysis in the brain. The hydrolysis of bicisate forms the monoacid and diacid bicisate derivatives. The formation of these derivatives results in high brain uptake and retention. The uptake of bicisate depends on the blood flow directed to the brain and thus the presence of a stroke will be translated into specific zones in the brain that would not include the complex of bicisate and technetium Tc-99m.",null,"Indication associated"]
[1347,"DB11193","approved","small molecule","Papain","Papain",null,null,"Papain, also known as papaya proteinase I, is a cysteine protease (EC 3.4.22.2) enzyme that is found in species of papaya, _Carica papaya_ and _Vasconcellea cundinamarcensis_. The enzyme is found to be localized in the skin of papaya, and is collected from slashed unripe papayas as a crude latex. Papain is used in food, pharmaceutical, textile, and cosmetic industries. While it has been used for the treatment of inflammation and pain via topical administration, papain has also shown to have anthelmintic and tooth-whitening properties. Present in over-the-counter mixture products consisting of different digestive enzymes, its active site contains a catalytic diad that plays a role in breaking peptide bonds. Papain is also used as an ingredient in various enzymatic debriding preparations.","9001-73-4",null,"No FDA-approved therapeutic indications.","Papain is a digestive enzyme and often acts as a skin allergen.","When topically applied, papain induces an allergen-like inflammatory response via recruiting neutrophils, mast cells, and CD3-positive cells and by induction of a TH2-biased antibody response . _In vitro_, treatment of papain resulted in the breakdown of tight junctions of primary human keratinocytes that maintain the epithelial barrier integrity. These tight junction proteins include zonula occludens-1, claudin-4, and occludin . It is proposed that papain induces allergic responses via activation of TLR4, leading to an increase in neutrophils, CD3+ cells, mast cells, and CCL8-positive cells .","Toll-like receptor 4 activator","Therapeutic strategy associated"]
[1348,"DB11198","approved; investigational","biotech","Peppermint oil","English black mint oil; Mentha crispa oil; Mentha dumetorum oil; Mentha piperita (peppermint) leaf water; Mentha piperita (peppermint) oil; Mentha piperita flowering top oil; Mentha piperita oil; Mentha X piperita oil; Menthae piperitae aetheroleum; Oil of peppermint; Pepermint oil; Peppermint american far west bulked; Peppermint american willamette natural; Peppermint flowering top oil; Peppermint indian rectified; Peppermint oil america; Peppermint oil mongolia; Peppermint oil yakima; Peppermint volatile oil",null,null,"Extracted from the stem, leaves, and flowers of _Mentha piperita_ L. plant, peppermint oil (Mentha piperita) is a popular essential oil used in aromatherapy for both external and internal use. Mentha piperita is a hybrid of spearmint (Mentha spicata) and water mint (Mentha aquatica) . Medicinal use of herbal ingredients such as peppermint oil has a long history of treating digestive disorders and upper respiratory symptoms and cough . There are various over-the-counter and commercial uses of peppermint oil due to its carminative, cholagogue, antibacterial, secretolytic, and choleretic actions . Peppermint oil contains pulegone, which is a naturally-occurring pesticide . Other active constituents of peppermint oil include , menthone, cineol, and several other volatile oils . \r\n\r\nPeppermint oil is used as a flavouring agent in foods and fragrance in hygienic or cosmetic products, and as an anti-itch and cooling agent in topical pharmaceutical products. It is also an active ingredient in topical analgesics for the relief of joint and muscle pain. Peppermint oil can be applied topically to temporarily relieve tension-type headache. The use of peppermint oil in the management of irritable bowel syndrome (IBS) has been investigated in many clinical studies due to its relaxing effects on smooth muscle; however the evidence supporting this use is unclear. Due to its effectiveness in relaxing GI smooth muscle but ability to induce gastroesophageal reflux, enteric-coated formulations of peppermint oil has been established which bypass the upper GI tract unmetabolized, thereby facilitating its effect in the lower GI tract without effects in the upper tract . Peppermint oil is safe and well-tolerated at commonly recommended dosage .","8006-90-4",null,"Indicated for the over-the-counter use for:\r\n\r\n-the symptomatic relief of minor spasms of the gastrointestinal tract, flatulence and abdominal pain, especially in patients with irritable bowel syndrome.\r\n\r\n-the temporary relief of itching associated with insect bites, eczema, minor burn, sunburn, minor skin irritations, minor cuts, scrapes, atopic dermatitis and other skin disorders.\r\n\r\n-the temporary symptomatic relief of mild joint and muscle pain as a local topical analgesic.\r\n\r\n-the temporary relief of tension-type headache.","Peppermint oil induces a dose-related antispasmodic effects on the gastrointestinal smooth muscles . A meta-analysis study and additional clinical studies of patients with IBS demonstrated that the treatment with peppermint oil improves abdominal symptoms compared to the placebo group, resulting in reduced severity of abdominal pain, decreased abdominal distension, reduced stool frequency, and reduced flatulence . The use of enteric-coated peppermint oil was shown to be effective in reducing gastrointestinal symptoms of non-ulcer dyspepsia . In rats, peppermint oil promoted a time-dependent choleretic  effect in increasing bile production and biliary output . In randomized controlled trials, topical application of peppermint oil was associated with a significant analgesic effect and a reduction in headache intensity compared to placebo . In a study of C57BL/6 mice, topical application of peppermint oil for 4 weeks was associated with a prominent hair growth effects; a significant increase in dermal thickness, follicle number, and follicle depth .","Dose-dependent antispasmodic effect of peppermint oil is largely mediated by its menthol constituent . It is proposed that peppermint oil relaxes gastrointestinal smooth muscle and attenuates contractile responses by reducing the influx of extracellular calcium ions. In rabbit jejunum smooth muscle cells investigated via whole cell clamp configuration technique, peppermint oil was shown to inhibit the potential-dependent calcium currents in a concentration-dependent manner . Both a reduction in peak current amplitude and an increase in the rate of current decay were observed, indicating that the pharmacological activity peppermint oil resembles that of dihydropyridine calcium antagonists . In a rat small intestine study, peppermint oil in the intestinal lumen inhibited enterocyte glucose uptake via a direct action on the brush border membrane and inhibited intestinal secretion . There is also evidence that menthol is an antagonist of L-type Ca2+ channels via interacting with dihydropyridine binding sites and blocks the currents of low-voltage-activated calcium channels . Peppermint oil may facilitate hair growth by promoting the conservation of vascularization of hair dermal papilla, which may contribute to the induction of early anagen stage of active growth phase of hair follicles .",null,"Indication associated"]
[1349,"DB11201","approved","small molecule","Menthyl salicylate","1-Menthyl salicylate; Menthyl salicylate, (+/-)-","C17H24O3","CC(C)[C@@H]1CC[C@@H](C)C[C@H]1OC(=O)C1=CC=CC=C1O","Menthyl salicylate is an ester of menthol and salicylic acid .\r\n\r\nThis product is used to treat minor aches and pains of the muscles/joints (e.g., arthritis, backache, sprains) .","89-46-3","276.376","\r\n\r\nFor the temporary relief of pain associated with rheumatism, arthritis, neuralgia, sprains and strains of joints and muscles, lumbago and fibrositis .","Menthol and methyl salicylate are known as counterirritants. They work by causing the skin to feel cool and then warm. Used together, they provide symptomatic relief for mild to moderate muscular and joint aches and pains, muscle cramps, shoulder aches and stiff neck..","\r\nMenthol dilates the blood vessels causing a sensation of coldness, followed by an analgesic effect. Menthol also acts as a penetration enhancer, increasing the penetration of drugs when applied on the skin, to give a faster onset of action .\r\n\r\nMethyl salicylate is a salicylic acid derivative, and when combined with menthol, produces menthyl salicylate .\r\n\r\nSalicylates inhibit cyclooxygenase, thereby reducing the formation of prostaglandins, and cause platelet dysfunction\r\nMethyl salicylate is used topically as a counter-irritant. Upon application, it is absorbed through the skin and is applied for the relief of pain in rheumatic conditions and painful muscle or joints .\r\n\r\nThe menthol dilates blood vessels,  why the salicylate portion provides a topical anesthetic and analgesic action on the affected area. The cooling and warning action may interfere with the transmission of pain signals through nerves .","Prostaglandin G/H synthase 1 antagonist; Prostaglandin G/H synthase 2 antagonist","Indication associated"]
[1350,"DB11204","approved","small molecule","Panthenol","DL-panthenol; DL-Pantothenol; Panthenol","C9H19NO4","CC(C)(CO)C(O)C(=O)NCCCO","Panthenol is an alcohol derivative of pantothenic acid, a component of the B complex vitamins and an essential component of a normally functioning epithelium. Panthenol exists as a racemic mixture containing both the dextrorotatory form (dexpanthenol) and the levorotatory form (levopanthenol). While pantothenic acid is optically active, only the dextrorotatory form () is biologically active.\r\n\r\nDexpanthenol, the active form of panthenol, is enzymatically cleaved to form pantothenic acid (Vitamin B5), which is an essential component of Coenzyme A that acts as a cofactor in many enzymatic reactions that are important for protein metabolism in the epithelium .\r\n\r\nDue to its good penetration and high local concentrations, dexpanthanol is used in many topical products, such as ointments and lotions for treatment of dermatological conditions to relieve itching or promote healing. Dermatological effects of the topical use of dexpanthenol include increased fibroblast proliferation and accelerated re-epithelialization in wound healing. Furthermore, it acts as a topical protectant, moisturizer, and has demonstrated anti-inflammatory properties .","16485-10-2","205.254","Panthenol (containing a racemic mixture of dexpanthenol and levopanthenol) is not currently available in any FDA-approved products and therefore does not have an indication.\r\n\r\nPlease see  for FDA-approved uses of the dextrorotatory form of Panthenol.","Pantothenic acid is a precursor of coenzyme A, which serves as a cofactor for a variety of enzyme-catalyzed reactions involving transfer of acetyl groups. The final step in the synthesis of acetylcholine consists of the choline acetylase transfer of acetyl group from acetylcoenzyme A to choline. Acetylcholine is the neurohumoral transmitter in the parasympathetic system and as such maintains the normal functions of the intestine. Decrease in acetylcholine content would result in decreased peristalsis and in extreme cases adynamic ileus.","Panthenol is an alcohol derivative of pantothenic acid, a component of the B complex vitamins and an essential component of a normally functioning epithelium. Dexpanthenol, the active form of panthenol, is enzymatically cleaved to form pantothenic acid (Vitamin B5), which is an essential component of Coenzyme A that acts as a cofactor in many enzymatic reactions that are important for protein metabolism in the epithelium .\r\n\r\nDermatological effects of the topical use of dexpanthenol include increased fibroblast proliferation and accelerated re-epithelialization in wound healing. Furthermore, it acts as a topical protectant, moisturizer, and has demonstrated anti-inflammatory properties .",null,"Therapeutic strategy associated"]
[1351,"DB11207","approved","small molecule","Amiloxate","3-(4-Methoxyphenyl)-2-propenoic acid, 3-methylbutyl ester; Amiloxate; Isoamyl p-methoxycinnamate; Isoamyl-p-methoxycinnamate","C15H20O3","COC1=CC=C(\\C=C\\C(=O)OCCC(C)C)C=C1","Amiloxate is an EMA-approved chemical UV-filter found in over-the-counter sunscreen products at concentrations up to 10%m . It is often referred to as isoamyl 4-methoxycinnamate or isoamyl p-methoxycinnamate. Amiloxate is a cinnamic acid derivative with an anti-inflammatory activity .","71617-10-2","248.322","Indicated as an active sunscreen agent.","In a mouse study, amiloxate exerted a dose-dependent anti-inflammatory action and inhibited edema by about 70% even at a low dose . Due to structural similarities, amiloxate may also display antioxidant and antimicrobial properties of cinnamic acid .","Amiloxate is a UV-B filter that selectively absorbs UV-B rays . It is proposed that amiloxate mediates an antioxidant action by acting as a free radical scavenger .",null,"Therapeutic strategy associated"]
[1352,"DB11217","approved","small molecule","Arbutin","4-Hydroxyphenyl-beta-D-glucopyranoside; beta-Arbutin; hydroquinone O-β-D-glucopyranoside; Hydroquinone-O-beta-D-glucopyranoside; p-hydroxyphenyl β-D-glucopyranoside; p-hydroxyphenyl β-D-glucoside","C12H16O7","OC[C@H]1O[C@@H](OC2=CC=C(O)C=C2)[C@H](O)[C@@H](O)[C@@H]1O","Extracted from the dried leaves of bearberry plant in the genus _Arctostaphylos_ and other plants commonly in the _Ericaceae_ family, arbutin is a beta-D-glucopyranoside of . It is found in foods, over-the-counter drugs, and herbal dietary supplements . Most commonly, it is an active ingredient in skincare and cosmetic products as a skin-lightening agent for the prevention of melanin formation in various skin conditions that involve cutaneous hyperpigmentation or hyperactive melanocyte function . It has also been used as an anti-infective for the urinary system as well as a diuretic . Arbutin is available in both natural and synthetic forms; it can be synthesized from acetobromglucose and  . Arbutin is a competitive inhibitor of tyrosinase (E.C.1.14.18.1) in melanocytes , and the inhibition of melanin synthesis at non-toxic concentrations was observed _in vitro_. Arbutin was shown to be less cytotoxic to melanocytes in culture compared to  .","497-76-7","272.2512","Indicated for over-the-counter use for epidermal hyperpigmentation in various skin conditions, such as melasma, freckles, and senile lentigines.","At non-toxic concentrations, arbutin inhibited the activity of tyrosinase in cultured human keratinocytes, while having minimal effect on the expression of tyrosinase mRNA or the synthesis of the enzyme . α-Arbutin produced a concentration-dependent inhibition of melanin synthesis of human melanoma cells, HMV-II . No inhibitory effect on HMV-II cell growth was seen at concentrations lower than 1.0 mM. At concentrations of 0.5 mM of arbutin, tyrosinase activity was reduced to 60% of that in non-treated cells . The addition of arbutin blocked and inhibited α-MSH-stimulated melanogenesis in B16 melanoma cells, brownish guinea pig, and human skin tissue . In a pilot study of healthy male adults exposed to UV B irradiation, topical administration of arbutin inhibited UV-induced nuclear factor-kappaB activation in human keratinocytes . In mouse skin, arbutin counteracted oxidative stress induced by 12-O-tetradecanoylphorbol-13-acetate .","Arbutin is a hydroquinone glycoside, however the hydroquinone moiety is not solely responsible for the de-pigmentating actions of arbutin . It acts as a competitive inhibitor of tyrosinase enzyme by acting on the L-tyrosine binding site to suppress melanogenesis and mediate its de-pigmenting actions on human skin . Tyrosinase is an enzyme involved in the regulation of rate-limiting steps during the synthesis of melanin; it regulates the conversion of L-tyrosine into L-dopa, and subsequent conversion of L-dopa to L-dopaquinone . Via inhibition of tyrosinase activity in a concentration-dependent manner, arbutin attenuates the production of melanin in melanocytes. While most studies suggest that arbutin has negligible effect on the tyrosinase mRNA expression, a study assessing the effect of arbutin on melanocyte differentiation inducement system using ES cells propose that arbutin may also downregulate the expression of tyrosinase in addition to its inhibitory action on the enzyme . The contradictory findings across studies may be due to previous studies using terminally-differentiated melanocytes and melanoma cells .","Tyrosinase inhibitor","Therapeutic strategy associated"]
[1353,"DB11218","experimental; nutraceutical","biotech","Tea tree oil","Australian tea tree oil; Melaleuca alternifolia (tea tree) leaf oil; Melaleuca alternifolia (tea tree) leaf water; Melaleuca alternifolia leaf oil; Melaleuca alternifolia oil; Melaleuca oil; Narrow-leaved tea-tree leaf oil; Narrow-leaved ti-tree leaf oil; Narrowleaf paperbark leaf oil; Snow-in-summer leaf oil; Tea tree oil; Tea tree oil australia; Tea tree volatile oil; Ti tree oil",null,null,"Tea tree oil is an essential oil derived mainly from the Australian native plant _Melaleuca alternifolia_ via steam distillation of the of the leaves and terminal branches . It may be referred to as _Melaleuca alternifolia_ oil. It has been a popular ingredient in a variety of household and cosmetic products due to its antiseptic, anti-inflammatory, broad-spectrum antimicrobial and antioxidant properties . The dermatological use of tea tree oil has been investigated by various studies, where several studies have suggested the uses of this oil for the treatment of acne vulgaris, seborrheic dermatitis, and chronic gingivitis . Terpene hydrocarbons and related alcohols constitute tea tree oil, with  being the major antimicrobial component .","68647-73-4",null,"Indicated for topical use to help protect against infection in minor cuts, scrapes, and burns. No FDA-approved therapeutic indications.","Tea tree oil exhibits antibacterial, antifungal, antiviral, and antiprotozoal activities . It mostly mediates bactericidal actions at concentrations of 1.0% or less in most bacteria such as _Staphylococcus aureus_ and _Escherichia coli_, and causes bacteriostatic effects at lower concentrations . Organisms such as commensal skin staphylococci and micrococci, _Enterococcus faecalis_, and Pseudomonas aeruginosa_emphasized text_ were susceptible to tea tree oil concentrations of 2% . It is proposed that water-soluble components of tea tree oil are capable in inducing anti-inflammatory actions; terpinen-4-ol attenuates the vasodilation and plasma extravasation associated with histamine-induced inflammation in humans .","The components of tea tree oil, particularly terpinen-4-ol and α-terpineol, mediate antimicrobial actions by disrupting the structural and functional integrity of bacterial membrane. Hydrocarbons are capable of partitioning into the cell and cytoplasmic membrane of microorganisms and disrupt their vital functions, which may result in leakage of ions such as potassium, and the inhibition of respiration . Eventually, cell lysis may occur due to weakening of the cell wall, and loss of turgor pressure and subsequent rupture of the cytoplasmic membrane . The loss of 260-nm-absorbing material may be indicative of a damaged cytoplasmic membrane and loss of nucleic acids . In _E. coli_, perturbed potassium homeostasis, glucose-dependent respiration, cell morphology, and ability to exclude propidium iodide was observed. \r\n\r\nTea tree oil also mediates its antifungal actions in a similar way, where it alters the permeability of Candida albicans and inhibits its respiration in a dose-dependent manner . Plasma and mitochondrial membranes of fungal species are also thought to be negatively affected by inhibition of glucose-induced medium acidification by tea tree oil, which involves inhibition of membrane ATPase responsible for the expulsion of protons . Tea tree oil also inhibits the formation of germ tubes, or mycelial conversion, in _C. albicans_, thereby disrupting cell morphogenesis . Water-soluble fraction of TTO, terpinen-4-ol, and α-terpineol, can inhibit the lipopolysaccharide-induced production of the inflammatory mediators such as TNF-α, IL-1β and IL-10 by human peripheral monocytes by approximately 50% and that of prostaglandin E2 by about 30% after 40 h . These components of tea tree oil may also suppress superoxide production by agonist-stimulated monocytes and decrease the production of reactive oxygen species by both stimulated neutrophils and monocytes .",null,"Therapeutic strategy associated"]
[1354,"DB11228","approved","small molecule","Methylcellulose","Cellulose methyl; cellulose methyl ether; Cellulose methylate; Methyl cellulose; methylated cellulose; Methylcellulose",null,null,"Methyl cellulose polymer consisting of numerous linked glucose molecules used as a stabiliser, thickener and emulsifier for foodstuffs and cosmetics. The Degree of Substitution (DS) of a given form of methyl cellulose is defined as the average number of substituted hydroxyl groups per glucose with a theoretical maximum of 3, however more typical values are 1.3 2.6. Methyl cellulose is a hydrophilic white powder in pure form and dissolves in cold (but not in hot) water, forming a clear viscous solution or gel. It is available under a variety of trade names as a treatment for constipation. Like cellulose, it is not digestible, not toxic, and not allergenic","9004-67-5",null,"Solutions containing methyl cellulose are used as substitute for tears or saliva if the natural production of these fluids is disturbed. It is also used or constipation, diverticulosis, hemorrhoids and irritable bowel syndrome. Used in the manufacture of capsules in nutritional supplements. Its edible and nontoxic properties provide a vegetarian alternative to the use of gelatin.","It increases the bulk in your stool, an effect that helps to cause movement of the intestines. It also works by increasing the amount of water in the stool, making the stool softer and easier to pass.","Methylcellulose absorbs water in the gastrointestinal lumen thereby increasing  the bulk of the stool. This leads to distension and stimulation of peristalsis. The ability of methylcellulose to absorb water may contribute to its efficacy in the management of diarrhea by once again increasing the bulk and consistency of the stool.",null,"Indication associated"]
[1355,"DB11239","approved","small molecule","Aluminum sulfate","Aluminium sulfate; Aluminium sulfate anhydrous; Aluminum sulfate anhydrous; Aluminum sulphate anhydrous; Dialuminum sulfate; Dialuminum trisulfate","Al2O12S3","[Al+3].[Al+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O","Aluminum (Al), also spelled aluminum, chemical element, a lightweight, silvery-white metal of main Group 13 (IIIa, or boron group) of the periodic table .\r\n\r\nIt is a chemical agent used in water purification, the pH regulation of garden soil, and other commercial or industrial applications. Medically, it is primarily used as a coagulating agent in minor cuts and abrasions as well as deodorant .\r\n\r\nAluminum (Al) is ubiquitous and represents the third most common element in the Earth’s crust. It most commonly exists in a combined state with various other elements. Al is found in materials used in the pharmaceutical industry, and in manufactured foodstuffs, cosmetics, and tap water. By overcoming the body barriers, Al may infiltrate into the blood and lead to toxic effects in liver, bone and the central nervous system .","10043-01-3","342.151","Solutions containing 5 to 10% aluminum sulfate have been used as local applications to ulcers and to arrest foul discharges from mucous surfaces. Aluminum sulfate is also used in the preparation of aluminum acetate ear drops .  It is often purchased over the counter and is available in solid stick or powder form for minor cuts and abrasions after shaving , . Aluminum sulfate is also used as an adjuvant in vaccines .","Aluminum sulfate may be used as a deodorant, as well as an astringent . Aluminum sulfate is also known as an astringent. Astringents are substances that cause contraction or shrinkage of tissues and that dry up secretion .\r\n\r\nUsed as a post-shaving treatment, it can eliminate bleeding from superficial wounds , .   \r\n\r\nIt has also shown in vitro anti-microbial activity .\r","When used as a deodorant, the volume of sweat produced is reduced by narrowing sweat ducts. The inhibition of body odor causing bacteria is another important strategy for deodorization . \r\n\r\nBy inhibiting or deactivating odor-producing bacteria, there is little to none metabolism of sweat components thus decreasing the occurrence of body odor . \r\n\r\nRecent studies suggest that the active binding of alum to the membranes of dendritic cells (DCs) result in alteration of lipid membranes structures as a key process in alum's adjuvant effect in vaccines. As new adjuvants are being developed, alum may remain as an ingredient of adjuvant combinations, or it may eventually be supplemented by other agents that more effectively provide depot and local inflammatory responses to accentuate host immune responses .",null,"Therapeutic strategy associated"]
[1356,"DB11242","approved; vet_approved","small molecule","Gelatin","Gelatin, unspecified; Gelatine",null,null,"Gelatin is a multifunctional ingredient that is used in foods, pharmaceuticals, cosmetics, and photographic films as a gelling agent, stabilizer, thickener, emulsifier, as well as film former . \r\n\r\nAs a thermoreversible hydrocolloid with a small gap between its melting and gelling temperatures, gelatin provides unique advantages over carbohydrate-based gelling agents. Gelatin is mainly produced from porcine skin, and cattle hides and bones .\r\n\r\nSome alternative raw substances have recently garnered attention from both researchers and the industry not only because they overcome religious concerns shared by both Jews and Muslims but also because they may provide scientific advantages over gelatins from mammal origins .\r\n\r\nFish skins from a number of fish species a type of substance that has been comprehensively studied as a source for gelatin production. Fish skins have a significant potential for the production of high-quality gelatin with different melting and gelling temperatures over a much larger range than mammalian gelatins but have a sufficiently high level of gel strength and viscosity .\r\n\r\nGelatin is generally recognized as safe (GRAS) by the FDA to be a non-hazardous food or food ingredient .\r\n\r\nInterestingly, horse gelatin has been studied and it was found that in the horse, gelatin influences the homeostasis of the amino acids required for cartilage synthesis . An increasing number of novel applications have been found for collagen and gelatin .","9000-70-8",null,"Gelatin is used for weight loss and for treating osteoarthritis, rheumatoid arthritis, and brittle bones (osteoporosis). Some people also use it for strengthening bones, joints, and fingernails. Gelatin is also used for improving hair condition and to shorten the recovery after exercise and sports-related injury . Gelatin is used in preparations of foods, cosmetics, and medicine .\r\n\r\nPlasma volume expander in hypovolaemic shock . Haemostatic .\r\n\r\nGelatin-based hydrogels are being used in drug delivery and tissue engineering because they are able to promote cell adhesion and proliferation. In addition, these hydrogels can be used as wound dressings because of their attractive fluid absorbance properties. Manufacturing technologies such as ultraviolet stereolithography and two-photon polymerization can be used to prepare structures containing photosensitive gelatin-based hydrogels .","Gelatin contains collagen, which is one of the materials that make up cartilage and bone .\r\n\r\nIn addition to their well-established value as a nutritional protein source, collagen and collagen-derived products may exhibit various potential biological activities on cells and the extracellular matrix through the corresponding food-derived peptides post-ingestion.  This could justify their applications in dietary supplements and pharmaceutical agents .\r\n\r\nGelatin is a protein that is used as a hemostatic in surgical procedures.  It is also used as a plasma volume expander in hypovolemic shock. Gelatin rods structures may also be used to temporarily block tear outflow in cases of dry eye .","It works as a hemostatic by providing a physical framework within which clotting may occur .\r\n\r\nAs a volume expander, gelatin remains in the vascular space. When used in the treatment of hypovolaemia gelatin can produce a significant increase in blood volume, cardiac output, stroke volume, blood pressure, urinary output and oxygen delivery, increasing volume and pressure .\r\n\r\nFor intravascular volume expansion, the majority or gelatins produce an effect which is almost equivalent to of which are mild, although severe reactions albumin, with a duration of action of 3 to 4 hours to have been reported .\r\n\r\nGelatin or collagen chains suspended in solution can be covalently cross-linked to form matrices that are able to swell in the presence of aqueous solutions, forming what are called _gelatin hydrogels_. Hydrogels, characterized by their hydrophilicity and insolubility in water, have the capability of swelling into an equilibrium volume while maintaining their shape. The chemical cross-linkers used may be either small bifunctional molecules or polyfunctional macromolecules, for example, glutaraldehyde .",null,"Indication associated"]
[1357,"DB11251","approved; investigational","small molecule","Tocopherol","Methyltocols; Tocopherols",null,null,"Tocopherol exists in four different forms designated as α, β, δ, and γ. They present strong antioxidant activities, and it is determined as the major form of vitamin E. Tocopherol, as a group, is composed of soluble phenolic compounds that consist of a chromanol ring and a 16-carbon phytyl chain. The classification of the tocopherol molecules is designated depending on the number and position of the methyl substituent in the chromanol ring. The different types of tocopherol can be presented trimethylated, dimethylated or methylated in the positions 5-, 7- and 8-. When the carbons at position 5- and 7- are not methylated, they can function as electrophilic centers that can trap reactive oxygen and nitrogen species. Tocopherols can be found in the diet as part of vegetable oil such as corn, soybean, sesame, and cottonseed. It is currently under the list of substances generally recognized as safe (GRAS) in the FDA for the use of human consumption.","1406-66-2",null,"Tocopherol can be used as a dietary supplement for patients with a deficit of vitamin E; this is mainly prescribed in the alpha form. Vitamin E deficiency is rare, and it is primarily found in premature babies of very low birth weight, patients with fat malabsorption or patients with abetalipoproteinemia.\r\n\r\nTocopherol, due to its antioxidant properties, is studied for its use in prevention or treatment in different complex diseases such as cancer, atherosclerosis, cardiovascular diseases, and age-related macular degeneration.","The antioxidant effects of tocopherol can be translated into different changes at the pharmacodynamic level. In vitro studies have shown that this antioxidant activity can produce modification in protein kinase C (PKC) which will later be translated into an inhibition of cell death. Some other derivate effects are the anti-inflammatory properties of tocopherol which can be related to the modulation of cytokines or prostaglandins, prostanoids and thromboxanes.","Tocopherol acts as a radical scavenger. It mainly acts as an antioxidant for lipid bilayers. Tocopherol's functions depend on the H-atom donating ability, location, and movement within the membrane, as well as the efficiency in the radical recycling by some cytosolic reductants such as ascorbate. Tocopherol actions are related to the trap of radicals, and it has been shown that even in the absence of substituents in the ortho-positions, tocopherol can trap more than two radicals. The type of radicals available for tocopherol are alkyl and peroxy.","Free radicals binder","Therapeutic strategy associated"]
[1358,"DB11254","approved","small molecule","Hexylresorcinol","4-hexyl-1,3-benzenediol; 4-hexylresorcinol; Hexylresorcinol","C12H18O2","CCCCCCC1=C(O)C=C(O)C=C1","Hexylresorcinol is a substituted dihydroxybenzene. It exhibits antiseptic, anthelmintic, and local anesthetic properties. It can be found in topical applications for minor skin infections and in oral solutions or throat lozenges for pain relief and first aid antiseptic.\r\n\r\nThe compound may also be used commonly in various commercial cosmetic anti-aging creams while ongoing studies research the possibility of using hexylresorcinol as an anti-cancer therapy - indications all of which require further study and testing at the current moment.","136-77-6","194.2701","Hexylresorcinol is predominantly employed as the active ingredient in lotions, sprays, or lozenges indicated as a (a) topical antiseptic to help prevent skin infection in minor cuts, scrapes, or burns, or (b) as an antiseptic and local anesthetic for the relief of a sore throat and its associated pain .\r\n\r\nIn addition, hexylresorcinol is used as an active ingredient in various commercial cosmetic skincare products as an anti-aging cream  while other studies have looked into whether or not the compound could be used effectively as an anti-inflammatory agent or even as an anti-cancer therapy .","Hexylresorcinol is a phenol derivative, and in typical therapeutic usage is primarily a local anesthetic for topical use on the mucous membranes of the mouth and throat . The local anesthetic like properties of hexylresorcinol is likely due to its sodium channel blocking effects . The agent also demonstrates mild antiseptic activity as well as an apparent anti-inflammatory, demulcent action .","When acting as an oral anesthetic for relieving sore throats, it is generally believed that hexylresorcinol is possibly capable of blocking voltage-gated neuronal sodium channels, which in turn would inhibit the initiation and conduction of nerve impulses for feeling or transmitting pain signals in the local area to which the hexylresorcinol is applied .\r\n\r\nAs an antiseptic agent, studies have demonstrated that hexylresorcinol is capable of eliciting actions like reducing or inhibiting the generation of bacterial biofilm, interfering with bacterial cell chain formation, reducing bacterial adherence of the pharynx, inhibition of glycolytic enzyme and pH drops, and alteration of cell surface hydrophobicity . Unfortunately, there are either antibiotics that function even more effectively at formally treating bacterial growth or there are also other plant-derived phenolic compounds similar to hexylresorcinol that elicit stronger such mechanisms of action . Nevertheless, it is useful for hexylresorcinol to have both anesthetic and certain antiseptic actions for its use in treating various relatively self-limiting scrapes and sore throats that are treated by the over-the-counter products that feature the compound. Early studies in the 1930s and 1940s suggested that there were more effective medicines over hexylresorcinol that could be employed for their anthelmintic effects .\r\n\r\nAs an anti-inflammatory and anti-aging agent, some studies have shown that it may be possible for hexylresorcinol to inhibit the phosphorylation of the immune response mediator NF-kappaB and also elicit a significant skin lightening effect owing to a strong inhibitory effect on tyrosinase and peroxidase and a stimulatory effect on glutathione and E-cadherin syntheses . It is proposed that hexylresorcinol can bind to tyrosinase directly and inhibits its enzyme activity . Literature data suggests that low glutathione levels relates to the deposition of melanin in the skin of humans and other animals, while high glutathione levels inhibit melanogenesis . And ultimately, it is also reported that glutathione depletion increases tyrosinase activity in human melanoma cells, which makes hexylresorcinol's effects on tyrosinase desirable .\r\n\r\nFinally, there are ongoing studies that have reported hexylresorcinol's abilities to induce the differentiation of SCC-9 squamous cell cell-line by way of the modulation of the E2F-mediated signaling pathway and suppress the growth of squamous cell carcinoma SCC-9 cells in a dose-dependent manner . Moreover, such studies have also shown that hexylresorcinol is seemingly capable of dose-dependent induction of SCC-9 cell apoptosis as well as the inhibition of transglutaminase-2 enzyme activity which can facilitate chemotherapy resistance .","DNA topoisomerase 1 inhibitor; Protein-glutamine gamma-glutamyltransferase 2 inhibitor; Tyrosinase inhibitor","Therapeutic strategy associated"]
[1359,"DB11256","approved; investigational","small molecule","Levomefolic acid","(6S)-5-methyltetrahydrofolate; (6S)-5-Methyltetrahydrofolic acid; (6S)-5-MTHF; 5-methyl-(6S)-tetrahydrofolic acid; L-5-methyltetrahydrofolate; L-5-MTHF; L-methylfolate; Levomefolate; Levomefolic acid; LMSR; N-[4-[[[(6S)-2-Amino-3,4,5,6,7,8-hexahydro-5-methyl-4-oxo-6-pteridinyl]methyl]amino]benzoyl]-L-glutamic acid","C20H25N7O6","CN1[C@@H](CNC2=CC=C(C=C2)C(=O)N[C@@H](CCC(O)=O)C(O)=O)CNC2=C1C(=O)N=C(N)N2","Levomefolic acid (INN) is the metabolite of folic acid (Vitamin B9) and it is a predominant active form of folate found in foods and in the blood circulation, accounting for 98% of folates in human plasma . It is transported across the membranes including the blood-brain barrier into various tissues where it plays an essential role in the DNA synthesis, cysteine cycle and regulation of homocysteine, where it methylates homocysteine and forms methionine and tetrahydrofolate (THF). Levomefolate is approved as a food additive and is designated a GRAS (generally regarded as safe) compound . It is available commercially as a crystalline form of the calcium salt (Metafolin(R)), which has the stability required for use as a supplement . Supplementation of levomefolic acid is desired over folic acid due to reduced potential for masking vitamin B12 deficiency symptoms.","31690-09-2","459.4558","For the treatment and prevention of folate deficiency and for use as an antidote against folic acid antagonists. Contained in oral contraceptives to reduce the risk of neural tube defects arising from folic acid deficiency for pregnant women who conceived during use or shortly after the discontinuation of the product. Being studied for use as a treatment for cardiovascular diseases  and adjunct therapy for patients undergoing antidepressant pharmacotherapy .","Levomefolic acid is an active metabolite of folic acid and a methyl group donor in one-carbon metabolism reactions. It regulates important cellular functions such as DNA biosynthesis, gene expression regulation, amino acid synthesis and metabolism, and myelin synthesis and repair. As a only form of folate that can cross the blood-brain barrier, it acts as a cofactor in the production of monoamine neurotransmitters such as dopamine, serotonin and norepinephrine . Levomefolic acid is also involved in red blood cell formation .","Levomefolic acid plays a critical role in methylating homocysteines into methionine by acting as a methyl donor in a reaction catalyzed by vitamine B12-dependent methionine synthase. Homocysteine must either be further metabolized via transulfuration to become cysteine, taurine, and glutathione via a B6-dependent process, or re-methylated to become methionine again. Methionine formed from remethylation of homocysteine by levomefolic acid forms the downstream metabolite S-adenosylmethionine (SAMe), which is involved in numerous biochemical methyl donation reactions, including reactions forming monoamine neurotransmitters . Studies suggest that high plasma levels of homocysteine is associated with increased incidences of arterial plaque formation .",null,"Indication associated"]
[1360,"DB11265","nutraceutical","biotech","Curcuma xanthorrhiza oil","Curcuma xanthorrhiza root oil; Curcuma xanthorrhiza volatile oil; Curcuma zanthorrhiza oil; Curcuma zanthorrhiza root oil; Temu lawak oil",null,null,"_Curcuma xanthorrhiza_ oil is extracted from _Curcuma xanthorrhiza_ Roxb., a member of the ginger family (_Zingiberaceae_) that is widely distributed in the region of Southeastern Asia .  _Curcuma xanthorrhiza_ is also known as Javanese Turmeric or Temoe Lawak . For centuries, _Curcuma xanthorrhiza_ oil has been used as a traditional medicine due to its antibacterial, antispasmodic, antioxidative, antitumor, anti-inflammatory and protective effects . It has been used in the treatment of stomach diseases, liver disorders, constipation, bloody diarrhoea, dysentery, children’s fevers, hypotriglyceridaemic, haemorrhoids and skin eruptions . _Curcuma xanthorrhiza_ oil is comprised of 1-2% of curcumin and 3-12% volatile oil, which mainly contains sesquiterpenes, 44.5% of xanthorrhizol, and a small amount of  . However the principal active components of Curcuma xanthorrhiza are  and xanthorrhizol that display a wide range of pharmacological activities and synergistic effects . Curcumin is a mixture of dicinnamoylmethane derivatives and other phenolic and non-phenolic diarylheptanoids . _Curcuma xanthorrhiza_ oil is found as an active ingredient in cosmetic and hygienic products, and marketing of products containing _Curcuma xanthorrhiza_ oil is authorized in some European countries including Germany and the Netherlands .",null,null,"Indicated for the symptomatic relief of digestive disturbances, such as feelings of fullness, slow digestion and flatulence .","_Curcuma xanthorrhiza_ oil is reported to exert diuretic, anticancer, anti-inflammatory, antioxidant, antihypertensive, antirheumatic, antihepatotoxic, antidysmenorrheal, antispasmodic, antileucorrhoeal, antibacterial, and antifungal actions experimentally and in literature . _In vivo_, oral administration of _Curcuma xanthorrhiza_ oil in rats caused a persistent but transient (5h) increase of bile secretion due to the increase in the total bile acids in the excretive bile . This cholagogic effect is attributable for a major part to d-camphor contained  in the oil . In a study of rats with cisplastin-induced hepatotoxicity, administration of _Curcuma xanthorrhiza_ extract resulted in serum enzyme levels such as alanine aminotransferases (ALT), aspartate aminotransferases (AST), and y-glutamate transferases . In addition, it was shown to mediate hepatoprotective actions against β-D-galactosamine-induced liver damage and alcohol . In male ICR mice treated with cisplatin known to induce toxicity of kidneys and liver, xanthorrhizol demonstrated nephroprotective and hepatoprotective actions to attenuate the elevated levels of blood urea nitrogen and serum creatinine, as well as blood glutamate-pyruvate transaminase (GPT) and glutamate–oxaloacetate transaminase (GOT) levels .\r\n\r\n**Anti-inflammatory actions:** Curcuminoid derivatives and xanthorrhizol elicit anti-inflammatory effects by inhibiting oedema formation . \r\n\r\n**Antibacterial effects:** Xanthorrhizol displays a broad-spectrum antibacterial activity. In a study, it showed the highest antibacterial activity against dental caries causing bacteria (_Streptococcus_ species) to disrupt their biofilm formation _in vitro_, followed by periodontitis causing bacteria (_Actinomyces viscosus_ and _Porphyromona gingialis_) . It also strongly inhibited Gram-positive bacteria _Staphylococcus aureus_, methicillin-resistant _Staphylococcus aureus_ (MRSA), Gram-negative bacteria _Escherichia coli_, and acne-causing bacteria _Propionibacterium acnes_ . Xanthorrhizol additionally exhibits anticandidal and antifungal properties . \r\n\r\n**Antiplatelet effects:** _In vitro_, both curcumin and xanthorrhizol showed a strong inhibition towards platelet aggregation stimulated by arachidonic acid, collagen, and ADP in human whole blood .\r\n\r\n**Anticancer effects:** Co-administration of curcumin and xanthorrhizol in MDA-MB-231 cells resulted in synergistic growth inhibition of breast cancer cells . Topical application of 2 and 6 μmol xanthorrhizol in rats inhibited TPA-induced tumour formation .","The prinicipal components,  and xanthorrhizol, mediate the main pharmacological actions of _Curcuma xanthorrhiza_ oil. \r\n\r\n**Anti-inflammatory and antioxidant actions:** Curcumin and xanthorrhizol are natural antioxidant to exert an anti-inflammatory effect by scavenging the reactive oxygen species, such as hydroxyl radical, superoxide anion, and singlet oxygen, or by chemically reducing oxidized compounds . Curcumin inhibits liposomal peroxidation and peroxide-induced DNA damage, and the mechanism of action is thought to involve modulation of cell adhesion molecules (CAMs) and stimulation of ICAM- 1 . Based on the findings _in vitro_, xanthorrhizol may be a potent inhibitor of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) to decrease their expression via NF-kB pathway and subsequently inhibit the production of pro-inflammatory prostaglandin E2 (PGE2) and nitric oxide (NO) . In activated primary cultured microglial cells, xanthorrhizol was found to inhibit COX-2, iNOS, proinflammatory cytokine interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) . \r\n\r\n**Hepatoprotective actions:** The hepatoprotective effect of _Curcuma xanthorrhiza_ oil is considered mainly a result of its antioxidant properties, as well as its ability to decrease the levels of pro-inflammatory cytokines . Xanthorrhizol may also attenuate phosphorylation of c-Jun N-terminal kinases (JNKs) . \r\n\r\n**Antibacterial actions:** While the mode of antibacterial action of xanthorrhizol is not fully understood, it is thought to involve suppression of nuclear factor kappaB (NF-kB) and mitogen-activated protein kinase (MAPK) induced by microbial infection . \r\n\r\n**Anticancer actions:** The cytotoxic actions of xanthorrhizol against tumour cells is thought to be contributed by its phenol group and may involve its antioxidative and anti-inflammatory activities, induction of apoptosis and cell cycle arrest by reducing cyclin D1 proto-oncogene expression or triggering cyclin-dependent kinase inhibitors (CDKIs) . In various cancer cell models, xanthorrhizol was shown to induce apoptosis via activation of p53-dependent mitochondrial pathway. In HeLa cervical cancer cells, xanthorrhizol upregulated p53 and Bax without any effects on Bax/Bcl-2 expression . There is also evidence that xanthorrhizol-induced cell death is mediated by the activation of caspase. Xanthorrhizol increased the expression and promoter activity pro-apoptotic non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1), which is notably inhibited during the development of human colorectal cancer and neoplastic tumors . Other mode of action involves the regulation of MAPK pathway and inhibition of Akt/NF-kB pathway .\r\n\r\n**Estrogenic and anti-estrogenic actions:** _In vitro_, xanthorrhizol upregulated pS2 and promoted  the interaction of ER-estrogen response elements in MCF-7 cells. It acted as a partial estrogen antagonist of hERα in T47D cells . Curcumin also activates gene expression in the breast cancer cell line MCF7, indicating that it may have low estrogenic activity .",null,"Therapeutic strategy associated"]
[1361,"DB11269","approved","small molecule","Diethylamino hydroxybenzoyl hexyl benzoate","Hexyl 2-(4-(diethylamino)-2-hydroxybenzoyl)benzoate","C24H31NO4","CCCCCCOC(=O)C1=CC=CC=C1C(=O)C1=CC=C(C=C1O)N(CC)CC","Diethylamino hydroxybenzoyl hexyl benzoate is a UV filter with high absorption in the UV-A range. Minimizing the overexposure of human skin to ultraviolet radiation that may lead to acute and chronic photodamage, diethylamino hydroxybenzoyl hexyl benzoate is an oil-soluble UV filter that may be incorporated in the oil phase of emulsions . Diethylamino hydroxybenzoyl hexyl benzoate was approved in Europe in 2005, and is also marketed in the U.S., South America, Mexico, Japan and Taiwan. It has a chemical structure similar to the classical benxophoenone drug class, and displays good photostability . It is used in concentrations up to 10% in sunscreen products, either alone or in combination with other UV absorbers .","302776-68-7","397.515","Indicated for use as a sunscreen agent.","Diethylamino hydroxybenzoyl hexyl benzoate is an organic UV filter that attenuates the exposure of UV radiation on human skin . _In vitro_, topical application of diethylamino hydroxybenzoyl hexyl benzoate exerted an anti-inflammatory effect on inflammation-evoked mouse ears by inhibiting oedema formation .","Diethylamino hydroxybenzoyl hexyl benzoate absorbs in the UV-A range with the peak at 354 nm .",null,"Therapeutic strategy associated"]
[1362,"DB11296","experimental","small molecule","Prezatide","GHK; Gly-His-Lys; Glycyl-L-histidyl-L-lysine; Glycylhistidyllysine; Growth-modulating peptide (human); Liver cell growth factor; Tripeptide-1","C14H24N6O4","NCCCC[C@H](NC(=O)[C@H](CC1=CNC=N1)NC(=O)CN)C(O)=O","Prezatide is a tripeptide consisting of glycine, histidine, and lysine which readily forms a complex with copper ions . Prezatide is used in cosmetic products for the skin and hair. It is known to aid wound healing and its potential applications in chronic obstructive pulmonary disease and metastatic colon cancer are currently being investigated.","49557-75-7","340.384","Commonly used in cosmetic products for the skin and hair .","Prezatide in complex with copper improve skin elasticity, density, and firmness, reduces fine lines and wrinkles, reduces photodamage, increases keratinocyte proliferation . Prezatide also displays anti-oxidant and angiogenic effects and appears to modulate tissue remodeling in injury.","Prezatide in complex with copper increases the synthesis and deposition of type I collagen and glycosaminoglycan  . It also increases the expression of matrix metalloproteinase-2 as well as tissue inhibitor of matrix metalloproteinases-1 and -2, suggesting that it plays a role in the modulation of tissue remodeling . It is thought that prezatide's antioxidant activity is due to its ability to supply copper for superoxide dismutase and its anti inflammatory ability due to the blockage the of iron (Fe2+) release during injury . Prezatide also increases angiogenesis to injury sites. The precise mechanisms of these effects are unknown. It is also unknown whether prezatide's effects are due to the action of the tripeptide itself or its ability to localize and transport copper . Prezatide is known to be bound by heparin and heparin sulfate",null,"Therapeutic strategy associated"]
[1363,"DB11321","nutraceutical; vet_approved","small molecule","Cod liver oil","Cod liver oil; Cod-liver oil; Gadus morhua liver oil; Oils, cod liver; Oleum morrhuae",null,null,"Cod liver oil is extracted from the liver of cod fish and mainly consists of omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Also being a rich source of vitamin A and D, cod liver oil can be taken orally as daily supplements. It is used as an adjunct treatment and preventative therapy of rickets, osteomalacia and osteoporosis while meeting the consumption criteria.","8001-69-2",null,"Cod liver oil is predominantly manufactured, marketed, and used by the population at large as a general nutraceutical dietary supplement .\r\n\r\nHistorically, cod liver oil was often given to children because the vitamin d content in the oil had been shown to prevent or treat vitamin D deficiency and condition of rickets associated with it . Over time, this common use in children growing up may have conferred upon cod liver oil its identity as a healthy and useful all-purpose dietary supplement.\r\n\r\nHowever, since cod liver oil is a composite of several other nutritional compounds including the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as well as vitamin A and vitamin D , the presence in varying amounts of all of these compounds at once makes it difficult to recommend or use cod liver oil as an appropriate supplement to confer any one particular health effect or for any one particular nutritional deficiency.\r\n\r\nRegardless, because it does contain a combination of a number of important and healthy nutritional compounds, cod liver oil has sometimes been recommended in the literature for conferring the health effects of some of these compounds, such as the potential use of cod liver oil supplements in post-heart attack patients for secondary prophylaxis associated with the use of omega-3 fatty acids .","As cod liver oil is a composite of several other nutritional compounds including the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as well as vitamin A and vitamin D , the presence in varying amounts of all of these compounds at once makes it difficult to recommend or use cod liver oil as an appropriate supplement to confer any one particular health effect or for any one particular nutritional deficiency.\r\n\r\nFor example, one tablespoon of cod liver oil contains approximately 4,080 ug of retinol (vitamin A) and 34 ug (1,360 IU) of vitamin D . Since the general dietary reference intake of vitamin A is only 900 ug per day for adult men, 700 ug per day for women, and 3000 ug per day as the tolerable upper intake level, the regular intake of cod liver oil as a regular supplement can result in harmful levels of vitamin A accumulating in the liver and sufficient to cause hypervitaminosis A , which is associated with various symptoms such as blurred vision, changes in consciousness, skin and hair changes, liver damage, among many others.\r\n\r\nMoreover, while cod liver oil only contains a certain percentage of the omega-3 fatty acids EPA and DHA per amount of the oil , separate fish oils supplement products that exclusively consist of only EPA and DHA are available in a great variety of different percentage content formulations, even including prescription strength formulations should certain patients need such a level of therapy. Furthermore, such exclusive omega-3 fatty acid supplement products do not contain any vitamin A or D either, which allows patients to use the supplements without any concern about affecting their vitamin A or D levels or exposing themselves to the unnecessary excess intake of vitamins.\r\n\r\nSubsequently, although cod liver oil contains a combination of healthy dietary supplements like EPA, DHA, vitamin A, and vitamin D, the presence in varying amounts of all of these compounds all at once makes it difficult to effectively titrate for appropriate amounts of intake for all the compounds involved when using cod liver oil as a general supplement, often resulting in either an excess or insufficient amount of one or more the aforementioned compounds.\r\n\r\nNevertheless, because cod liver oil does consist of the component compounds of EPA, DHA, vitamin A, and vitamin D, further information about the pharmacodynamics of these cod liver oil components can be found by searching for fish oil, vitamin A, and vitamin D on DrugBank.","As cod liver oil consists of the component compounds of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), vitamin A, and vitamin D  further information about the mechanisms of action of these cod liver oil components can be found by searching for fish oil, vitamin A, and vitamin D on DrugBank.",null,"Indication associated"]
[1364,"DB11323","approved","small molecule","Glycol salicylate","2-hydroxybenzoic acid 2-hydroxyethyl ester; 2-hydroxyethyl 2-oxidanylbenzoate; 2-hydroxyethyl salicylate; Ethylene glycol monosalicylate; Ethylene glycol salicylate; Glycol salicylate","C9H10O4","OCCOC(=O)C1=CC=CC=C1O","Glycol salicylate, also known as _2-hydroxyethyl salicylate_, is a benzoate ester formed from the condensation of the carboxy group of salicylic acid with one of the hydroxy groups of ethylene glycol. It is found as an active ingredient and topical analgesic in patches used to provide relief for mild to moderate muscle and joint pain . \r\n\r\nThis drug belongs to the _salicylate_ group of drugs, which are used as analgesic agents for the treatment of mild to moderate pain .\r\n\r\nGlycol salicylate (GS), composed of salicylic acid (SA) and ethylene glycol, is a non-steroidal anti-inflammatory drug . \r\n\r\nThis ingredient is an important component of many topical creams and sprays for the relief of aches, pains, and stiffness of the muscles, joints, and tendons .","87-28-5","182.175","This drug is only recommended for topical usages for the relief of muscular and rheumatic pain in human and animals .","Temporarily relieves minor to moderate aches and pains .  Works with ingredients such as menthol, which has counter-irritant properties . Counter-irritants are externally applied, and lead to irritation or mild inflammation of the skin to relieve pain in muscles or joints by reducing inflammation in deeper adjacent structures . Counter-irritants relieve pain by disrupting the brain from receiving pain signals resulting from conditions such as osteoarthritis (OA) or injuries such as sprains or strains.  These agents may cause vasodilatation or skin irritation, leading to a false sensation of heat or warmth .","Similar to other salicylates. Salicylates and other analgesics and anti-inflammatory drugs, particularly the non-steroidal anti-inflammatory drugs (NSAID) mainly used in rheumatology, inhibit cyclooxygenase, therefore reducing prostaglandin synthesis . \r\n\r","Prostaglandin G/H synthase 1 antagonist; Prostaglandin G/H synthase 2 antagonist","Therapeutic strategy associated"]
[1365,"DB11324","investigational","small molecule","Nonivamide","Hydroxymethoxybenzyl pelargonamide; N-Nonanoyl vanillylamide; N-Vanillylnonamide; N-Vanillylpelargonamide; Nonivamide; Pelargonyl vanillylamide; Pseudocapsaicin; Vanillyl-N-nonylamide","C17H27NO3","CCCCCCCCC(=O)NCC1=CC(OC)=C(O)C=C1","Nonivamide is found in herbs and spices. It is an alkaloid from the Capsicum species. The structures of  and nonivamide differ only slightly with respect to the fatty acid moiety of the side chain (8-methyl nonenoic acid versus nonanoic acid) .\r\n\r\nNonivamide is a flavoring ingredient. Nonivamide is an organic compound and a capsaicinoid. It is an amide of pelargonic acid and _vanillylamine_.  It is naturally found in chili peppers but manufactured to produce a synthetic form for various pharmacologic preparations .\r\n\r\nThis drug has been studied in combination with Nicarboxil in the treatment of lower back pain .\r\n\r\nNonivamide has also been studied for its anti-inflammatory properties, as well as in fat loss therapies and has demonstrated promising results , , , .","2444-46-4","293.4012","Nonivamide is used as a topical analgesic and is also used as a flavoring ingredient , , .","Relieves minor aches and pains of muscles and joints , .","Nonivamide is a naturally occurring analog of , isolated from peppers, described to produce effects similar to . It is an agonist of the VR1 (vanilloid/TRPV1 receptor) . It serves as a transient agonist of these receptors, which are potentiated by pro-inflammatory drugs, a phenomenon that leads to thermal hyperalgesia, or increased heat sensation .\r\n\r\nNonivamide has been shown to stimulate afferent neurons with about half the potency of . Agonism of the VR1 (TRPV1) (vanilloid) receptor by Nonivamide was demonstrated to induce the release of Ca2+ from the endoplasmic reticulum (ER) of human lung cells, producing ER stress and cell death .\r\n\r\nNonivamide, like other capsaicinoids, acts on the vanilloid receptors located in the peripheral afferent nerve fibers, providing short-acting irritant and algesic properties. Applied dermally, these substances act by stimulating sensitive chemoreceptors of the skin and by reflex,  hyperemia and a local elevation in temperature. After repetitive administration, capsaicinoids have been reported to lead to desensitization to nociceptive stimuli possibly by long-acting depletion of peptide neurotransmitters (substance P) from peripheral sensory neurons. Capsaicinoids can modulate muscle tone (in bladder, bronchus etc.). Intravenous injection of nonivamide to rats (10 μg/kg) has been found to lead to bradycardia. The cardiovascular effects are partly explained by substance P release. Nonivamide given to rats subcutaneously (1 mg/kg) was found to cause body temperature decrease, vasodilatation, and increased salivation. Capsaicinoids have shown to illicit bronchospastic effects in guinea pigs. Capsaicin and its analogs were reported to increase barbiturate sleeping time in rats by interacting with hepatic metabolizing enzymes .","Transient receptor potential cation channel subfamily V member 1 agonist","Therapeutic strategy associated"]
[1366,"DB11332","approved","small molecule","Sinapultide",null,"C126H238N26O22","CC(C)C[C@H](NC(=O)[C@@H](N)CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(O)=O","Sinapultide (also known as KL4 peptide) is a synthetic protein used to mimic human lung surfactant protein B. This protein has a weight of 2469.40.\r\n\r\nSinapultide is a 21-residue peptide made up of lysine (K) and leucine (L) residues with the sequence KLLLLKLLLLKLLLLKLLLLK (KL4), in aqueous dispersion with the phospholipids DPPC (dipalmitoylphosphatidylcholine), POPG (palmitoyloleoyl-phosphatidylglycerol), and palmitic acid, to create the drug .\r\n\r\nThe product was originally developed by the Scripps Research Institute, then licensed to Windtree Therapeutics. Windtree Therapeutics plans a phase III trial for Respiratory distress syndrome in 2018.\r\n\r\nRespiratory distress syndrome (RDS) is a major cause of mortality and morbidity in preterm infants. Surfactant replacement therapy has been commonly used to prevent and treat RDS in these newborns and is now a standard of care. First-generation synthetic surfactants that were previously used, such as _Exosurf_ did not contain any surfactant protein. This large disadvantage was overcome with animal-derived surfactant products which contain specific proteins but are limited, but must be derived from animal sources. This has led to the development of newer synthetic surfactants such as lucinactant (Surfaxin), which contains sinapultide. Phase 3 clinical trials with Surfaxin show promising results with similar efficacy as animal-derived surfactants while avoiding the use of animal-origin products.\r\n\r\nWindtree is currently developing aerosolized KL4 surfactant to treat RDS in premature infants, and thereafter, to potentially address a range of indications in neonatal, pediatric and adult critical care patient populations.","138531-07-4","2469.45","Infant respiratory distress syndrome , , , .","Windtree’s KL4 surfactant technology produces a synthetic surfactant that is structurally similar to human pulmonary surfactant and contains a proprietary synthetic peptide KL4 (sinapultide), cost a 21-amino acid peptide that is formulated to mimic the essential attributes of the human surfactant protein B (SP-B). This protein is one of four surfactant proteins and is the most important for the adequate function of the respiratory system. Windtree has demonstrated in pre-clinical studies that KL4 surfactant may possess certain other beneficial properties, including alteration of the inflammatory process, antimicrobial properties as well as non-immunogenicity .","Endogenous pulmonary surfactant lowers surface tension at the air-liquid interface of the alveolar surfaces during respiration and stabilizes the alveoli against collapse at resting transpulmonary pressures. A deficiency of pulmonary surfactant in premature infants results in RDS. Surfaxin, the drug in which this protein is included,  compensates for the deficiency of surfactant and restores surface activity to the lungs of these infants .\r\n\r\nTo explore the mechanisms of protection that this sinapultide offers against RDS, in vitro assays were performed with human and murine endothelial cell monolayers, and polymorphonuclear leukocyte (PMN) transmigration in the presence or absence of KL(4)-surfactant or lipid controls was studied. Based on morphology, histopathology, white blood cell count, percentage of PMNs, and protein concentration in bronchoalveolar lavage fluid, the results that showed KL(4)-surfactant, blocked neutrophil influx into alveoli and thus prevented lung injury. Additionally, in vitro assays demonstrated KL(4)-surfactant decreased neutrophil transmigration at the endothelial cell level. KL(4)-surfactant diminished inflammation and lung permeability when compared with controls in both mouse models of lung injury. Evidence suggests the anti-inflammatory mechanism of the KL(4)-peptide is achieved through inhibition of PMN transmigration through the endothelium .","Lung epithelial cells agonist","Therapeutic strategy associated"]
[1367,"DB11333","approved; investigational","small molecule","Poloxamer 188","Pluronic F68; Poloxamer-188; Vepoloxamer",null,null,"Poloxamer 188 (P188) is a nonionic block linear copolymer that exhibits rheologic, anti-thrombotic, anti-inflammatory, and cytoprotective activities in various tissue injury models . Composed of two hydrophilic side-chains attached to a hydrophobic center core , its average molecular weight is 8400 Daltons. P188 was originally approved by the FDA in the 1960s as a therapeutic agent to reduce viscosity in the blood before transfusions, however it is no longer available in any approved products . Due to its sufactant properties, P188 may also be found in over-the-counter (OTC) products such as toothpaste, laxatives and mouthwash, and used in various cosmetic, industrial and pharmaceutical applications. There is an evidence of P188 increasing the structural stability and resealing of the plasma membrane via direct incorporation into the phospholipid bilayer . The ability of P188 in attenuating membrane damage and cell injury has been demonstrated in a variety of _in vivo_ and _in vitro_ models . The use of P188 as a potential treatment in different pathological conditions, such as chronic microvascular diseases and skeletal muscle deficiencies, is under investigation .","691397-13-4",null,"Indicated to reduce viscosity in the blood before transfusions.","Poloxamer 188 (P188) exerts a protective action against oxidative stress and inflammation in tissue injury in various experimental models. In the rat model of excitotoxic injury, immediate intrathecal administration of P188 reduced neuronal loss, indicated by smaller spherical excitotoxic lesions . In a murine hind-limb model, P188 mediated a protective action against ischemia-reperfusion injury as indicated by decreased myocyte injury, preserved tissue adenosine 5'-triphosphate levels, and improved survival rates, suggesting that P188 can seal defects in cell membranes and attenuate damage induced by reactive oxygen species . P188 was shown to elicit protective effects against excitotoxic injury, and trauma-induced necrotic and apoptotic cell death in cultured neurons . In the mouse stroke models, P188 exerted a neuroprotective effect in brain ischemia-reperfusion induced acute injury by significantly reducing infarct volume and water content in brain edema and ameliorating the neurological symptoms 24 h after ischemia or reperfusion injury . P188 also significantly inhibited inflammatory, coagulation, and apoptotic responses resulting from superior mesenteric artery occlusion . In the experimental model of striatum injury in rats, P188 was shown to reduce excitotoxicity-induced tissue loss and macrophage infiltrate .","P188 seals stable defects in cell membranes induced by skeletal muscle cell membranes rupture induced by ischemia-reperfusion injury, electroporation, irradiation, and heat damage . The full mechanism of action of P188 in inducing cytoprotective effects is not clear; however, based on _in vitro_ experiments and the structural similarity to plasmalemma, P188 may be directly incorporated into the phospholipid bilayer to attenuate the extent of tissue injury . Its high surface activity facilitates P188 to be inserted into lipid monolayers . P188 is proposed to exert localized actions by only interacting with damaged and compromised bilayers where the local lipid packing density is reduced . In addition to the direct interaction with the membrane, P188 was shown to inhibit MMP-9 protein levels and activity, as well as the NF-κB signal pathway, in the model of acute cerebral ischemia, which is associated with increased BBB permeability leading to cerebral edema and increased penetration . MMP-9 is a key factor in extracellular matrix (ECM) degradation and BBB disruption.",null,"Therapeutic strategy associated"]
[1368,"DB11338","approved; nutraceutical","biotech","Clove oil","Caryophylii floris aetheroleum; Caryophyllus aromaticus bud oil; Clove bud oil; Clove volatile oil; Ding xiang bud oil; Eugenia aromatica bud oil; Eugenia caryophyllata bud oil; Eugenia caryophyllus (clove) bud oil; Eugenia caryophyllus (clove) flower oil; Syzygium aromaticum bud oil; Syzygium aromaticum oil",null,null,"Clove oil is obtained by extraction from the dried flower buds of the clove plant. Traditionally, it has been used as a flavouring spice in foods, or as a fragrance. It is also found in topical analgesics. Clove oil has shown to exert some antimicrobial activities. The antioxidant and antimicrobial activity of clove is higher than that of many fruits, vegetables, and other spices .\r\n\r\nClove is native of Indonesia but is now cultured in several parts of the world, including Brazil in the state of _Bahia_. This plant represents one of the richest source of phenolic compounds such as _eugenol_, _eugenol acetate_ and _gallic acid_ and has great potential for pharmaceutical, cosmetic, food and agricultural applications .\r\n\r\nInterestingly, clove oil has been studied for its potential benefit in treating neuropathic pain, as well as vaginal candidiasis with promising results , .\r\n\r\nThe FDA categorizes clove oil as generally recognized as safe (GRAS) for use in dental cement or as a food additive .","8000-34-8",null,"Clove oil is primarily indicated in conditions like colic, flatulence, and toothache .","Clove (Eugenia caryophyllata Thunb. ) essential oil (CEO) has been demonstrated to possess antimicrobial, antifungal, antiviral, antioxidant, anti-inflammatory, anti-histamine, and anticancer properties. However, few studies have focused on its topical use , .\r\n\r\nClove essential oil, used as an antiseptic in oral infections, inhibits gram-negative and gram-positive bacteria as well as yeast .\r\n\r","The chief constituent present in clove oil is the phenol \"_eugenol_\" which is present in amounts up to 85%. Clove oil acts as a germicide  to Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa . \r\n\r\nClove oil is thought to inhibit prostaglandin synthesis, thereby reducing painful symptoms .\r\n\r\nEugenol, the main constituent of clove oil is purported to have anticancer action. In one study, eugenol-treated HL-60 cells showed features of apoptosis including DNA fragmentation and formation of DNA ladders in agarose gel electrophoresis. It was observed that eugenol transduced the apoptotic signal via reactive oxygen species (ROS) generation, inducing mitochondrial permeability transition (MPT), decreasing anti-apoptotic protein _bcl-2_ level, inducing _cytochrome c_ release to the cytosol, and subsequent apoptotic cell death. When taken together, the study showed that ROS plays a critical role in eugenol-induced apoptosis in _HL-60_, and this is the first report on the mechanism of the anticancer effect of eugenol .","Vascular cell adhesion protein 1 antagonist; C-X-C motif chemokine 10; Collagen alpha-1(I) chain; Granulocyte-macrophage colony-stimulating factor receptor subunit alpha","Therapeutic strategy associated"]
[1369,"DB11358","investigational; nutraceutical","biotech","Evening primrose oil","Oenothera biennis (evening primrose) oil; Oenothera biennis (evening primrose) seed extract; Oenothera biennis l. oil; Oenothera biennis seed extract; Oenothera biennis seed oil; Oenothera lamarckiana l. oil; Oenothera muricata seed oil; Oenothera oil; Oenothera pycnocarpa seed oil; Oenotherae biennis oleum; Oils, glyceridic, evening primrose; Oleum oenotherae erythrospinae; Primrose oil",null,null,"Evening primrose oil comes from the extraction from _Oenothera biennis_ seeds and it is commonly used as an alternative source for omega-6 essential fatty acids. In its composition it presents some fatty acids such as  and . Evening primrose oil has been filled for the FDA by Humanetics Corporation on April 2000 to be a new dietary ingredient but its current status is \"Inadequate basis for expectation of safety\". By Health Canada, evening primrose oil is approved in over-the-counter combination dietary supplements. By the EMA, evening primrose oil is approved in herbal preparations.","308064-97-3",null,"Evening primrose oil is used as part of over-the-counter dietary supplements.\r\n\r\nIt is also used for the treatment of systemic inflammatory diseases and for women's health conditions such as cyclical mastalgia. These indications do not have sufficient evidence of their effectiveness. It was used for the treatment of atopic dermatitis in the United Kingdom but it is currently withdrawn due to lack of evidence of effectiveness.","The effectivity of evening primrose oil is debatable as the evidence is very limited. Evening primrose oil improves the essential fatty acid content in plasma, erythrocyte, and platelet lipids. It has also been registered to increase alpha-tocopherol levels in non-diabetic and type I diabetic patients. Evening primrose oil affects the fatty acid composition of serum lipids and adipose tissue as well as it helps maintain normal cellular structures and it serves as a prostaglandin precursor. Administration of evening primrose oil is part of long-term therapy and thus, immediate results are never expected.","Evening primrose oil presents a content of 74%  and 9%  from which the later seems to be the key active ingredient of this oil. These major essential fatty acids are required for the normal structure of cell membranes and they are not synthesized endogenously. The therapeutic activity of evening primrose oil is attributed to the direct action of its essential fatty acids on immune cells as well as to an indirect effect on the synthesis of eicosanoids. The actions of highly unsaturated fatty acids in tissues and eicosanoids are thought to be implicated in inflammatory and immunologic pathogeneses.\r\n\r\nThe essential fatty acids found in evening primrose oil are involved in the biosynthesis of prostaglandin. For this activity, the main involved component is the . The presence of this essential fatty acid allows the synthesis of anti-inflammatory substances such as 15-hydroxy-eicosatrienoic acid and prostaglandin E1.",null,"Therapeutic strategy associated"]
[1370,"DB11362","approved","small molecule","Selexipag","Selexipag","C26H32N4O4S","CC(C)N(CCCCOCC(=O)NS(C)(=O)=O)C1=NC(C2=CC=CC=C2)=C(N=C1)C1=CC=CC=C1","Selexipag was approved by the United States FDA on December 22, 2015 for the treatment of pulmonary arterial hypertension (PAH) to delay disease progression and reduce risk of hospitalization. PAH is a relatively rare disease with usually a poor prognosis requiring more treatment options to prolong long-term outcomes. Marketed by Actelion Pharmaceuticals under brand name Uptravi, selexipag and its active metabolite, ACT-333679 (MRE-269), act as agonists of the prostacyclin receptor to increase vasodilation in the pulmonary circulation and decrease elevated pressure in the blood vessels supplying blood to the lungs.","475086-01-2","496.63","Selexipag is indicated for the treatment of pulmonary arterial hypertension (PAH) to delay disease progression and reduce risk of hospitalization.","At the maximum tolerated dose of 1600 mcg twice per day, selexipag was not found to prolong the QT interval to a clinically relevant extent. Both selexipag and its metabolite caused concentration-dependent inhibition of platelet aggregation in vitro with IC50 of 5.5 µM and 0.21 µM, respectively. However, at clinically relevant concentrations, there was no effect on platelet aggregation test parameters following multiple dose administration of selexipag in healthy patients.","Selexipag is a selective prostacyclin (IP, also called PGI2) receptor agonist. The key features of pulmonary arterial hypertension include a decrease in prostacyclin and prostacyclin synthase (enzyme that helps produce prostacyclin) in the lung. Prostacyclin is a potent vasodilator with anti-proliferative, anti-inflammatory, and anti-thrombotic effects; therefore, there is strong rationale for treatment with IP receptor agonists. Selexipag is chemically distinct as it is not PGI2 or a PGI2 analogue and has high selectivity for the IP receptor. It is metabolized by carboxylesterase 1 to yield an active metabolite (ACT-333679) that is approximately 37 times more potent than selexipag. Both selexipag and its metabolite are selective for the IP receptor over other prostanoid receptors.","Prostacyclin receptor agonist","Therapeutic strategy associated"]
[1371,"DB11365","experimental","small molecule","Sennosides","Senna glycosides; Sennoside; Sennosides","C42H38O20","OCC1OC(OC2=C3C(=O)C4=C(C=C(C=C4O)C(O)=O)C(C4C5=CC=CC(OC6OC(CO)C(O)C(O)C6O)=C5C(=O)C5=C4C=C(C=C5O)C(O)=O)C3=CC=C2)C(O)C(O)C1O","Sennosides (also known as senna glycoside or senna) is a medication used to treat constipation and empty the large intestine before surgery. The medication is taken by mouth or via the rectum. It typically begins working in minutes when given by rectum and within twelve hours when given by mouth. It is a weaker laxative than bisacodyl or castor oil. Sennoside A, one of the sennosides present in the laxative medication, has recently proven effective in inhibiting the ribonuclease H (RNase H) activity of human immunodeficiency virus (HIV) reverse transcriptase .","517-43-1","862.746","For the over the counter treatment of constipation.","Senna stimulates peristalsis and increases fecal water content to increase motility of feces through the large intestine.","Sennoside A and B, the components of senna, are metabolized by gut bacteria into the active metabolite rheinanthrone . Rheinanthrone  appears to increase cyclooxegenase 2 (COX2) expression in macrophage cells leading to an increase in prostaglandin E2 (PGE2). This increase in PGE2 is associated with a decrease in aquaporin 3 expression in mucosal epithelial cells of the large intestine. A decrease in aquaporin 3 expression likely produces the laxative effect by restricting water reabsorption by the large intestine thereby increasing fecal water content. The exact mechanism by which rheinanthrone increases COX2 expression is unknown. Rheinanthrone  also stimulates peristalsis in the large intestine although the mechanism behind this effect is unknown. Rhein , another active metabolite is thought to excite submucosal acetylcholinergic neurons resulting in increased chloride and prostaglandin secretion. The movement of chloride ions into the large intestine would also help to draw water into the lumen.","Aquaporin-3 inhibitor; Reverse transcriptase/RNaseH inhibitor","Therapeutic strategy associated"]
[1372,"DB11367","withdrawn","small molecule","Cefroxadine","Cefroxadine","C16H19N3O5S","[H][C@]12SCC(OC)=C(N1C(=O)[C@H]2NC(=O)[C@H](N)C1=CCC=CC1)C(O)=O","Cefroxadine is an orally available cephalosporin antibiotic. As part of its drug class, it shares structural properties to  as well as its activity spectrum. It was used in Italy but has since been withdrawn.","51762-05-1","365.4","Was used for the treatment of bacterial infections.","Cefroxadine is a cephalosporin antibiotic which produces a bactericidal effect on susceptible bacteria .","Cefrixadine is a cephalosporin antibiotic, a class of β-lactam antibiotics similar to penicillins, which binds to and inhibits penicillin binding proteins (PBPs) . PBPs are responsible for catalyzing the transpeptidase reaction which cross-links the peptide side chains on the sugar residues of a peptidoglycan unit, adding the unit to the peptidoglycan layer. This disrupts the balance between the hydrolysis of peptidoglycan, in order to insert new peptidoglycan units, by murein hydrolase and the attachment of the new units which leads to overall destruction of the peptidoglycan layer. With the loss of its peptidoglycan layer the cell also loses its resistance to the high osmotic pressure inside its membrane and lyses.","Penicillin-binding protein 1B inhibitor","Indication associated"]
[1373,"DB11386","approved; investigational; vet_approved","small molecule","Chlorobutanol","Chloretone; Chlorobutanol","C4H7Cl3O","CC(C)(O)C(Cl)(Cl)Cl","Chlorobutanol, or chlorbutol, is an alcohol-based preservative with no surfactant activity . It also elicits sedative-hypnotic and weak local anesthetic actions in addition to antibacterial and antifungal properties. Similar in nature to chloral hydrate, it is formed by the simple nucleophilic addition of chloroform and acetone. \r\n\r\nAs a long-term stabilizer of multi-ingredient preparations, chlorobutanol is normally used at a concentration of 0.5%. At this concentration, it also conserves its antimicrobial activity. \r\n\r\nDue to the long terminal half-life of 37 days, the use of chlorobutanol as a sedative is limited because of the considerable accumulation which will occur following multiple dosing . Chlorobutanol is a common detergent preservative in eye drops and other ophthalmic therapeutic formulations .","57-15-8","177.45","No approved therapeutic indications on its own.","Chlorobutanol is a detergent preservative with a broad spectrum of antimicrobial activity . _In vitro_, chlorobutanol demonstrated to inhibit platelet aggregation and release via unknown mechanisms . A study proposes that the antiplatelet effect of chlorobutanol may occur from inhibition of the arachidonic acid pathway . It attenuated thromboxane B2 formation, elevation of cytosolic free calcium, and ATP release, and additionally exhibited a significant inhibitory activity toward several aggregation inducers in a time- and concentration-dependent manner . Chlorobutanol may exert a direct negative inotropic effect on myocardial cells to isometric tension produced by the heart . Chlorobutanol was shown to induce conjunctival and corneal cell toxicity _in vitro_: at a concentration of 0.1%, Cbl caused near depletion of the squamous layer while degeneration of corneal epithelial cells, generation of conspicuous membranous blebs, cytoplasmic swelling, and occasional breaks in the external cell membrane were observed at a concentration of 0.5% .","As a detergent, chlorobutanol disrupts the lipid structure of the cell membrane and increases the cell permeability, leading to cell lysis . It induces conjunctival and corneal cell toxicity via causing cell retraction and cessation of normal cytokines, cell movement, and mitotic activity . It disrupts the barrier and transport properties of the corneal epithelium as well as inhibits the utilization of oxygen by the cornea . Chlorobutanol also inhibits oxygen use by the cornea, which increases susceptibility to infection .","Potassium voltage-gated channel subfamily H member 2","Therapeutic strategy associated"]
[1374,"DB11560","approved; investigational","small molecule","Lesinurad","{[5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}acetic acid; Lesinurad","C17H14BrN3O2S","OC(=O)CSC1=NN=C(Br)N1C1=CC=C(C2CC2)C2=C1C=CC=C2","Lesinurad is an oral uric acid transporter 1 (URAT1) inhibitor indicated for the treatment of hyperuricemia associated with gout. It reduces serum uric acid concentration through the inhibition of URAT1, an enzyme responsible for reuptake of uric acid from the renal tubule, and OAT4, another uric acid transporter associated with diuretic-induced hyperuricemia.\r\n\r\nMarketed as the product Zurampic, it is indicated for use in combination with a xanthine oxidase inhibitor for the treatment of hyperuricemia associated with gout in\r\npatients who have not achieved target serum uric acid levels with a xanthine oxidase inhibitor alone. In August 2017, a combination oral therapy consisting of lesinurad and  was FDA-approved under the brand name Duzallo indicated for the treatment of gout-related hyperuricemia in patients with uncontrolled gout.","878672-00-5","404.28","For use, in combination with a xanthine oxidase inhibitor, for the treatment of hyperuricemia associated with gout in patients who have not achieved target serum uric acid levels with a xanthine oxidase inhibitor alone.","Dose-dependent reductions in serum uric acid levels and increases in urinary uric acid excretion have been observed following single and multiple oral doses of lesinurad.","Lesinurad inhibits the activity of uric acid transporter 1 (URAT1) and organic anion transporter 4 (OAT4). URAT1 is a major transporter enzyme responsible for reuptake of uric acid from the renal tubules; inhibition of URAT1 function thereby increases excretion of uric acid.","Solute carrier family 22 member 12 inhibitor; Solute carrier family 22 member 11 inhibitor","Indication associated"]
[1375,"DB11569","approved; investigational","biotech","Ixekizumab","Ixekizumab",null,null,"Ixekizumab is a humanized immunoglobulin G subclass 4 (IgG4) monoclonal antibody (mAb) against interleukin-17A (IL-17A) and prevents it from interacting with the IL-17A receptor. As IL-17A is a pro-inflammatory cytokine involved in inflammation and immune responses, blocking its effect is beneficial for use in inflammatory conditions. In particular, IL-17A has been found to be implicated in a variety of autoimmune diseases including Rheumatoid Arthritis and plaque psoriasis. \r\n\r\nIxekizumab is produced by recombinant DNA technology in a recombinant mammalian cell line and purified using standard technology for bioprocessing. Ixekizumab is comprised of two identical light chain polypeptides of 219 amino acids each and two identical heavy chain polypeptides of 445 amino acids each, and has a molecular weight of 146,158 Daltons for the protein backbone of the molecule. It is indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.","1143503-69-8",null,"Ixekizumab is indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.",null,"Ixekizumab is a humanized immunoglobulin G subclass 4 (IgG4) monoclonal antibody (mAb) against interleukin-17A (IL-17A) and prevents it from interacting with the IL-17A receptor. As IL-17A is a pro-inflammatory cytokine involved in inflammation and immune responses, blocking its effect is beneficial for use in inflammatory conditions. In particular, IL-17A has been found to be implicated in a variety of autoimmune diseases including Rheumatoid Arthritis and plaque psoriasis.","Interleukin-17A antibody","Therapeutic strategy associated"]
[1376,"DB11580","approved; investigational","biotech","Ravulizumab","Ravulizumab; ravulizumab-cwvz",null,null,"Ravulizumab is considered a long-acting complement 5 (C5) inhibitor that has been undergoing clinical trials for the treatment of paroxysmal nocturnal haemoglobinuria (PNH) as of 4 February, 2016. A drug similar to ravulizumab (ALXN1210), called eculizumab, is currently approved for the treatment of PNH in 46 countries under the brand name Soliris®. Ravulizumab is considered by Alexion Pharmaceuticals Inc. to be a \"next-generation\" eculizumab molecule. Ravulizumab was subsequently approved by the US FDA in December of 2018 for a variety of beneficial characteristics that make it an advanced, next-generation agent in comparison to eculizumab . In particular, ravulizumab is currently the first and only long-acting C5 complement inhibitor that can be administered every eight weeks for the treatment of adult patients with PNH whereas eculizumab is a bi-weekly treatment . Moreover, virtually all of the phase 3 trial results for ravulizumab have demonstrated the equivalent efficacy and safety established by eculizumab and that patients transition safely and effectively from using eculizumab to ravulizumab . Subsequently, whereas PNH patients may have needed to previously plan their lives rather strictly around the bi-weekly infusion administrations of eculizumab, with ravulizumab such patients can find a more relaxed dosing schedule of only six or seven infusions over an entire year .\r\n\r\nJust as the US FDA permitted a timely and expedited approval of ravulizumab ahead of the Prescription Drug User Fee Act (PDUFA) date of February 18, 2019 following the use of a rare disease priority review voucher by Ultomiris (ravulizumab) developer Alexion for many of the aforementioned beneficial treatment reasons, regulatory authorities in the European Union (EU) and Japan have currently accepted and are reviewing applications for the approval of Ultomiris (ravulizumab) as a treatment for adults with PNH as well .","1803171-55-2",null,"Ravulizumab is indicated for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH) .","Immediate and complete inhibition of serum-free complement protein C5 (concentration of less than 0.5 mcg/mL) was observed by the end of the first ravulizumab infusion and sustained throughout the entire 26-week treatment period in all patients, both complement-inhibitor naïve and previously treated with eculizumab .\r\n\r\nThe extent and duration of the pharmacodynamic response in patients with PNH were exposure dependent for ravulizumab . Free C5 levels of <0.5 mcg/mL were correlated with maximal intravascular hemolysis control and complete terminal complement inhibition .\r\n\r\nComplete terminal complement inhibition following initiation of ravulizumab treatment led to normalization of serum LDH by week 4 in complement-inhibitor naïve patients and maintained LDH normalization in patients previously treated with eculizumab .","Paroxysmal nocturnal hemoglobinuria (PNH) is a chronic, progressive, debilitating and life-threatening ultra-rare blood disorder characterized by hemolysis (destruction of red blood cells) that is mediated by the uncontrolled activation of the complement system, a component of the body’s immune system .\r\n\r\nRavulizumab is subsequently a terminal complement inhibitor that specifically binds to the particular complement protein C5 with high affinity, thereby inhibiting its cleavage to C5a (the proinflammatory anaphylatoxin) and C5b (the initiating subunit of the terminal complement complex ) and preventing the generation of the terminal complement complex C5b9 . Ravulizumab inhibits terminal complement-mediated intravascular hemolysis in patients with PNH .","Complement C5 inhibitor","Therapeutic strategy associated"]
[1377,"DB11581","approved; investigational","small molecule","Venetoclax","4-{4-[(4'-chloro-5,5-dimethyl[3,4,5,6-tetrahydro[1,1'-biphenyl]]-2-yl)methyl]piperazin-1-yl}-N-(3-nitro-4-{[(oxan-4-yl)methyl]amino}benzene-1-sulfonyl)-2-[(1H-pyrrolo[2,3-b]pyridin-5-yl)oxy]benzamide; Venetoclax","C45H50ClN7O7S","CC1(C)CCC(CN2CCN(CC2)C2=CC=C(C(=O)NS(=O)(=O)C3=CC=C(NCC4CCOCC4)C(=C3)[N+]([O-])=O)C(OC3=CN=C4NC=CC4=C3)=C2)=C(C1)C1=CC=C(Cl)C=C1","Venetoclax is a BCL-2 inhibitor that was initially approved by the FDA in April 2016 . Proteins in the B cell CLL/lymphoma 2 (BCL-2) family are important regulators of the apoptotic (programmed cell death) process , .  Venetoclax is used to treat chronic lymphocytic leukemia (CLL) and certain types of small lymphocytic lymphoma . CLL is the most prevalent leukemia diagnosed in Western countries . Venetoclax was developed through reverse engineering of the BCL-2 protein family inhibitor, navitoclax . Venetoclax is approximately 10 times more potent than navitoclax with regard to induction of apoptosis in CLL cells . A new indication was approved in 2018 for the treatment patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy .  Previously, this drug was indicated only for patients with 17p gene deletion .","1257044-40-8","868.45","A BCL-2 inhibitor indicated for the treatment of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy .","Venetoclax induces rapid and potent onset apoptosis of CLL cells, powerful enough to act within 24h and to lead to tumor lysis syndrome  , , . Selective targeting of BCL2 with venetoclax has demonstrated a manageable safety profile and has been shown to induce significant response in patients with relapsed CLL (chronic lymphocytic leukemia) or SLL (small lymphocytic leukemia), including patients with poor prognostic features .  This drug is not expected to have a significant impact on the cardiac QT interval . Venetoclax has demonstrated efficacy in various types of lymphoid malignancies, including relapsed/ refractory CLL harboring deletion 17p, with an overall response rate of approximately 80% .","Proteins in the B cell CLL/lymphoma 2 (BCL-2) family are necessary regulators of the apoptotic (anti-cell programmed death) process. This family comprises proapoptotic and prosurvival proteins for various cells. Cancer cells evade apoptosis by inhibiting programmed cell death (apoptosis). The therapeutic potential of directly inhibiting prosurvival proteins was unveiled with the development of navitoclax, a selective inhibitor of both BCL-2 and BCL-2-like 1 (BCL-X(L)), which has demonstrated clinical efficacy in some BCL-2-dependent hematological cancers . Selective inhibition of BCL-2 by venetoclax, sparing BCL-xL enables therapeutic induction of apoptosis without the negative effect of thrombocytopenia , .   Venetoclax helps restore the process of apoptosis by binding directly to the BCL-2 protein, displacing pro-apoptotic proteins, leading to mitochondrial outer membrane permeabilization and the activation of caspase enzymes. In nonclinical studies, venetoclax has shown cytotoxic activity in tumor cells that overexpress BCL-2 .","Apoptosis regulator Bcl-2 antagonist&inhibitor","Therapeutic strategy associated"]
[1378,"DB11582","experimental","small molecule","Thiocolchicoside","TCC; Thiocolchicine 2-glucoside analog; Thiocolchicoside","C27H33NO10S","COC1=C(O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)C=C2CC[C@H](NC(C)=O)C3=CC(=O)C(SC)=CC=C3C2=C1OC","Thiocolchicoside is a semi-synthetic derivative of the colchicine, a natural anti-inflammatory glycoside which originates from the flower seeds of _Superba gloriosa_.  It is a muscle relaxant with anti-inflammatory and analgesic effects.  It has potent convulsant activity and should not be administered to individuals prone to seizures.","602-41-5","563.62","\r\nThiocolchicoside is a  skeletal muscle-relaxant drug used in the treatment of orthopedic, traumatic and rheumatologic disorders . It is indicated as an adjuvant drug in the treatment of painful muscle contractures and is indicated in acute spinal pathology, for adults and adolescents 16 years of age and older . Recent studies have examined its effect on muscle tone, stiffness, contractures, and soreness experienced by athletes during sporting competitions .","Thiocholchicoside is a muscle relaxing agent that works through selective binding to the GABA-A receptor. It prevents muscle contractions by activating the GABA inhibitory motor pathway .\r\n\r\nThis medication acts as a competitive GABA receptor antagonist and inhibits glycine receptors with similar potency as nicotinic acetylcholine receptors. It has powerful convulsant activity and should not be used in individuals at risk for seizures .\r\n\r\nUsed in combination with glafenine and meprobamate to tranquilize patients undergoing hysterosalpingography. In the treatment of painful muscle spasms. Thiocolchicoside acts both in contractures with a central cause and in contractures of reflex type, rheumatic and traumatic. It also alleviates symptoms of spastic sequelae of hemiparesis, Parkinson's disease and iatrogenic Parkinson symptoms, particularly neurodyslectic syndrome.  Some other conditions that may benefit from this medication are acute and chronic lumbar and sciatic pain, cervico-brachial neuralgia, persistent torticollis, post-traumatic and post-operative pain .","Thiocolchicoside, is a synthetic sulfur derivative of colchicoside, a naturally occurring glucoside contained in the Colchicum autumnale plant. Thiocolchicoside has a selective and potent afﬁnity for g-aminobutyric acid A (GABA-A) receptors and acts on muscular contractures by activating the GABA inhibitory pathways thereby behaving as a potent muscle relaxant .  Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the human cortex .  GABAergic neurons are involved in myorelaxation, anxiolytic treatment, sedation, and anesthetics. GABA can also modulate heart rate and blood pressure.\r\n\r\nIt also has an affinity for the inhibitory glycine receptors (i.e., have glycomimetic and GABA mimetic activity), therefore acts as a muscle relaxant. Glycine is an inhibitory neurotransmitter and acts as an allosteric regulator of NMDA (N-methyl-D-aspartate) receptors. It is involved in the processing of motor and sensory data, thereby regulating movement, vision, and audition. Inhibitory neurotransmitter in spinal cord, allosteric regulator of NMDA receptors .\r\n\r\nIn one study, thiocolchicoside inhibited the function of recombinant human strychnine-sensitive glycine receptors composed of the alpha1 subunit with a potency (median inhibitory concentration of 47 microM) lower than that apparent with recombinant GABA(A) receptors. The drug also inhibited the function of human nicotinic acetylcholine receptors made of the alpha4 and beta2 subunits, however, this effect was partial and moreover only apparent at high concentrations. Thiocolchicoside demonstrated no effect on the function of 5-HT(3A) serotonin receptors .","GABA(A) Receptor antagonist; Glycine receptor subunit alpha-1 antagonist; Tumor necrosis factor ligand superfamily member 11 antagonist","Target associated"]
[1379,"DB11584","approved","small molecule","Pipradrol","Pipradrol","C18H21NO","[H]N1CCCCC1C(O)(C1=CC=CC=C1)C1=CC=CC=C1","Pipradrol (Meratran)  was initially developed in the 1950s as an antidepressant, however, the adverse effects associated with its use and its abuse potential led to its withdrawal and international regulation .  Pipradrol was made illegal in many countries in 1970s because of its potential for abuse. It is currently classified under the Misuse of Drugs Act as a Class C substance .\r\n\r\nExperimentation with the drug and its derivatives for recreational purposes has led to many cases of acute toxicity and has been linked to three fatalities. The social and in particular acute clinical harms of pipradrol derivatives have led to their control under the Misuse of Drugs Act 1971 in the UK in 2012 .\r\n\r\nInterestingly, this drug has been studied for bactericidal properties, however, is not currently, used for this purpose . In addition to this, it has shown favorable effects in postpartum depressive symptoms .","467-60-7","267.372","Used to manage fatigue  and depression , , , . Used as an adjunct therapy in the management of obesity .","Pipradrol (Meratran) is a psychoactive agent and a central nervous system stimulant that has proven useful in the field of psychiatry .\r\n\r\nPipradrol was initially used as an adjunct in the dietary management of obesity as well as for the management of dementia symptoms. Numerous reports have been made on the properties of pipradrol, demonstrating its favorable effects in the treatment of depression and fatigue in addition to a variety of other conditions including narcolepsy, spasmodic torticollis, schizophrenia and in geriatric practice .","Pipradrol and pipradrol derivatives are norepinephrine and dopamine reuptake inhibitors .  \r\n\r\nIn a pharmacokinetic study, it was shown that pipradrol conditioned place preference (CPP)  was blocked by selective D1 dopamine antagonist, implicating that a rewarding effect of pipradrol may involve the activation of D1 dopamine receptors.\r\n\r\nPipradrol has a definite cerebral stimulating effect without affecting the blood pressure or respiration and has been used to counteract post-anaesthetic and chlorpromazine depression in man. Structurally related to phenylmethylamphetamine, a potent stimulant with a long half-life, pipradrol differs from amphetamine in that its action is more intense at higher centers, it does not exhibit pressor activity, there is no post-excitement depression, and this drug does not decrease appetite, as occurs with amphetamine .","D(1) dopamine receptor agonist","Therapeutic strategy associated"]
[1380,"DB11588","approved; investigational","small molecule","Carbon monoxide","Carbon monoxide; carbon(II) oxide; CO","CO",null,"Carbon monoxide (CO) is a colorless, odorless, and tasteless gas that has a slightly lower density than air. It is toxic to hemoglobin utilizing animals (including humans), when encountered in concentrations above about 35 ppm, although it is also formed in normal animal metabolism in low quantities, and is thought to have some normal biological/homeostatic functions . Carbon monoxide (CO), is a ubiquitous environmental product of organic combustion, which is also formed endogenously in the human body, as the byproduct of heme metabolism . Exhaled CO (eCO), similar to exhaled nitric oxide (eNO), has been evaluated as a candidate breath biomarker of pathophysiological states, including smoking status, and inflammatory diseases of the lung and other organs. Exhalation of corbon monoxide values have been studied as potential indicators of inflammation in asthma, stable COPD and exacerbations, cystic fibrosis, lung cancer, and during surgery or critical care .\r\n\r\nA test of the diffusing capacity of the lungs for carbon monoxide (DLCO), is one of the most clinically valuable tests of lung function testing. The technique was first described  100 years ago, and applied to clinical practice many years after. The DLCO measures the ability of the lungs to transfer gas from inhaled air to the red blood cells in pulmonary capillaries. The DLCO test is both convenient and simple for the patient to undergo. The ten seconds of breath-holding required for the DLCO maneuver is easier for most patients to perform than the forced exhalation required for other respiratory tests .\r\n\r\nCarbon monoxide is presently used in small amounts in low oxygen modified atmosphere packaging systems (MAP) for fresh meat to stabilize and maintain natural meat color. This use of CO has been generally recognized as safe (GRAS) in several packaging applications for fresh meat products. Since 2002, FDA has favorably reviewed three GRAS notifications for carbon monoxide use in fresh meat packaging . The FDA classifies this drug as permitted as a food additive in the packaging and preparation of food products, while following the federal code of regulations .\r\n\r\nThere have been several concerns voiced of over the use of carbon monoxide in food products , , . The European Union has banned the use of carbon monoxide as a color stabilizer in meat and fish. A December 2001 report from the European Commission's Scientific Committee on Food concluded that the gas did not pose a risk provided that food was maintained adequately cold during storage and transport to prevent the growth of microorganisms .  In New Zealand, the use of carbon monoxide in fish preparation has been banned, as it may mask the effects of food spoilage and bacterial growth .","630-08-0","28.01","Used as a marker of respiratory status in spirometry tests , .\r\n\r\nFood additive for pigment fixation in meat .","Carbon monoxide is used to measure the diffusing capacity for carbon monoxide (DLCO), also known as the transfer factor for carbon monoxide. It is a measure of the gas transfer from inspired gas to the circulatory system (red blood cells in particular) .  It is used in a particular pulmonary function test called \"the single-breath test\" .\r\n\r\nDLCO, measured for clinical and research purposes almost exclusively by the single-breath method is an important and very useful pulmonary function test. It is useful in the evaluation of patients with dyspnea, obstructive lung diseases, restrictive lung diseases, and in patients with diseases of the pulmonary vasculature.  The measurement of DLCO using carbon monoxide is representative of the surface area available, the volume of blood present in the pulmonary capillaries, as well as the thickness of the alveolar-capillary membrane .\r\n\r\n\r\n**Conditions that increase DLCO:** Heart failure, erythrocythemia, alveolar hemorrhage, asthma\r\n\r\n\r\n**Conditions that decrease DLCO:** emphysema, pulmonary fibrosis, pulmonary hypertension, pulmonary embolism\r\n\r\n\r\nIn addition to the above uses, carbon monoxide (CO) is increasingly being accepted in recent years as a protective molecule with important signaling capabilities in both physiological/homeostatic and pathophysiological situations. The endogenous production of CO occurs via the activity of constitutive (heme oxygenase 2) and inducible (heme oxygenase 1) heme oxygenase enzymes, which are both responsible for the breakdown of heme. Through the generation of its products, which in addition to carbon monoxide, includes the biliary pigments biliverdin, bilirubin and ferrous iron, the heme oxygenase 1 system also have an essential role in the regulation of the stress response and in cell adaptation to injury. Preclinical studies have suggested potential benefits of carbon monoxide in cardiovascular disease, inflammatory disorders, as well as organ transplantation .","\r\nIn respiratory testing, the diffusing capacity for carbon monoxide (DLCO) is a measure of the ability of gas to transfer from the alveoli across the alveolar epithelium and the capillary endothelium to the red blood cells. The DLCO depends not only on the area and thickness of the blood-gas barrier but additionally on the volume of blood in the pulmonary capillaries. The distribution of alveolar volume and ventilation also has an impact on the measurement .\r\n\r\nDLCO is measured by sampling end-expiratory gas for carbon monoxide (CO) after patients inspire a small and safe amount of exogenous CO, hold their breath, and exhale. Measured DLCO is adjusted for alveolar volume (which is estimated from dilution of helium) and the patient’s hematocrit level. DLCO is reported as mL/min/mm Hg and as a percentage of a predicted value .\r\n\r\nCarbon monoxide exerts effects on cell metabolism through both hypoxic and non-hypoxic modes of action. Both mechanisms of action are thought to be the result of the ability of carbon monoxide to bind strongly to heme and alter the function and/or metabolism of heme proteins. The binding affinity of carbon monoxide for hemoglobin is more than 200 times greater than that of oxygen for hemoglobin. The formation of carboxyhemoglobin (COHb) decreases the O2 carrying capacity of blood and disrupts the release of O2 from Hb for its use in tissues. Through similar mechanisms, carbon monoxide diminishes the O2 storage in muscle cells by binding to and displacing O2 from, myoglobin. Though all human tissues are vulnerable to carbon monoxide-induced hypoxic injury, those with the highest O2 demand are especially vulnerable, including the brain and heart .\r\n\r\nMost of the non-hypoxic mechanisms of action of carbon monoxide have been thought to be due to binding of carbon monoxide to heme in proteins other than Hb. The most notable targets of carbon monoxide include components of many important physiological regulatory systems, including brain and muscle oxygen storage and use(myoglobin, neuroglobin); nitric oxide cell signaling  (e.g., nitric oxide synthase, guanylyl cyclase); prostaglandin cell signaling (cyclooxygenase, prostaglandin H synthase); energy metabolism and mitochondrial respiration (cytochrome c oxidase, cytochrome c, NADPH oxidase); steroid and drug metabolism (cytochrome P450); cellular redox balance and reactive oxygen species (ROS; catalase, peroxidases); and numerous transcription factors (e.g., neuronal PAS domain protein, NPAS2, implicated in regulation of circadian rhythm) .\r\n\r\nIn meat processing, carbon monoxide reacts with myoglobin, to form carboxymyoglobin, imparting a red appearance to the meat .\r","Myoglobin inhibitor","Therapeutic strategy associated"]
[1381,"DB11590","approved","small molecule","Thimerosal","[(o-carboxyphenyl)thio]ethylmercury sodium salt; BTL-TML-COVID; BTL-TML-HSV; BTL-TML001; ethyl(2-mercaptobenzoato-S)mercury sodium salt; ethylmercurithiosalicylate sodium; ethylmercurithiosalicylic acid sodium salt; mercurothiolate; o-(ethylmercurithio)benzoic acid sodium salt; sodium ethylmercurithiosalicylate; sodium merthiolate; Thimerosal; Thiomersal; Thiomersalate","C9H9HgNaO2S","[Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O","Thiomersal (INN), commonly known in the U.S. as thimerosal, is an organomercury compound. This compound is a well-established and widely used antiseptic and antifungal agent. \r\n\r\nDeveloped in 1927, thimerosal has been and is still being used as a preservative in some cosmetics, topical pharmaceuticals, and biological drug products, which includes vaccines. There has been significant concern regarding its safety and toxicity in the last several decades. Although thimerosal is banned in several countries, it continues to be included as a preservative in some vaccines in the United States and many vaccines in the developing world .","54-64-8","404.81","Used as preservative in some cosmetics, topical pharmaceuticals, and biological drug products, which includes vaccines .","Thimerosal is an organomercurial compound and derivative of thiosalicyclic acid with antibacterial and antifungal properties . Thimerosal, which consists of approximately 50% mercury by weight, has been one of the most widely used preservatives in vaccines. It is metabolized/degraded to ethylmercury and thiosalicylate. Ethylmercury is an organomercurial that must be carefully distinguished from methylmercury, a closely related substance that has been the focus of many studies. Methylmercury is the type of mercury found in various species of fish .    Experimental data demonstrates that the toxicokinetics of thimerosal (ethylmercury) is vastly different from that of methyl-mercury. Thus, methyl-mercury is not a suitable reference for assessing the risk from exposure to thimerosal-derived mercury .\r\n\r\nPrior to the recent initiative to reduce or eliminate thimerosal from childhood vaccines, the maximum cumulative exposure to mercury via routine childhood vaccinations during the first 6 months of life was 187.5 micrograms. In the most recently formulated vaccines, the maximum cumulative exposure during the first 6 months of life should now be less than 3 micrograms of mercury. Currently, thimerosal may still be used in the early stages of manufacturing of certain childhood vaccines, however, only a trace remains after a chemical purification process. Note that the dose above is indicated for children 1-6 months of age is applicable only in the United States, and other countries may have varying indications .","Although its mechanism of action is not fully understood, thimerosal inhibits sulfhydryl-containing active site of various enzymes and binds to sulfhydryl compounds, including glutathione, cysteine, and sulfhydryl groups of proteins. In addition, thimerosal activates the InsP3 calcium channel on the endoplasmic reticular membrane, thereby triggering the release of intracellular calcium resulting in a calcium-induced calcium-influx of extracellular calcium. Therefore, thimerosal may induce or inhibit various cellular functions that are dependent on the signaling of calcium .\r\n\r\nEthylmercury is metabolized to inorganic mercury more rapidly than methylmercury. This difference in metabolism may account for kidney pathology that can result from toxic quantities. Also, whereas the increase in oxidative stress and induction of apoptosis observed in vitro with large doses (405 μg/L to 101 mg/L) of thimerosal may explain its damaging neurological effects. The effects of low-dose ethylmercury are not completely understood to date. It is known, however, that the shorter half-life of ethylmercury (the metabolite of thimerosal) allows for very limited opportunities of ethylmercury derived from thimerosal in vaccines .\r\n\r\nEthylmercury is a lipophilic cation that is capable of crossing the blood-brain barrier. The octanol/water partition coefficients of methyl and ethylmercury are 1.4 to 1.8, at intracellular pH and , therefore, both organomercury compounds will primarily exist as intracellular lipophilic cations. It has been demonstrated that lipophilic cations accumulate inside mitochondria, in a Nernstian fashion, driven by the steady state membrane potential. As the typical mitochondrial membrane potential of astrocytes and neurons is between 140–170 mV, one would expect the concentration of these organomercury compounds within mitochondria to be approximately 1000 times greater than the cytosolic concentration .\r\n\r\n\r\n\r\n\r\n\r","Methionine synthase antagonist; Cystine/glutamate transporter antagonist; Sodium/potassium-transporting ATPase subunit gamma antagonist","Therapeutic strategy associated"]
[1382,"DB11601","approved","biotech","Tuberculin purified protein derivative","Mycobacterium tuberculosis purified protein derivative; Purified protein derivative of tuberculin; Tuberculin PPD; Tuberculin, purified protein derivative; Tuberculin,purified protein derivative; Tuberculinum",null,null,"Tuberculin Purified Protein Derivative (PPD) is a sterile aqueous solution of a purified protein fraction for intradermal administration as an aid in the diagnosis of tuberculosis. The diagnostic test is commonly referred to as the Mantoux test which serves to minimize the risk of transmission of infection with *Mycobacterium tuberculosis* through early diagnosis and appropriate therapeutic intervention. The purified protein fraction is isolated from culture media filtrates of a human strain of Mycobacterium tuberculosis. It is included in the World Health Organization's List of Essential Medicines.","92129-86-7",null,"Indicated as a diagnostic agent in Mantoux Test used to detect infection with *Mycobacterium tuberculosis*.","It is intradermally administered to facilitate detection of active tuberculosis caused by *Mycobacterium tuberculosis*. Tuberculin PPD is an inactivated purified protein fraction obtained from human strain of *Mycobacterium tuberculosis*and antigen that induces a delayed hypersensitivity response after few hours following administration. When the person has already acquired the tuberculin antigen, the immune response is stimulated to produce antigen-specific T cells that circulate in the bloodstream for up to several months and years. Clinically, a delayed hypersensitivity reaction to tuberculin is a manifestation of previous infection with M tuberculosis or a variety of non-tuberculosis bacteria. In most cases sensitization is induced by natural mycobacterial infection or by vaccination with BCG Vaccine. The antigen causes, pain, edema and infiltration of immune cells in the injection area.","When exposed to *M. tuberculosis* antigen, the sensitization initiates in the regional lymph nodes where T lymphocytes proliferate in response to the antigenic stimulus to give rise to specifically sensitized lymphocytes which may exist in the circulation up to many years. Antigen is presented to T cells by being ingested by antigen presenting cells (APC), which then present it on their surface to lymphocytes in combination with various MHC molecules once they reach local lymph nodes . Tuberculin PPD most likely interacts with toll-like receptor 2 expressed on APCs that initiates an inflammatory response. Subsequent restimulation of these sensitized lymphocytes with the same or a similar antigen, such as the intradermal injection of tuberculin PPD, evokes a local reaction mediated by these cells. This reaction is referred to as a delayed-type hypersensitivity response that includes vasodilation, edema, and the infiltration of lymphocytes, basophils, monocytes, and neutrophils into the site of antigen injection. The sensitized antigen-specific T lymphocytes proliferate and release lymphokines, which mediate the accumulation of other cells at the site . In vitro studies show that Tuberculin PPD promotes the upregulation of vascular endothelial growth factor (VEGF) expression in T lymphocytes through major histocompatibility (MHC) class II interaction with CD4+ T lymphocyte interaction . The reactions are evident after 5-6 hours following administration.","Toll-like receptor 2 ligand","Therapeutic strategy associated"]
[1383,"DB11605","approved","small molecule","Myrrh","Bola resin; Commiphora molmol resin; Commiphora myrrha gum resin; Commiphora myrrha resin; Commiphora myrrha resin extract; Common myrrh; Hirabol myrrh; Mo yao; Moyao (commiphora molmol); Moyao (commiphora myrrha); Myhrra; Myrrh; Myrrh (commiphora molmol); Myrrh (commiphora myrrha); Myrrha; Myrrha (commiphora molmol); Myrrha (commiphora myrrha)",null,null,"Extractives and their physically modified derivatives such as tinctures, concretes, absolutes, essential oils, oleoresins, terpenes, terpene-free fractions, distillates, residues, obtained from Commiphora abyssinica, Burseraceae.","9000-45-7",null,"FDA approved only for use in food. Historically used for indigestion, ulcers, colds, cough, asthma, bronchial congestion, arthritic pain, cancer, leprosy, and syphilis. It is also used orally as a stimulant, antispasmodic, and to increase menstrual flow. Topically, myrrh is used for mild inflammation of the oral and pharyngeal mucosa, aphthous ulcers, gingivitis, chapped lips, hemorrhoids, bedsores, wounds, abrasions, furunculosis, bad breath, and loose teeth. In foods and beverages, myrrh is used as a flavoring component. In manufacturing, myrrh is used as a fragrance and fixative in cosmetics. It is also used in embalming and as incense.","Myrrh reduces the production of cytokines and reduces the effects of inflammation . It is also suggested to produce an analgesic effect . Myrrh produces cell damage and death in various cancer cell types . Myrrh has been observed to exert anantibacterial, antiparasitic, and antifungal activities . Myrrh reduces liver injury in response to carbon tetrachloride insult, suggesting hepoprotective action . It also displays antioxidant properties . Myrrh reduces low density lipoprotein levels . Myrrh appears to be cardioprotective, producing a decrease in heart rate and restoring blood pressure in response to isoproteronol challenge . Myrrh lowers plasma glucose and insulin levels in type 2 diabetes mellitus models suggesting an improvement in insulin sensitivity . Myrrh has been observed to protect against both substance and stress induced gastric lesions .","**Anti-inflammatory:** Myrrh is thought to mediate its anti-inflammatory activity through inducing haem oxygenase activity . Haem oxygenase then appears to prevent the degradation of IKBalpha in response to inflammatory receptor activation. This prevents translocation of nuclear factor kappaB (NFkappaB) to the nucleus and inhibits the expression of genes under its control like cyclooxygenase-2 and the inducible form of nitric oxide synthase. The suppression of the NFkappaB pathway likely also reduces the expression of inflammatory cytokines. Myrhh also inhibits the mitogen activated protein kinase (MAPK) pathway, specifically producing inhibition of p38 and c-jun N-terminal kinase (JNK) . This is associated with a reduction in c-jun and c-fos expression which would likely result in a reduction in activator protein-1 and and inhibition of its associated inflammatory gene expression. Myrrh exibits inhibitory activity against 5-lipoxygenase helping to suppress the production of leukotrienes, another class of inflammatory cytokine . In addition to its effects on the NFkappaB system, myrrh also inhibits the signal transducer and activator of transcription (STAT) -1 and -3 resulting in a decrease in cytokine production by the janus kinase/STAT pathway . Myrrh also reduces the downregulation of suppresor of cytokine synthesis (SOCS) in response to interleukin-1beta and interferon-gamma. SOCS serves as an autoregulator of the JAK/STAT pathway under transcriptional control of STATs and inhibits activation of the pathway.\r\n\r\n**Analgesic:** Myrrh appears to produce an analgesic effect associated with its suppression of prostaglandin production . Myrrh is also suggested to block inward sodium currents .\r\n\r\n**Anticancer:** Myrrh displays an pro-apoptotic effect on cancer cells . This seems to involve members of the Bcl family of proteins . Myrrh induces the expression of the pro-apoptotic protein Bax while decreasing the expression of Bcl-2 and Bcl-xl, the anti-apoptotic members of the Bcl family. At low doses Myrrh seems to activate the MAPK pathway in cancer cells, promoting the phosphorylation of p38 and JNK . The JNK activation in particular appears to mediate an apoptotic influence. Additionally, myrrh appears to induce reactive oxygen species generation in cancer cells further promoting apoptosis.\r\n\r\n**Antibacterial/Antiparasitic/Antifungal:** The precise antibacterial, antiparasitic, and antifungal mechanisms of myrrh are unknown .\r\n\r\n**Hepatoprotective:** Myrrh has been shown to reduce liver injury and upregulation of superoxide dismutase, glutathione peroxidase and catalase in response to carbon tetrachloride insult. This is thought to be due to anti-oxidant properties of myrrh . \r\n\r\n**Antioxidant:** The precise mechanism of myrrh's antioxidant property is unknown.\r\n\r\n**Lipid lowering:** Compounds in myrrh bind to and inhibit the farnesoid X receptor resulting in a reduction in low density lipoprotein . This effect is likely to due the attenuation of the suppression of bile synthesis and a reduction in ileal bile acid binding protein in response to farnesoid X receptor stimulation . Together these would ensure processing of cholesterol into bile and subsequent loss of that bile by reducing reuptake.\r\n\r\n**Cardioprotective:** The exact mechanism of myrrh's cardioprotective effect is unknown.\r\n\r\n**Antidiabetic:** Much of myrrh's antidiabetic action is attrbutable to it's anti-inflammatory action which protects islet beta cells from inflammatory damage during hyperglycemia . The antioxidant properties of myrrh also likely contribute to this effect. \r\n\r\n**Antiulcer:** The antiulcer activity of myrrh is suggested to be due to inhibition of gastric acid secretion, increasing gastric mucus secretion, and myrrh's antioxidant properties .\r\n\r\n\r","Bile acid receptor antagonist; Nuclear receptor subfamily 1 group I member 2 partial agonist; Peroxisome proliferator-activated receptor alpha agonist","Therapeutic strategy associated"]
[1384,"DB11611","approved","small molecule","Lifitegrast","Lifitegrast","C29H24Cl2N2O7S","CS(=O)(=O)C1=CC(C[C@H](NC(=O)C2=C(Cl)C3=C(CN(CC3)C(=O)C3=CC=C4C=COC4=C3)C=C2Cl)C(O)=O)=CC=C1","Lifitegrast is a FDA approved drug for the treatment of keratoconjunctivitis sicca (dry eye syndrome). It is a tetrahydroisoquinoline derivative and lymphocyte function-associated antigen-1 ( LFA-1) antagonist that was discovered through the rational design process. The ophthalmic solution was approved in July, 2016 under the trade name Xiidra. It has shown to protect the corneal surface and alleviate the symptoms of dry eye syndrome with fast onset of action and well tolerated profile in both local and systemic setting .","1025967-78-5","615.48","For the treatment of signs and symptoms of keratoconjunctivitis sicca (dry eye syndrome).","Lifitegrast addresses both the symptoms and the resulting ocular surface damage by interfering with ocular inflammatory cycle . Lifitegrast is a lymphocyte function–associated antigen-1 antagonist through direct competitive antagonism and sequentially inhibits the T-cell recruitment, activation, and proinflammatory cytokine release associated with dry eye syndrome .","Lifitegrast binds to the integrin lymphocyte function-associated antigen-1 (LFA-1), a cell surface protein found on leukocytes and blocks the interaction of LFA-1 with its cognate ligand intercellular adhesion molecule-1 (ICAM-1). ICAM-1 may be overexpressed in corneal and conjunctival tissues in dry eye disease. LFA-1/ICAM-1 interaction can contribute to the formation of an immunological synapse resulting in T-cell proliferation/activation and migration to target tissues. In vitro studies demonstrated that lifitegrast may inhibit T-cell adhesion to ICAM-1 in a human T-cell line and may inhibit secretion of inflammatory cytokines, inflammatory mediators, chemokines, TNF-α, and IL-1 in human peripheral blood mononuclear cells.","Integrin alpha-L antagonist","Therapeutic strategy associated"]
[1385,"DB11626","approved","biotech","Tasonermin","Tasonermin; Tumor necrosis factor, soluble form, nonglycosylated",null,null,"Tasonermin is recombinant soluble form tumor necrosis factor &alpha; produced via _Escherichia coli_ cell culture.  It was approved for use by the European Medicines Agency in April of 1999 for use as an adjunt to surgery for the subsequent removal of the tumor and in palliative care for irresectable soft tissue sarcoma of the limbs as the product Beromun. It is administered with  via mild hyperthermic isolated limb perfusion.","94948-59-1",null,"For use in adults as an adjunct to surgery for subsequent removal of the tumour so as to prevent or delay amputation, or in palliative care, for irresectable soft tissue sarcoma of the limbs . Used in combination with melphalan via mild hyperthermic isolated limb perfusion.","Tasonermin is thought to contribute to the destruction of tumor tissue via several direct and indirect effects . \r\n\r\nTasonermin directly inhibits cell proliferation in a variety of cancer cells. It also modifies endothelial cell morphology and reduces their proliferation in tumor microvasculature. Modification of the expression of cell adhesion proteins, proteins affecting coagulation, interleukins, and hematopoietic growth factors favors a procoagulant state resulting in microvascular thrombosis. These changes also increase infiltration of the tumor tissue by leukocytes. \r\n\r\nMonocytes, macrophages, and granulocytes are activated allowing better adherence to the endothelium and subjecting the tumor cells to phagocytosis and respiratory bursts as well as producing degranulation of immune cells to further enhance inflammatory activity. Active antigen presenting cells are able to activate and induce proliferation of T- and B-lymphocyte cells to allow the adaptive immune system to contribute to tumor cell damage.\r\n\r\nThese changes lead to hemorraghic necrosis of the tumor.","Since tasonermin is recombinant TNF-&alpha;, it functions exactly as endogenous TNF-&alpha; does. The direct cytotoxic effect of TNF-&alpha; is mediated by TNF-&alpha; receptor 1 . The bound receptor activates the well-reviewed death receptor pathway involving the activation of initiator caspases 8 and 9 then ultimately ending in the activation of effector caspase 3 which begins the process of apoptosis.\r\n\r\nThe effect on tumor vasculature is mediated by the inflammatory signalling pathway of TNF-&alpha;, the NF&kappa;B pathway . This pathway is also activated by TNFR1 when bound to TNF&alpha;. The NF&kappa;B transcription factor increases expression of proteins in vascular endothelial cells. These proteins include cell adhesion molecules, inflammatory mediators like prostaglandins and interleukins, and growth factors . TNF-&alpha also increases the expression of inducible nitric oxide synthase via this pathway which contributes to the generation of reactive nitrogen species . These species are able to damage cells in the tumor and microvasculature.\r\n\r\nThe cytokines produced from NF&kappa;B activation and TNF-&aplha; itself serve to activate the cells of the immune system which further damage tumor cells with respiratory bursts, phagocytosis and subsequent breakdown of the cell, and release of cytotoxic enzymes. The antigen presenting cells which phagocytose the tumor cells are able to activate lymphocytes and allow the adaptive immune system to further damage the tumor tissue .","Tumor necrosis factor receptor superfamily member 1A agonist; Tumor necrosis factor receptor superfamily member 1B agonist","Therapeutic strategy associated"]
[1386,"DB11627","approved; withdrawn","biotech","Hepatitis B Vaccine (Recombinant)","HBSAG; Hepatitis B antigen; Hepatitis B surface antigen; Hepatitis B Surface Antigen (rDNA); Hepatitis B surface antigen (recombinant); Hepatitis B surface antigen vaccine; Hepatitis B surface antigens; Hepatitis B Vaccine; Hepatitis B virus hbsag surface protein antigen; Hepatitis-B surface antigen",null,null,"Hepatitis B Vaccine is an ingredient in the EMA-withdrawn product Quintanrix. It is marketed in Canada as Engerix B. It is also a part of Twinrix (Hep A/Hep B vaccine) available also in Canada.\r\nThe hepatitis B virus induces a severe form of viral hepatitis. Other causative agents are hepatitis A virus, and the non-A, non-B hepatitis viruses. Hepatitis D virus, a defective virus requiring the “keeper function” of the hepatitis B virus, occurs either as a co-infection or super-infection in a HBsAg carrier.\r\n\r\nTransmission of the virus occurs through percutaneous contact with contaminated blood, serum or plasma. Infection may also occur by the exposure of mucous surfaces, or intact or damaged skin to other body fluids such as saliva, mucosal secretions and semen.\r\n\r\nThere is no specific treatment for hepatitis. The incubation period may be as long as 6 months, followed by a very complex clinical course of an acute or chronic nature, often leading to hospitalization.\r\n\r\nViral hepatitis caused by hepatitis B virus is a major worldwide health problem, though the incidence and epidemiology vary widely among geographical areas and population subgroups.\r\n\r\nIn Canada, the United States and Northern Europe, 4% to 6% of the population are infected during their lifetime (mostly young adults); between 5% and 10% of infections lead to persistent viremia (carrier state). Certain population subgroups in these areas, however, are at high risk (see Indications and Clinical Use).\r\n\r\nIn Asia, infection often occurs early in life, leading to a hepatitis B marker prevalence of more than 70% in the general population and a carrier rate of up to 20%.\r\n\r\nIt is estimated that the reservoir of persistent hepatitis B surface antigen carriers amounts to 350 million people worldwide. Carriers are at a high risk of developing chronic liver disease which may lead to cirrhosis or primary hepatocellular carcinoma. A significant reduction in the incidence of hepatocellular carcinoma has been observed in children aged 6 to14 years following a nationwide hepatitis B vaccination in Taiwan. This resulted from a significant decline in the prevalence of hepatitis B antigen, the persistence of which is an essential factor in the development of hepatocellular carcinoma.\r\n\r\nVaccination against hepatitis B is expected in the long term to reduce the overall incidence of both hepatitis B and the chronic complications such as chronic active hepatitis and cirrhosis.",null,null,"Active immunization against hepatitis B virus infection.\r\n\r\nThe vaccine will not protect against infection caused by hepatitis A and non-A non-B hepatitis viruses. As hepatitis D (caused by the delta agent) does not occur in the absence of hepatitis B infection or carrier state, it can be expected that hepatitis D will also be prevented by vaccination with hepatitis B virus vaccine.\r\n\r\nThe vaccine can be administered at any age from birth onwards. It may be used to start a primary course of vaccination or as a booster dose. It may also be used to complete a primary course of vaccination started with plasma-derived or yeast-derived vaccines or as a booster dose in subjects who have previously received a primary course of vaccination with plasma-derived or yeast-derived vaccines.\r\n\r\nIn areas of low prevalence of hepatitis B, vaccination is strongly recommended in subjects who are at increased risk of infection. These include the following groups:\r\n\r\n* Health professionals: physicians and surgeons; oral surgeons and dentists; nurses, dental nurses, dental hygienists, podiatrists; IV teams and operating room personnel; paramedical personnel in close contact with patients; staff in hemodialysis, nephrology, hepatology, hematology and oncology units; laboratory personnel handling blood and other clinical specimens; blood bank and plasma fractionation workers; pathologists and morgue attendants; cleaning staff who handle waste in hospitals; emergency and first aid workers; ambulance staff; dental, medical and nursing students.\r\n* Patients: patients receiving frequent blood transfusion or clotting factor concentrates, such as those in oncology units and those with thalassemia, sickle-cell anemia, cirrhosis, hemophilia, etc.; patients on hemodialysis; patients with type 2 diabetes.\r\n* Personnel and residents of institutions: persons with frequent and/or close contacts with high-risk groups; prisoners and prison staff; residents and staff of institutions for the developmentally challenged (those who are in contact with aggressive biting residents being at highest risk).\r\n* Persons at increased risk due to their sexual practices: males having sexual contact with other males; others with multiple sexual partners or with a recent history of sexually transmitted disease.\r\n* Persons who use injectable drugs illicitly.\r\n* Travellers to areas of high endemicity and their close contacts.\r\n* Household contacts of any of the above groups and of patients with acute or chronic hepatitis B infection.\r\n* Infants born of HBsAg-positive mothers.\r\n* Chronic Liver Disease (CLD): subjects with chronic liver disease; subjects at risk of developing CLD (e.g. Hepatitis C virus carriers, persons who abuse alcohol).\r\n* Others: police; fire fighters; armed forces personnel; morticians and embalmers; those who through their work or personal lifestyle may be exposed to the hepatitis B virus.\r\n* In areas of both low and high prevalence, vaccination should be offered to all young children and neonates at risk, as well as to adult high risk groups.","ENGERIX-B induces specific humoral antibodies against the surface antigen of hepatitis B virus (anti-HBs antibodies). An anti-HBs antibody titre above 10 IU/l correlates with protection to HBV infection.","ENGERIX®-B induces specific humoral antibodies against HBsAg (anti-HBs antibodies). It is generally accepted that an anti-HBs titre greater than 10 IU/L correlates with protection against hepatitis B virus infection. More than 90% of healthy adults, children and neonates developed protective anti-HBs titres one month after completing a\r\nprimary vaccination schedule of ENGERIX®-B (hepatitis B vaccine (recombinant)).",null,"Indication associated"]
[1387,"DB11635","approved","small molecule","Tocofersolan","Tocofersolan; Tocophersolan; TPG-S; TPGS","C33H54O5(C2H4O)n",null,"D-Alpha-tocopheryl polyethylene glycol 1000 succinate (Tocofersolan, Vedrop), has been developed in Europe as an orally bioavailable source of vitamin E in children suffering from cholestasis . Cholestasis is the reduction or stoppage of bile flow, either to impaired secretion by _hepatocytes_ (liver cells) or obstruction , .\r\n\r\nTocofersolan is a polyethylene glycol derivative of α-tocopherol and synthetic water-soluble version of . Tocofersolan is an oral treatment of vitamin E deficiency due to digestive malabsorption in pediatric patients with congenital chronic cholestasis or hereditary chronic cholestasis. It was approved by the European Medicines Agency (EMA) in June 2009 under the market name Vedrop. Moreover, the agent is capable of demonstrating antioxidant effects that make it a popular component to include in cosmetics and pharmaceuticals as well.\r\n\r\nIn addition to the above, tocofersolan has been studied as a promising application as an absorption enhancer in drug delivery .","9002-96-4",null,"Tocofersolan is indicated in vitamin E deficiency caused by digestive malabsorption in pediatric patients with congenital chronic cholestasis or hereditary chronic cholestasis from birth (full term newborns) up to 18 years of age .","\r\nBecause of its increased solubility , , , this medication readily penetrates cells, unlike other types of vitamin E , which are strictly fat-soluble . Specific to cholestasis, tocofersolan normalizes vitamin E levels relieving the symptoms of deficiency because of its facilitation of vitamin E absorption , .","Vitamin E is a major lipo-soluble antioxidant in humans. It acts as a free radical chain breaking molecule, halting the peroxidation of polyunsaturated fatty acids and it plays an important role in maintaining both the stability and integrity of cell membranes .","P-glycoprotein 1 antagonist","Indication associated"]
[1388,"DB11641","approved; investigational","small molecule","Vinflunine","20',20'-difluoro-3',4'-dihydrovinorelbine; 4'-deoxy-20',20'-difluoro-5'-norvincaleukoblastine; 4'-deoxy-20',20'-difluoro-8'-norvincaleukoblastine","C45H54F2N4O8","CC[C@@]12C=CCN3CC[C@@]4([C@H]13)[C@@H](N(C)C1=CC(OC)=C(C=C41)[C@]1(C[C@@H]3C[C@H](C[N@@](C3)CC3=C1NC1=CC=CC=C31)C(C)(F)F)C(=O)OC)[C@](O)([C@@H]2OC(C)=O)C(=O)OC","Vinflunine is a third-generation member of the vinca alkaloid family with anti-tumour actions. It was first described in 1998 at the Pierre Fabre research center in France. Like other vinca agents, vinflunine is an anti-mitotic agent that induces a cell cycle arrest at the G2/M phase and promotes cell death via apoptosis . Vinflunine is a microtubule inhibitor that binds to tubulin at or near to the vinca binding sites to inhibits its polymerization into microtubules during cell proliferation . In murine tumors and human tumor xenografts, vinflunine exhibits an antitumor efficacy than , , and  . \r\n\r\nHaving an incidence of 429,700 new cases per year worldwide, urothelial carcinoma of the bladder is one of the most common malignancies that mostly affects individuals aged 50–79 years . Some patients with advanced urothelial carcinoma experience inadequate therapeutic response from a prior platinum-containing regimen. While these patients have a median survival of approximately 4 months and a poor prognosis , there is currently no standard therapy in patients with advanced urothelial carcinoma . In 2009, vinflunine was approved by the European Medicines Agency (EMA) as a second-line therapy of metastatic and advanced urothelial cancer after failure of platinum-based treatment . Vinflunine ditartrate is an active ingredient in the EMA-authorised product Javlor for intravenous infusion. Efficacy and safety of vinflunine has not been studied in patients with performance status of 2 or less. The clinical use of vinflunine in other urologic malignancies, such as inoperable cancer of the penis, are currently have been investigated .","162652-95-1","816.944","For use as a monotherapy in adults with advanced or transitional cell carcinoma of the urothelial tract after failure of a prior platinum-containing therapy .","The antitumour effects of vinflunine are dependent on concentration and exposure duration of the drug . Vinflunine mediates an anti-mitotic action by inhibiting the microtubule assembly at micromolar concentrations and reducing the rate and extent of microtubule growing events . _In vivo_, vinflunine displays a significant antitumor activity against a broad spectrum of human xenografts in mice both in terms of survival prolongation and tumour growth inhibition . Compared with other vinca alkaloids, vinflunine is a less-potent inductor of drug resistance _in vitro_ .","Microtubules are a major component of the cytoskeleton that have a critical role in maintenance of cell shape, mobility, adhesion and intracellular integrity. They also play a role in the formation of the mitotic spindle and chromosomal segregation to the daughter cells at mitosis . Via GTP hydrolysis at the β-tubulin subunit and polymerization of tubulin into linear polymers, microtubules, or macromolecular filaments composed of tubulin heterodimers, are formed via a mechanism of nucleation-elongation . At the onset of mitosis, the interphase microtubule network disassembles into the tubulin. The tubulin reassembles into a new population of mitotic spindle microtubules that further undergo rapid successions of lengthening and shortening until they are attached to the newly duplicated sister chromatids at their centromeres . The dynamic behaviour of microtubules are characterized by two mechanical process: dynamic instability indicating repeated switches of growth and shortening at the ends, and microtubule treadmilling that involves the fast-growing (+) end of the microtubule accompanied by a net loss of the opposite slow-growing (-) end . Microtubule treadmilling plays a critical role in mitosis by generating the forces for separation of the chromosomes in the mitotic spindle from centrosome and kinetochores. \r\n\r\nIn both cancer and normal cells, vinflunine binds to tubulin at or near to the vinca binding sites at β-tubulin. It is proposed that in similarity to other vinca alkaloids, vinflunine is most likely to bind to β-tubulin subunit at the interdimer interface . Via direct binding to tubulin, vinflunine inhibits microtubule polymerization and induces a G2+M arrest, or a mitotic arrest . Vinflunine disrupts the dynamic function of microtubules by suppressing treadmilling and slowing the microtubule growth rate while increasing growth duration . Ultimately, mitotic accumulation at the metaphase/anaphase transition results in cell apoptosis .","Tubulin beta chain inhibitor","Therapeutic strategy associated"]
[1389,"DB11660","approved; investigational","small molecule","Latanoprostene bunod","Latanoprostene bunod","C27H41NO8","O[C@H](CC[C@H]1[C@H](O)C[C@H](O)[C@@H]1C\\C=C/CCCC(=O)OCCCCO[N+]([O-])=O)CCC1=CC=CC=C1","Latanoprostene Bunod has been used in trials studying the treatment of Glaucoma, Ocular Hypertension, Open-Angle Glaucoma, Open Angle Glaucoma, and Intraocular Pressure.\r\n\r\nAs of November 2, 2017 the FDA approved Bausch + Lomb's Vyzulta (latanoprostene bunod opthalmic solution), 0.024% for the indication of reducing intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Latanoprostene bunod is the first prostaglandin analog with one of its metabolites being nitric oxide (NO). The novelty of this agent subsequently lies in the proposed dual mechanism of action that stems from both its prostaglandin F2-alpha analog latanoprost acid metabolite and its ability to donate NO for proposed tissue/cell relaxation effects.\r\n\r\nIn comparison, both latanoprost and latanoprostene bunod contain a latanoprost acid backbone. Conversely however, latanoprostene bunod integrates an NO-donating moiety in lieu of the isopropyl ester typically found in latanoprost.","860005-21-6","507.624","Latanoprostene bunod opthalmic solution is indicated for the reduction of intraocular pressure in patients with open-angle glaucoma or ocular hypertension .","Upon applying an appropriate dose of latanoprost bunod, reduction in intraocular pressure begins approximately 1 to 3 hours later with a maximum intraocular pressure reduction effect demonstrated after 11 to 13 hours .","Open-angle glaucoma (OAG) is a medical condition that is associated with progressive visual field damage and the loss of vision .\r\n\r\nOccular hypertension (OHT) is considered a key risk factor for OAG and reducing intraocular pressure (IOP) and being able to maintain unique and appropriate target IOPs for various different patients having OHT can delay or prevent the onset of primary OAG or slow the disease progression of established glaucoma .\r\n\r\nOrdinary physiological IOP results from aqueous humor produced by the ocular ciliary body and its outflow through a) the trabecular meshwork (TM) and Schlemm's canal (SC) in what is called the conventional pathway, and b) the uveoscleral pathway via the ciliary muscle/choroid/sclera in what is refered to as the unconventional pathway .\r\n\r\nIn patients with OHT or OAG there is increased resistance to aqueous humor outflow by way of the TM/SC pathway, which causes increased IOP. This increase in IOP is believed to be the cause of mechanical stress on the posterior structures of the eye which can result in the dysfunction of optic nerve fibers and the destruction of retinal ganglion cells - all of which ultimately contributes to vision loss .\r\n\r\nAs there is no cure for glaucoma, therapeutic management is predominantly focused on minimizing disease progression and clinical sequelae via the reduction and maintainenance of appropriate target IOPs .\r\n\r\nSubsequently, latanoprostene bunod is thought to lower intraocular pressure via a dual mechanism of action since the medication is metabolized into two relevant moieties upon administration: (1) latanoprost acid, and (2) butanediol mononitrate .\r\n \r\nAs a prostaglandin F2-alpha analog , the latanoprost acid moiety operates as a selective PGF2-alpha (FP) receptor agonist . Since FP receptors occur in the ciliary muscle, ciliary epithelium, and sclera the latanoprost acid moiety primarily acts in the uveoscleral pathway where it increases the expression of matrix metalloproteinases (MMPs) like MMP-1, -3, and -9 which promote the degradation of collagen types I, III, and IV in the longitudinal bundles of the ciliary musicle and surrounding sclera . The resultant extracellular matrix remodeling of the ciliary muscle consequently produces reduced outflow resistance via increased permeability and increased aqueous humor outflow through the uveoscleral route .\r\n\r\nConversely, the butanediol mononitrate undergoes further metabolism to NO and an inactive 1,4-butanediol moiety. As a gas that can freely diffuse across plasma membranes, it is proposed that the relaxing effect of NO to induce reductions in the cell volume and contractility of vascular smooth muscle like cells is dependant upon activation of the sGC/cGMP/PKG cascade pathway. NO released from butanediol mononitrate consequently enters the cells of the TM and inner wall of SC, causing decreases in myosin light chain-2 phosphorylation, increased phosphorylation of large-conductance calcium-activated potassium (BKCa) channels, and a subsequent efflux of potassium ions through such BKCa channels. All of these changes serve to decrease the cell contractility and volume, as well as to rearrange the actin cytoskeleton of the TM and SC cells. These biomechanical changes ultimately allow for enhanced conventional outflow of aqueous humor .","Prostaglandin F2-alpha receptor agonist","Indication associated"]
[1390,"DB11689","approved; investigational","small molecule","Selumetinib",null,"C17H15BrClFN4O3","CN1C=NC2=C(F)C(NC3=C(Cl)C=C(Br)C=C3)=C(C=C12)C(=O)NOCCO","Activation of the Raf-MEK-ERK signaling pathway is known to be implemented in several types of malignancies, thus, mitogen-activated protein kinase kinase (MEK) inhibitors such as selumetinib are important tools that can target the problematic overactivity of this pathway.\r\nResults from clinical trials investigating earlier developed MEK inhibitors were underwhelming. However, selumetinib demonstrated impressive efficacy and tolerability in Phase I trials, leading to its continued investigation for the treatment of various types of tumors in Phase II trials.\r\n\r\nCurrently, the novel MEK 1 / 2 inhibitor, selumetinib, is approved solely for the treatment of Neurofibromatosis type 1 (NF-1) in a limited age group. NF-1 is considered rare with an estimated incidence of 1/3000 individuals. It is a genetic, autosomal dominant condition resulting from mutations of the NF1 gene, which can lead to various complications including the development of multiple tumors in the nervous system. Some patients with this disorder develop plexiform neurofibromas (PN); however, this is considered to be relatively uncommon compared to other variants of NF-1. Luckily, the use of selumetinib in patients with NF-1 has shown efficacy in shrinking associated tumors and is linked to other positive clinical outcomes.","606143-52-6","457.68","Although selumetinib has been investigated for the treatment of several types of cancer, it is currently only indicated for the treatment of neurofibromatosis type 1 (NF1) in patients ≥2 years who have symptomatic, inoperable plexiform neurofibromas (PN).","Selumetinib is a non-ATP-competitive mitogen-activated protein kinase kinase 1 and 2 (MEK1 and MEK2) inhibitor. By selectively targeting MEK1 and MEK2, selumetinib is able to inhibit oncogenic downstream effects of the Raf-MEK-ERK signaling pathway, which is often overactive in certain types of cancer. Indeed, a study investigating the effects of selumetinib in children with NF-1 found that treatment with the anti-neoplastic resulted in reduced tumor size. Decreases in tumor-associated pain and improvements in overall function were also subjectively reported.\r\n\r\nSelumetinib has minimal off-target activity, contributing to its impressive safety profile.","The Ras-Raf-MEK-ERK signaling cascade is known to be activated in several types of cancer, and regulates the transcription of proteins involved in apoptosis. In addition, studies have shown that mutations of the Raf component of the pathway can contribute to chemotherapy drug resistance. \r\n\r\nRas as well as several kinases and phosphatases are responsible for regulating the Raf-MEK-ERK pathway. Often in cancers, Ras (a G-protein coupled receptor) is deregulated, allowing downstream signalling to proceed unchecked. Through several complex steps, Raf phosphorylates and activates MEK, which then phosphorylates and activates ERK. ERK is then able to exert its effects on several downstream targets. \r\n\r\nAs such, therapies inhibiting upstream components of this pathway have become attractive targets for cancer treatment. Selumetinib exerts its effects by selectively inhibiting MEK1 and MEK2 which can effectively blunt the pleiotropic effects of the Ras-Raf-MEK-ERK cascade. By inhibiting this oncogenic pathway, selumetinib reduces cell proliferation, and promotes pro-apoptotic signal transduction.","Dual specificity mitogen-activated protein kinase kinase 1 inhibitor; Dual specificity mitogen-activated protein kinase kinase 2 inhibitor","Therapeutic strategy associated"]
[1391,"DB11691","approved; investigational","small molecule","Naldemedine","Naldemedine","C32H34N4O6","[H][C@@]12OC3=C4C(C[C@@]5([H])N(CC6CC6)CC[C@@]14[C@@]5(O)CC(C(=O)NC(C)(C)C1=NC(=NO1)C1=CC=CC=C1)=C2O)=CC=C3O","Naldemedine is an opioid receptor antagonist . It is a modified form of  to which a side chain has been added to increase molecular weight and polar surface area resulting in restricted transport across the blood brain barrier. Naldemedine was approved in 2017 in both the US and Japan for the treatment of Opioid-induced Constipation.","916072-89-4","570.646","For the treatment of opioid-induced constipation .","Naldemedine is an opioid receptor antagonist with restricted movement across the blood brain barrier . This allows it to antagonize the periperal effects of opioid drugs such as constipation without interfering with the effects on the central nervous system.","Naldemedine binds to and antagonizes mu-, delta-, and kappa-opioid receptors . The binding of opioid agonists to peripheral mu-opioid receptors slows the transit of feces through the intestine resulting in constipation. By antagonizing mu-opioid receptors, naldemedine inhibits this effect.","Mu-type opioid receptor antagonist; Delta-type opioid receptor antagonist; Kappa-type opioid receptor antagonist","Indication associated"]
[1392,"DB11693","approved; investigational","small molecule","Voclosporin","Voclosporin","C63H111N11O12","[H][C@@]1([C@H](O)[C@H](C)C\\C=C\\C=C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C(=O)[C@H](CC)NC1=O)C(C)C","Lupus nephritis (LN) is a type of glomerulonephritis occurring in patients with systemic lupus erythematosus (SLE).  LN is a significant cause of renal failure,  morbidity, and death in patients with SLE. Within 10 years of being diagnosed with SLE, 5-20% of those suffering from LN develop end-stage kidney disease, a fatal condition. Early and accurate intervention for LN is important in improving clinical outcomes.  \r\n\r\nVoclosporin, marketed as Lupkynis, is a calcineurin-inhibitor immunosuppressant for the treatment of LN. This  A analog was approved by the FDA on January 22, 2021 following promising results in clinical trials. Early intervention with voclosporin coupled with a kidney response is believed to prevent irreversible damage to the kidney and lead to better long-term clinical outcomes for patients with LN. Voclosporin has demonstrated a more stable pharmacokinetic and pharmacodynamic relationship than cyclosporine, a higher potency than cyclosporine, and an improved metabolic profile when compared to older calcineurin inhibitors.","515814-01-4","1214.646","Voclosporin is used in combination with a background immunosuppressive regimen for the treatment of lupus nephritis.  Safety has not been established in combination with cyclophosphamide.","Voclosporin inhibits calcineurin, leading to the inhibition of T cell activation by blocking the transcription of early inflammatory cytokines. This reduces inflammation in the kidney, treating lupus nephritis and preventing permanent renal damage.","Through the inhibition of calcineurin, voclosporin blocks IL-2 expression and T-cell mediated immune responses, stabilizing podocytes in the kidneys.\r\n\r\nVoclospoprin is a cyclosporine A analog. It is structurally similar to cyclosporine A (CsA) with the exception of an amino acid modification in one region. This modification changes the binding of voclosporin to calcineurin. Cyclosporine inhibitors reversibly inhibit T-lymphocytes. They also inhibit lymphokine production and release. Cyclosporine A exerts its inhibitory effects on T-lymphocytes by binding to cyclophilin. A cyclophilin-cyclosporine complex is formed, leading to the inhibition of calcium- and calmodulin-dependent serine-threonine phosphatase activity of calcineurin. Along with calcineurin inhibition, the inhibition of many transcription factors necessary for the induction of various cytokine genes such as IL-2, IFN-γ, IL-4 and GM-CSF occurs. This, in turn, reduces inflammation, treating renal glomerulonephritis associated with systemic lupus erythematosus.","Calcineurin subunit B type 1 inhibitor; Calcineurin subunit B type 2 inhibitor; Calcium signal-modulating cyclophilin ligand binder","Therapeutic strategy associated"]
[1393,"DB11700","approved; investigational","small molecule","Setmelanotide","Setmelanotide","C49H68N18O9S2","[H]N([H])C(=O)[C@@H]1CSSC[C@H](N([H])C(=O)[C@H](CCCN=C(N([H])[H])N([H])[H])N([H])C(C)=O)C(=O)N[C@H](C)C(=O)N[C@@H](CC2=CN=CN2[H])C(=O)N[C@H](CC2=CC=CC=C2)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC2=CN([H])C3=CC=CC=C23)C(=O)N1","Setmelanotide is the first available treatment for patients with pro-opiomelanocortin, proprotein subilisin/kexin type 1, or leptin deficiencies. It is an agonist of the melanocortin 4 receptor. Earlier attempts at agonizing MC4R (such as LY2112688) lead to successful weight loss, but also an increase in blood pressure and heart rate. Other earlier treatments for these patients included gastric bypass surgery. Patients taking setmelanotide experienced an average weight loss of 0.6 kg/week.\r\n\r\nImcivree was granted EMA orphan designation on 19 November 2018 and FDA approval on 25 November 2020.","920014-72-8","1117.32","Setmelanotide is indicated for chronic weight management in patients 6 years and older with obesity due to pro-opiomelanocortin deficiency, proprotein subtilisin/kexin type 1 deficiency, or leptin receptor deficiency. These conditions affect the MC4R signalling pathway.","Setmelanotide agonizes MC4R, downstream of multiple potential genetic deficiencies, to induce a feeling of satiety for chronic weight management. It has a moderate duration of action as it is given daily. Patients should be counselled regarding the risk of disturbances in sexual arousal, depression and suicidal ideation, and darkening of skin pigmentation. Exercise caution in neonates and low birth weight infants, as they may experience serious adverse effects due to benzyl alcohol.","Grehlin and other hunger signals from the gastrointestinal tract stimulate orexigenic neurons, stimulating the release of agouti-related protein. Agouti-related protein inhibits melanocortin 4 receptor (MC4R) activation until satiety signals such as insulin or leptin stimulate anorexigenic neurons. Insulin and leptin stimulate production of the POMC-derived melanocortin peptide α-melanocyte simulating hormone, which is a ligand of MC4R.\r\n\r\nOrexigenic and anorexigenic neurons contain prohormone convertase 1/3 (PC1/3), which is encoded by the gene proprotein subtilisin/kexin type 1. PC1/3 preforms activation cleavage of a number of peptide hormone precursors, including α-melanocyte simulating hormone.\r\n\r\nSetmelanotide is a pro-opiomelanocortin derived peptide that is an agonist of MC4R. It is an approximately 20-fold more potent agonist of MC4R than endogenous α-melanocyte stimulating hormone, with an EC<sub>50</sub> of 0.27 nM. By directly agonizing MC4R, upstream genetic deficiencies in the MC4R signalling pathway cannot inhibit satiety, food intake is decreased, and weight loss is achieved.\r\n\r\nMC4R is a 332 amino acid G-protein coupled receptor (G-PCR). Although the lack of cardiovascular adverse effects with setmelanotide treatment are not well understood, it is believed that earlier MC4R antagonists activated multiple G-protein signalling pathways. Earlier drugs that targeted G-PCRs either bound with high affinity to the highly conserved orthosteric binding site, or with high specificity to less conserved allosteric sites. Setmelanotide is an atypical bitopic ligand that interacts with both the orthosteric and putative allosteric binding site, allowing for both high affinity and specificity.","Melanocortin receptor 4 agonist","Therapeutic strategy associated"]
[1394,"DB11712","approved; investigational","small molecule","Tezacaftor","Tezacaftor","C26H27F3N2O6","CC(C)(CO)C1=CC2=CC(NC(=O)C3(CC3)C3=CC=C4OC(F)(F)OC4=C3)=C(F)C=C2N1C[C@@H](O)CO","Tezacaftor is a drug of the cystic fibrosis transmembrane conductance regulator (CFTR) potentiator class. It was developed by Vertex Pharmaceuticals and FDA approved in combination with  to manage cystic fibrosis. This drug was approved by the FDA on February 12, 2018.\r\n\r\nCystic Fibrosis is an autosomal recessive disorder caused by one of several different mutations in the gene for the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, an ion channel involved in the transport of chloride and sodium ions across cell membranes. CFTR is active in epithelial cells of organs such as of the lungs, pancreas, liver, digestive system, and reproductive tract. Alterations in the CFTR gene result in altered production, misfolding, or function of the protein and consequently abnormal fluid and ion transport across cell membranes. As a result, CF patients produce thick, sticky mucus that clogs the ducts of organs where it is produced making patients more susceptible to complications such as infections, lung damage, pancreatic insufficiency, and malnutrition.","1152311-62-0","520.505","Tezacaftor is combined with ivacaftor in one product for the treatment of cystic fibrosis (CF) in patients aged 12 years or older with two copies of the _F508del_ gene mutation or at least one mutation in the CFTR gene that is responsive to this drug.\r\n\r\nTezacaftor, when used in combination with ivacaftor and  in the product Trikafta, is also indicated for the treatment of CF in patients 12 years of age and older that have at least one _F508del_ mutation in the CFTR gene.\r","Clinical studies have shown a significant decrease in sweat chloride and an increase in the forced expiratory volume (FEV), a measure of lung function, following Tevacaftor/Ivacaftor therapy. Phase 3 clinical studies have shown that a significant increase in forced expiratory volume was attained at 4 and 8 weeks after initiating this drug. The above effects lead to improvement of the respiratory symptoms of cystic fibrosis. Tezacaftor does not induce clinically significant QT prolongation. When given with ivacaftor, tezacaftor can lead to liver transaminase elevations. Testing of transaminases (ALT and AST) levels should occur before starting this combination every 3 months during the first year of treatment, and every year afterwards. Patients with a history of transaminase elevations should be monitored more frequently.","The transport of charged ions across cell membranes is normally achieved through the actions of the cystic fibrosis transmembrane regulator (CFTR) protein. This protein acts as a channel and allows for the passage of chloride and sodium. This process affects the movement of water in and out of the tissues and impacts the production of mucus that lubricates and protects certain organs and body tissues, including the lungs. In the _F508del_ mutation of the CFTR gene, one amino acid is deleted at the position 508, therefore, the CFTR channel function is compromised, resulting in thickened mucus secretions.  CFTR correctors such as tezacaftor aim to repair F508del cellular misprocessing. This is done by modulating the position of the CFTR protein on the cell surface to the correct position, allowing for adequate ion channel formation and increased in water and salt movement through the cell membrane. The concomitant use of ivacaftor is intended to maintain an open channel, increasing the transport of chloride, reducing thick mucus production.","Cystic fibrosis transmembrane conductance regulator activator","Therapeutic strategy associated"]
[1395,"DB11714","approved; investigational","biotech","Durvalumab","Durvalumab",null,null,"Durvalumab is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody and a novel immune-checkpoint inhibitor for cancer treatment. Produced by recombinant DNA technology in Chinese Hamster Ovary (CHO) cell suspension culture, durvalumab is a programmed death-ligand 1 (PD-L1) blocking antibody that works to promote normal immune responses that attack tumour cells.\r\n\r\nDurvalumab is marketed under the brand name Imfinzi, which is available for intravenous injections. It was granted accelerated approval by the FDA in May 2017  for the treatment of selected patients with locally advanced or metastatic urothelial carcinoma. In September 2018, durvalumab was approved by the EMA for the treatment of adult patients with  locally advanced, unresectable non-small cell lung cancer (NSCLC), only if PD-L1 is expressed in ≥ 1% of tumour cells and there was no observable disease progression following platinum-based chemoradiation therapy. On March 27, 2020, durvalumab was approved by the FDA for use in combination with  and either  or  as first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC).","1428935-60-7",null,"Durvalumab is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.\r\n\r\nDurvalumab is indicated for the treatment of patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy. It is also approved for the treatment of patients with extensive-stage small cell lung cancer (ES-SCLC) in combination with  and either  or  as first-line therapy.\r\n\r\nDurvalumab is indicated as monotherapy used for the treatment of locally advanced, unresectable non-small cell lung cancer (NSCLC) in adults whose tumours express PD-L1 on ≥ 1% of tumour cells and whose disease has not progressed following platinum-based chemoradiation therapy.","Durvalumab is an anticancer antibody that works to promote the antitumour responses mediated by immune cells. By blocking the action of PD-L1, durvalumab exerts its anticancer effects by increasing T-cell activation, enhancing detection and ablation of tumour cells. In _in vitro_ assays, durvalumab inhibited the activity of PD-L1 in a concentration-dependent manner. In co-engrafted human tumor and immune cell xenograft mouse models, durvalumab was effective in decreasing tumour size. Durvalumab does not mediate antibody-dependent cell-mediated cytotoxicity (ADCC).","Because cancer cells express antigens that are recognized and taken up by antigen-presenting cells (APCs), the immune responses prime and activate cytotoxic T cells, and allow them to travel to the site of tumour to destroy cancer cells. However, tumours often evade T cell-mediated immune responses to enhance their survival. Inflammatory mediators, such as IFN-gamma, induce the expression of programmed cell death ligand-1 (PD-L1), which is a type 1 transmembrane protein expressed on tumour cells and tumour-associated immune cells in the tumour microenvironment. PD-L1 acts as an immune checkpoint to regulate immune responses. PD-L1 is a ligand to PD-1, which is a cell surface receptor expressed on activated T cells in peripheral tissues following antigen exposure. Both PD-L1 and PD-1 are co-inhibitory molecules involved in blocking T cell-mediated immune responses. PD-L1 also interacts with CD-80, which is a receptor constitutively expressed by T cells and is upregulated early after T cell activation.\r\n\r\nThe expression of PD-L1 is an adaptive immune response by tumour cells, resulting in over-expression of the molecule in some cancers. PD-L1 interacts with PD-1 and CD80, which leads to blocked cytotoxic T cell activation, T cell proliferation, and cytokine production. By binding to PD-L1 and preventing its association with PD-1 and CD80, durvalumab activates the immune responses mediated by cytotoxic T cells that attack tumour cells. Durvalumab displays selective and high affinity toward PD-L1 but not PD-L2, which is a regulatory ligand expressed in tumour cells to a lesser extent and involved in regulating inflammation and differentiation of T cells.","Programmed cell death 1 ligand 1 inhibitor&antibody","Therapeutic strategy associated"]
[1396,"DB11721","investigational","small molecule","Mitoglitazone","MSDC-0160","C19H18N2O4S","CCC1=CN=C(C=C1)C(=O)COC1=CC=C(CC2SC(=O)NC2=O)C=C1","Mitoglitazone has been used in trials studying the treatment of Type 2 Diabetes and Alzheimer's Disease.","146062-49-9","370.422",{"$nulls":3},"Peroxisome proliferator-activated receptor gamma","Target associated"]
[1397,"DB11735","approved; investigational","small molecule","Galactose","D-Galactose; D(+)-Galactose; Galactose","C6H12O6","[H]C(=O)[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CO","Galactose has been used in trials studying the treatment and diagnosis of Hepatitis C, Hepatic Cancer, Wilsons Disease, Diabetic Macular Oedema, and Focal Segmental Glomerulosclerosis, among others. There are even proposals for its use in accelerating senescence in mice, rats, and Drosophila, for its association with ovarian cancer, or even for the potential treatment of focal segmental glomerulosclerosis. Nevertheless, none of these ongoing studies have yet provided formal elucidation for their proposals.\r\n\r\nAs a naturally occurring sugar, it may be found in a number dairy products. Even then, however, it is not generally used as a sweetener considering it is only about 30% as sweet as sucrose. Regardless, although it is predominantly used as a pathway to generate glucose fuel for the human body, galactose is involved as an ingredient in some commonly used vaccines and non-prescription products.","59-23-4","180.1559","There are limited therapeutic uses for which galactose is formally indicated. Some predominant indications include (a) the use of galactose to facilitate the construction of structurally and immunologically effective attenuated vaccines , and (b) the role galactose plays as an essential element in the formation of lactulose - a synthetic disaccharide indicated for the treatment of constipation and/or hepatic encephalopathy (HE); hepatic coma .\r\n\r\nNevertheless, there are many studies looking into a variety of possible uses for galactose, including the use of the monosaccharide sugar for accelerating senescence in mice, rats, and Drosophila , the proposed association between galactose in consumed milk and ovarian cancer , a possible role in the therapy of focal segmental glomerulosclerosis , among various others. Regardless, none of these proposed indications have yet been formally elucidated for practical use.","Galactose is a naturally occurring monosaccharide that forms the disaccharide lactose when combined with glucose (another monosaccharide) . Subsequently, when lactose or small amounts of free galactose found in various common dairy products (and other foods) are consumed, the hydrolysis of lactose to glucose and galactose occurs and galactose is itself further metabolized to generate glucose . Such glucose is, of course, ultimately relied upon and used as the primary metabolic fuel for humans in a variety of biological reactions.\r\n\r\nConversely, however, the ways in which galactose is commonly used in therapeutic agents generally do not rely upon such pharmacodynamics, even though they ultimately remain the most important ways in which galactose exerts or elicits useful biological actions for the human body.","In the development of typhoid Ty21a live oral vaccine, the use of exogenous galactose is critical. When dealing with Salmonella typhimurium, it has been shown that rough strains with incomplete lipopolysaccharide (LPS) lacking O-specific side chains are much less virulent than smooth strains with complete LPS with O-specific side chains . Salmonella typhimurium gal E mutants used to produce the vaccine are effectively avirulent and highly protective but lack the specific UDP-galactose 4-epimerase enzyme which allows for the normal synthesis of UDP-galactose from UDP-glucose . The consequence of this mutant defect is that the gal E mutants can only generate incomplete LPS without O-specific antigen side chains, which are not capable enough as the complete LPS with O-specific side chains at generating an immunologic response . When exogenous galactose is added to the vaccine medium, however, it allows the mutants to generate UDP-galactose via galactose 1-phosphate . This ultimately allows the mutants to form smooth-type LPS with O-specific side chains . Regardless, the mutant's epimerase defect ultimately results in the accumulation of such intermediary products like galactose 1-phosphate and UDP-galactose, which consequently causes lysis of the mutant cells. The resultant vaccine is subsequently effective enough to elicit an immunologic response while the bacteriolysis prevents the mutant cells from regaining virulence under conditions where smooth type LPS similar to the active parental strain is synthesized .\r\n\r\nGalactose is also an essential element to the chemical structure of the commonly used laxative solution lactulose. Lactulose itself is a synthetic disaccharide that is made in parts from lactose, galactose, and various other sugars . It is poorly absorbed from the gastrointestinal tract and no enzyme capable of hydrolysis of lactulose is present in human gastrointestinal tissue . Oral doses of lactulose subsequently arrive at the colon largely unchanged . At the colon, lactulose is finally broken down predominantly to lactic acid, and also small amounts of formic and acetic acids by the action of colonic bacteria, which results in an increase in osmotic pressure and slight acidification of the colonic contents . This action consequently causes an increase in stool water content and softens the stool for a laxative effect .",null,"Indication associated"]
[1398,"DB11737","experimental; investigational","small molecule","Icotinib","BPI-2009","C22H21N3O4","C#CC1=CC=CC(NC2=NC=NC3=CC4=C(OCCOCCOCCO4)C=C23)=C1","Icotinib is a potent and specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)\r\nIcotinib was approved in China by the SFDA in June, 2011 and in January 2014, Beta Pharma, Inc. was given a “May Proceed” from the US FDA to conduct a Phase I study for the evaluation of icotinib as a treatment of EGFR+ Non-Small Cell Lung Cancer (NSCLC).","610798-31-7","391.427","Icotinib hydrochloride is a novel epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitor, exhibits encouraging efficacy and tolerability in patients with advanced non-small-cell lung cancer (NSCLC) who failed previous chemotherapy.","In vitro: Icotinib inhibits EGFR activity in a dose-dependent manner, with an IC50 value of 5 nM and complete inhibition at 62.5 nM. Icotinib selectively solely inhibits the EGFR members including the wild type and mutants with inhibition efficacies of 61-99%. Icotinib blocks EGFR-mediated intracellular tyrosine phosphorylation in human epidermoid carcinoma A431 cells in a dose-dependent manner. Meanwhile, in the proliferation assay performed on A431, BGC-823, A549, H460, HCT8, KB and Bel-7402 cell lines, it was found that the relative sensitivity of cell lines to Icotinib is A431 > BGC-823 > A549 > H460 > KB > HCT8 and Bel-7402. Icotinib exhibits a broad spectrum of antitumor activity and it is especially effective against tumors expressing higher levels of EGFR.\r\nIn vivo: In vivo studies demonstrated that Icotinib exhibited potent dose-dependent antitumor effects in nude mice carrying a variety of human tumor-derived xenografts. The drug was well tolerated at doses up to 120 mg/kg/day in mice without mortality or significant body weight loss during the treatment. A head to head randomized, double blind phase III trial using Gefitinib as an active control for patients with advanced non-small cell lung cancer (NSCLC) was finished recently (Trial registration ID: NCT01040780).","Icotinib is a highly selective, first generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) which binds reversibly to the ATP binding site of the EGFR protein, preventing completion of the signal transduction cascade. EGFR is an oncogenic receptor and patients with activating somatic mutations, such as an exon 19 deletion or exon 21 L858R mutation, within the tyrosine kinase domain display unchecked cell proliferation.","Epidermal growth factor receptor antagonist","Therapeutic strategy associated"]
[1399,"DB11752","investigational","small molecule","Bryostatin 1",null,"C47H68O17","[H][C@]12C[C@H](OC(C)=O)C(C)(C)[C@](O)(C[C@]3([H])C\\C(C[C@@]([H])(O3)\\C=C\\C(C)(C)[C@]3(O)O[C@@]([H])(C\\C(=C/C(=O)OC)[C@@H]3OC(=O)\\C=C\\C=C\\CCC)C[C@@]([H])(OC(=O)C[C@H](O)C1)[C@@H](C)O)=C\\C(=O)OC)O2","Bryostatin 1 has been investigated for the treatment of HIV Infection and Alzheimer's Disease.","83314-01-6","905.044",{"$nulls":3},"Protein kinase C alpha type activator; Protein kinase C epsilon type activator; Caspase-8 inhibitor; Serine/threonine-protein kinase D1 activator; T-lymphocyte activation antigen CD86 inducer; Prostaglandin G/H synthase 2 inducer; G1/S-specific cyclin-D1 inhibitor; Tumor necrosis factor inducer; Protein unc-13 homolog B ligand","Target associated"]
[1400,"DB11753","approved; investigational","small molecule","Rifamycin","Rifamicine SV; Rifamycin; Rifamycin SV; Rifomycin SV","C37H47NO12","CO[C@H]1\\C=C\\O[C@@]2(C)OC3=C(C)C(O)=C4C(O)=C(NC(=O)\\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@@H]1C)C=C(O)C4=C3C2=O","Rifamycin is the prime member of the rifamycin family which are represented by drugs that are a product of fermentation from the gram-positive bacterium _Amycolatopsis mediterranei_, also known as _Streptomyces mediterranei_. The parent compound of rifamycin was rifamycin B which was originally obtained as a main product in the presence of diethylbarburitic acid. Some small modifications where performed in this inactive compound and with the creation of rifamycin SV there was the first antibiotic used intravenously for the treatment of tuberculosis.\r\n\r\nRifamycin has had several direct derivative products such as rifamycin SV, rifaximin, rifampin and rifamycin CV. All of the derivatives have slight different physicochemical properties when compared to the parent structure.\r\n\r\nRifamycin was further developed by Cosmo Technologies Ltd and approved in November 16, 2018 by the FDA as a prescription drug after being granted the designation of Qualified Infectious Disease Product which allowed it to have a status a priority review. This drug was also sent for review to the EMA in 2015 by Dr. Falk Pharma Gmbh and it was granted a waiver for the tested conditions.","6998-60-3","697.778","Rifamycin is indicated for the treatment of adult patients with travelers' diarrhea caused by noninvasive strains of _E. coli_. The status of the disease should not be complicated by fever or blood in the stool. To prevent drug-resistant bacteria, it is important to mention that the use of rifamycin for this indication should be only done in cases where the infection is proven or strongly suspected to be caused by bacteria.\r\n\r\nTravallers' diarrhea is very common problem affecting 20-60% of the travellers and it is defined as an increase in frequency of bowel movements to three or more loose stools per day during a trip abroad. This condition is rarely life threatening but in severe cases it can produce dehydration and sepsis. The most common cause of travellers' diarrhea is a pathogen and from the pathogens identified, bacteria is the most common cause followed by norovirus, rotavirus and similar viruses.","Rifamycin is known to be effective against Gram-positive and Gram-negative pathogens and mycobacteria. It is very effective against _E. coli_ reporting a MIC90 of 64-128 mcg/ml without showing cross-resistance with other antimicrobial agents.\r\n\r\nThe specific indication of rifamycin is extremely important as ther were previous reports that indicated a high risk factor in the generation of resistant _E. coli_ strains in patients with inflammatory bowel disease.\r\n\r\nIn clinical trials, rifamycin was tested in a randomized clinical trial of travellers' coming from Mexico and Guatemala. In this trial, rifamycin was proven to significantly reduce the symptoms of travellers' diarrhea.","Rifamycins, as well as all the other members of this group, present an antibacterial mechanism of action related to the inhibition of RNA synthesis. This mechanism of action is done by the strong binding to the DNA-dependent RNA polymerase of prokaryotes. The inhibition of the RNA synthesis is thought to be related with the initiation phase of the process and to involve stacking interactions between the naphthalene ring and the aromatic moiety in the polymerase. As well, it has been suggested that the presence of zinc atoms in the polymerase allows for the binding of phenolic -OH groups of the naphthalene ring. \r\n\r\nIn eukaryotic cells, the binding is significantly reduced making them at least 100 to 10,000 times less sensitive to the action of rifamycins. The members of the rifamycin family present the same mechanism of action and the structural modifications are usually related to pharmacokinetic properties as well as to the interaction with eukaryotic cells.","DNA-directed RNA polymerase subunit beta binder; DNA-directed RNA polymerase subunit alpha binder; DNA-directed RNA polymerase subunit beta' binder","Therapeutic strategy associated"]
[1401,"DB11755","investigational","small molecule","Tetrahydrocannabivarin","THCV","C19H26O2","CCCC1=CC(O)=C2[C@@H]3C=C(C)CC[C@H]3C(C)(C)OC2=C1","Tetrahydrocannabivarin (THCV) is a propyl analogue of tetrahydrocannabinol (Δ9-THC), one of the primary pharmacological components of . Δ9-THC is currently available in several synthetic forms, including , while purified or isolated THCV is not approved for any medical uses and is not available as any marketed products. As a major phytocannabinoid, however, THCV is accessible within  along with other identified cannabinoids including  (CBD),  (CBN),  (CBG),  (CBC),  (CBV), and  (CBDV). \r\n\r\nTHCV is one of four cannabinoids with identified potential as anticonvulsant agents, which also includes Δ9-tetrahydrocannabinolic acid,  (CBD), and  (CBDV) .\r\n\r\nAlthough THCV possesses an almost identical structure to Δ9-THC (varying only by the length of its lipophilic alkyl chain), it has different molecular targets and pharmacological profile . Compared to THC which demonstrates its effects through weak partial agonist activity of both endocannabinoid receptors Cannabinoid-1 (CB1R) and Cannabinoid-2 (CB2R), THCV acts as a CB1 antagonist and a partial agonist of CB2 . Further evidence has also shown that THCV acts as an agonist of GPR55 and l-α-lysophosphatidylinositol (LPI) . Beyond the endocannabinoid system, THCV has also been reported to activate 5HT1A receptors to produce an antipsychotic effect that has therapeutic potential for ameliorating some of the negative, cognitive and positive symptoms of schizophrenia . Furthermore, THCV interacts with different transient receptor potential (TRP) channels including TRPV2, which may contribute to the analgesic, anti-inflammatory and anti-cancer effects of cannabinoids and Cannabis extracts . It has also shown antiepileptiform and anticonvulsant properties, that suggest possible therapeutic application in the treatment of pathophysiologic hyperexcitability states such as untreatable epilepsy .\r\n\r\nCannabinoid receptors are utilized endogenously by the body through the endocannabinoid system, which includes a group of lipid proteins, enzymes, and receptors that are involved in many physiological processes. Through its modulation of neurotransmitter release, the endocannabinoid system regulates cognition, pain sensation, appetite, memory, sleep, immune function, and mood among many others. These effects are largely mediated through two members of the G-protein coupled receptor family, cannabinoid receptors 1 and 2 (CB1 and CB2). CB1 receptors are found in both the central and peripheral nervous systems, with the majority of receptors localized to the hippocampus and amygdala of the brain. Physiological effects of using cannabis make sense in the context of its receptor activity as the hippocampus and amygdala are primarily involved with regulation of memory, fear, and emotion. In contrast, CB2 receptors are mainly found peripherally in immune cells, lymphoid tissue, and peripheral nerve terminals .\r\n\r\nReliably studying the effects of Cannabis (and of THCV) is complicated by the numerous other compounds that Cannabis contains such as terpenes, flavonoids, phenols, amino acids, and fatty acids among many others that have the potential to modulate the plant's pharmacological effect .","31262-37-0","286.415","THCV does not currently have any FDA, Health Canada, or EMA approved indications.","Compared to THC which demonstrates its effects through weak partial agonist activity at Cannabinoid-1 (CB1R) and Cannabinoid-2 (CB2R) receptors, THCV acts as a CB1 antagonist and a partial agonist of CB2 . Further evidence has also shown that THCV acts as an agonist of GPR55 and l-α-lysophosphatidylinositol (LPI) . Beyond the endocannabinoid system, THCV has also been reported to activate 5HT1A receptors to produce an antipsychotic effect that has therapeutic potential for ameliorating some of the negative, cognitive and positive symptoms of schizophrenia . Furthermore, THCV interacts with different transient receptor potential (TRP) channels including TRPV1, which may contribute to the analgesic, anti-inflammatory and anti-cancer effects of cannabinoids and Cannabis extracts .",null,"Cannabinoid receptor 1 antagonist; Cannabinoid receptor 2 partial agonist; G-protein coupled receptor 55 partial agonist; 5-hydroxytryptamine receptor 1A agonist; Transient receptor potential cation channel subfamily V member 2 agonist; Transient receptor potential cation channel subfamily M member 8 antagonist; Transient receptor potential cation channel subfamily A member 1 agonist","Therapeutic strategy associated"]
[1402,"DB11761","approved; investigational","small molecule","Tenapanor","Tenapanor","C50H66Cl4N8O10S2","CN1C[C@@H](C2=CC(=CC=C2)S(=O)(=O)NCCOCCOCCNC(=O)NCCCCNC(=O)NCCOCCOCCNS(=O)(=O)C2=CC(=CC=C2)[C@@H]2CN(C)CC3=C2C=C(Cl)C=C3Cl)C2=C(C1)C(Cl)=CC(Cl)=C2","Tenapanor is a novel, small molecule medication approved in September 2019 for the treatment of constipation-predominant irritable bowel-syndrome (IBS-C). It was first designed and synthesized in 2012. As an inhibitor of the sodium/hydrogen exchanger isoform 3 (NHE3) transporter, it is the first and currently only medication within its class and therefore exists as a novel alternative in the treatment of IBS-C.","1234423-95-0","1145.04","Tenapanor is indicated for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) in adults. It is also currently being investigated as a treatment for hyperphosphatemia in chronic kidney disease patients undergoing dialysis (NCT02081534 and NCT02675998).","Through the inhibition of dietary sodium absorption tenapanor causes an increase in water secretion into the intestines, thereby decreasing transit time and softening stool consistency.","Tenapanor is a locally-acting small molecule inhibitor of the sodium/hydrogen exchanger isoform 3 (NHE3), an antiporter expressed on the apical surface of enterocytes in the small intestine and colon which is involved in sodium-fluid homeostasis. By inhibiting this antiporter tenapanor causes retention of sodium within the lumen of the intestine - this results in an osmotic gradient that draws water into the lumen and softens stool consistency.\r\n\r\nThere is some evidence that tenapanor can inhibit the uptake of dietary phosphorus in the gastrointestinal tract, though the exact mechanism of this activity has yet to be elucidated.","Sodium/hydrogen exchanger 3 inhibitor","Indication associated"]
[1403,"DB11772","investigational","small molecule","Pilaralisib","Pilaralisib","C25H25ClN6O4S","COC1=CC=C(Cl)C(NC2=C(NS(=O)(=O)C3=CC(NC(=O)C(C)(C)N)=CC=C3)N=C3C=CC=CC3=N2)=C1","Pilaralisib is an orally available small molecule that selectively inhibits the activity of phosphoinositide-3 kinase (PI3K). Pilaralisib has been used in trials studying the treatment of Cancer, Lymphoma, Solid Tumors, Glioblastoma, and Breast Cancer, among others.","934526-89-3","541.02",null,"In preclinical studies, Pilaralisib slowed tumor growth or caused tumor shrinkage in multiple preclinical cancer models, including breast, lung, ovarian, and prostate cancers, and gliomas. Pilaralisib has also been shown to enhance the anti- tumor effects of several chemotherapeutic agents and an inhibitor of epidermal growth factor receptor (EGFR) in preclinical cancer models.","Pilaralisib is an orally available small molecule that selectively inhibits the activity of phosphoinositide-3 kinase (PI3K). Activation of PI3K is a frequent event in human tumors, promoting tumor cell growth, survival, and resistance to chemotherapy and radiotherapy. Inactivation of PI3K has been shown to inhibit growth and induce apoptosis (programmed cell death) in tumor cells.","Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform","Therapeutic strategy associated"]
[1404,"DB11776","approved; investigational","biotech","Brodalumab","Brodalumab",null,null,"Brodalumab has been used in trials studying the treatment of Asthma, Psoriasis, Crohn's Disease, Psoriatic Arthritis, and Rheumatoid Arthritis. Brodalumab was FDA approved in February, 2017 as Siliq for the treatment of moderate-to-severe plaque psoriasis.","1174395-19-7",null,"Brodalumab has been approved for the treatment of psoriasis vulgaris, psoriatic arthritis, pustular psoriasis and psoriatic erythroderma.","Increase in the level of IL-17 due to blocking of its receptors.","Brodalumab binds with high affinity to interleukin (IL)-17 receptor A, thereby inhibiting several pro-inflammatory cytokines from the IL-17 family.",null,"Therapeutic strategy associated"]
[1405,"DB11781","investigational","small molecule","Tosedostat","Tosedostat","C21H30N2O6","CC(C)C[C@H]([C@H](O)C(=O)NO)C(=O)N[C@H](C(=O)OC1CCCC1)C1=CC=CC=C1","Tosedostat has been used in trials studying the treatment and supportive care of AML, Leukemia, Pancreas Cancer, Multiple Myeloma, and Pancreatic Cancer, among others.\r\n\r\nTosedostat is an inhibitor of the M1 family of aminopeptidases, in particular PuSA, and LTA4 hydrolase. It has demonstrated anti-tumour activity in a number of models of cancer, both as a single agent and in synergy with cytotoxic agents such as carboplatin and paclitaxel. It entered the clinical trial in patients with haematological malignancies.","238750-77-1","406.479",null,"Tosedostat has pleiotropic effects against a range of human tumor cell lines originating from diverse tumor types in vitro and in vivo.","Tosedostat is anti-proliferative agent which induces apoptosis in leukemic cell lines in vitro. The mechanism underlying these anti-cancer actions is unclear, particularly since normal cells are much less sensitive to the agents than transformed cells. It exerts potent anti-proliferative, pro-apoptotic and anti-angiogenic effects in vitro and shows selectivity for transformed over non-transformed cells. It inhibits a number of M1 aminopeptidase enzyme family members in vitro (eg puromycin-sensitive aminopeptidase (PSA), leukotriene A4 hydrolase (LTA4H)).","Puromycin-sensitive aminopeptidase; Leukotriene A-4 hydrolase","Therapeutic strategy associated"]
[1406,"DB11793","approved; investigational","small molecule","Niraparib","Niraparib","C19H20N4O","NC(=O)C1=CC=CC2=CN(N=C12)C1=CC=C(C=C1)[C@@H]1CCCNC1","Niraparib is an orally active PARP inhibitor developed by Tesaro to treat ovarian cancer. FDA approval on March 2017.","1038915-60-4","320.396","Niraparib is indicated for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy","Cardiovascular Effects:\r\nNiraparib has the potential to cause effects on pulse rate and blood pressure in patients receiving the recommended dose, which may be related to pharmacological inhibition of the dopamine transporter (DAT), norepinephrine transporter (NET) and serotonin transporter (SERT).\r\nIn the NOVA study, mean pulse rate and blood pressure increased over baseline in the niraparib arm relative to the placebo arm at all on-study assessments. Mean greatest increases from baseline in pulse rate on treatment were 24.1 and 15.8 beats/min in the niraparib and placebo arms, respectively. Mean greatest increases from baseline in systolic blood pressure on treatment were 24.5 and 18.3 mmHg in the niraparib and placebo arms, respectively. Mean greatest increases from baseline in diastolic blood pressure on treatment were 16.5 and 11.6 mmHg in the niraparib and placebo arms, respectively.  \r\nCardiac Electrophysiology \r\nThe potential for QTc prolongation with niraparib was evaluated in a randomized, placebo-controlled trial in cancer patients (367 patients on niraparib and 179 patients on placebo). No large changes in the mean QTc interval (>20 ms) were detected in the trial following the treatment of niraparib 300 mg once daily.","Niraparib is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, PARP-1 and PARP-2, which play a role in DNA repair. In vitro studies have shown that niraparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes resulting in DNA damage, apoptosis and cell death. Increased niraparib-induced cytotoxicity was observed in tumor cell lines with or without deficiencies in BRCA1/2. Niraparib decreased tumor growth in mouse xenograft models of human cancer cell lines with deficiencies in BRCA1/2 and in human patient-derived xenograft tumor models with homologous recombination deficiency that had either mutated or wild type BRCA1/2.","Poly [ADP-ribose] polymerase 1 antagonist; Poly [ADP-ribose] polymerase 2 antagonist","Therapeutic strategy associated"]
[1407,"DB11811","investigational","small molecule","Arhalofenate","Arhalofenate","C19H17ClF3NO4","CC(=O)NCCOC(=O)[C@H](OC1=CC=CC(=C1)C(F)(F)F)C1=CC=C(Cl)C=C1","Arhalofenate has been investigated for the treatment of Gout and Hyperuricemia.","24136-23-0","415.79",null,null,"Partial agonist of peroxisome proliferator-activated receptor (PPAR) gamma; results in improved glucose, lipid, and weight management.","Peroxisome proliferator-activated receptor gamma","Target associated"]
[1408,"DB11817","approved; investigational","small molecule","Baricitinib","Baricitinib","C16H17N7O2S","CCS(=O)(=O)N1CC(CC#N)(C1)N1C=C(C=N1)C1=C2C=CNC2=NC=N1","Baricitinib is a selective and reversible Janus kinase 1 (JAK1) and 2 (JAK2) inhibitor. Janus kinases belong to the tyrosine protein kinase family and play an important role in the proinflammatory pathway signalling that is frequently over-activated in autoimmune disorders such as rheumatoid arthritis. By blocking the actions of JAK1/2, baricitinib disrupts the activation of downstream signalling molecules and proinflammatory mediators. \r\n\r\nRheumatoid arthritis is a progressive autoimmune disease commonly associated with discomfort, diasability, and joint damage. Throughout disease progression, the disease may further lead to joint erosions and deformities, causing premature mortality, functional impairment, and reduced quality of life . While there are several disease modifying antirheumatic drugs (DMARDs) available for treatment, patients often experience inadequate threapeutic resposes to these drugs. In animal models of inflammatory arthritis, baricitinib was shown to have significant anti-inflammatory effects, but also led to preservation of cartilage and bone, with no detectable suppression of humoral immunity or adverse hematologic effects .\r\n\r\nIn the EU, baricitinib was approved in February of 2017 as a second-line orally administered treatment for moderate to severe active rheumatoid arthritis in adults, either as a monotherapy or when combined with methotrexate. It is marketed under the trade name Olumiant.\r\n\r\nBaricitinib in combination with  for the treatment of COVID-19, was granted an FDA Emergency Use Authorization on 19 November 2020.","1187594-09-7","371.42","Indicated for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs as monotherapy or in combination with methotrexate.",null,"JAK enzymes are part of the family of tyrosine kinases that constitutively bind to the intracellular domains of cytokine receptors  and promote the signalling cascades of cytokines and growth factors involved in haematopoiesis, inflammation and immune function that are also implicated in the pathogenesis of rheumatoid arthritis . Circulating proinflammatory cytokines bind to these cell surface receptors. Upon binding of extracellular cytokines and growth factors, JAKs are phosphorylated and activate signal transducers and activators of transcription (STATs). Through the signalling cascades, inflammatory cytokine and chemokine transcription is induced to form inflammatory mediators including IL-2, IL-6, IL-12, IL-15, IL-23, IFN-γ and GM-CSF . \r\n\r\nBaricitinib selectively and reversibly inhibits JAK1 and JAK2 to modulates their signalling pathways, thereby reducing the phosphorylation and activation of STATs . In isolated enzyme assays, baricitinib also exhibited an inhibitory effect on other types of JAK enzymes,Tyrosine Kinase 2 and JAK3, at higher concentrations needed for JAK1/2 inhibition.","Tyrosine-protein kinase JAK1 inhibitor; Tyrosine-protein kinase JAK2 inhibitor; Protein-tyrosine kinase 2-beta inhibitor; Tyrosine-protein kinase JAK3 inhibitor","Therapeutic strategy associated"]
[1409,"DB11823","approved; investigational","small molecule","Esketamine","(-)-Ketamine; (−)-ketamine; (S)-(−)-ketamine; (S)-2-(o-chlorophenyl)-2-(methylamino)cyclohexanone; (S)-ketamine; Esketamine; L-ketamine; S-(-)-Ketamine; S-ketamine","C13H16ClNO","CN[C@@]1(CCCCC1=O)C1=CC=CC=C1Cl","Major depressive disorder (MDD) is a significant cause of disability worldwide and the most common illness preceding suicide , . On March 5, 2019, the nasal spray drug, _esketamine_, also known as _Spravato_ (by Janssen Pharmaceuticals), was approved by the FDA for treatment-resistant major depression. \r\n\r\nEsketamine is the s-enantiomer of . Ketamine is a mixture of two enantiomers (mirror image molecules). This is the first time that the FDA has approved esketamine for any use. The FDA approved ketamine (Ketalar) in 1970 .\r\n\r\nEsketamine may prove to be a promising treatment for patients diagnosed with major depressive disorder who have not experienced an improvement in symptoms despite treatment with various medications and therapies. The intranasal route of administration for this drug allows for easy administration and a fast onset of action, which sets it apart from many other antidepressant agents that may take several weeks to take effect.","33643-46-8","237.73","This drug is indicated in conjunction with an oral antidepressant for the treatment of treatment-resistant depression (TRD) in adults .\r\n\r\nNote: Esketamine is not approved as an anesthetic agent. The safety and effectiveness of esketamine as an anesthetic agent have not been established to this date .","**General effects**\r\n\r\nEsketamine is considered a central nervous system (CNS) depressant agent. It may cause sedation, dizziness, and lethargy, among other symptoms . This drug has dissociative and antidepressant properties . Acutely, esketamine may impair attention, judgment, thinking, reaction speed, and motor skills. Two placebo-controlled studies were performed to evaluate the effects of ketamine on the ability to drive. The effects of esketamine 84 mg were comparable to placebo at 6 hours and 18 hours post ingestion .\r\n\r\n**Effects on cardiac electrophysiology**\r\n\r\nThe effect of esketamine (84 mg nasal spray and 0.8 mg/kg esketamine intravenously infused over 40 minutes) on the QTc interval was studied in a randomized, double-blind, placebo-, and positive-controlled (moxifloxacin 400 mg), 4-period, crossover study in 60 healthy volunteers. A marked increase in heart rate (higher than 10 bpm) was measured in subjects receiving intranasal and intravenous esketamine. Summative evidence from both nonclinical and clinical data suggests a lack of clinically relevant QTc prolongation at the normal therapeutic dose of esketamine . \r\n\r\n**Effects on blood pressure**\r\n\r\nEskestamine causes increases in systolic and/or diastolic blood pressure at all therapeutic doses. Peak blood pressure elevation after esketamine administration occurs about 40 minutes after administration and lasts approximately 4 hours . \r\n\r\n**Cognitive effects**\r\n\r\nIn a study of healthy volunteers, one dose of this agent caused decline in cognitive performance 40 minutes after administration.  Compared to subjects ingesting a placebo, esketamine-treated subjects required a higher level of effort to complete assigned cognitive tests at 40 minutes after administration. Cognitive performance and mental effort were found to be similar between esketamine and placebo at 2 hours after administration .\r\n\r\nReports of long-term memory or cognitive impairment have been made following repeated ketamine misuse or abuse. No adverse effects of esketamine nasal spray on cognitive function were seen in a one-year open-label safety study. The long-term cognitive effects of esketamine have not been studied for more than a 1 year period, therefore, the risk of cognitive decline with long-term use is not yet confirmed .","Esketamine, the S-enantiomer of racemic ketamine, is a non-selective, non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, an ionotropic glutamate receptor. The exact mechanism by which esketamine acts as an antidepressant is unknown. The primary circulating metabolite of esketamine (_noresketamine_) shows activity at the same receptor with a weaker affinity . \r","NMDA receptor antagonist; Glutamate receptor ionotropic, NMDA 2B antagonist; Elongation factor 2 inhibitor; Brain-derived neurotrophic factor agonist; BDNF/NT-3 growth factors receptor","Indication associated"]
[1410,"DB11827","approved; investigational","small molecule","Ertugliflozin","Ertugliflozin","C22H25ClO7","CCOC1=CC=C(CC2=CC(=CC=C2Cl)[C@]23OC[C@](CO)(O2)[C@@H](O)[C@H](O)[C@H]3O)C=C1","Ertugliflozin belongs to the class of potent and selective inhibitors of the sodium-dependent glucose cotransporters (SGLT), more specifically the type 2 which is responsible for about 90% of the glucose reabsorption from glomerulus. This drug was developed under the collaboration of Merck and Pfizer. It was FDA approved as monotherapy and in combination with sitagliptin or metformin hydrochloride on December 22, 2017.","1210344-57-2","436.89","Ertugliflozin as a monotherapy is indicated to improve the glycemic control in adult patients with type 2 diabetes. Ertugliflozin, in combination with metformin hydrochloride, is indicated to improve glycemic control in patients with diabetes type 2 who are not controlled on a regimen of ertugliflozin or metformin or in patients who are already treated with both ertugliflozin and metformin. The administration of ertugliflozin in combination with sitagliptin is indicated to improve glycemic control in adult patients with type 2 diabetes when treatment with ertugliflozin and sitagliptin is appropriate. It is pointed out that the use of ertugliflozin has to be an adjunct therapy to the use of diet and exercise.\r\nThe type 2 diabetes mellitus is characterized by insulin resistance in muscle and liver, which results in the elevation of glucose levels in blood, or by presence of insulin deficiency. The insulin resistance is related to genetic factors, obesity, sedentary lifestyle or/and aging. This increase in the blood glucose can cause severe damage to kidney, eyes and vascular system.","Administration of ertugliflozin increases urinary glucose excretion which leads to a negative balance and osmotic diuresis. Thus, this antidiabetic agent has been reported to significantly reduce the body weight and blood pressure of diabetic patients.","As part of a normal process, the glucose from the blood is filtered for excretion and reabsorbed in the glomerulus so less than one percent of this glucose is excreted in the urine. The reabsorption is mediated by the sodium-dependent glucose cotransporter (SGLT), mainly the type 2 which is responsible for 90% of the reabsorbed glucose. Ertugliflozin is a small inhibitor of the SGLT2 and its activity increases glucose excretion, reducing hyperglycemia without the requirement of excessive insulin secretion.","Sodium/glucose cotransporter 2 antagonist","Target associated"]
[1411,"DB11830","investigational","small molecule","Mocetinostat","Mocetinostat","C23H20N6O","NC1=CC=CC=C1NC(=O)C1=CC=C(CNC2=NC=CC(=N2)C2=CC=CN=C2)C=C1","Mocetinostat has been used in trials studying the treatment of Lymphoma, Urothelial Carcinoma, Relapsed and Refractory, Myelodysplastic Syndrome, and Metastatic Leiomyosarcoma, among others.","726169-73-9","396.454",null,"All HDAC inhibitors induce histone H3 hyperacetylation, correlating with inhibition of proliferation, induction of cell differentiation and apoptosis.","Mocetinostat is a novel isotypic-selective inhibitor of the enzyme histone deacetylase (HDAC). HDAC inhibitors act by turning on tumour suppressor genes that have been inappropriately turned off. Tumour suppressor genes are a natural defense against cancer. It is therefore hypothesized that specifically inhibiting those HDACs involved in cancer with Mocetinostat may restore normal cell function and reduce or inhibit tumour growth.","Histone deacetylase 1; Histone deacetylase 3; Histone deacetylase 2","Therapeutic strategy associated"]
[1412,"DB11834","approved; investigational","biotech","Guselkumab","Guselkumab",null,null,"Guselkumab is a human immunoglobulin G1 lambda (IgG1λ) monoclonal antibody that selectively blocks interleukin-23. IL-23 is an inflammatory cytokine that activates the CD4+ T-helper (Th17) cell pathway to mediate the inflammatory cascade that induces psoriatic plaque formation . In clinical trials, guselkumab demonstrated improved skin clearance and symptomatic improvements in dermatological manifestations of psoriasis. \r\n\r\nDeveloped by Janssen, the subcutenous injection form of guselkumab was approved in July 2017 under the market name Tremfya for the treatment of adult patients with moderate-to-severe plaque psoriasis.","1350289-85-8",null,"Indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.","Guselkumab is shown to reduce serum levels of IL-17A, IL-17F and IL-22 .","Guselkumab targets the p19 alpha subunit of IL-23. While IL-23 promotes the normal inflammatory and immune responses, the p19 and p40 subunits of IL-23 are found to be over-expressed in the condition of psoriasis and other autoimmune inflammatory skin diseases . Guselkumab selectively binds to the p19 subunit of IL-23 in dendritic cells and keratinocytes and blocks its interaction with IL-23 receptor, which further prevents the release of other pro-inflammatory cytokines and chemokines via stimulation of immune cells such as Th17 cells . Thus, guselkumab blocks the abnormally-heightened signalling of inflammatory cascades that promote epidermal abnormalities including keratinocyte hyperproliferation and psoriatic plaque formation .","Interleukin-23 subunit alpha blocker","Therapeutic strategy associated"]
[1413,"DB11842","approved; investigational","small molecule","Angiotensin II","5-isoleucine-angiotensin II; 5-L-isoleucineangiotensin II; Angiotensin; Angiotensin II; Angiotensin II (human); Angiotonin; Human angiotensin II; Hypertensin; Ile5-angiotensin II; isoleucine5-angiotensin II","C50H71N13O12","CC[C@H](C)[C@H](NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(=O)N[C@@H](CC1=CN=CN1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O","Angiotensin II is under investigation for the treatment of Sepsis, Septic Shock, Diabetes Mellitus, and Acute Renal Failure. Angiotensin II has been investigated for the treatment, basic science, and diagnostic of Hypertension, Renin Angiotensin System, and Idiopathic Membranous Nephropathy.\r\n\r\nAs of December 21, 2017 the FDA approved La Jolla Pharmaceutical's Giapreza (angiotensin II) Injection for Intravenouse Infusion for the indication of acting as a vasoconstrictor to increase blood pressure in adults with septic or other distributive shock. The novelty of the medication lies in the fact that it is the first and only use of synthetic human angiotensin II to help maintain body blood pressure. \r\n\r\nShock is the inability to maintain blood flow to vital tissues and the potential resultant organ failure and death within hours, no matter young or o ld. As distributive shock is the most common type of shock in the inpatient setting and affects up to one third of patients in the intensive care unit, the FDA determined that there is a need for treatment options for critically ill hypotensive patients who do not adequately respond to currently available therapies.","4474-91-3","1046.1786","Angiotensin II is a vasoconstrictor indicated for increasing blood pressure in adults with septic or other distributive shock .","Angiotensin II is a naturally occurring peptide hormone of the renin-angiotensin-aldosterone-system (RAAS) that has the capacity to cause vasoconstriction and an increase in blood pressure in the human body. \r\n\r\nIn the RAAS, juxtaglomerular cells of the renal afferent arteriole synthesize the proteolytic enzyme renin. Although stored in an inactive form called pro-renin, decreases in arterial blood pressure or extracellular fluid volume depletion can cause various enzymatic reactions to release active renin into the systemic circulation and surrounding tissues. Such renin release allows for the production of the alpha-2-globulin angiotensinogen predominantly in the liver and to some extent, the kidneys and other organs. \r\n\r\nAngiotensin I, itself a decapeptide with weak biological activity, is produced from angiotensinogen and then quickly converted to angiotensin II by angiotensin converting enzymes (ACE). Consequently, angiotensin II demonstrates its strong vasopressor activity when it is rapidly degraded by aminopeptidases A and M into further entities like angiotensin III and angiotensin IV, respectively. Such species like angiotensin III can then bind and interact with specific G protein coupled receptors like angiotensin receptor 1, or AT-1  where strong vasoconstricson can occur. \r\n\r\nFurthermore, in the ATHOS-3 clinical trial, for the 114 (70%) patient subjects in the angiotensin II arm who reached the target mean arterial pressure (MAP) at Hour 3, the median time to reach the target MAP endpoint was approximately 5 minutes. The angiotensin II was titrated to effect for each individual patient. .","As part of the renin-angiotensin-aldosterone-system (RAAS), angiotensin II raises blood pressure by vasoconstriction, increased aldosterone release by the adrenal zona glomerulosa, sodium and water reabsorption in the proximal tubular cells, and vasopressin secretion \r\n\r\nThe direct action of angiotensin II on surrounding vessel walls is facilitated by binding to the G-protein-coupled angiotensin II receptor type 1 (AT-1) on vascular smooth muscle cells, which stimulates Ca2+/calmodulin-dependent phosphorylation of myosin and causes smooth muscle contraction that results in vasoconstriction .\r\n\r\nThe RAAS is ultimately regulated by a negative feedback effect of angiotensin II on renin production by the juxtaglomerular cells of the renal afferent arteriole. Unresuscitated septic shock associated with marked hypovolemia, extracellular fluid volume depletion, decreased cardiac output, low arterial blood pressure and decreased systemic vascular resistance causes an increase in renin secretion by the juxtaglomerular cells, resulting in elevated angiotensin II plasma levels and an increased secretion of aldosterone from the adrenal cortex. Angiotensin II binding to AT-1 receptors causes dose-dependent vasoconstriction of both afferent and efferent glomerular arterioles. The most pronounced effect of angiotensin II results on efferent arterioles, resulting in reduced renal blood flow and increased glomerular filtration pressure.","Type-1 angiotensin II receptor agonist","Target associated"]
[1414,"DB11856","investigational","biotech","Ligelizumab","Ligelizumab",null,null,"Ligelizumab is a humanized IgG1k monoclonal antibody targeted against immunoglobulin E (IgE). Similar in mechanism to , another IgE-directed monoclonal antibody, ligelizumab has a distinct binding epitope as compared to its peer (with a small degree of overlap) which appears to confer a greater affinity for free serum IgE and an altered sensitivity to IgE conformation.\r\n\r\nLigelizumab is currently under investigation for the treatment of chronic spontaneous urticaria (CSU), an autoimmune-driven inflammatory condition. While the precise pathogenesis of CSU is not entirely clear, autoantibodies against IgE receptors, and sometimes against IgE itself, are thought to exist in 30-40% of patients, and the efficacy anti-IgE antibody therapy in the treatment of CSU has been previously established with omalizumab. Initial trials of ligelizumab suggest a greater efficacy over its predecessor for the treatment of CSU.","1322627-61-1",{"$nulls":3},"Immunoglobulin E (IgE) is a key driver of hypersensitivity reactions, and has thus become an attractive target in the treatment of immune-mediated hypersensitivity disorders. Immediate hypersensitivity reactions are due to IgE binding with FcεRI, which activates allergic effector cells that undergo degranulation to release vasoactive and pro-inflammatory mediators. IgE also binds to CD23/FcεRII, which appears responsible for antigen presentation, antigen transport across airway/epithelial barriers, and the regulation of IgE synthesis. \r\n\r\nLigelizumab is a monoclonal antibody directed at IgE, binding specifically to an epitope in the IgE Cε3 domain. It neutralizes serum IgE and also appears to inhibit the production of IgE via inhibition of IgE-FcεRI binding activity and, to a lesser extent, IgE binding to CD23.","Immunoglobulin heavy constant epsilon antibody","Therapeutic strategy associated"]
[1415,"DB11859","approved; investigational","small molecule","Brexanolone","3alpha-OH DHP; allopregnan-3α-ol-20-one; Allopregnanolone; Brexanolone","C21H34O2","[H][C@@]1(CC[C@@]2([H])[C@]3([H])CC[C@@]4([H])C[C@H](O)CC[C@]4(C)[C@@]3([H])CC[C@]12C)C(C)=O","As of March 2019, brexanolone - developed and made available commercially by Sage Therapeutics Inc. as the brand name product Zulresso - is the first drug to have ever been approved by the US FDA specifically for the treatment of postpartum depression (PPD) in adult females . Since PPD, like various other types of depression, is characterized by feelings of sadness, worthlessness or guilt, cognitive impairment, and/or possibly suicidal ideation, it is considered a life-threatening condition . Studies have consequently found that PPD can genuinely have profound negative effects on the maternal-infant bond and later infant development . The development and availability of brexanolone for the treatment of PPD in adult females subsequently provides a new and promising therapy where few existed before .\r\n\r\nIn particular, the use of brexanolone in treating PPD is surrounded with promise because it acts in part as a synthetic supplement for possible deficiencies in endogenous brexanolone (allopregnanolone) in postpartum women susceptible to PPD whereas many commonly used anti-depressive medications elicit actions that may modulate the presence and activity of substances like serotonin, norepinephrine, and/or monoamine oxidase but do not mediate activities directly associated with PPD like natural fluctuations in the levels of endogenous neuroactive steroids like allopregnanolone .\r\n\r\nAnd finally, although brexanolone may also be undergoing clinical trials to investigate its abilities to treat super-refractory status epilepticus, it appears that some such studies have failed to meet primary endpoints that compare success in the weaning of third-line agents and resolution of potentially life-threatening status epilepticus with brexanolone vs. placebo when added to standard-of-care .","516-54-1","318.4935","Brexanolone is a synthetic neuroactive steroid gamma-aminobutyric acid A (GABA(a)) receptor positive modulator indicated for the treatment of postpartum depression (PPD) in adult women .","Brexanolone potentiated GABA-mediated currents from recombinant human GABA(a) receptors in mammalian cells expressing α1β2γ2 receptor subunits, α4β3δ receptor subunits, and α6β3δ receptor subunits .\r\n\r\nMoreover, it was determined during a Phase 1 randomized, placebo and positive-controlled, double-blind, three-period crossover thorough QT study in 30 healthy adult subjects that brexanolone use did not prolong the QT interval to any clinically relevant extent when administered at 1.9-times the exposure occurring at the highest recommended infusion rate (90 mcg/kg/hour) .","Brexanolone is a neuroactive steroid that occurs naturally (referred to as natural allopregnanolone) in the body when the female sex hormone progesterone is metabolized . This steroid compound is also believed to exhibit activity as a barbiturate-like, positive allosteric modulator of both synaptic and extrasynaptic GABA(a) receptors . In doing so, brexanolone can enhance the activity of GABA at such receptors by having GABA(a) receptor calcium channels open more often and for longer periods of time. Furthermore, it is believed that brexanolone elicits such action on GABA(a) receptors at a binding site that is distinct from those associated with benzodiazepines .\r\n\r\nConcurrently, GABA is considered the principal inhibitory neurotransmitter in the human body . When GABA binds to GABA(a) receptors found in neuron synapses, chloride ions are conducted across neuron cell membranes via an ion channel in the receptors . With enough chloride ions conducted, the local, associated neuron membrane potentials are hyperpolarized - making it more difficult or less likely for action potentials to fire, ultimately resulting in less excitation of the neurons, like those involved in neuronal pathways that may be in part responsible for eliciting certain traits of PPD like stress, anxiety, etc . \r\n\r\nPostpartum depression (PPD) is a mood disorder that can affect women after childbirth . Women with PPD experience feelings of extreme sadness, anxiety, and exhaustion that can make it difficult or even dangerous for them to perform various daily activities or care for themselves or for others, including newborn . Although the exact pathophysiology of PPD remains unknown, it is believed that altered profiles and rapid, unpredictable fluctuations in the blood concentrations of neuroactive steroids like endogenous brexanolone (among others), GABA, and GABA receptors occur in women who are at risk of PPD after childbirth .\r\n\r\nIn particular, within the context of PPD, it is proposed that endogenous brexanolone levels can quickly drop or fluctuate variedly after childbirth and that GABA(a) receptor levels and expression are decreased and down-regulated throughout pregnancy . Such fluctuations and decreases may consequently leave women susceptible to the possibility of PPD. As a medication, synthetic brexanolone can subsequently facilitate a return of positive allosteric modulator GABA(a) modulation while GABA(a) receptor levels and expression gradually return to normal in the time following postpartum . As such, studies suggest the potential for the development of brexanolone as a new mechanism for treatment of PPD that is directly related to the underlying pathophysiology as opposed to many other antidepressant medications whose pharmacological actions are usually entirely unrelated.","GABA(A) Receptor positive allosteric modulator","Indication associated"]
[1416,"DB11866","approved; investigational","biotech","Romosozumab","Romosozumab; romosozumab-aqqg",null,null,"Romosozumab is a humanized monoclonal antibody indicated for the treatment of osteoperosis in postmenopausal women at high risk of fracture and patients who have failed in other treatments or are intolerant to other osteoperosis therapies. Romosozumab prevents bone resorption and induces the formation of bone though it is associated with an increased risk of cardiac death, heart attack, and stroke in one study. In a comparison study of post menopausal women with osteoporosis and a past fracture, romosozumab for 12 months followed by alendronic acid for 12 months was superior to alendronic acid alone for 24 months. Romosozumab also demonstrates a faster and larger increase in bone density than teriparatide. Romosozumab is marketed in the United States by Amgen under the brand name Evinity. Romosozumab was granted FDA approval on April 9,2019.","909395-70-6",null,"Romosozumab is indicated for the treatment of osteoporosis in post menopausal women at high risk of fractures and also in patients with osteoperosis who are intolerant to other treatments or who have failed in other treatments.","Romosozumab is a subcutaneously injected humanized monoclonal antibody that inhibits the secreted protein sclerostin. Inhibition of this protein allows Wnt signalling in osteoblasts to promote bone formation and allows for the inhibition of receptor activator of nuclear factor kappa-beta-ligand (RANKL) mediated bone resorption by osteoclasts.","Osteocytes secrete sclerostin which inhibits bone formation by binding to low-density lipoprotein (LDL) receptor-related proteins 5 and 6 of osteoblasts, inhibiting the Wnt signal pathway.\r\n\r\nRomosozumab targets and inhibits the protein sclerostin, thereby preventing inhibition of bone formation by allowing Wnt to bind to LDL receptor-related proteins 5 and 6. Activation of the Wnt pathways leads to downstream signalling, translocation of beta catenin to the osteoblast nucleus where it promotes survival and proliferation of osteoblasts.\r\n\r\nSclerostin also promotes bone resorption through increasing production of receptor activator of nuclear factor kappa-beta-ligand (RANKL).\r\n\r\nRomosozumab's inhibition of sclerostin also inhibits the increase in RANKL dependant increases in osteoclast activity and bone resorption. Both effects from the same therapy have not been seen in other osteoporosis treatments to date.","Sclerostin inhibitor","Indication associated"]
[1417,"DB11921","approved; investigational","small molecule","Deflazacort","Deflazacort","C25H31NO6","[H][C@@]12C[C@@]3([H])[C@]4([H])CCC5=CC(=O)C=C[C@]5(C)[C@@]4([H])[C@@]([H])(O)C[C@]3(C)[C@@]1(N=C(C)O2)C(=O)COC(C)=O","Deflazacort, also known as Emflaza, is a corticosteroid prodrug used as an agent to manage Duchenne Muscular Dystrophy (DMD). It is marketed by Marathon Pharmaceuticals and was approved in February 2017 by the FDA.\r\n\r\nDuchenne Muscular Dystrophy is an inherited disorder resulting from mutations of the dystrophin gene, which is important for muscle function. This disease can cause serious muscle weakness and progressive breathing and cardiovascular disability, severely impacting patient quality of life and survival. This disease usually manifests by muscle weakness in early childhood followed by loss of the ability to walk (ambulation) as early as age 7.\r\n\r\nDeflazacort delays the onset of muscle related complications resulting from DMD, prolonging the lives of children diagnosed with this disease and exerting less harmful effects on the bone health and weight than other steroid medications.","14484-47-0","441.524","Deflazacort is indicated for the treatment of Duchenne Muscular Dystrophy (DMD) in patients 2 years of age and older.","Deflazacort exerts anti-inflammatory activity in DMD, likely improving various symptoms, including muscle weakness and cardiorespiratory symptoms in addition to delaying their onset. This allows for an increased quality of life and prevents the necessity for surgical procedures, such as those for scoliosis, which is associated with DMD. Studies showed significant preservation of muscle mass in patients generally treated with 0.9 mg/kg/day of deflazacort compared to a control group. The following findings are based on clinical studies using deflazacort on a long term basis:\r\n\r\n**Effects on muscle strength** \r\n\r\nAt age 16, individuals treated with long-term deflazacort had 63 ± 4% score in muscle strength compared to a mean muscle strength score of 31 ± 3% for control patients. Significant improvements in climbing stairs and rising from a supine position were also seen in patients taking deflazacort. \r\n\r\n**Effects on ambulation**\r\n\r\nAmbulation was significantly higher by 12 years of age and 18 years of age in patients taking deflazacort when compared with the control group. The control group showed a mean loss of ambulation of 2 years sooner than with deflazacort treatment.  \r\n\r\n**Effects on cardiac function**\r\n\r\nMean left ventricular ejection fraction (a measure of cardiac function) was higher in patients treated with deflazacort over the long term. Preservation of cardiac function was demonstrated by a mean difference in ejection fraction of about 7%, favoring study groups taking deflazacort over control groups.\r\n\r\n**Effects on spinal alignment**\r\n\r\nChildren treated with deflazacort also significantly lowered the rate and severity of scoliosis and eliminated the need for scoliosis surgery after long-term treatment.","Deflazacort is a corticosteroid prodrug with an active metabolite, 21-deflazacort, which binds to the glucocorticoid receptor to exert anti-inflammatory and immunosuppressive effects on the body. The exact mechanism by which deflazacort exerts its therapeutic effects in patients with DMD is unknown but likely occurs via its anti-inflammatory activities.","Glucocorticoid receptor agonist","Therapeutic strategy associated"]
[1418,"DB11928","approved; investigational","biotech","Vosoritide","Vosoritide",null,null,"Achondroplasia is an autosomal dominant genetic disease and the most common cause of dwarfism in humans. It results from a gain-of-function missense mutation in _FGFR3_ that results in a dramatic suppression of bone growth, both in volume and in length. Treatment for achondroplasia includes both surgical and pharmacological interventions, the latter of which includes C-type natriuretic peptide (CNP) analogs. \r\n\r\nEndogenous CNP, first described in 1998, is primarily responsible for the stimulation of chondrocytes and long bone growth via activity at the NPR-B receptor, making it an attractive target in the treatment of a condition like achondroplasia. While the remarkably short half-life of endogenous CNP - 2 to 3 minutes due to its rapid degradation by endopeptidases - makes it ineffective as a therapeutic intervention, the development of a peptidase-resistant formulation has allowed for its use as a viable treatment option in achondroplasia.\r\n\r\nVosoritide is an analog of CNP with proline-glycine on its N-terminus to convey resistance to neutral endopeptidase. It was approved for use under the brand name Voxzogo (BioMarin Pharmaceutical Inc.) in the EU in August 2021 and the US in November 2021, becoming the first pharmacological intervention approved for the treatment of achondroplasia in both regions.","1480724-61-5",null,"Vosoritide is indicated for the promotion of linear growth in pediatric patients with achondroplasia who are 5 years of age and older with open epiphyses.","Vosoritide is an analog of C-type natriuretic peptide that promotes bone growth to combat growth suppression in children with achondroplasia. Urinary cyclic guanosine monophosphate (cGMP) and serum collagen type X marker (CXM) are both elevated following daily therapy with vosoritide and serve as biomarkers for evidence of increased endochondral bone growth, with cGMP indicative of NPR-B binding activity and CXM indicative of bone metabolism. \r\n\r\nAlthough relatively well-tolerated, transient episodes of hypotension have been observed in clinical studies. Patients with pre-existing cardiovascular disease and those taking antihypertensive medications were excluded from clinical trials. The risk of hypotension may be reduced by ensuring adequate food and fluid intake prior to the administration of vosoritide. The use of vosoritide in patients with an eGFR <60 mL/min/1.73m<sup>2</sup> should also be avoided as there are no data on the influence of renal impairment on its pharmacokinetics.","Achondroplasia is a congenital disease resulting from a missense mutation in the fibroblast growth factor receptor 3 (_FGFR3_) gene, resulting in a gain-of-function that negatively regulates endochondral bone growth. Under normal conditions, _FGFR3_ is expressed during both embryonic and postnatal development, but serves a different role in each. During initial development, FGFR3 signaling promotes proliferation of chondrocytes (i.e. growth), whereas postnatal skeletal growth is actually inhibited by FGFR3 - as a result, the pathologic activation of FGFR3 observed in patients with achondroplasia leads to suppressed pre-pubertal skeletal growth.\r\n\r\nVosoritide is an analog of C-type natriuretic peptide (CNP), a signaling molecule that appears primarily responsible for the stimulation of chondrocytes and the growth of long bones. The binding of CNP (or vosoritide) with its corresponding receptor, NPR-B, results in a signaling cascade that ultimately inhibits the MAPK/ERK pathway via inhibition of RAF-1 and stimulates the proliferation and differentiation of chondrocytes. This activity serves to antagonize the downstream signaling resulting from FGFR3 and its resultant effects on bone growth.","Atrial natriuretic peptide receptor 2 agonist","Therapeutic strategy associated"]
[1419,"DB11936","approved; investigational","small molecule","Bempedoic acid","Bempedoic acid","C19H36O5","CC(C)(CCCCCC(O)CCCCCC(C)(C)C(O)=O)C(O)=O","High levels of LDL cholesterol (LDL-C) are a major risk factor for cardiovascular events. Caused by genetic mutations or lifestyle factors, hypercholesterolemia can significantly reduce quality of life and increase the risk of mortality from cardiovascular disease. About 1 in 4 patients, or 15 million Americans with elevated LDL-C, are insufficiently managed with maximally tolerated statin therapy alone, requiring additional treatment for hypercholesterolemia.\r\n\r\nBempedoic acid is first-in-class adenosine triphosphate-citrate lyase (ACL) inhibitor used once a day for reducing LDL cholesterol levels in statin-refractory patients. It was developed by Esperion Therapeutics Inc. and approved by the FDA on February 21, 2020. A combination product of bempedoic acid and  was approved on February 26, 2020 for increased control of LDL cholesterol levels in patients experiencing refractory elevations despite previous statin treatment.","738606-46-7","344.492","Bempedoic acid is indicated as an adjunct to diet and maximally tolerated statin therapy for adults with heterozygous familial hypercholesterolemia or existing atherosclerotic cardiovascular disease that warrants additional lowering of LDL-C.\r\n\r\nThe combination of bempedoic and ezetimibe is also indicated with diet management and maximally tolerated statin therapy to treat elevated LDL-C levels in adults with heterozygous familial hypercholesterolemia or existing atherosclerotic cardiovascular disease who require further lowering of LDL-C.","Bempedoic acid inhibits the synthesis of cholesterol in the liver, reducing LDL-C levels. This reduces the development of atherosclerotic plaques that may increase the risk of cardiovascular events. Earlier clinical trials studying the effects of bempedoic acid showed a dose‐dependent reduction of LDL‐C levels in addition to decreased LDL particle number, and reduced levels of apolipoprotein B, non–HDL cholesterol, and high‐sensitivity C‐reactive protein.\r\n\r\nDue to its unique mechanism of action, bempedoic acid is not associated with myositis, an adverse effect that frequently accompanies statin therapy.\r\n\r\nMore recent trials have supported that this drug significantly decreases LDL-C levels after 12 weeks of therapy and provides additional lowering of LDL-C when combined with ezetimibe and statin therapy. The effects of bempedoic acid on mortality are currently unknown.","Normally, LDL cholesterol is produced in the liver and circulates in the blood. When the blood becomes saturated, excess LDL deposits in blood vessels including the coronary arteries, increasing the risk of cardiovascular events.\r\n\r\nBempedoic acid is a prodrug that requires activation in the liver. The very-long-chain acyl-CoA synthetase-1 (ACSVL1) enzyme is responsible for its activation to ETC-1002-CoA, the pharmacologically active metabolite. ATP lyase (also known as ATP synthase) plays an important part of cholesterol synthesis. BETC-1002-CoA directly inhibits this enzyme after the parent drug is activated in the liver by coenzyme A (CoA).\r\n\r\n This inhibition leads to upregulation of the LDL cholesterol receptor, reducing serum LDL-C via increased uptake and LDL clearance in the liver. By the above mechanisms, bempedoic acid causes a total decrease of circulating LDL-C that normally damages blood vessels and leads to atherosclerosis. Lastly, ETC-1002 activates AMP-activated protein kinase (AMPK) in rodents, which inhibits the synthesis of cholesterol via the inhibition of HMG-CoA reductase. The relevance of this to humans is unknown.","ATP-citrate synthase inhibitor","Indication associated"]
[1420,"DB11942","approved; investigational","small molecule","Selinexor","Selinexor","C17H11F6N7O","FC(F)(F)C1=CC(=CC(=C1)C1=NN(\\C=C/C(=O)NNC2=NC=CN=C2)C=N1)C(F)(F)F","Selinexor is a first-in-class selective inhibitor of nuclear transport (SINE) compound. It is currently approved for the treatment of multiple myeloma, a cancer which forms from antibody-producing plasma cells. This condition is typically treated with high dose  and dexamethasone chemotherapy followed by autologous stem-cell transplant. Other chemotherapies for multiple myeloma include  and , , and may include  if the patient is not eligible for transplant. Selinexor was approved by the FDA in June 2019. It was granted fast track and orphan designation as well as accelerated approval based on single arm, open label trial data. The Bortezomib, Selinexor, and Dexamethasone in Patients With Multiple Myeloma (BOSTON) trial is planned to finish in 2020.","1393477-72-9","443.313","Selinexor is indicated for the treatment of relapsed or refractory multiple myeloma in combination with dexamethasone. Patients must have received at least 4 prior therapies and have disease which is refractory to least two proteasome inhibitors, at least two immunomodulatory agents, and an anti‐CD38 monoclonal antibody.","Selinexor causes cell cycle arrest and apoptosis in cancer cells.","Selinexor binds to and inhibits exportin-1 (XPO1). XPO1 is a nuclear exporter protein which contains a pocket to which nuclear proteins can bind. When complexed with these proteins and Ran, activated through guanosine triphosphate (GTP) binding, the XPO1-protein-Ran-GTP complex is able to exit the nucleus through a nuclear pore. Once outside, GTP is hydrolyzed and the complex dissociates. The inhibition of this process in cancer cells allows the targets of XPO1, many of which are tumor suppressors, to collect in the nucleus and result in increased transcription of tumor suppressor genes. Tumor suppressor proteins known to be affected by XPO1 inhibition include p53, p73, adenomatous polyposis coli, retinoblastoma, forkhead box protein O, breast cancer 1, nucleophosmin, and merlin. Regulators of cell cycle progression are also affected, namely p21, p27, galectin-3, and Tob. Inhibitor of NFκB also collects in the nucleus as a result leading to reduced activity of NFκB, a known contributor to cancer. XPO1 participates in the formation of a complex with eukaryotic initiation factor 4E and contributes to the transport of messenger RNA for several oncegenes including cell cycle promotors, cyclin D1, cyclin E, and CDK2/4/6, as well as antiapoptotic proteins, Mcl-1 and Bcl-xL. These wide ranging changes in protein expression and gene transcription culminate in cell cycle arrest and the promotion of apoptosis in cancer cells.\r\n\r","Exportin-1 inhibitor","Therapeutic strategy associated"]
[1421,"DB11943","approved; investigational","small molecule","Delafloxacin","Delafloxacin","C18H12ClF3N4O4","NC1=NC(N2C=C(C(O)=O)C(=O)C3=CC(F)=C(N4CC(O)C4)C(Cl)=C23)=C(F)C=C1F","Delafloxacin is a fluoroquinolone antibiotic which has been used in trials studying the treatment and basic science of Gonorrhea, Hepatic Impairment, Bacterial Skin Diseases, Skin Structure Infections, and Community Acquired Pneumonia, among others. It was approved in June 2017 under the trade name Baxdela for use in the treatment of acute bacterial skin and skin structure infections.","189279-58-1","440.76","Delafloxacin is indicated for the treatment of acute bacterial skin and skin structure infections caused by the Gram-positive organisms Staphylococcus aureus (including methicillin-resistant and methicillin-susceptible isolates), Staphylococcus haemolyticus, Staphylococcus lugdunensis, Streptococcus agalactiae, Streptococcus anginosus Group (including Streptococcus anginosus, Streptococcus intermedius, and Streptococcus constellatus), Streptococcus pyogenes, and Enterococcus faecalis as well as the Gram-negative organisms Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, and Pseudomonas aeruginosa .","Delafloxacin is a fluoroquinolone antibacterial drug which kills bacterial cells .","Delafloxacin inhibits the activity of bacterial DNA topoisomerase IV and DNA gyrase (topoisomerase II) . This interferes with bacterial DNA replication by preventing the relaxation of positive supercoils introduced as part of the elongation process . The resultant strain inhibits further elongation. Delafloxacin exerts concentration-dependent bacteriocidal activity .","DNA topoisomerase 4 subunit A inhibitor; DNA gyrase subunit A inhibitor","Indication associated"]
[1422,"DB11952","approved; investigational","small molecule","Duvelisib","Duvelisib","C22H17ClN6O","C[C@H](NC1=C2N=CNC2=NC=N1)C1=CC2=CC=CC(Cl)=C2C(=O)N1C1=CC=CC=C1","Duvelisib, also known as IPI-145 and INK-1197, is a small-molecule inhibitor of phosphoinositide-3 kinases that was designed initially to prove that simultaneous inhibition of the isoforms delta and gamma can produce a broad adaptative and innate immune cell inhibitory activity. All the work around duvelisib showed that this agent is a potent inhibitor of both forms. Duvelisib was developed by Verastem, Inc and FDA approved on September 24, 2018.","1201438-56-3","416.87","Duvelisib is indicated for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least two prior therapies.\r\n\r\nThe CLL is a cancer of the blood stem cells which are the blood cells that can develop into different types of cells. In leukemia, there is an overproduction of cells that are abnormal and do not mature into blood cells and thus, they just crowd out normal cells and impair their normal function. In lymphocyte leukemia, the abnormal cell growth is observed in the lymphoid cells which are the type of blood cells that mature into lymphocytes. The CLL is the type of lymphocytic leukemia that develops slowly over months or years. The SLL is a very similar disease to the CLL and these terms are usually referred interchangeably. The only difference between these two diseases is that in CLL the cells are found mostly in the blood and bone marrow while in SLL, the cells are mainly found in the lymph nodes.\r\n\r\nAs well, duvelisib obtained an accelerated approval for the treatment of adult patients with relapsed or refractory follicular lymphoma after at least two prior systemic therapies. This approval is still under the status of continued approval and it is restrained to confirmatory trials.\r\n\r\nThe follicular lymphoma is a B-cell lymphoma that clusters in the lymph nodes or other tissues.","Preclinical data showed that duvelisib presents cytotoxic actions at micromolar doses and antagonizes the activation of downstream signaling even in the presence of the mutation BTK C481S, which allows for the treatment of patients resistant to ibrutinib.\r\n\r\nIn clinical trials, duvelisib was compared to ofatumumab in patients with chronic lymphocytic leukemia or small lymphocytic leukemia. This trials reported a median progression-free survival of 16.4 months and an overall response rate of 78% which were almost 2-fold what it was reported for ofatumumab.\r\n\r\nIn clinical trials of follicular lymphoma, duvelisib presented and overall response rate of 42% from which almost all the patients observed a partial response. Of the responding patients, 43% maintained the response for at least 6 months and 17% for at least 12 months.","Duvelisib acts as a strong reversible inhibitor of the isoform gamma and delta of the phosphoinositide3-kinase (PI3K).  PI3K plays a very important role in innate and adaptative immunity and the inhibition of the form delta and gamma has been very important for the suppression of immunity.\r\n\r\nThe activity of PI3K gamma and delta is restricted to hematopoietic cells and it is necessary for normal B cell development. In lymphomas, the activation of PI3K is enlarged to promote unlimited growth and survival. Hence, inhibition of PI3K can provide an inhibition of the signaling from BCR, inhibition of a cytokine signaling from the microenvironment and enhancement of anti-tumor immunity. The specific mechanism of this PI3K inhibitors are further described as follows:\r\n\r\n-BCR activates signaling pathways after antigen engagement and it is also critical for the physiologic life of the lymphocytes and neoplastic lymphomas. In CLL, BCR reacts to auto- and exo-antigens to promote clonal expansion. This sustained presence of BCR activates delta PI3K producing a pro-survival pathway of the neoplastic cells which already present a higher activity of PI3K. Thus, the blockade of PI3K will limit the activity of BCR and the driven physiology of the lymphoma.\r\n\r\n-The inhibition of PI3K can also inhibit paracrine and autocrine pro-survival signals mediated by adhesion molecules, chemokines and soluble factors. This activity is attained due to the fact that several downstream signals convey on PI3K.\r\n\r\n-It has been reported that inactivation of PI3K produces a significant resistance to tumorigenesis. This data suggests that inhibition of PI3K can facilitate recognition and elimination of tumor cells.\r\n\r\nIn summary, duvelisib inhibits the isoform delta of PI3K which is necessary for cell proliferation and survival and the isoform gamma which is critical for cytokine signaling and the pro-inflammatory response.","Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform inhibitor; Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform inhibitor","Therapeutic strategy associated"]
[1423,"DB11967","approved; investigational","small molecule","Binimetinib","Binimetinib","C17H15BrF2N4O3","CN1C=NC2=C(F)C(NC3=CC=C(Br)C=C3F)=C(C=C12)C(=O)NOCCO","Binimetinib, also known as _Mektovi_, is a potent and selective oral mitogen-activated protein kinase 1/2 (MEK 1/2) inhibitor which is combined with  .\r\n\r\nOn June 27, 2018, the Food and Drug Administration approved the combination of  and binimetinib (BRAFTOVI and MEKTOVI, from Array BioPharma Inc.) in combination for patients with unresectable or metastatic melanoma with the BRAF V600E or V600K mutations, as detected by an FDA-approved test.","606143-89-9","441.233","\r\nOn June 27, 2018, the Food and Drug Administration approved encorafenib and binimetinib in combination patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test .","Binimetinib is a MEK inhibitor. MEK is an enzyme that regulates the biosynthesis of the inflammatory cytokines TNF, IL-6 and IL-1. MEK inhibitors interfere with these biosynthetic processes .   It is a chemotherapeutic agent that has anti-tumor activity , .","\r\nBinimetinib, noncompetitive with ATP, binds to and inhibits the activity of MEK1/2. The inhibition of MEK1/2 prevents the activation of MEK1/2-dependent effector proteins and transcription factors. This process can result in the inhibition of growth factor-mediated cell signaling. This may lead to the inhibition of tumor cell proliferation and an inhibition in the production of various inflammatory cytokines including interleukin-1, -6 and tumor necrosis factor. MEK1/2 are themselves threonine and tyrosine kinases that possess a dual specificity. They subsequently contribute critically to the activation of the RAS/RAF/MEK/ERK pathway and are typically upregulated in a number of different tumor cell types .","Interleukin-6; Tumor necrosis factor; Interleukin-1 beta; Mitogen-activated protein kinase kinase kinase 1 inhibitor; Dual specificity mitogen-activated protein kinase kinase 2 inhibitor","Therapeutic strategy associated"]
[1424,"DB11976","approved; investigational","biotech","Anifrolumab","Anifrolumab; anifrolumab-fnia",null,null,"Anifrolumab, or MEDI-546, is a type 1 interferon receptor (IFNAR) inhibiting IgG1κ monoclonal antibody indicated in the treatment of adults with moderate to severe systemic lupus erythematosus. The standard therapy for systemic lupus erythematosus consists of antimalarials like , glucocorticoids like , and  disease modifying antirheumatic drugs like .\r\n\r\nThree monoclonal antibodies (anifrolumab, , and ) that target the type 1 interferon pathway entered clinical trials as potential treatments for systemic lupus erythematosus, but so far only anifrolumab has been approved.\r\n\r\nThe design of early clinical trials of anti-interferon treatments such as anifrolumab, rontalizumab, and sifalimumab have come under criticism. The design of the clinical trials use different definitions of autoantibody positivity, making comparison between trials difficult; all trials involve large portions of patients also using corticosteroids, which may alter patient responses in the experimental and placebo groups; and patient populations were largely homogenous, which may have increased the odds of success of the trial.\r\n\r\nAnifrolumab has also been investigated for the treatment of Scleroderma.\r\n\r\nAnifrolumab was granted FDA approval on 30 July 2021.","1326232-46-5",null,"Anifrolumab is indicated in the treatment of adults with moderate to severe systemic lupus erythematosus.","Anifrolumab is a type 1 interferon receptor (IFNAR) inhibiting IgG1κ monoclonal antibody indicated in the treatment of adults with moderate to severe systemic lupus erythematosus. It has a long duration of action as it is given every 4 weeks. Patients should be counselled regarding the risks of serious infections, hypersensitivity reactions, and malignancies.","Systemic lupus erythematosus (SLE) is an autoimmune disorder affecting multiple systems in the body. SLE may manifest as a rash on the skin, and can progress to life-threatening autoimmune reactions in the kidney or nervous system.\r\n\r\nType 1 interferon pathway activation has been identified as a mediator of pathogenesis in SLE, and the level of type 1 interferon expression is correlated with severity of SLE. Activation of the type 1 interferon receptor (INFAR1) by interferons alpha, beta, epsilon, kappa, and omega lead to stimulation of gene transcription. Activation of INFAR1 and INFAR2 lead to phosphorylation of STAT1 and STAT2, which are translocated with interferon regulatory factor 9 (IRF9) to the cell nucleus to activate the interferon-stimulated response element (ISRE). Activation of ISRE leads to the expression of many proinflammatory and immunomodulatory proteins, as well as the activation of a positive feedback loop that produces more type 1 interferons.\r\n\r\nInterferon alpha stimulates monocytes to mature into myeloid dendritic cells that express self antigens. CD4+ and CD8+ T-cells, as well as B cells, that are autoreactive will respond to the self antigens and induce inflammmation and apoptosis in cells. This self-reactive immune response damages otherwise healthy tissue throughout the body.\r\n\r\nAnifrolumab is an immunoglobulin gamma 1 kappa (IgG1κ) monoclonal antibody that selectively binds to subunit 1 of INFAR1. The binding of anifrolumab to IFNAR1 inhibits the activity of the receptor, decreasing downstream signalling and gene transcription of inflammatory mediators.\r\n\r\nThe Fc region of anifrolumab carries the triple mutaion L234F/L235E/P331S to prevent binding of the Fc region of the antibody to cell surface Fc receptors.\r\n\r\nIn a phase IIb clinical trial, the primary endpoint was reached by 34.3% of patients in the 300 mg treatment group, 28.8% of patients in the 1000 mg treatment group, and 17.6% of patients in the placebo group. Patients with higher interferon-stimulated gene transcription at baseline showed a greater response to treatment.","Interferon alpha/beta receptor 1 inhibitor","Therapeutic strategy associated"]
[1425,"DB11986","approved; investigational","small molecule","Entrectinib","Entrectinib","C31H34F2N6O2","CN1CCN(CC1)C1=CC=C(C(=O)NC2=NNC3=CC=C(CC4=CC(F)=CC(F)=C4)C=C23)C(NC2CCOCC2)=C1","Entrectinib is a tropomyosin receptor tyrosine kinase (TRK) TRKA, TRKB, TRKC, proto-oncogene tyrosine-protein kinase ROS1, and anaplastic lymphoma kinase (ALK) inhibitor. It was approved by the FDA in August 2019 for use in the treatment of ROS1-positive metastatic non-small cell lung cancer and NTRK gene fusion positive solid tumors. Entrectinib's approved use is meant as a last line of therapy due to its accelerated approval based on early trial data. This therapy offers benefit over similar ALK inhibitors such as , , and  due to a wider range of targets.","1108743-60-7","560.65","Entrectinib is indicated for the treatment of metastatic ROS1-positive non-small cell lung cancer in adults. Entrectinib is also indicated in adults and children over 12 years old for the treatment of NTRK gene fusion-positive solid tumors which have metastasized or for which surgical resection is likely to result in severe morbidity and for which has progressed on previous therapies or for which no comparable alternative therapies are available.","Entrectinib and its active metabolite suppress several pathways which contribute to cell survival and proliferation. This suppression shifts the balance in favor of apoptosis thereby preventing cancer cell growth and shrinking tumors.","Entrectinib is a tyrosine kinase inhibitor which acts on several receptors. It functions as an ATP competitor to inhibit tropomyosin receptor tyrosine kinases (TRK) TRKA, TRKB, TRKC, as well as proto-oncogene tyrosine-protein kinase ROS1 and anaplastic lymphoma kinase (ALK). TRK receptors produce cell proliferation via downstream signalling through the mitogen activated protein kinase, phosphoinositide 3-kinase, and phospholipase C-γ. ALK produces similar signalling with the addition of downstream JAK/STAT activation. Inhibition of these pathways suppresses cancer cell proliferation and shifts the balance in favor of apoptosis resulting in shrinking of tumor volume.","High affinity nerve growth factor receptor inhibitor; BDNF/NT-3 growth factors receptor inhibitor; NT-3 growth factor receptor inhibitor; Proto-oncogene tyrosine-protein kinase ROS inhibitor; Tyrosine-protein kinase JAK2 inhibitor; Activated CDC42 kinase 1","Therapeutic strategy associated"]
[1426,"DB11988","approved; investigational","biotech","Ocrelizumab","Ocrelizumab; Ocrelizumab (genetical recombination)",null,null,"Ocrelizumab is a CD20-directed cytolytic antibody indicated for the treatment of patients with relapsing or primary progressive forms of multiple sclerosis. It is a second-generation recombinant humanized monoclonal IgG1 antibody that selectively targets the B lymphocytes that express the CD20 antigen. As a humanized molecule, ocrelizumab is expected to be less immunogenic with repeated infusions which improves the benefit-to-risk profile for patients with relapsing or progressive forms of MS. \r\n\r\nMultiple sclerosis (MS) is a chronic, inflammatory, autoimmune disease of the central nervous system that leads to neurological disabilities and significantly reduced quality of life . Most patients with MS experience episodes of relapses with worsening function, followed by recovery periods, or remissions. Primary progressive multiple sclerosis (PPMS) accounts for 10-15% of the overall population of patients with MS, and involves gradual worsening of neurologic disability from symptom onset, often without early relapses or remissions .\r\n\r\nDeveloped by Genentech/Roche, ocrelizumab was approved by the FDA in March 2017 under the market name Ocrevustm for intravenous injection. It was later approved by Health Canada (as Ocrevus) in August 2017, making the drug the first available treatment for PPMS in both U.S. and Canada. In clinical trials of patients with relapsing forms of MS, treatment with ocrelizumab resulted in reduced relapse rates and reduced worsening of disability compared to interferon beta-1a . In phase 3 clinical trials of patients with PPMS, treatment with ocrelizumab demonstrated lower rates of clinical and MRI progression than placebo .","637334-45-3",null,"Indicated for the treatment of adult patients with relapsing or primary progressive forms of multiple sclerosis .","Since ocrelizumab interferes with the CD20 assay, CD19+B-cells were used to assess B-cell counts after ocrelizumab treatment. 14 days following infusion, a reduction in CD19+B-cell counts was observed. In clinical studies, B-cell counts rose to above the lower limit of normal (LLN) or above baseline counts between infusions of ocrelizumab at least one time in 0.3% to 4.1% of patients. In a clinical study involving 51 patients, the time for B-cell counts to return to baseline or LLN was ranged from 27 to 125 weeks, with the median time of 72 weeks, after the last infusion. Within 2.5 years after the last infusion, B-cell counts returned to either baseline or LNN in 90% of the patients .","B lymphocytes are known to contribute to the pathogenesis of MS through activation of pro-inflammatory T cells and secretion of proinflammatory cytokines. B cells may differentiate into plasma cells that can produce autoantibodies directed against myelin and cause complement-mediated attack on the myelin sheath . CD20 is a cell-surface antigen found on pre-B cells, naïve and mature B cells and memory B cells. However, this activated glycosylated phosphoprotein is not expressed on haematopoietic stem cells, pro-B cells (precursors), or differentiated plasma cells . \r\n\r\nWhile the exact mechanism of ocrelizumab leading to B-cell depletion is unknown, there are several different proposed mechanisms. Upon cell surface binding to CD20-expressing B lymphocytes, ocrelizumab promotes antibody-dependent cellular cytotoxicity and complement-mediated cell lysis. The capacity for B-cell reconstitution and preexisting humoral immunity is preserved , such as levels of IgG and IgM antibodies in the blood of cerebrospinal fluid. Ocrelizumab may induce antibody-dependant cellular cytotoxicity involving macrophages, natural killer cells, and cytotoxic T cells that act together to cause cell death . Another mechanism is apoptosis, which may result from cross-linking membrane CD20 on the target cell surface .","B-lymphocyte antigen CD20 antagonist&antibody","Therapeutic strategy associated"]
[1427,"DB12007","experimental","small molecule","Isoflavone","3-phenyl-4H-1-benzopyran-4-one; 3-Phenylchromone; Isoflavon","C15H10O2","O=C1C(=COC2=CC=CC=C12)C1=CC=CC=C1","Isoflavone is a soy phytoestrogen and a biologically active component of several agriculturally important legumes such as soy, peanut, green peas, chick peas and alfalfa . Soybean is an exceptionally rich source of dietary isoflavones, where the average isoflavone content is 1-2 mg/gram . The main soy isoflavones are mostly present in glycosylated forms and include , , and glycitein, which accounts for approximately 50%, 40%, and 10%, respectively, of the total soybean isoflavone content . The clinical benefits of soy proteins have been studied and demonstrated for many years, with some evidence of soy products associated with a reduced incidences of coronary heart disease, atherosclerosis, type II diabetes mellitus, and breast and prostate cancer . While existing data are consistent or inadequate in supporting most of the suggested health benefits of consuming soy proteins and isoflavones , the trials investigating isoflavone as a potential treatment for atrophy, menopause, and postmenopausal symptoms are ongoing. Isoflavone is found as one of constituents in oral over-the-counter dietary supplements indicated for improved bone mass density and body fat regulation.","574-12-9","222.243","Indicated for over-the-counter use as a dietary supplement for increasing bone density and regulating blood fat.","Isolated soy protein with isoflavones was shown to decrease LDL cholesterol levels in randomized trials assessed by the American Heart Association . In a study of postmenopausal women, daily dietary intake of 101 mg of aglycone isoflavones (indicating  and ) was associated with lowered LDL cholesterol and apolipoprotein B levels by 8% and reduced systolic and diastolic blood pressure by 6.8% in hypertensive women . In a meta-analysis of randomized controlled trials of menopausal women, soy isoflavones attenuated bone loss of the spine and decreased the levels of deoxypyridinoline, a bone resorption marker, while increasing serum bone-specific alkaline phosphatase, a bone formation marker . The findings from studies investigating the effects of soy consumption on menopausal symptoms, breast cancer, and prostate cancer remain somewhat controversial and inconclusive. Consumption of soy isoflavones may decrease the markers of cancer development and progression in prostate cells, including prostate-specific antigen (PSA), testosterone, and androgen receptor in patients with prostate cancer but not in normal subjects . Although epidemiologic data in Asian women demonstrate that high soy food intake is associated with protection against breast cancer, soy foods have little effect on intermediary markers of breast cancer risk and postmenopausal soy intake may not reduce the risk of developing breast cancer . However, preliminary studies  show that soy food intake reduces tumor recurrence in breast cancer patients . Soy isoflavones reported to interfere with thyroid peroxidase, which are involved in the production of thyroid hormones .","Isoflavones are selective estrogen receptor modulators that exert estrogenic-like effects under certain experimental conditions , as they are structurally similar to mammalian 17β-estradiol. They may bind to both α and β isoforms of estrogen receptor (ER), but with binding affinities to ERβ approximately 20 times higher than that to ERα . The role of isoflavones on estrogen-dependent cancer has been studied, since they may mediate antiestrogenic actions by blocking the binding of endogenous estrogens and their receptor signalling . In cell culture,  inhibited the proliferation of MDA-MB-231 human breast cancer cells, probably by arresting the cell cycle progression at the G2–M transition . In addition, genistein was shown to induce apoptosis, modify eicosanoid metabolism, and inhibit angiogenesis . There is an evidence that soy isoflavones may act on androgen receptors to inhibit tyrosine kinase activity, thereby blocking the growth and proliferation of cancer cells . \r\n\r\nIsoflavones may not significantly contribute to the hypolipidemic effects of soy protein, but may exert coronary benefits by improving endothelial function; in clinical trials of postmenopausal women, isoflavones improved flow-mediated dilation in women with impaired endothelial function . Some observational data suggests that isoflavones improve endothelial function by increasing the number of circulating endothelial progenitor cells, which replace damaged endothelial cells . Isoflavone may modulate the key transcription factors involved in the regulation of lipid metabolism by acting on the peroxisome proliferator-activated receptors (PPAR) alpha and gamma, which are receptors that regulate the transcription of genes involved in lipid and glucose homeostasis and lipid metabolism . Multiple biological actions of isoflavones, such as favorable effect on the blood lipid profile and inhibition of LDL cholesterol oxidation, may lead to cardio protective effects . \r\n\r\n has been shown to have antioxidant properties on hydrogen peroxide production _in vitro_ and blocks the formation of oxygen free radicals . Studies also suggest that at micromolar concentrations, genistein increases glucose-stimulated insulin secretion in cell lines and mouse pancreatic islets via a cAMP-dependent protein kinase mechanism . Based on the findings of experimental studies, genistein may exert a positive effect on bone formation by decreasing osteoclastic resorption factor, such as collagen C-telopeptide, and increasing osteoblastic formation markers, such as bone-alkaline phosphatase . _In vitro_, it antagonized the catabolic effects of parathyroid hormone (PTH) in osteoblasts by reversing the PTH-induced increase in soluble receptor activator of nuclear factor-xB ligand and decrease in osteoprotegerin expression .","Peroxisome proliferator-activated receptor alpha agonist; Peroxisome proliferator-activated receptor gamma agonist","Therapeutic strategy associated"]
[1428,"DB12010","approved; investigational","small molecule","Fostamatinib","Fostamatinib","C23H26FN6O9P","COC1=CC(NC2=NC=C(F)C(NC3=NC4=C(OC(C)(C)C(=O)N4COP(O)(O)=O)C=C3)=N2)=CC(OC)=C1OC","Fostamatinib has been investigated for the treatment and basic science of Rheumatoid Arthritis and Immune Thrombocytopenic Purpura (ITP). It was approved on April 17, 2018, under the trade name Tavalisse for use in ITP . Fostamatinib has also been granted orphan drug status by the FDA .\r\n\r\nRecently, fostamatinib has been identified as a potential therapeutic for controlling acute respiratory distress syndrome (ARDS) in patients with severe COVID-19 through its ability to modulate the SYK kinase.","901119-35-5","580.4595","Fostamatinib is indicated for use in the treatment of chronic immune thrombocytopenia (ITP) in patients who have had insufficient response to previous therapy .","The active metabolite of fostamatinib, R406, inhibits signal transduction by Fcγ receptors involved in the antibody-mediated destruction of platelets by immune cells in chronic ITP . This results in increased platelet counts in this population.\r\n\r\nR406 produces inhibition of T and B lymphocyte activation by T-cell receptors (TCRs) and B-cell receptors (BCRs) respectively . It can also inhibit signalling via Fcε receptors which could have applications in treating allergic symptoms through prevention of mast cell degranulation . Inhibition of Fc receptor signalling system also affected by R406 suppresses both dendritic cell maturation and antigen presentation and may contribute to the effects of fostamatinib . As a knock-on effect of disabling signal transduction from Fc receptors, TCRs, and BCRs, the production of inflammatory mediators and cytokines like tumour necrosis factor α, leukotriene C4, interleukin-8, and granulocyte-macrophage colony-stimulating factor.\r\n\r\nFostamatinib can produce hypertension through off-target effects \r","The active metabolite of fostamatinib, R406, is an inhibitor of spleen tyrosine kinase (Syk) . It binds reversibly to the ATP binding pocket with high affinity (Ki = 30nM), inhibiting the kinase activity with an IC50 of 41nM.\r\n\r\nSyk is a cytosolic protein kinase and part of the signalling cascade which occurs with Fc receptors, TCRs, and BCRs . It contains two src homology 2 (SH2) domains separated by a linker domain. These SH2 domains bind to tyrosine residues on the immunoreceptor tyrosine-based activating motif phosphorylated by Lyn, another kinase in the cascade. This motif is located on the cytoplasmic regions of several immune receptors including Fc receptors, TCRs, BCRs, and natural killer cell receptors. The flexibility provided by the linker enables the protein to bind to many receptor types. Inhibition of Syk suppresses downstream signal transduction .\r\n\r\nWhile Syk plays a role in some pathways involved in the generation of the oxidative burst by neutrophils or phagocytosis by macrophages, R406 does not have a significant effect on these processes . This is likely due to redundant pathways which do not involve Syk. Similarly Syk does not produce significant effects on platelet activation despite its involvement in glycoprotein IV and integrin based signalling. Activation of antibody-dependent cell-mediated toxicity by natural killer cells is also unaffected despite the involvement of Syk in Fc receptor signalling .\r\n\r\nR406 binds to the adenosine A3 receptor as an antagonist as well as the adenosine and monoamine uptake transporters as an inhibitor . It has also been found to be an inhibitor of UDP glucuronosyltransferase UGT1A1, phosphodiesterase PDE5, fatty acid amide hydrolase, 5-lipoxygenase, cathepsin L, and cathepsin S . R406 appears to inhibit a wide range of kinases at higher concentrations . It is thought that inhibition of some of these targets may be responsible for the increase in blood pressure seen with fostamatinib.\r\n\r","Tyrosine-protein kinase SYK inhibitor; Adenosine receptor A3 antagonist; vesicular monoamine transporter 2 (VMAT2) inhibitor; Fatty-acid amide hydrolase 1 inhibitor; Equilibrative nucleoside transporter 1 inhibitor; UDP-glucuronosyltransferase 1-1 inhibitor; cGMP-specific 3',5'-cyclic phosphodiesterase inhibitor; Arachidonate 5-lipoxygenase inhibitor; Cathepsin S inhibitor; Cathepsin L1 inhibitor; Tyrosine-protein kinase ABL1 inhibitor; Calcium-dependent protein kinase 1 inhibitor; Serine/threonine-protein kinase PknB inhibitor; Ribosomal protein S6 kinase alpha-6 inhibitor; Non-receptor tyrosine-protein kinase TYK2 inhibitor; Atypical kinase COQ8A, mitochondrial inhibitor; Tyrosine-protein kinase JAK1 inhibitor; Hepatocyte growth factor receptor inhibitor; Serine/threonine-protein kinase NIM1 inhibitor; Serine/threonine-protein kinase MST4 inhibitor; cAMP-dependent protein kinase catalytic subunit alpha inhibitor; Serine/threonine-protein kinase 24 inhibitor; Serine/threonine-protein kinase 3 inhibitor; Tyrosine-protein kinase Tec inhibitor; Serine/threonine-protein kinase 33 inhibitor; Serine/threonine-protein kinase 35 inhibitor; Serine/threonine-protein kinase 36 inhibitor; Serine/threonine-protein kinase 38 inhibitor; Serine/threonine-protein kinase 38-like inhibitor; STE20/SPS1-related proline-alanine-rich protein kinase inhibitor; Serine/threonine-protein kinase TAO1 inhibitor; Serine/threonine-protein kinase TAO2 inhibitor; Serine/threonine-protein kinase TAO3 inhibitor; Serine/threonine-protein kinase TBK1 inhibitor; Angiopoietin-1 receptor inhibitor; Dual specificity testis-specific protein kinase 1 inhibitor; TGF-beta receptor type-1 inhibitor; TGF-beta receptor type-2 inhibitor; Tyrosine-protein kinase receptor Tie-1 inhibitor; Serine/threonine-protein kinase tousled-like 1 inhibitor; Serine/threonine-protein kinase tousled-like 2 inhibitor; TRAF2 and NCK-interacting protein kinase inhibitor; Non-receptor tyrosine-protein kinase TNK1 inhibitor; Activated CDC42 kinase 1 inhibitor; Serine/threonine-protein kinase TNNI3K inhibitor; Testis-specific serine/threonine-protein kinase 1 inhibitor; Dual specificity protein kinase TTK inhibitor; Tyrosine-protein kinase TXK inhibitor; Tyrosine-protein kinase receptor TYRO3 inhibitor; Serine/threonine-protein kinase ULK1 inhibitor; Serine/threonine-protein kinase ULK2 inhibitor; Serine/threonine-protein kinase ULK3 inhibitor; Wee1-like protein kinase inhibitor; Tyrosine-protein kinase Yes inhibitor; Mitogen-activated protein kinase kinase kinase 19 inhibitor; Mitogen-activated protein kinase kinase kinase MLT inhibitor; Tyrosine-protein kinase ZAP-70 inhibitor; AP2-associated protein kinase 1 inhibitor; Abelson tyrosine-protein kinase 2 inhibitor; Activin receptor type-1 inhibitor; Activin receptor type-1B inhibitor; Atypical kinase COQ8B, mitochondrial inhibitor; ALK tyrosine kinase receptor inhibitor; Ankyrin repeat and protein kinase domain-containing protein 1 inhibitor; Aurora kinase A inhibitor; Aurora kinase B inhibitor; Aurora kinase C inhibitor; Tyrosine-protein kinase receptor UFO inhibitor; Tyrosine-protein kinase Blk inhibitor; BMP-2-inducible protein kinase inhibitor; Bone morphogenetic protein receptor type-1B inhibitor; Bone morphogenetic protein receptor type-2 inhibitor; Cytoplasmic tyrosine-protein kinase BMX inhibitor; Serine/threonine-protein kinase B-raf inhibitor; Tyrosine-protein kinase BTK inhibitor; Calcium/calmodulin-dependent protein kinase type 1 inhibitor; Calcium/calmodulin-dependent protein kinase type 1D inhibitor; Calcium/calmodulin-dependent protein kinase type 1G inhibitor; Calcium/calmodulin-dependent protein kinase type II subunit alpha inhibitor; Calcium/calmodulin-dependent protein kinase type II subunit beta inhibitor; Calcium/calmodulin-dependent protein kinase type II subunit delta inhibitor; Calcium/calmodulin-dependent protein kinase type II subunit gamma inhibitor; Calcium/calmodulin-dependent protein kinase kinase 1 inhibitor; Calcium/calmodulin-dependent protein kinase kinase 2 inhibitor; Peripheral plasma membrane protein CASK inhibitor; Kappa-casein inhibitor; Cyclin-dependent kinase 1 inhibitor; Serine/threonine-protein kinase MRCK gamma inhibitor; Cyclin-dependent kinase 4 inhibitor; Cyclin-dependent kinase-like 1 inhibitor; Cyclin-dependent kinase-like 2 inhibitor; Serine/threonine-protein kinase Chk1 inhibitor; Serine/threonine-protein kinase Chk2 inhibitor; Citron Rho-interacting kinase inhibitor; Dual specificity protein kinase CLK1 inhibitor; Dual specificity protein kinase CLK2 inhibitor; Dual specificity protein kinase CLK3 inhibitor; Dual specificity protein kinase CLK4 inhibitor; Macrophage colony-stimulating factor 1 receptor inhibitor; Tyrosine-protein kinase CSK inhibitor; Casein kinase I isoform alpha inhibitor; Casein kinase II subunit alpha inhibitor; Casein kinase II subunit alpha' inhibitor; Death-associated protein kinase 1 inhibitor; Death-associated protein kinase 2 inhibitor; Death-associated protein kinase 3 inhibitor; Serine/threonine-protein kinase DCLK1 inhibitor; Serine/threonine-protein kinase DCLK2 inhibitor; Serine/threonine-protein kinase DCLK3 inhibitor; Epithelial discoidin domain-containing receptor 1 inhibitor; Discoidin domain-containing receptor 2 inhibitor; Dual specificity tyrosine-phosphorylation-regulated kinase 1A inhibitor; Dual specificity tyrosine-phosphorylation-regulated kinase 1B inhibitor; Epidermal growth factor receptor inhibitor; Eukaryotic translation initiation factor 2-alpha kinase 1 inhibitor; Interferon-induced, double-stranded RNA-activated protein kinase inhibitor; eIF-2-alpha kinase GCN2 inhibitor; Ephrin type-A receptor 1 inhibitor; Ephrin type-A receptor 2 inhibitor; Ephrin type-A receptor 3 inhibitor; Ephrin type-A receptor 4 inhibitor; Ephrin type-A receptor 5 inhibitor; Ephrin type-A receptor 6 inhibitor; Ephrin type-A receptor 7 inhibitor; Ephrin type-A receptor 8 inhibitor; Ephrin type-B receptor 1 inhibitor; Ephrin type-B receptor 2 inhibitor; Ephrin type-B receptor 4 inhibitor; Ephrin type-B receptor 6 inhibitor; Receptor tyrosine-protein kinase erbB-2 inhibitor; Receptor tyrosine-protein kinase erbB-4 inhibitor; Serine/threonine-protein kinase/endoribonuclease IRE1 inhibitor; Tyrosine-protein kinase Fer inhibitor; Tyrosine-protein kinase Fes/Fps inhibitor; Fibroblast growth factor receptor 1 inhibitor; Fibroblast growth factor receptor 2 inhibitor; Fibroblast growth factor receptor 3 inhibitor; Tyrosine-protein kinase Fgr inhibitor; Vascular endothelial growth factor receptor 1 inhibitor; Receptor-type tyrosine-protein kinase FLT3 inhibitor; Vascular endothelial growth factor receptor 3 inhibitor; Serine/threonine-protein kinase mTOR inhibitor; Tyrosine-protein kinase FRK inhibitor; Tyrosine-protein kinase Fyn inhibitor; Cyclin-G-associated kinase inhibitor; Glycogen synthase kinase-3 alpha inhibitor; Glycogen synthase kinase-3 beta inhibitor; Tyrosine-protein kinase HCK inhibitor; Homeodomain-interacting protein kinase 2 inhibitor; Homeodomain-interacting protein kinase 3 inhibitor; Serine/threonine-protein kinase ICK inhibitor; Inhibitor of nuclear factor kappa-B kinase subunit beta inhibitor; Inhibitor of nuclear factor kappa-B kinase subunit epsilon inhibitor; Insulin receptor inhibitor; Insulin receptor-related protein inhibitor; Interleukin-1 receptor-associated kinase 1 inhibitor; Interleukin-1 receptor-associated kinase 3 inhibitor; Interleukin-1 receptor-associated kinase 4 inhibitor; Tyrosine-protein kinase ITK/TSK inhibitor; Tyrosine-protein kinase JAK2 inhibitor; Tyrosine-protein kinase JAK3 inhibitor; Vascular endothelial growth factor receptor 2 inhibitor; Serine/threonine-protein kinase SIK3 inhibitor; Mast/stem cell growth factor receptor Kit inhibitor; Serine/threonine-protein kinase LATS1 inhibitor; Tyrosine-protein kinase Lck inhibitor; LIM domain kinase 1 inhibitor; LIM domain kinase 2 inhibitor; Leucine-rich repeat serine/threonine-protein kinase 2 inhibitor; Leukocyte tyrosine kinase receptor inhibitor; Tyrosine-protein kinase Lyn inhibitor; Dual specificity mitogen-activated protein kinase kinase 2 inhibitor; Dual specificity mitogen-activated protein kinase kinase 3 inhibitor; Dual specificity mitogen-activated protein kinase kinase 5 inhibitor; Dual specificity mitogen-activated protein kinase kinase 6 inhibitor; Mitogen-activated protein kinase kinase kinase 1 inhibitor; Mitogen-activated protein kinase kinase kinase 10 inhibitor; Mitogen-activated protein kinase kinase kinase 11 inhibitor; Mitogen-activated protein kinase kinase kinase 12 inhibitor; Mitogen-activated protein kinase kinase kinase 13 inhibitor; Mitogen-activated protein kinase kinase kinase 15 inhibitor; Mitogen-activated protein kinase kinase kinase 2 inhibitor; Mitogen-activated protein kinase kinase kinase 3 inhibitor; Mitogen-activated protein kinase kinase kinase 4 inhibitor; Mitogen-activated protein kinase kinase kinase 6 inhibitor; Mitogen-activated protein kinase kinase kinase 9 inhibitor; Mitogen-activated protein kinase kinase kinase kinase 1 inhibitor; Mitogen-activated protein kinase kinase kinase kinase 2 inhibitor; Mitogen-activated protein kinase kinase kinase kinase 3 inhibitor; Mitogen-activated protein kinase kinase kinase kinase 4 inhibitor; Mitogen-activated protein kinase kinase kinase kinase 5 inhibitor; Mitogen-activated protein kinase 10 inhibitor; Mitogen-activated protein kinase 13 inhibitor; Mitogen-activated protein kinase 14 inhibitor; Mitogen-activated protein kinase 15 inhibitor; Mitogen-activated protein kinase 4 inhibitor; Mitogen-activated protein kinase 7 inhibitor; Mitogen-activated protein kinase 9 inhibitor; MAP kinase-activated protein kinase 5 inhibitor; Serine/threonine-protein kinase MARK1 inhibitor; Serine/threonine-protein kinase MARK2 inhibitor; MAP/microtubule affinity-regulating kinase 3 inhibitor; MAP/microtubule affinity-regulating kinase 4 inhibitor; CLIP-associating protein 1 inhibitor; Microtubule-associated serine/threonine-protein kinase 1 inhibitor; Megakaryocyte-associated tyrosine-protein kinase inhibitor; Maternal embryonic leucine zipper kinase inhibitor; Tyrosine-protein kinase Mer inhibitor; Misshapen-like kinase 1 inhibitor; MAP kinase-interacting serine/threonine-protein kinase 1 inhibitor; MAP kinase-interacting serine/threonine-protein kinase 2 inhibitor; Macrophage-stimulating protein receptor inhibitor; Muscle, skeletal receptor tyrosine-protein kinase inhibitor; Myosin light chain kinase, smooth muscle inhibitor; Myosin light chain kinase 2, skeletal/cardiac muscle inhibitor; Myosin light chain kinase 3 inhibitor; Myosin light chain kinase family member 4 inhibitor; Myosin-IIIa inhibitor; Serine/threonine-protein kinase Nek1 inhibitor; Serine/threonine-protein kinase Nek11 inhibitor; Serine/threonine-protein kinase Nek2 inhibitor; Serine/threonine-protein kinase Nek3 inhibitor; Serine/threonine-protein kinase Nek4 inhibitor; Serine/threonine-protein kinase Nek5 inhibitor; Serine/threonine-protein kinase Nek9 inhibitor; High affinity nerve growth factor receptor inhibitor; BDNF/NT-3 growth factors receptor inhibitor; NT-3 growth factor receptor inhibitor; NUAK family SNF1-like kinase 1 inhibitor; NUAK family SNF1-like kinase 2 inhibitor; Serine/threonine-protein kinase OSR1 inhibitor; Serine/threonine-protein kinase PAK 1 inhibitor; Serine/threonine-protein kinase PAK 2 inhibitor; Serine/threonine-protein kinase PAK 3 inhibitor; Serine/threonine-protein kinase PAK 4 inhibitor; Serine/threonine-protein kinase PAK 6 inhibitor; Serine/threonine-protein kinase PAK 5 inhibitor; Cyclin-dependent kinase 16 inhibitor; Cyclin-dependent kinase 17 inhibitor; Platelet-derived growth factor receptor alpha inhibitor; Platelet-derived growth factor receptor beta inhibitor; 3-phosphoinositide-dependent protein kinase 1 inhibitor; Cyclin-dependent kinase 15 inhibitor; Phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform inhibitor; Phosphatidylinositol 4-kinase beta inhibitor; Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta inhibitor; Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit gamma inhibitor; Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform inhibitor; Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform inhibitor; Serine/threonine-protein kinase pim-1 inhibitor; Serine/threonine-protein kinase pim-3 inhibitor; Phosphatidylinositol 5-phosphate 4-kinase type-2 beta inhibitor; Phosphatidylinositol 5-phosphate 4-kinase type-2 gamma inhibitor; Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase inhibitor; Serine/threonine-protein kinase N1 inhibitor; Serine/threonine-protein kinase N2 inhibitor; Serine/threonine-protein kinase PLK1 inhibitor; Serine/threonine-protein kinase PLK2 inhibitor; Serine/threonine-protein kinase PLK3 inhibitor; Serine/threonine-protein kinase PLK4 inhibitor; 5'-AMP-activated protein kinase catalytic subunit alpha-1 inhibitor; 5'-AMP-activated protein kinase inhibitor; cAMP-dependent protein kinase catalytic subunit beta inhibitor; Protein kinase C delta type inhibitor; Protein kinase C epsilon type inhibitor; Protein kinase C gamma type (PRKCG) inhibitor; Protein kinase C iota type inhibitor; Protein kinase C theta type inhibitor; Serine/threonine-protein kinase D1 inhibitor; cGMP-dependent protein kinase 2 inhibitor; Serine/threonine-protein kinase PRP4 homolog inhibitor; Focal adhesion kinase 1 inhibitor; Protein-tyrosine kinase 2-beta inhibitor; Protein-tyrosine kinase 6 inhibitor; RAF proto-oncogene serine/threonine-protein kinase inhibitor; Proto-oncogene tyrosine-protein kinase receptor Ret inhibitor; Serine/threonine-protein kinase RIO1 inhibitor; Serine/threonine-protein kinase RIO2 inhibitor; Serine/threonine-protein kinase RIO3 inhibitor; Receptor-interacting serine/threonine-protein kinase 1 inhibitor; Receptor-interacting serine/threonine-protein kinase 2 inhibitor; Receptor-interacting serine/threonine-protein kinase 4 inhibitor; Rho-associated protein kinase 2 inhibitor; Proto-oncogene tyrosine-protein kinase ROS inhibitor; Ribosomal protein S6 kinase alpha-1 inhibitor; Ribosomal protein S6 kinase alpha-3 inhibitor; Serine/threonine-protein kinase SBK1 inhibitor; Uncharacterized serine/threonine-protein kinase SBK3 inhibitor; Serine/threonine-protein kinase Sgk3 inhibitor; Serine/threonine-protein kinase SIK1 inhibitor; Serine/threonine-protein kinase SIK2 inhibitor; STE20-like serine/threonine-protein kinase inhibitor; SNF-related serine/threonine-protein kinase inhibitor; Proto-oncogene tyrosine-protein kinase Src inhibitor; Tyrosine-protein kinase Srms inhibitor; Serine/threonine-protein kinase 10 inhibitor; Serine/threonine-protein kinase 16 inhibitor; Serine/threonine-protein kinase 17A inhibitor; Serine/threonine-protein kinase 17B inhibitor; Serine/threonine-protein kinase 32A inhibitor","Target associated"]
[1429,"DB12023","approved; investigational","biotech","Benralizumab","Benralizumab",null,null,"Benralizumab is a humanized recombinant monoclonal antibody of the isotype IgG1k immunoglobulin that specifically binds to the alpha chain of the interleukin 5 receptor (IL-5R) expressed on eosinophils and basophils. It inhibits the binding of IL-5 as well as the hetero-oligomerization of the alpha and beta subunits of the IL-5R, thus blocking, signal transduction. Besides, it is an afucosylated IgG which gives it high affinity for the FcγRIIIα receptor in natural killer cells, macrophages and neutrophils. Benralizumab, FDA approved on November 14, 2017, was developed by MedImmune, the AstraZeneca's global biologic research and development arm.","1044511-01-4",null,"Benralizumab is indicated as a maintenance treatment of patients 12 years or older with severe asthma and an eosinophilic phenotype. The pathology of severe asthma with eosinophilic phenotype is also denotated as TH2-high phenotype. The patients with this phenotype are characterized by the expression of IL-5 and IL-13, airway hyperresponsiveness, responsiveness to inhaled corticosteroids, high serum IgE and eosinophilia in blood and airway. In the TH2-high phenotype, IL-5 presents a central role as it is responsible for eosinophil differentiation, survival, activation and migration to the lungs.","Eosinophils are the key target of inflammatory respiratory diseases and they undergo apoptosis in absence of IL-5. Therefore, benralizumab action on the IL-5 receptor in basophils and eosinophils produces the apoptosis and its significant reduction in the blood. On the other hand, Benralizumab binding to natural killer cells FcγRIIIα receptor produces a direct antibody-dependent cell-mediated cytotoxicity. All these effects produce a reduction in eosinophil count in airway mucosa, submucosa, sputum, blood and bone marrow.","Interleukin-5 (IL-5) induces an eosinophil-mediated inflammatory response by binding to the IL-5 receptor (IL-5R) expressed in eosinophils, basophils and some mast cells. Benralizumab, unlike IL-5 low-affinity binding, binds with high affinity to the domain I of the α-chain of IL-5R and blocks its signaling and the proliferation of IL-5-dependent cell lines. On the other hand, Benralizumab is an afucosylated antibody in the CH2 region which gives it a high affinity for the FcγRIIIa on natural killer cells, macrophages and neutrophils. This binding triggers a magnified apoptosis response in eosinophils via antibody-dependent cell-mediated cytotoxicity.","Interleukin-5 receptor subunit alpha antibody; Low affinity immunoglobulin gamma Fc region receptor III-A binding","Therapeutic strategy associated"]
[1430,"DB12035","approved; investigational","small molecule","Sarecycline","Sarecycline","C24H29N3O8","[H][C@@]12CC3=C(CN(C)OC)C=CC(O)=C3C(=O)C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@]1([H])C2","Sarecycline is a semi-synthetic derivative of tetracycline that was initially discovered by Paratek Pharmaceuticals from Boston, MA but then licensed to Warner Chilcott of Rockaway, NJ in July of 2007 . After completing various phase-II and phase-III trials demonstrating its effectiveness in treating moderate to severe facial acne vulgaris  the US Food and Drug Administration approved Barcelona based Almirall, S.A.'s Seysara (sarecylcine) as a new first in class narrow spectrum tetracycline derived oral antibiotic for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients nine years of age and older . Seysara (sarecycline) was originally part of Allergan's US Medical Dermatology portfolio, before Almirall acquired the portfolio in the second half of 2018 as a means of consolidating and reinforcing the dermatology-focused pharmaceutical company's presence in the United States .\r\n\r\nAcne vulgaris itself is a common chronic skin condition associated with the blockage and/or inflammation of hair follicles and their accompanying sebaceous glands . The acne often presents physically as a mixture of non-inflammatory and inflammatory lesions mainly on the face but on the back and chest as well . Based upon data from Global Burden of Disease studies, the acne vulgaris condition affects up to 85% of young adults aged 12 to 25 years globally - with the possibility of permanent physical and mental scarring resulting from cases of severe acne .\r\n\r\nSubsequently, while a number of first line tetracycline therapies like doxycycline and minocycline do exist for treating acne vulgaris, sarecycline presents a new and innovative therapy choice because it exhibits the necessary antibacterial activity against relevant pathogens that cause acne vulgaris but also possesses a low propensity for resistance development in such pathogens and a narrower, more specific spectrum of antibacterial activity, resulting in fewer off-target antibacterial effects on endogenous intestinal flora and consequently fewer resultant adverse effects associated with diarrhea, fungal overgrowth, etc.","1035654-66-0","487.509","Sarecycline is a tetracycline-class drug indicated for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 9 years of age and older .","Compared to various examples of first-line tetracycline therapies for moderate to severe acne like doxycycline and minocycline, studies have shown that sarecycline can be sixteen to thirty-two fold less active against aerobic Gram-negative bacilli present within the normal human intestinal microbiome . Furthermore, it has also been demonstrated that sarecycline may be four to eight fold less active against various anaerobic bacteria that also comprise the normal human intestinal microbiome . Subsequently, while doxycycline and minocycline typically elicit broad-spectrum antimicrobial activity that can often cause adverse effects like diarrhea, fungal overgrowth, vaginal candidiasis, etc. due to undesirable off-target antibacterial effects on endogenous intestinal flora, sarecycline demonstrates a noticeably more target specific narrow spectrum activity with lower incidence of such side effects .\r\n\r\nMoreover, sarecycline also shares a relatively low propensity for resistance development in Cutibacterium acnes - one of the principal anaerobic organisms associated with acne lesions - with doxycycline and minocycline treatments .","It has been demonstrated that tetracyclines like sarecycline elicit their antimicrobial action by targeting and inhibiting protein synthesis in microbial agents like Cutibacterium acnes present in acne lesions . In particular, it is believed that sarecycline's mechanism of action revolves around the inhibition of various macromolecular biosynthesis activities like the macromolecular biosynthesis of microbial DNA, RNA, proteins, lipids, and cell wall . Specifically, it has been observed that while sarecycline demonstrates appreciable inhibition of microbial macromolecular DNA and protein synthesis, the compound has little to no effect on lipid biosynthesis, cell wall synthesis, and RNA synthesis . In addition, because Cutibacterium acnes also generates proteins and enzymes that are capable of causing inflammation, it is also believed that tetracyclines like sarecyclines can also affect an anti-inflammatory effect via the inhibition of such microbial protein synthesis .",null,"Therapeutic strategy associated"]
[1431,"DB12077","investigational","biotech","Urelumab","Urelumab",null,null,"Urelumab has been used in trials studying the treatment of Leukemia, Multiple Myeloma, Malignant Tumors, and Cancer - Solid Tumors and B-Cell Non-Hodgkin's Lymphoma. Urelumab is a fully human antibody that targets CD137. The antibody product was developed using Medarex's UltiMAb(R) technology and was the first UltiMAb- derived antibody in clinical development by Bristol-Myers Squibb under the December 2003 agreement with Medarex.","934823-49-1",{"$nulls":4},"Tumor necrosis factor receptor superfamily member 9","Target associated"]
[1432,"DB12107","approved; investigational","small molecule","Vaborbactam","Vaborbactam","C12H16BNO5S","OB1O[C@H](CC(O)=O)CC[C@@H]1NC(=O)CC1=CC=CS1","Vaborbactam is a β-lactamase inhibitor based on a cyclic boronic acid pharmacophore. It has been used in trials investigating the treatment of bacterial infections in subjects with varying degrees of renal insufficiency. In August 2017, a combination antibacterial therapy under the market name Vabomere was approved by the FDA for the treatment of adult patients with complicated urinary tract infections (cUTI). Vabomere consists of vaborbactam and  for intravenous administration. Vaborbactam is added to the therapy to reduce the extent meropenem degradation by inhibiting the serine beta-lactamases expressed by the microorganism of target. The treatment aims to resolve infection-related symptoms of cUTI and achieve negative urine culture, when the infections are proven or strongly suspected to be caused by susceptible bacteria.","1360457-46-0","297.13","Indicated in combination with meropenem for the treatment of patients 18 years of age and older with complicated urinary tract infections (cUTI) including pyelonephritis caused by the following susceptible microorganisms: _Escherichia coli_, _Klebsiella pneumoniae_, and _Enterobacter cloacae_ species complex.","Vaborbactam shows no antibacterial activity alone; it serves to restore the antibacterial activity of other antibacterial agents such as meropenem by attenuating their degradation by inhibiting certain serine beta-lactamases of microorganisms. Vaborbactam does not decrease the activity of meropenem against meropenem-susceptible organisms. Vaborbactam in combination with meropenem, which is a penem antibacterial drug, potentiates the bactericidal actions of meropenem against carbapenem-resistant KPC-containing _Escherichia coli_, _Klebsiella pneumoniae_, and _Enterobacter cloacae_ in a concentration-dependent manner. It restored the antimicrobial activity of meropenem in animal models of infection caused by some meropenem non-susceptible KPC-producing Enterobacteriaceae.","Vaborbactam is a cyclic boronic acid pharmacophore β-lactamase inhibitor that elicits potent inhibition of _Klebsiella pneumoniae_ carbapenemase (KPC) enzymes and other Ambler class A and C enzymes such as serine β-lactamases that confer resistance to commonly-used antibiotics such as Carbapenems. Vaborbactam is a potent inhibitor of class A carbapenemases, such as KPC, as well as an inhibitor of other class A (CTX-M, SHV, TEM) and class C (P99, MIR, FOX) beta-lactamases. Vaborbactam interacts with β-lactamases of Ambler classes A and C via precovalent and covalent binding. It exerts no inhibitory actions on class D or class B carbapenemases. The production of contemporary β-lactamase by bacterial isolates potentiate the degradation of β-lactam antibiotic agents, rendering them clinically ineffective and posing challenges for patients receiving the standard antibiotic therapy. In combination with meropenem, varborbactam acts as a non-suicidal beta-lactamase inhibitor that protects meropenem from degradation mediated by serine beta-lactamases such as _Klebsiella pneumoniae_ carbapenemase (KPC).","Beta-lactamase inhibitor; Carbapenem-hydrolyzing beta-lactamase KPC inhibitor; Beta-lactamase (KPC-2) inhibitor; Beta-lactamase CTX-M inhibitor; Beta-lactamase (blaSHV) inhibitor; Beta-lactamase SHV-1 inhibitor; Beta-lactamase TEM inhibitor; Beta-lactamase (MIR-1) inhibitor; Beta-lactamase inhibitor","Indication associated"]
[1433,"DB12140","investigational","small molecule","Dilmapimod","Dilmapimod","C23H19F3N4O3","CC1=CC(F)=CC=C1C1=C2C=CC(=O)N(C2=NC(NC(CO)CO)=N1)C1=C(F)C=CC=C1F","Dilmapimod has been used in trials studying the treatment and diagnostic of Nerve Trauma, Inflammation, Pain, Neuropathic, Arthritis, Rheumatoid, and Coronary Heart Disease, among others. Dilmapimod (SB-681323) is a p38 MAP-kinase inhibitor that has potential uses in inflammatory conditions such as RA (Rheumatoid Arthritis). Previous p38 MAP-kinase inhibitors have been hindered in development by liver toxicity. Methotrexate (common treatment for RA patients) also has potential liver toxicity.}","444606-18-2","456.425","Dilmapimod has been used in trials studying the treatment and diagnostic of Nerve Trauma, Inflammation, Pain, Neuropathic, Arthritis, Rheumatoid, and Coronary Heart Disease, among others.",null,"Dilmapimod reduces the levels of proinflammatory cytokines and chemokines and reduce cellular infiltration to sites of inflammation, thereby reducing local damage. \r\nIn diseases such as RA and IBD, TNFα blockade through either anti-TNFα antibodies or use of soluble TNFα receptors. Inhibition of p38α offers significant inhibition of TNFα, and cytokines such as IL-1β and IL-6, which offer additional therapeutic efficacy.","Tumor necrosis factor; Interleukin-1 beta; Interleukin-6","Therapeutic strategy associated"]
[1434,"DB12147","approved; investigational","small molecule","Erdafitinib","Erdafitinib","C25H30N6O2","COC1=CC(=CC(OC)=C1)N(CCNC(C)C)C1=CC=C2N=CC(=NC2=C1)C1=CN(C)N=C1","In early April of 2019, the US FDA approved Janssen Pharmaceutical Companies' brand name Balversa (erdafitinib) as the first-ever fibroblast growth factor receptor (FGFR) kinase inhibitor indicated for patients with locally advanced or metastatic urothelial carcinoma, with susceptible FGFR3 or FGFR2 genetic alterations, that has progressed during or following platinum-containing chemotherapy, including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy . At the same time, the FDA also approved the therascreen FGFR RGQ RT-PCR Kit (Qiagen) for utilization as a companion diagnostic with erdafitinib for selecting patients for the indicated therapy .\r\n\r\nErdafitinib's innovation lies in the fact that it is the first personalized treatment targeting susceptible FGFR genetic alterations for patients with metastatic bladder cancer, which demonstrates the design of erdafitinib in developing more personalized and precision medicines with the capacity to target cancer treatment to a patient's specific genetic mutation . Considering urothelial cancer is statistically the fourth most common kind of cancer in the world , the introduction of erdafitinib offers a welcome new option in the ever-expanding therapeutic tool kit to treat such prevalent medical conditions.\r\n\r\nNevertheless, although erdafitinib was granted Breakthrough Therapy designation and Accelerated Approval from the FDA so as to allow the agency to focus on and expedite the approval process for a medication indicated for a serious condition that fills an unmet medical need using clinical trial data that is believed to predict a genuine clinical benefit for patients with the given condition, such designations mean further ongoing clinical trials are necessary to confirm the clinical benefit of erdafitinib going forward .","1346242-81-6","446.555","Erdafitinib is a pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor  that is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma that has:\r\ni) susceptible FGFR3 or FGFR2 genetic alterations and has ,\r\nii) progressed during or following at least one line of prior platinum-containing chemotherapy including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy .\r\n\r\nThe selection of patients for the treatment of locally advanced or metastatic urothelial carcinoma with erdafitinib should be based on the presence of susceptible FGFR genetic alterations in tumor specimens as detected by an FDA-approved companion diagnostic like the FDA approved therascreen FGFR RGQ RT-PCR Kit as developed by QIAGEN .\r\n\r\nThis above indication is approved under accelerated approval by the US FDA based on tumor response rate . Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials .","Upon administration, it was observed that erdafitinib increased serum phosphate level as a consequence of FGFR inhibition . Erdafitinib should be increased to the maximum recommended dose to achieve target serum phosphate levels of 5.5– 7.0 mg/dL in early cycles with continuous daily dosing .\r\n\r\nSubsequently, in erfatinib clinical trials, the use of drugs which could increase serum phosphate levels, such as potassium phosphate supplements, vitamin D supplements, antacids, phosphate-containing enemas or laxatives, and medications known to have phosphate as an excipient were prohibited unless no alternatives existed . To manage phosphate elevation, phosphate binders were utilized . Additionally, the concomitant use of agents that can alter serum phosphate levels before the initial erfatinib dose increase period based on serum phosphate levels was also avoided .\r\n\r\nFurthermore, based on the evaluation of QTc interval in an open-label, dose escalation, and dose expansion study in 187 patients with cancer, erdafitinib had no large effect (i.e., > 20 ms) on the QTc interval .","Urothelial cancer is statistically the fourth most common kind of cancer in the world . In general, such urothelial cancers originate in the urothelium - or the transitional epithelium - a membrane that covers the renal pelvis to the ureter, the bladder, and the proximal two-thirds of the urethra . While 90 to 95% of urothelial cancers are bladder cancers and the other 5 to 10% are upper tract urothelial cancers, the bladder cancers can also be either superficial or invasive (either not having or having invaded the deeper layers of the bladder) .\r\n\r\nMoreover, fibroblast growth factor receptor (FGFR) is a transmembrane protein that is expressed ubiquitously in normal tissues and is involved in various endogenous bio-physiological processes including the homeostasis of phosphate and vitamin D, cell proliferation, cell anti-apoptotic signaling, and cell migration in a variety of cell types . Concurrently, genetic mutations or changes like deregulation of FGFR pathways and FGFR aberrations such as gene amplification, point mutations, and chromosomal translocations have been implicated in the pathogenesis of urothelial cancer, including the possibility of such changes to all four FGFR genes (FGFR1, FGFR2, FGFR3, and FGFR4) . Changes to the FGFR genes are consequently thought to promote cell proliferation, migration, angiogenesis, and anti-apoptosis in many cancers including urothelial cancer .\r\n\r\nErdafitinib is subsequently an oral selective pan-FGFR kinase inhibitor that binds to and inhibits the enzymatic activity of expressed FGFR1, FGFR2, FGFR3, and FGFR4 based on in vitro data . In particular, erdafitinib demonstrates inhibition of FGFR phosphorylation and signaling as well as decreased cell viability in cell lines expressing FGFR genetic alterations, including point mutations, amplifications, and fusions . Erdafitinib demonstrated antitumor activity in FGFR-expressing cell lines and xenograft models derived from tumor types, including bladder cancer .","Fibroblast growth factor receptor 1 inhibitor; Fibroblast growth factor receptor 2 inhibitor; Fibroblast growth factor receptor 3 inhibitor; Fibroblast growth factor receptor 4 inhibitor; RET proto-oncogene substrate; Macrophage colony-stimulating factor 1 receptor substrate; Platelet-derived growth factor receptor alpha substrate; Platelet-derived growth factor receptor beta substrate; Mast/stem cell growth factor receptor Kit substrate; Vascular endothelial growth factor receptor 2 substrate","Therapeutic strategy associated"]
[1435,"DB12157","investigational","biotech","Fasinumab","Fasinumab",null,null,"Fasinumab is a human IgG1k monoclonal antibody targeted against nerve growth factor (NGF). It is currently under investigation for the treatment osteoarthritic pain and has demonstrated significantly greater pain relief and functional improvement as compared to standard therapy (i.e. NSAIDs and/or opioids) in this patient population.\r\n\r\nNGF was first discovered in the 1950s and was the first neurotrophic factor to be identified and biochemically characterized. It has since been recognized for its role in nociceptive signaling transduction and has thus become an attractive target in the treatment of chronic pain conditions.","1190239-42-9",{"$nulls":3},"During embryonic development, nerve growth factor (NGF) binds to tropomyosin receptor kinase A receptor (TrkA) and the low-affinity p75 neurotrophin receptor (NTR) on developing neuronal cell surfaces, which activates signaling pathways involved in neuronal growth and survival. In adults, the primary role of NGF shifts towards influencing nociceptive signaling transduction by releasing inflammatory mediators and regulating ion channels or receptors.\r\n\r\nFasinumab is a human IgG1k monoclonal antibody targeted against NGF, interrupting pain signaling pathways and thus alleviating pain and improving function in patients suffering from chronic pain conditions.","Beta-nerve growth factor inhibitor","Therapeutic strategy associated"]
[1436,"DB12159","approved; investigational","biotech","Dupilumab","Dupilumab",null,null,"Dupilumab is a fully human monoclonal antibody of the immunoglobulin G4 subclass that binds to the interleukin-4 (IL-4) receptor, inhibiting the receptor signaling pathways. As an interleukin-4 receptor alpha antagonist, dupilumab inhibits the signaling of pro-inflammatory cytokines, called interleukins (IL), that induce inflammatory and immunological reactions in several atopic or allergic conditions, such as eczema, allergic reaction, and rhinosinusitis. Dupilumab was generated by recombinant DNA technology in Chinese Hamster Ovary cell suspension culture.\r\n\r\nDupilumab is commonly marketed as Dupixent®, which is available as a formulation for subcutaneous injection. It was first approved by the FDA in 2017 for patients 12 and older with eczema or atopic dermatitis. Dupilumab is also approved by Health Canada for the same indication and the European Commission for use in atopic dermatitis as well as severe asthma with type 2 inflammation. It is the first biologic therapy to have been approved for the treatment of adult patients with moderate-to-severe AD in the EU and USA. In 2018, FDA approved the use of dupilumab as an add-on maintenance treatment for patients 12 years and older with moderate-to-severe eosinophilic asthma or with oral corticosteroid-dependent asthma. In June 2019, dupilumab was also approved by the FDA as an add-on maintenance treatment for inadequately controlled chronic rhinosinusitis with nasal polyps in adult patients. Dupilumab is currently under investigations for potential therapeutic use in diseases driven by allergic reactions or type 2 inflammation, such as pediatric atopic dermatitis, eosinophilic esophagitis, and chronic obstructive pulmonary disease. It is also being studied in combination with another antibody that which targets IL-33.","1190264-60-8",null,"Dupilumab is indicated, as monotherapy or in combination with topical corticosteroids, for the treatment of patients aged 12 years and older with moderate-to­-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.\r\n\r\nIt is also used as an add-on maintenance treatment in patients with moderate-to-severe asthma aged 12 years and older with an eosinophilic phenotype or with oral corticosteroid dependent asthma. It is not indicated for the relief of acute bronchospasm or status asthmaticus.\r\n\r\nDupilumab is indicated as an add-on maintenance treatment in adult patients with inadequately controlled chronic rhinosinusitis with nasal polyposis.","Dupilumab is an recombinant human IgG4 antibody to the IL-4 receptor that works by inhibiting the activation of certain pro-inflammatory cytokines that are implicated in the pathophysiology of several allergic and atopic conditions, including asthma, chronic rhinosinusitis with nasal polyps, and food and environmental allergies. _In vivo_, dupilumab was shown to reduce the levels of type 2 inflammatory biomarkers associated with atopic dermatitis, such as thymus and activation-regulated chemokine (TARC/CCL17), total serum IgE, allergen-specific IgE, and lactate dehydrogenase (LDH). A decrease in the levels of biomarkers of asthma, such as FeNO, eotaxin-3, IgE, periostin, and eotaxin-3 (CCL26) was also observed. Since dupilumab works to suppress the immune response, it is proposed that it may influence the immune response against some infections, such as helminth infections, by inhibiting IL-4/IL-13 signaling. It is advised that infections are appropriately treated until resolved before initiating dupilumab therapy. \r\n\r\nWhile findings of some _in vitro_ and _in vivo_ studies suggest that some cytokine modulators may influence the expression and activity of specific cytochrome P450 (CYP450) enzymes, an open-label drug-drug interaction study demonstrated that dupilumab displays no significant effect on the activity of CYP450 enzymes studied (CYP3A, CYP2C19, CYP2C9, CYP1A2, and CYP2D6).","Type 2 inflammatory processes in various allergic and atopic conditions, such as asthma and atopic diseases, involve the type 2 helper T-cell (Th2) immunity. Upregulation of this Type 2/Th2 pathway is commonly observed in other inflammatory conditions  and the activation of Th2 cells is linked to the production of Th2-associated cytokines, such as interleukin (IL) 4, IL-5, IL-9, and IL-13. IL-4 and IL-13 play a central role in inducing inflammatory conditions such as allergic rhinitis, asthma, and atopic dermatitis, by regulating Type 2 inflammation and immune function. These inflammatory cytokines work by modulating gene expression downstream of receptor signalling, regulating Th2 cell differentiation, and activating inflammatory cells such as mast cells and macrophages. \r\n\r\nThere are two types of receptors for IL-4: the type 1 receptor, which is composed of the IL-4 chain (IL-4Rα) and a γ chain (γC), and the type 2 receptor, which is composed of the IL-4Rα chain and the α1 chain of the IL-13 receptor (IL-13Rα1). Essentially, IL‐4Rα is a component shared by the IL‐4 and IL-13 receptor complexes  and is ubiquitously expressed on both innate and adaptive immune cells to promote the signaling of IL-4 and IL-13. The type I receptor is primarily expressed on lymphocytes and controls Th2-cell differentiation, whereas the type II receptor is mostly found across resident and myeloid cells. Dupilumab is a fully human monoclonal antibody directed against IL‐4Rα to inhibit the signalling of IL‐4 and IL‐13. Dupilumab inhibits IL-4 signalling via the Type I receptor (IL-4Rα/γc), and both IL-4 and IL-13 signaling through the Type II receptor (IL-4Rα/IL-13Rα). It ultimately downregulates type-2 immunity.","Interleukin-4 receptor subunit alpha antagonist","Therapeutic strategy associated"]
[1437,"DB12169","approved; investigational","biotech","Tralokinumab","Tralokinumab",null,null,"Atopic dermatitis (AD) is an inflammatory skin disorder that causes skin inflammation, skin barrier dysfunction, and chronic pruritus. It is estimated to affect up to 20% of adults and children worldwide, and is frequently associated with other atopic conditions such as asthma or allergic rhinitis. While AD is a heterogenous condition with a variety of apparent genetic and environmental causes, it is primarily driven by the pro-inflammatory cytokine interleukin-13 (IL-13).\r\n\r\nTralokinumab is a fully human IgG4 monoclonal antibody targeted against IL-13. It neutralizes IL-13 activity by inhibiting its ability to bind with receptors, thus helping to alleviate AD symptoms. Tralokinumab was first approved for the treatment of atopic dermatitis by the EMA in June 2021, under the brand name Adtralza (Leo Pharma), and was subsequently approved in Canada in October 2021.","1044515-88-9",null,"Tralokinumab is indicated in Canada and the EU for the treatment of adult patients with moderate-to-severe atopic dermatitis who are candidates for systemic therapy and are inadequately controlled with topical interventions.","Tralokinumab exerts its therapeutic effects by inhibiting the inflammatory cytokine (IL-13) primarily responsible for the pathogenesis of atopic dermatitis. It is administered subcutaneously with a loading dose of 600mg followed by a maintenance dose of 300mg every two weeks. In clinical studies, tralokinumab treatment decreased the concentrations of a number of Th2 and Th22 immunity biomarkers in the blood, including periostin, IL-22, serum IgE. It also reduced epidermal thickness and decreased the expression of Keratin 16 and Ki-67 in skin affected by atopic dermatitis.\r\n\r\nHypersensitivity reactions, including anaphylaxis, have been reported following the use of tralokinumab. Patients experiencing a systemic hypersensitivity reaction should discontinue treatment and initiate immediate therapy as clinically indicated. Tralokinumab should not be used in patients with pre-existing helminth infections, as the influence of tralokinumab on the immune response against helminth infections is unclear. Patients with helminth infections should be treated prior to therapy with tralokinumab. Patients becoming infected during the course of therapy may be treated with anti-helminth medications, but should discontinue tralokinumab if the infection fails to resolve.","Interleukin-13 (IL-13) is a pro-inflammatory cytokine that has been implicated as the primary driver of atopic dermatitis (AD). IL-13 binds with high affinity to both a heterodimeric form of IL-13Rα1 - complexed with IL-4Rα - and to IL-13Rα2, both of which are expressed on keratinocytes and fibroblasts. While IL-13Rα2 does not appear to act as a signal mediator, the binding of IL-13 to heterodimeric IL-4Rα and IL-13Rα1 activates downstream Janus kinase 2 (JAK2) and tyrosine kinase 2 (TYK2) pathways which proceed to activate various signal transducer and activator of transcription (STAT) pathways. STAT signalling induces the expression of periostin, an extracellular matrix protein which serves a number of physiological functions in addition to its pathogenic role in skin fibrosis and chronic allergic inflammation. IL-13 also appears to contribute to skin barrier dysfunction via an indirect downregulation of filaggrin (FLG), a structural protein essential for correct skin barrier functioning.\r\n\r\nTralokinumab is a monoclonal antibody targeted against IL-13. It neutralizes the activity of IL-13 by blocking its interaction with both the IL-13Rα1/IL-4Rα receptor complex and IL-13Rα2 receptors.","Interleukin-13 antibody","Therapeutic strategy associated"]
[1438,"DB12240","approved; investigational","biotech","Polatuzumab vedotin","Polatuzumab vedotin; polatuzumab vedotin-piiq",null,null,"Polatuzumab vedotin is a CD79b specific antibody conjugated to the antineoplastic agent monomethyl auristatin E. This medication was granted accelerated FDA approval on 10 June 2019.","1313206-42-6",null,"This medication is indicated to treat adults with relapsed or refractory diffuse large B-cell lymphoma in combination with bendamustine and rituximab that has returned of progressed after 2 or more previous therapies.","The binding of the unconjugated drug to microtubules in B cells leads to a number of immunosuppressant adverse effects including neutropenia and thrombocytopenia.\r\n\r\nThe incidence of peripheral neuropathy also increases with increasing doses and time exposed to the drug.\r\n\r\nPolatuzumab vedotin does not prolong the QTc interval.","Polatuzumab vedotin is an antibody targeted to CD79b conjugated to the antineoplastic agent monomethyl auristatin E (MMAE). The antibody binds to CD79b on the surface of B cells, causing the conjugate to be endocytosed. Once inside the cell, lysosomal proteases cleave the link between MMAE and the antibody allowing MMAE to bind to microtubules, inhibit cell division, and induce apoptosis.","B-cell antigen receptor complex-associated protein beta chain","Therapeutic strategy associated"]
[1439,"DB12243","approved; investigational","small molecule","Edaravone","1-phenyl-3-methyl-5-oxo-2-pyrazoline; 2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-one; 3-methyl-1-phenyl-2-pyrazolin-5-one; 3-methyl-1-phenyl-5-pyrazolone; 3-methyl-1-phenylpyrazol-5-one; Edaravone; Methylphenylpyrazolone; Norphenazone; Phenyl methyl pyrazolone; Phenylmethylpyrazolone","C10H10N2O","CC1=NN(C(=O)C1)C1=CC=CC=C1","Edaravone is a free radical scavenger approved in May, 2017 for the treatment of amyotrophic lateral scleorosis (ALS). Clinical studies showed that the treatment attenuated deterioration of the disease when compared to placebo. It has been previously investigated for the treatment of ischemic stroke, reperfusion Injury, and myocardial Infarction as it possesses antioxidant and anti-apoptotic properties. Being a low molecular weight molecule with good water and lipid-soluble properies, it is therapeutically advantageous in crossing the blood-brain barrier to mediate nootropic and neuroprotective effects. Oral formulation of edaravone is currently under development.","89-25-8","174.203","Indicated for improving neurological symptoms and damage from acute ischemic stroke and delaying disease progression of ALS.","Edaravone scavenges free hydroxyl radicals and peroxynitrite radicals which are highly associated with neuronal damage/death from many cerebral vascular disorders such as ischemic strokes and degenerative neurological disorders such as ALS. It exerts a neuroprotective and antioxidant effect and delays disease progression by limiting the extent of lipid peroxidation via free radical generation and cell membrane damage from oxidative stress. It reversed the reduction in regional blood flow and cerebral edema in a case of ischemic stroke.","Nootropic and neuroprotective effects are mediated through inhibiting lipid peroxidation and scavenging free radicals. Edaravone acts to increase prostacyclin production, decrease lipoxygenase metabolism of arachidonic acid by trapping hydroxyl radicals, and inhibit alloxan-induced lipid peroxidation and quench active oxygen species. It targets various kinds of cells, including neurons, endothelial cells and myocardial cells . There is also evidence of reduction of neuronal nitric oxide synthase (nNOS) levels and potentiation of SOD1 levels after transient ischemia in rabbits thus preventing spinal cord injury.",null,"Therapeutic strategy associated"]
[1440,"DB12249","approved; investigational","biotech","Stem bromelain","Bromelain, stem; Pineapple stem bromelain",null,null,"The primary therapeutic use for which stem bromelain is currently and formally indicated is as a burn wound eschar debridement agent that has been approved by the EMA since 2012 and marketed under the brand name Nexobrid .\r\n\r\nBromelain itself belongs to a category of protein-digesting enzymes that are obtained commercially from the fruit or stem of pineapples . Although both fruit and stem bromelain are prepared differently and contain different enzymatic compositions, the general term bromelain typically refers to stem bromelain . Bromelain is consequently a composite mixture of several different endopeptidases that can facilitate many different reactions with many different substrates. This action allows bromelain to demonstrate a wide range of therapeutic benefits ranging from cardiovascular to anticancer therapy - but the specific mechanisms of action by which it can elicit these effects are currently not properly understood.","37189-34-7",null,"The primary medical purpose for which stem bromelain (SB) is currently indicated for is the removal of eschar in adults with deep partial- and full-thickness thermal burns .\r\n\r\nBesides this official indication, however, it is also believed that SB may be used as a treatment for several other purposes as well, including cardiovascular health, osteoarthritis, autoimmunity, blood clotting, diarrhea, cancer, surgery, and debridement - although the specific mechanisms of action for these indications remain to be elucidated .","Stem bromelain is ultimately a mixture of various different thiol endopeptidases  that are capable of catalyzing a range of reactions on a number of different substrates, which is perhaps why stem bromelain can evidently be used as some manner of treatment in a range of therapeutic contexts. This notion is facilitated by the fact that various topical and oral administration stem bromelain preparations exist as well, further diversifying the ways in which the medication can be used. Perhaps the most important aspect of stem bromelain, however, is its ability to undergo intestinal absorption undegraded in a functionally intact form, ultimately preserving its proteolytic actions in the plasma . This kind of pharmacodynamic characteristic is another element that perhaps allows stem bromelain to remain active within the body and elicit a number of actions at several major body systems.","Stem bromelain is ultimately a mixture of a number of thiol endopeptidases and other elements including phosphatases, glucosidase, peroxidases, cellulases, glycoproteins, carbohydrates, and various protease inhibitors . The many different substrates and reactions that these varied enzymes can catalyze results in a number of different and possible mechanisms of action.\r\n\r\nStem bromelain is currently principally used as a topical agent for debridement of necrotic tissue from wounds or second to third-degree burns . As bromelain can contain escharase as one of its component enzymes, it is thought that various stem bromelain creams or gels can accelerate the healing process of wounds by facilitating the rapid removal of necrotic layers of dermis while preserving unburned/unharmed tissues  and/or perhaps by accelerating the recovery of blood perfusion in wound tissue, control the expression of TNF-alpha, and raise the expression of TGT-beta, as demonstrated in the pig animal model . This kind of enzymatic debridement is ultimately preferred to surgical debridement as physical, surgical procedures are naturally painful, non-selective, and involve the possibility of repeat or excessive anesthesia and/or bleeding .\r\n\r\nWith regards to cardiovascular health, certain studies suggest that stem bromelain is capable of breaking down cholesterol plaques, eliciting a strong fibrinolytic activity, and inhibiting blood platelet aggregation - all of which protect against ischemia/reperfusion injury in skeletal muscle and minimize the risk of arterial thrombosis and embolism . Additionally, stem bromelain has also been shown to attenuate allergic airway disease by altering CD4+ and CD8+ T lymphocyte populations - an action that may be beneficial in treating human asthma or hypersensitivity disorders . Finally, stem bromelain has also been used to induce cardioprotection against ischemia-reperfusion injury via the Akt/Foxo pathway in rat model myocardium .\r\n\r\nIn the treatment of osteoarthritis, it is believed that stem bromelain has analgesic properties which are thought to be the result of direct influence on pain mediators such as bradykinin . In addition, various trials suggest that the medication could be useful in reducing swelling, bruising, and pain in women having surgery like episiotomy . Moreover, stem bromelain may also be used for treating acute inflammation and sports injuries .\r\n\r\nFurthermore, stem bromelain has also been studied as an adjuvant therapy for chronic inflammatory, malignant, and autoimmune diseases . Certain in vitro experiments have demonstrated that stem bromelain can modulate surface adhesion molecules on T cells, macrophages, and natural killer cells and also cause the secretion of IL-1B, IL-6, and Tumor Necrosis Factor-alpha (TNF-alpha) via peripheral blood mononuclear cells . The agent has also been able to block the Raf-1/extracellular-regulated-kinase-2 (ERK-2) pathways by preventing T cell signal transduction . In particular however, treating cells with stem bromelain decreases the activation of CD4(+) T cells and reduces the expression of CD25 . Additionally, there is also evidence to suggest that oral therapy with stem bromelain produces certain analgesic and anti-inflammatory effects in patients with rheumatoid arthritis, which is a particularly common autoimmune disease .\r\n\r\nStem bromelain also affects blood coagulation by increasing the serum fibrinolytic ability and by preventing the synthesis of fibrin, a protein involved in blood clotting . In the rat animal model, the reduction of serum fibrinogen level seems to be dose-dependent when both prothrombin time and activated partial thromboplastin time become markedly prolonged at higher concentrations of administered stem bromelain . In vitro and in vivo studies also suggest stem bromelain can act as an effective fibrinolytic agent since it stimulates the conversion of plasminogen to plasmin, causing an increased fibrinolysis by degrading fibrin .\r\n\r\nIn terms of potential antimicrobial effects of stem bromelain, there are varying observations regarding its specific mechanism of action . When counteracting the effects of some intestinal pathogens like Vibrio cholera or Escherichia coli (whose enterotoxin causes diarrhea in animals), some studies suggest that stem bromelain interacts with intestinal secretory signaling pathways like adenosine 3':5'-cyclic monophosphatase, guanosine 3':5'-cyclic monophosphatase, and/or calcium-dependent signaling cascades . Conversely, other studies propose that stem bromelain supplementation can lead to antiadhesion effects which prevent E. coli bacteria from attaching to particular glycoprotein receptors on the intestinal mucosa by proteolytically modifying those receptor attachment sites .\r\n\r\nAdditionally, various studies have shown that stem bromelain also possesses anticancer activity. In particular, the agent has been found to increase the expression of p53 and Bax in mouse skin, both of which are well-known apoptosis activators . Stem bromelain can also evidently decrease the activity of cell survival regulators like Akt and Erk, therefore inducing apoptotic tumor cell death . Finally, stem bromelain has also been observed to downregulate NF-kB and Cox-2 expression in mouse papillomas and in models of skin tumorigenesis . It has also demonstrated the capability to inhibit bacterial endotoxin (LPS)-induced NF-kB activity as well as the expression of PGE2 and Cox-2 in human monocytic leukemia and murine microglial cell lines .",null,"Therapeutic strategy associated"]
[1441,"DB12281","approved; investigational","biotech","Luspatercept","Luspatercept; luspatercept-aamt",null,null,"Luspatercept is a recombinant fusion protein comprised of a modified extracellular domain of activin receptor type IIB fused to the FC domain of human IgG1. It was first approved for use in the United States in November 2019 under the brand name Reblozyl® for the treatment of anemia in patients with beta thalassemia who require regular blood transfusions. Luspatercept is novel in that it ameliorates anemia via action on late-stage erythropoiesis, in contrast to typical erythropoiesis-stimulating agents (ESAs), such as  and , which act only on early-stage erythropoiesis. Luspatercept's novel mechanism of action, then, is uniquely suited for the treatment of conditions in which late-stage erythropoiesis is defective, such as beta thalassemia and other myelodysplastic diseases.","1373715-00-4",null,"Luspatercept is indicated for the treatment of anemia in adults with beta thalassemia who require regular red blood cell transfusions.","Luspatercept binds to, and inhibits, several ligands that act as negative regulators of late-stage erythropoiesis, thereby alleviating the ineffective erythropoiesis observed in patients with beta thalassemia. Thromboembolic events (e.g. deep vein thrombosis, pulmonary embolism, ischemic stroke) have been reported in patients with beta thalassemia receiving luspatercept - patients with a greater baseline risk of thromboembolism may benefit from concomitant thromboprophylaxis while undergoing therapy with luspatercept. Luspatercept may carry some degree of embryo-fetal toxicity and should therefore be avoided in pregnancy. Women of child-bearing age should use an effective form of contraception during therapy and for 3 months after completion of therapy.","Beta thalassemia is a genetic red blood cell disorder caused by mutations in the β-globin gene - these mutations cause oxidative stress and premature apoptosis of erythroblasts, thereby leading to ineffective erythropoesis. The transforming growth factor beta (TGF-β) superfamily of endogenous ligands (including activins, growth differentiation factors, and bone morphogenetic proteins) are involved in the inhibition of erythroid differentiation via activation of the Smad2/3 subfamily of intracellular effectors.\r\n\r\nLuspatercept is a fusion protein comprising a modified extracellular domain of activin receptor type IIB (a target for many TGF-β ligands) fused to the FC domain of human IgG1. Luspatercept ameliorates ineffective erythropoiesis in patients with beta thalassemia by acting as a \"ligand trap\" for various members of the TGF-β superfamily, preventing their downstream signalling and subsequent inhibition of late-stage erythroid maturation. The specific members of the TGF-β superfamily targeted by luspatercept are currently unknown, though growth differentiation factor 11 (GDF11) has been experimentally excluded as a potential target.",null,"Therapeutic strategy associated"]
[1442,"DB12328","approved; investigational","small molecule","Cantharidin","1,2-Dimethyl-3,6-epoxyperhydrophthalic anhydride; Cantharidin; Cantharidine; Cantharone; exo-1,2-cis-Dimethyl-3,6-epoxyhexahydrophthalic anhydride","C10H12O4","[H][C@]12CC[C@]([H])(O1)[C@]1(C)C(=O)OC(=O)[C@]21C","Cantharidin is a naturally occurring odorless, colorless fatty substance of the terpenoid class that is produced as an oral fluid in the alimentary canal of the male blister beetle . For its natural purpose, the male blister beetle secretes and presents the cantharidin to a female beetle as a copulatory gift during mating. Post-copulation, the female beetle places the cantharidin over her eggs as protection against any potential predators.\r\n\r\nAvailable synthetically since the 1950s, topical applications of cantharidin have been used predominantly as a treatment for cutaneous warts since that time . In 1962 however, marketers of cantharidin failed to produce sufficient efficacy data, resulting in the FDA revision of approval of cantharidin .\r\n\r\nToday, topical cantharidin products do not necessarily demonstrate any particular better effectiveness at treating topical skin conditions like warts than other commonly available vesicant and/or keratolytics although various studies have also investigated the possibility of using cantharidin as an inflammatory model or in cancer treatment . Regardless, the onging lack of FDA approval is likely related to certain toxic effects that were observed following oral ingestion, which includes ulceration of the gastrointestinal and genitourinary tracts, along with electrolyte and renal function disturbance in humans and animals .","56-25-7","196.202","The only therapeutic use for which cantharidin is currently primarily indicated for is as an active ingredient in topical agents for treating common warts (verruca vulgaris), periungual warts, plantar warts, and molluscum contagiosum . \r\n\r\nAt the same time, such topical cantharidin applications have also been used for a number of off-label indications like callus removal, cutaneous leishmaniasis, herpes zoster, and acquired perforating dermatosis . Furthermore, since most topical cantharidin applications are most commonly available in a 0.7% formulation or a more potent 1% mixture, the 0.7% formulation is most commonly indicated for the treatment of common warts, periungual warts, and molluscum contagiosum while the more potent 1% mixture is typically limited only for use by healthcare professionals in a clinical setting for treating plantar warts and other more specialized off-label conditions .\r\n\r\nMoreover, there have also been studies into whether or not cantharidin could be effective at being used as an inflammatory model or in cancer treatment - either of which has yet to formally elucidate any results .","Cantharidin is a natural toxin produced by the blistering beetle that possesses both vesicant (blistering) and keratolytic effects . The substance elicits these effects by inducing acantholysis (loss of intercellular connections) through the targeting of the desmosomal dense plaque, resulting in the detachment of the desmosomes from the tonofilaments . Cantharidin's effectiveness against warts is proposed to be a result of the exfoliation of the wart body as a consequence of the compound's acantholytic action . This acantholytic action generally does not go beyond the epidermal cells so that the basal layer remains intact and minimal effect occurs on the corium . There is consequently no scarring from the topical application of cantharidin .","Cantharidin is specifically absorbed by lipids in the membrane of epidermal keratinocytes, where it activates the release of neutral serine proteases . These enzymes subsequently break the peptide bonds in surrounding proteins, leading to the progressive degeneration of desmosomal dense plaques, which are important cellular structures that participate in cell-to-cell adhesion . Such degeneration results in the detachment of the tonofilaments that hold cells together. This process as a whole leads to the selective acantholysis (loss of cellular connections) and blistering of the skin when the cantharidin topical application is applied upon specific topical developments like warts . A blister(s) at the application site develop within 24 to 48 hours of application and typically resolve within 4 to 7 days . Factors that can modify this proposed time frame include the volume or concentration of cantharidin used, physical contact time of the applied compound (usually between 4 to 24 hours), the presence of any occlusive dressings, or even patient sensitivity to cantharidin . The blistered lesions ultimately heal without scarring .\r\n\r\nFinally, there are some studies that suggest cantharidin's chemical profile as a potent and selective inhibitor of protein phosphatase 2A confers upon it an oxidative stress-independent growth inhibition of pancreatic cancer cells through cancer cell-cycle arrest and apoptosis . \r\n\r\nNevertheless, the fact that little data regarding the pharmacodynamics and pharmacokinetics of cantharidin in the human body exists  and certain toxic effects of cantharidin that have been observed following oral ingestion in humans like ulceration of the gastrointestinal and genitourinary tracts, along with electrolyte and renal function disturbance  are strong reasons as to why the compound currently lacks FDA approval is used fairly limitedly for formal therapeutic indications.","Aryl hydrocarbon receptor agonist","Therapeutic strategy associated"]
[1443,"DB12332","approved; investigational","small molecule","Rucaparib","Rucaparib","C19H18FN3O","CNCC1=CC=C(C=C1)C1=C2CCNC(=O)C3=C2C(N1)=CC(F)=C3","Rucaparib is a potent mammalian poly(ADP-ribose) polymerase (PARP) 1, 2 and 3 inhibitor with anticancer properties. PPAR is an enzyme that plays an essential role in DNA repair by activating response pathways and facilitating repair , and defects in these repair mechanisms have been demonstrated in various malignancies, including cancer. Regulation of repair pathways is critical in promoting necessary cell death. BRCA genes are tumor suppressor genes mediate several cellular process including DNA replication, transcription regulation, cell cycle checkpoints, apoptosis, chromatin structuring and homologous recombination (HR). Homologous recombination deficiency (HRD), along with PPAR inhibition, is a vulnerability that enhances the cell death pathway when the single mutations alone would permit viability. Ovarian cancer commonly possesses defects in DNA repair pathways such as HRD due to BRCA mutations or otherwise. \r\n\r\nThere are three main types of ovarian cancer: epithelial (90%), germ cell (5%) and sex cord stromal cell (5%). Epithelial ovarian, being the most common, fifth leading cause of cancer-related deaths in women in the United States. Advanced ovarian cancer particularly poses challenges due to reduced therapeutic response rates from standard platinum-based chemotherapy and overall survival rates. Rucaparib has shown to induce cytotoxicity in tumor cell lines with deficiencies in BRCA1/2 and other DNA repair genes . Of all the BRCA1/2 mutations in ovarian cancer, most are due to germline mutations (18%), and approximately 7% represent somatic mutations acquired within the tumor .\r\n\r\nThe indication of rucaparib as an oral monotherapy in patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer was granted accelerated approval in 2016 for selected patients who have previously received greater than two lines of platinum-based therapy. It is currently marketed in the US under the brand name Rubraca that contains rucaparib camsylate as the active ingredient. The identification of patients who are eligible for rucaparib therapy is performed via *in vitro* diagnostic tests to detect the presence of a deleterious BRCA mutation (germline and/or somatic). The FDA-approved test qualitatively detects sequence alterations in BRCA1 and BRCA2 (BRCA1/2) genes. More information can be found on the FDA Website .\r\n\r\nWhile rucaparib is indicated for deleterious BRCA mutation (germline and/or somatic)-associated advanced ovarian cancer, there is evidence that its antitumor activity is also clinically effective against ovarian tumors with high homologous recombination deficiency (HRD) loss of heterozygosity (LOH) .","283173-50-2","323.371","Indicated as monotherapy for the treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer who have been treated with two or more chemotherapies. Select patients for therapy based on an FDA-approved companion diagnostic for rucaparib.","Rucaparib has been shown to decrease tumor growth in mouse xenograft models of human cancer with or without deficiencies in BRCA .\r\n\r\nThe effect of multiple doses of rucaparib on QTc interval was evaluated in an open-label single-arm study in 56 patients with solid tumors who were administered continuous doses of rucaparib ranging from 40 mg once daily (0.03 times the approved recommended dosage) to 840 mg twice daily (1.4 times the approved recommended dosage). The mean QTcF increase from baseline (90% confidence interval ) in population pharmacokinetics estimated 95% percentile Cmax (3019 ng/mL) at steady state of 600 mg rucaparib twice daily was 14.9 msec (11.1-18.7 msec) .","Poly (ADP-ribose) polymerase (PARP) enzymes play a role in DNA repair. PPAR-1 is responsible in repairing single stranded breaks (SSBs) in base excision repair (BER). PARP1 also functions in nonhomologous end-joining (NHEJ) regulation, chromatin remodeling and homologous recombination (HR) DNA repair pathways . When PARP is inhibited, single-strand breaks become double-strand breaks, which are typically repaired via homologous recombination . Pre-existing homologous recombination deficiency (HRD) may occur through mutations in the BRCA1 or BRCA2 genes, which confers persistant cell repair and growth in cancer cells. \r\n\r\nRucaparib is an inhibitor of PARP-1, PARP-2, and PARP-3. Via an inhibitory effect on the PARP enzymatic activity, rucaparib decreases the formation of PARP-DNA complexes resulting in DNA damage, apoptosis, and cell death . It is proposed that PARP inhibition specifically targets tumor cells with preexisting HRD, such as those cells possessing mutations in the BRCA1 or BRCA2 genes . Rucaparib induces synthetic lethality by disrupting ingle- and double-strand repair pathways leading to tumor cell death. It is also suggested that PARP inhibition can lead to trapping of PARP-1 enzyme on damaged DNA, effectively preventing continuation of the DNA repair process; defective BRCA1 recruitment to damaged DNA; and activation of alternative DNA repair such as error-prone nonhomologous end joining (NHEJ) or alternative end joining pathways leading to mutations or chromosomal changes and ultimately cell death .","Poly [ADP-ribose] polymerase 1 antagonist; Poly [ADP-ribose] polymerase 2 antagonist; Poly [ADP-ribose] polymerase 3 antagonist","Therapeutic strategy associated"]
[1444,"DB12340","investigational","small molecule","Navitoclax","Navitoclax","C47H55ClF3N5O6S3","[H][C@@](CCN1CCOCC1)(CSC1=CC=CC=C1)NC1=C(C=C(C=C1)S(=O)(=O)NC(=O)C1=CC=C(C=C1)N1CCN(CC2=C(CCC(C)(C)C2)C2=CC=C(Cl)C=C2)CC1)S(=O)(=O)C(F)(F)F","Navitoclax has been used in trials studying the treatment and basic science of Solid Tumors, Non-Hodgkin's Lymphoma, EGFR Activating Mutation, Chronic Lymphoid Leukemia, and Hematological Malignancies, among others.\r\n\r\nNavitoclax is an orally bioavailable small molecule inhibitor of Bcl-2 family proteins. It is a substance being studied in the treatment of lymphomas and other types of cancer. It blocks some of the enzymes that keep cancer cells from dying.","923564-51-6","974.613",null,null,"Navitoclax targets the Bcl-2 family of proteins, the major negative regulators of apoptosis. The Bcl-2 proteins, including Bcl-2, Bcl-xL, and Bcl-w, work by binding to two other groups of proteins-the executioners (Bax, Bak) that actually start the destruction pathway, and the sentinel proteins. Cancer cells frequently overexpress the Bcl-2-like proteins, and thus, when they sustain DNA damage-from radiation, for example-they continue growing. Preventing the Bcl-2-like proteins from binding to the executioners might be able to trigger cell death in the tumor.","Apoptosis regulator Bcl-2; Bcl-2-like protein 2; Bcl2 antagonist of cell death","Therapeutic strategy associated"]
[1445,"DB12364","approved; investigational","small molecule","Betrixaban","Betrixaban; N-(5-chloropyridin-2-yl)-2-(4-(N,N-dimethylcarbamimidoyl)benzamido)-5-methoxybenzamide; N-(5-chloropyridin-2-yl)-2-[[4-(N,N-dimethylcarbamimidoyl)benzoyl]amino]-5-methoxybenzamide","C23H22ClN5O3","COC1=CC=C(NC(=O)C2=CC=C(C=C2)C(=N)N(C)C)C(=C1)C(=O)NC1=CC=C(Cl)C=N1","Betrixaban is a non-vitamin K oral anticoagulant whose action is driven by the competitive and reversible inhibition of the factor Xa . It was selected among all lead compounds due to its low hERG channel affinity while sustaining its factor Xa inhibition capacity . Betrixaban, now developed by Portola Pharmaceuticals Inc., is prescribed as a venous thromboembolism (VTE) prophylactic for adult patients with moderate to severe restricted motility or with other risks for VTE . VTE can be manifested as deep vein thrombosis or pulmonary embolism and it is a leading cause of preventable death in hospitalized patients .","330942-05-7","451.91","Betrixaban is indicated for prophylaxis of venous thromboembolism (VTE) in conditions of moderate to severe restricted mobility or in patients that qualify as in risk of VTE.","Betrixaban is an oral anticoagulant that excerts its action by preventing thrombin generation without having a direct effect on platelet aggregation .","Betrixaban is a cofactor-independent direct inhibitor of the Factor Xa and inhibits free and prothrombinase-bound Factor Xa .","Coagulation factor X inhibitor","Therapeutic strategy associated"]
[1446,"DB12371","approved; investigational","small molecule","Siponimod","Siponimod","C29H35F3N2O3","CCC1=CC(=CC=C1CN1CC(C1)C(O)=O)C(\\C)=N\\OCC1=CC=C(C2CCCCC2)C(=C1)C(F)(F)F","Siponimod, also known as _Mayzent_, by Novartis, is a new drug formulated for the management of Multiple Sclerosis (MS). It was approved by the FDA on March 26, 2019  and by Health Canada on February 20, 2020. This drug is considered a _sphingosine-1-phosphate (S1P) receptor modulator_ and is thought to play a role in suppressing the central nervous system inflammation that is associated with MS .\r\n\r\nMultiple Sclerosis (MS) is an autoimmune disease of the central nervous system that is chronic and inflammatory, disrupting communication between the brain and other parts of the body. Most patients diagnosed with this illness experience their initial disease symptoms between the age of 20 to 40, often the most productive years of life. Symptoms may include but are not limited to fatigue, gait changes, bowel or bladder dysfunction, abnormal muscle twitching, vision disturbance, and depressing or mood swings. MS is one of the most common causes of neurological disability in young adults and is found to occur more frequently in women than in men.","1230487-00-9","516.605","This drug is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease in adults .","**Immune system effects**\r\n\r\nSiponimod causes a dose-dependent decrease of the peripheral blood lymphocyte count within 6 hours of the first dose, caused by the reversible accumulation of lymphocytes in lymphoid tissues, due to lack of lymphocyte release .   This results in a decrease in the inflammation that is involved in multiple sclerosis. Lymphocyte counts return to normal in 90% of patients within 10 days after the cessation of therapy .\r\n\r\n**Effects on heart rate and rhythm**\r\n\r\nSiponimod causes a temporary decrease in heart rate and atrioventricular conduction upon beginning treatment. The maximum fall in heart rate is observed in the first 6 hours post ingestion. Autonomic heart responses, including diurnal variation of heart rate and response to exercise activities, are not altered by siponimod treatment .\r\n\r\n**Effects on pulmonary function**\r\n\r\nDose-dependent decreases in absolute forced expiratory volume over a time frame of 1 second were noted in siponimod-treated patients and were higher than in patients taking placebo .","Inflammation of the white and gray matter tissues in the central nervous system caused by localized immune cell infiltration and their cytokines are the initial cause of damage in MS. B lymphocytes and their cytokines are other factors in the pathogenesis of MS. Lymphotoxin  and TNF-α produced by these cells encourage inflammation . The S1P receptor is an important receptor related to the function of lymphocytes and can be found in the central nervous system .  S1P receptor (S1PR) signaling is associated with a wide variety of physiological processes for lymphocytes, including their egress and recirculation . \r\n\r\nSiponimod is classified as a sphingosine-1-phosphate (S1P) receptor modulator. Siponimod binds with high affinity to both S1P receptors 1 and 5. This drug blocks the ability of lymphocytes to release from the lymph nodes, decreasing the number of lymphocytes found in the peripheral blood. The mechanism by which siponimod exerts therapeutic effects in multiple sclerosis is not known at this time, but may involve the abovementioned decrease of lymphocytes into the central nervous system, decreasing the inflammatory effects of MS .","Sphingosine 1-phosphate receptor 5 modulator; Sphingosine 1-phosphate receptor 1","Therapeutic strategy associated"]
[1447,"DB12442","investigational","small molecule","Alvespimycin","17-(dimethylaminoethylamino)-17-demethoxygeldanamycin; 17-DMAG; Alvespimycin; DMAG","C32H48N4O8","CO[C@H]1C[C@H](C)CC2=C(NCCN(C)C)C(=O)C=C(NC(=O)\\C(C)=C\\C=C/[C@H](OC)[C@@H](OC(N)=O)\\C(C)=C\\[C@H](C)[C@H]1O)C2=O","Alvespimycin is a derivative of geldanamycin and heat shock protein (HSP) 90 inhibitor. It has been used in trials studying the treatment of solid tumor in various cancer as an antitumor agent. In comparison to the first HSP90 inhibitor tanespimycin, it exhibits some pharmacologically desirable properties such as reduced metabolic liability, lower plasma protein binding, increased water solubility, higher oral bioavailability, reduced hepatotoxicity and superior antitumor activity .","467214-20-6","616.7455","Investigated for use as an antineoplastic agent for solid tumors, advanced solid tumours or acute myeloid leukaemia.","Alvespimycin mediates an antitumor activity through HSP90 inhibition that targets client proteins for proteasomal destruction, including oncogenic kinases such as BRAF. The administration of the drug is shown to result in the depletion of client proteins that have oncogenic activity and potential induction of HSP70 (HSP72) . It is more selective for tumors over normal tissue. A study also reports that alvespimycin enhances the potency of telomerase inhibition by imetelstat in pre-clinical models of human osteosarcoma .","Alvespimycin inhibits HSP90 and its regulation of correct folding and function of many cellular signalling proteins, which are referred to as Hsp90 client proteins. These client proteins are also referred to as oncoproteins and include Her-2, EGFR, Akt, Raf-1, p53, Bcr-Abl, Cdk4, Cdk6 and steroid receptors that are involved in cellular signalling pathways that drive cellular proliferation and counteract apoptosis. They are often over-expressed or mutated in tumors, and contribute to cancer progression and therapy resistance . Alvespimycin promotes an anticancer activity by disrupting Hsp90's chaperone function and inducing the proteasomal degradation of oncoproteins. It is shown to reduce the levels of CDK4 and ERBB2 .","Heat shock protein HSP 90-alpha inhibitor","Therapeutic strategy associated"]
[1448,"DB12455","approved; investigational","small molecule","Omadacycline","Amadacycline; Omadacycline","C29H40N4O7","[H][C@@]12CC3=C(C=C(CNCC(C)(C)C)C(O)=C3C(=O)C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@]1([H])C2)N(C)C","Omadacycline has been used in trials studying the treatment of Bacterial Pneumonia, Bacterial Infections, Community-Acquired Infections, and Skin Structures and Soft Tissue Infections. Omadacycline represents a significant advance over the well-known tetracycline family, and has been shown to be highly effective in animal models at treating increasingly problematic, clinically prevalent infections caused by gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), and by gram-negative, atypical and anaerobic bacteria, including those resistant to currently available classes of antibiotics and known to cause diseases such as pneumonias, urinary tract infections, skin diseases and blood-borne infections in both the hospital and community settings.","389139-89-3","556.66","Omadacycline is indicated for the treatment of community acquired bacterial pneumonia and acute bacterial skin and skin structure infections caused by omadacycline-susceptible organisms in adults.","Omadacycline can be either bacteriostatic or bacteriocidal depending on the organism involved. It disrupts bacterial protein synthesis without affecting DNA, RNA, or peptidoglycan synthesis. Omadacycline represents an improvement over existing tetracycline agents as it has not been found to be subject to tetracycline resistance mediated by tetracycline efflux pumps encoded by the tet(K), tet(L), and tet(B) or to ribosomal protection proteins encoded by tet(O) and tet(M). Omadacycline is susceptible to RNA mutations which confer resistance to tetracyclines.","Omadacycline binds to the primary tetracycline binding site on the bacterial 30s ribosomal subunit with high specificity. There it acts to block protein synthesis, disrupting many facets of cellular function and resulting in either cell death or stasis.","30S ribosomal protein S3 inhibitor; 30S ribosomal protein S7 inhibitor; 30S ribosomal protein S8 inhibitor; 30S ribosomal protein S19 inhibitor; 30S ribosomal protein S14 inhibitor; 16S ribosomal RNA inhibitor","Indication associated"]
[1449,"DB12483","approved; investigational","small molecule","Copanlisib","Copanlisib","C23H28N8O4","COC1=C(OCCCN2CCOCC2)C=CC2=C1N=C(NC(=O)C1=CN=C(N)N=C1)N1CCN=C21","Copanlisib is a selective pan-Class I phosphoinositide 3-kinase (PI3K/Phosphatidylinositol-4,5-bisphosphate 3-kinase/phosphatidylinositide 3-kinase) inhibitor that was first developed by Bayer Healthcare Pharmaceuticals, Inc. The drug targets the enzyme that plays a role in regulating cell growth and survival. Copanlisib was granted accelerated approval on September 14, 2017 under the market name Aliqopa for the treatment of adult patients with relapsed follicular lymphoma and a treatment history of at least two prior systemic therapies. Follicular lymphoma is a slow-growing type of non-Hodgkin lymphoma that is caused by unregulated proliferation and growth of lymphocytes. The active ingredient in Aliquopa intravenous therapy is copanlisib dihydrochloride.","1032568-63-0","480.529","Indicated for the treatment of adult patients with relapsed follicular lymphoma (FL) who have received at least two prior systemic therapies.","Copanlisib has demonstrated potent anti-tumor and pro-apoptotic activity in various tumor cell lines and xenograft models . In clinical trials, 59 percent of patients receiving copanlisib achieved complete or partial shrinkage of their tumors after a median of 12.2 months . Higher systemic levels of copanlisib is associated with elevated plasma glucose levels.","Follicular lymphoma is a B-cell lymphoma that is one of the most common type of non-Hodgkin lymphoma (NHL). It involves unregulated growth and proliferation of lymphocytes that eventually may travel to other organs including the lymph nodes, spleen, and the bone marrow, to form tumors. The phosphatidylinositol 3-kinase (PI3K)-mediated pathway is involved in promoting cell survival proliferation and differentiation however abberant activation of this pathway may lead to tumorigenesis . Copanlisib mediates an inhibitory action on p110α and p110δ isoforms of phosphatidylinositol-3-kinase (PI3K) expressed in malignant B cells. It induces tumor cell death via apoptosis and inhibits the proliferation of primary malignant B cell lines . Copanlisib inhibits several key cell-signaling pathways, including B-cell receptor (BCR) signaling, CXCR12 mediated chemotaxis of malignant B cells, and NFκB signaling in lymphoma cell lines .","Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform inhibitor; Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform inhibitor","Therapeutic strategy associated"]
[1450,"DB12499","approved; investigational","small molecule","Clascoterone","11-deoxycortisol 17α-propionate; Clascoterone; Cortexolone 17alpha-propionate; Cortexolone 17α-propionate","C24H34O5","[H][C@@]12CC[C@](OC(=O)CC)(C(=O)CO)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C","Clascoterone (cortexolone 17α-propionate, CB-03-01) is a novel antagonist of androgen receptors. It binds to androgen receptors with high affinity. By competing with androgens for binding to androgen receptors, clascoterone works by blocking the androgen receptor signalling cascades that promote acne pathogenesis, such as sebaceous gland proliferation, excess sebum production, and inflammatory pathways. In August 2020, FDA approved clascoterone for the first-in-class topical treatment of acne (acne vulgaris) in male and female patients 12 years and older. Clascoterone is also being investigated as a novel treatment for androgenetic alopecia.","19608-29-8","402.531","Clascoterone is indicated for the topical treatment of acne vulgaris in patients 12 years of age and older.","Clascoterone exerts anti-androgenic effects by working as an antagonist at androgen receptors (ARs) expressed throughout the skin, including sebaceous glands, sebocytes, and dermal papilla cells. Clascoterone blocks the effects of testosterone and dihydrotestosterone (DHT), which are androgens that bind to the ARs and contribute to the development of androgen-dependent conditions such as acne and alopecia. _In vitro_, the antiandrogenic effects of clascoterone in human primary sebocytes occurred in a dose-dependent manner. Clascoterone mediates selective topical activity by mainly targeting androgen receptors at the site of application. It has limited systemic effects.\r\n\r\nIn clinical trials, HPA axis suppression was observed as a 30-minute post-stimulation serum cortisol level of ≤18 mcg/dL in 5% of adult subjects and 9% of adolescent subjects with acne vulgaris following two weeks of topical treatment of clascoterone. HPA axis function returned to normal following the discontinuation of drug treatment.","Acne is a multifactorial skin condition characterized by excess sebum production, epithelial hyperkeratinization, proliferation of the skin commensal bacteria, and inflammation. Circulating and locally synthesized natural ligands, testosterone and dihydrotestosterone (DHT), serve as causative factors in both males and females. Upon binding of DHT, the DHT-androgen receptor complex dimerizes and translocates to the nucleus where it promotes the transcription of genes involved in acne pathogenesis, including proliferation and differentiation of sebocytes, excess sebum production, and inflammatory cytokine production. Clascoterone is a potent antagonist at ARs and competes for androgens in binding to the receptor, thereby inhibiting downstream signalling of ARs that promote acne.\r\n\r\nAndrogenetic alopecia is also an androgen-dependent and highly genetic condition. Dihydrotestosterone (DHT) binds to ARs expressed on dermal papilla cells (DPC) in the scalp to induce AR-mediated transcription of genes that contribute to androgenic alopecia. By blocking the interaction between DHT and aARs, clascoterone inhibits AR-regulated transcription and DHT-induced IL-6 synthesis.","Androgen receptor antagonist","Therapeutic strategy associated"]
[1451,"DB12500","approved; investigational","small molecule","Fedratinib","Fedratinib","C27H36N6O3S","CC1=CN=C(NC2=CC=C(OCCN3CCCC3)C=C2)N=C1NC1=CC=CC(=C1)S(=O)(=O)NC(C)(C)C","Fedratinib, also known as SAR302503 and TG101348, is a tyrosine kinase inhibitor used to treat intermediate-2 and high risk primary and secondary myelofibrosis. It is an anilinopyrimidine derivative.\r\n\r\nFedratinib was granted FDA approval on August 16, 2019.","936091-26-8","524.678","Fedratinib is indicated to treat adults with primary or secondary myelofibrosis that is either intermediate-2 or high risk.","Fedratinib is a kinase inhibitor that inhibits cell division and induces apoptosis. Patients taking fedratinib may experience anemia, thrombocytopenia, gastrointestinal toxicity, hepatic toxicity, or elevated amylase and lipase. These effects should be managed by reducing the dose, temporarily stopping the medication, or providing transfusions on a case by case basis.","Fedratinib is an inhibitor of Janus Activated Kinase 2 (JAK2) and FMS-like tyrosine kinase 3. JAK2 is highly active in myeloproliferative neoplasms like myelofibrosis. Fedratinib's inhibition of JAK2 inhibits phosphorylation of signal transducer and activator of transcription (STAT) 3 and 5, which prevents cell division and induces apoptosis.","Tyrosine-protein kinase JAK2 inhibitor; Receptor-type tyrosine-protein kinase FLT3 inhibitor; Tyrosine-protein kinase JAK1 inhibitor","Therapeutic strategy associated"]
[1452,"DB12520","investigational","biotech","Plozalizumab","Plozalizumab",null,null,"Plozalizumab has been investigated for the treatment of Atherosclerosis. Plozalizumab, a novel humanized monoclonal antibody, specifically targets CCR2 chemokine receptors found on the surface of certain white blood cells including macrophages and monocytes. Preclinical studies suggest that CCR2 plays an important role in the trafficking of monocytes and macrophages to sites of inflammation. The recruitment of macrophages to the arterial wall is believed to be a critical step in the development of atherosclerosis.","1610761-46-0",{"$nulls":3},"Preclinical studies suggest that CCR2 plays an important role in the trafficking of monocytes and macrophages to sites of inflammation. The recruitment of macrophages to the arterial wall is believed to be a critical step in the development of atherosclerosis. Plozalizumab targets CCR2 chemokine receptors found on the surface of certain white blood cells including macrophages and monocytes.","C-C chemokine receptor type 2","Target associated"]
[1453,"DB12530","approved; investigational","biotech","Inebilizumab","Inebilizumab; inebilizumab-cdon",null,null,"Inappropriate growth of or self-directed antibody production by B-cells is the etiological underpinning of a variety of conditions, including the multiple sclerosis-like neurological condition neuromyelitis optica spectrum disorder (NMOSD). Inebilizumab is a humanized afucosylated monoclonal IgG1 antibody directed against the broadly expressed B-cell surface antigen CD19. Inebilizumab is cytolytic, resulting in B-cell depletion and offering therapeutic benefit to patients suffering from NMOSD. Compared to the anti-CD20 antibody , which is also used to treat NMOSD, inebilizumab has broader specificity.\r\n\r\nInebilizumab was granted FDA approval on June 11, 2020, for the treatment of anti-aquaporin 4 positive NMOSD patients. Given its mechanism of action and good safety profile, it may prove useful in the treatment of other conditions linked to autoimmune antibody production or B-cell malignancies.","1299440-37-1",null,"Inebilizumab is indicated for the treatment of aquaporin-4 (AQP4) immunoglobulin-positive (AQP4-IgG) neuromyelitis optica spectrum disorder (NMOSD) in adult patients.","Inebilizumab is a CD19-directed monoclonal antibody that results in immunosuppression through B-cell depletion with sufficient efficacy to allow a six-month dosing schedule. Due to this mechanism of action, patients undergoing inebilizumab treatment may be at higher risk of infections and should be monitored for active infections and immunoglobulin levels while undergoing treatment; vaccination is not recommended during inebilizumab treatment. Also, there is a risk of severe infusion reactions. Animal data suggests the possibility of fetal harm with inebilizumab and therefore, effective contraception during and for six months following inebilizumab treatment is recommended.","Neuromyelitis optica spectrum disorder (NMOSD), formerly referred to as Devic's disease, is an antibody-mediated autoimmune condition resulting in astroglial cell death, demyelination, and central nervous system (CNS) inflammation. The presence of anti-aquaporin 4 immunoglobulin (AQP4-IgG) is the most frequent biomarker, although AQP4-IgG negative, anti-myelin oligodendrocyte glycoprotein (anti-MOG) positive, variants with similar presentation also exist. The theoretical origin of symptoms is through AQP4-IgG-mediated astrocyte cytotoxicity and subsequent infiltration of neutrophils, eosinophils, and macrophages, leading to inflammatory-mediated oligodendrocyte damage and myelin sheath loss. In general, this manifests as optic neuritis and transverse myelitis with occasional involvement of the diencephalic, brainstem, and cerebral hemisphere.\r\n\r\nCD19 is a B-cell surface antigen expressed on most B-cells, including the expanded population of CD27<sup>high</sup> CD38<sup>high</sup> CD180<sup>-</sup> CD19<sup>+</sup> plasmablasts that are the origin of astrocytic AQP4-IgG in most NMOSD patients. Inebilizumab binds to CD19 and, through one of several potential mechanisms, results in cell death. Destruction of the specific AQP4-IgG-producing plasmablasts results in lower amounts of AQP4-IgG in the CNS and therefore slows neuronal damage and improves patient outcomes.","B-lymphocyte antigen CD19 binder","Therapeutic strategy associated"]
[1454,"DB12565","investigational","small molecule","Abexinostat","Abexinostat","C21H23N3O5","CN(C)CC1=C(OC2=CC=CC=C12)C(=O)NCCOC1=CC=C(C=C1)C(=O)NO","Abexinostat has been used in trials studying the treatment of Sarcoma, Lymphoma, Leukemia, Lymphocytic, and Hodgkin Disease, among others. It is a novel, broad-spectrum hydroxamic acid-based inhibitor of histone deacetylase (HDAC) with potential antineoplastic activity.","783355-60-2","397.431",null,null,"Abexinostat is a novel histone deacetylase (HDAC) inhibitor. HDAC inhibitors target HDAC enzymes and inhibit the proliferation of cancer cells and induce cancer cell death, or apoptosis. Histone deacetylation is carried out by a family of related HDAC enzymes. Inhibition of these enzymes causes changes to chromatin structure and to gene expression patterns, which results in the inhibition of proliferation of cancer cells, and induction of apoptosis .","Histone deacetylase 1","Therapeutic strategy associated"]
[1455,"DB12589","investigational","biotech","Dacetuzumab","Dacetuzumab",null,null,"Dacetuzumab has been used in trials studying the treatment of Multiple Myeloma, Non-Hodgkin Lymphoma, Leukemia, Lymphocytic, Chronic, and Lymphoma, Large B-Cell, Diffuse. It is a humanized anti-CD40 antibody and induces cytotoxicity in human multiple myeloma cells.","880486-59-9",null,"Investigated for use/treatment in lymphoma (non-hodgkin's) and multiple myeloma.",null,null,"Tumor necrosis factor receptor superfamily member 5","Target associated"]
[1456,"DB12592","investigational","small molecule","Mosedipimod","1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol; Mosedipimod","C39H70O6","CCCCCCCCCCCCCCCC(=O)OCC(COC(C)=O)OC(=O)CCCCCCC\\C=C/C\\C=C/CCCCC","Mosedipimod has been used in trials studying the supportive care and treatment of Chemotherapy-induced Neutropenia.","221139-79-3","634.983",null,null,"Mosedipimod is a proprietary compound originally derived from Sika deer antler. It accelerates endocytic trafficking of Pattern Recognition Receptors which allows for the swift removal of PAMPs/DAMPs. This drug has been shown to improve lung function and reduce inflammation and fibrosis in animal models. Currently, mosedipimod is being investigated against chemoradiation-induced oral mucositis and neutropenia, as well as against COVID-19.",null,"Therapeutic strategy associated"]
[1457,"DB12598","investigational","small molecule","Nafamostat","Nafamostat; p-Guanidinobenzoic acid ester with 6-hydroxy-2-naphthamidine","C19H17N5O2","NC(=N)NC1=CC=C(C=C1)C(=O)OC1=CC2=C(C=C1)C=C(C=C2)C(N)=N","Nafamostat is a synthetic serine protease inhibitor that is commonly formulated with hydrochloric acid due to its basic properties. It has been used in trials studying the prevention of Liver Transplantation and Postreperfusion Syndrome. The use of nafamostat in Asian countries is approved as an anticoagulant therapy for patients undergoing continuous renal replacement therapy due to acute kidney injury.","81525-10-2","347.378","Used as an anticoagulant in patients with disseminative blood vessel coagulation, hemorrhagic lesions, and hemorrhagic tendencies. It prevents blood clot formation during extracorporeal circulation in patients undergoing continuous renal replacement therapy and extra corporeal membrane oxygenation.","Nafamostat is a fast-acting proteolytic inhibitor used during hemodialysis to prevent the proteolysis of fibrinogen into fibrin by competitively inhibiting several serine proteases including thrombin. It improves acute pancreatitis and prevents blood clot formation during extracorporeal circulation and has an anti-inflammatory effect in vitro. A study suggets that nafamostat has a neuroprotective role during ischemia-induced brain injury from antithrombin activity .","Nafamostat mesilate inhibits various enzyme systems, such as coagulation and fibrinolytic systems (thrombin, Xa, and XIIa), the kallikrein–kinin system, the complement system, pancreatic proteases and activation of protease-activated receptors (PARs) . Nafamostat inhibits lipopolysaccharide-induced nitric oxide production, apoptosis, and interleukin (IL)-6 and IL-8 levels in cultured human trophoblasts. It is shown to act as an antioxidant in TNF-α-induced ROS production .","Prothrombin inhibitor; Coagulation factor X inhibitor; Coagulation factor XII inhibitor; Trypsin-1 inhibitor; Kallikrein-1 inhibitor; Intercellular adhesion molecule 1 inhibitor","Therapeutic strategy associated"]
[1458,"DB12651","investigational","small molecule","Bardoxolone","Bardoxolone","C31H41NO4","CC1(C)CC[C@@]2(CC[C@]3(C)[C@@H]([C@@H]2C1)C(=O)C=C1[C@@]2(C)C=C(C#N)C(=O)C(C)(C)[C@@H]2CC[C@@]31C)C(O)=O","Bardoxolone has been used in trials studying the treatment of LYMPHOMA and Solid Tumors. It is a synthetic triterpenoid and a highly potent activator of redox-sensitive signaling pathways that induce programmed cell death (apoptosis) in cancer cells that are under high levels of intrinsic oxidative stress. In contrast, Bardoxolone in normal cells induces protective antioxidant/anti-inflammatory responses.","218600-44-3","491.672",null,null,"Bardoxolone, a synthetic triterpenoid, is a highly potent activator of redox-sensitive signaling pathways that induce programmed cell death (apoptosis) in cancer cells that are under high levels of intrinsic oxidative stress. In contrast, Bardoxolone in normal cells induces protective antioxidant/anti-inflammatory responses. Intensive research in animal models of human cancer has demonstrated that Bardoxolone is a potent anticancer agent with a well-characterized ability to inhibit growth and cause regression of tumors as a single agent and in combination with radiation and chemotherapy. Bardoxolone also suppresses radiation- and chemotherapy-induced damage (e.g., oral mucositis) in normal tissues at dose levels that also produce an anti-cancer effect. Bardoxolone induces apoptosis through both caspase-independent and -dependent mechanisms, the latter involving caspase-8 activation, Bid cleavage, cytochrome c release, and caspase-3 activation. Furthermore, JNK, p38, and ERK pathways are involved in Bardoxolone-induced apoptosis of tumor cell lines mediated by disrupted intracellular redox balance and involving decreased glutathione and increased reactive oxygen species. Study shows that Bardoxolone enhances p42 CEBPA protein at the level of translation.","Caspase-8","Therapeutic strategy associated"]
[1459,"DB12662","investigational","small molecule","Naveglitazar","Naveglitazar","C25H26O6","CO[C@@H](CC1=CC=C(OCCCOC2=CC=C(OC3=CC=CC=C3)C=C2)C=C1)C(O)=O","Naveglitazar has been used in trials studying the treatment of Diabetes Mellitus, Non-Insulin-Dependent.","476436-68-7","422.477",{"$nulls":3},"Peroxisome proliferator-activated receptor gamma","Target associated"]
[1460,"DB12698","approved; investigational","biotech","Ibalizumab","Ibalizumab; Ibalizumab-uiyk",null,null,"Ibalizumab (also known as _ibalizumab-uiyk_ and formerly known as TNX-355) is a monoclonal antibody that binds to CD4 receptors on the surface of CD4-positive cells, preventing HIV particle entry into the lymphocytes. It is an advanced and current antibody in development for the treatment of HIV/AIDS.  It has been developed by Taimed biologics and Theratechnologies .\r\n\r\nThis drug was approved in March 2018 for the management of treatment-resistant HIV .","680188-33-4",null,"Indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in highly treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen .\r\n\r\nThe approval of Trogarzo was supported by a clinical trial of 40 treatment-experienced adults with MDR HIV-1 infection who persistently had elevated levels of HIV RNA in their blood despite heavy antiretroviral therapy. The majority of study patients had previously been treated with ≥10 antiretroviral medications .","Trogarzo safety and effectiveness have been confirmed in a clinical trial of 40 patients who suffer multidrug-resistant HIV. The majority of these patients experienced a substantial decrease in their HIV-RNA levels within 7 days after receiving the drug. Approximately 43 percent of patients continued to experience HIV-RNA inhibition after 24 weeks of taking Trogarzo .\r\n\r\nTrogarzo inhibits viral entry into cells, effectively managing HIV-1 infection in those who have attempted other therapies to no avail .","Ibalizumab is a monoclonal antibody and viral-entry inhibitor that coats CD4-positive cells, the main target of HIV infection. By blocking viral entry into CD4 cells, ibalizumab creates a barrier for HIV, which is a different mechanism from those of entry inhibitors that target viral proteins or chemokine co-receptors.\r\n\r\nIbalizumab is a CD4 domain 2-directed post-attachment HIV-1 inhibitor. This binding specificity of ibalizumab-uiyk to domain 2 of CD4 allows ibalizumab-uiyk to prevent viral entry into host cells without causing immunosuppression. Epitope mapping studies confirm that ibalizumab-uiyk binds to a conformational epitope located mainly in domain 2 of the extracellular region of the CD4 receptor. This epitope is located on the surface of CD4 opposite to the site in domain 1 that is essential for CD4 binding of the MHC class II molecules. This drug, therefore, does not interfere with CD4 cell-mediated immune functions. In addition, ibalizumab-uiyk does not interfere with gp120 attachment to CD4 .  Ibalizumab’s post-binding conformational effects block the gp120-CD4 complex from interacting with CCR5 or CXCR4 and thus prevents viral entry and fusion .\r\n\r\nCD4 is an integral cell surface glycoprotein that is able to enhance T cell-specific antigen responses when it interacts with its physiological ligand, class II major histocompatibility (MHC) molecules. In addition, CD4 is a specific cell-surface receptor for the human immunodeficiency virus-1 (HIV-1). \r\n\r\nThe entry of human immunodeficiency virus (HIV) into cells requires the sequential binding of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface.  In addition, the CD4/gp120 interaction may directly inhibit T cell function .\r\n\r\nIn addition to the above mechanism of action, it was found in one study that ibalizumab-uiyk inhibits the replication of CCR5- and CXCR4- receptor laboratory strains and primary isolates of HIV-1 in phytohemagglutinin-stimulated peripheral blood lymphocytes, further confirming its action .\r\n\r","T-cell surface glycoprotein CD4 antagonist; C-C chemokine receptor type 5 antagonist; C-X-C chemokine receptor type 4 antagonist","Target associated"]
[1461,"DB12764","investigational","small molecule","Opaganib","ABC-294640; ABC294640; Opaganib; Yeliva","C23H25ClN2O","ClC1=CC=C(C=C1)C12CC3CC(CC(C3)(C1)C(=O)NCC1=CC=NC=C1)C2","Opaganib, also known as ABC294640, is a selective (https://go.drugbank.com/polypeptides/Q9NRA0) inhibitor that is orally administered. This drug has potential anticancer, anti-inflammatory, and antiviral activities, with potential applications in oncology, inflammation, the gastrointestinal system, and COVID-19.","915385-81-8","380.92",null,null,"Opaganib selectively inhibits (https://go.drugbank.com/polypeptides/Q9NRA0). This inhibition blocks the synthesis of sphingosine 1-phosphate (S1P) and its activities (which includes regulation of fundamental biological processes such as cell proliferation, migration, immune cell trafficking, angiogenesis, immune-modulation, and suppression of innate immune responses from T-cells). This drug has dual anti-inflammatory and antiviral activity targeting a host cell component and is unaffected by viral mutation, contributing to minimization of the likelihood of resistance. It is currently being investigated against COVID-19 as it has demonstrated anti-SARS-CoV-2 activity in studies.","Sphingosine kinase 2 inhibitor","Therapeutic strategy associated"]
[1462,"DB12783","approved; investigational","small molecule","Benserazide","Benserazide","C10H15N3O5","NC(CO)C(=O)NNCC1=C(O)C(O)=C(O)C=C1","When levodopa is used by itself as a therapy for treating Parkinson's disease, its ubiquitous metabolism into dopamine is responsible for a resultant increase in the levels of circulating dopamine in the blood and to various extracerebral tissues. This can result in a number of side effects like nausea, vomiting, or even cardiac arrhythmias that may diminish patient adherence . A decarboxylase inhibitor like benserazide is consequently an effective compound to combine with levadopa as it is incapable of crossing the blood-brain barrier itself but acts to prevent the formation of dopamine from levadopa in extracerebral tissues - thereby acting to minimize the occurrence of extracerebral side effects .\r\n\r\nLevodopa/benserazide combination products are used commonly worldwide for the management of Parkinson's disease. In particular, although the specific levodopa/benserazide combination is formally approved for use in Canada and much of Europe, the FDA has approved another similar levodopa/dopa decarboxylase inhibitor combination in the form of levodopa and carbidopa.\r\n\r\nMoreover, the European Medcines Agency has conferred an orphan designation upon benseraside since 2015 for its potential to be used as a therapy for beta thalassaemia as well .","322-35-0","257.246","The primary therapeutic use for which benserazide is currently indicated for is as a combination therapy with levadopa for the treatment of Parkinson's disease in adults > 25 years of age, with the exception of drug-induced parkinsonism .\r\n\r\nAt certain doses, the combination product of levodopa and benserazide may also be used to treat restless legs syndrome, which is sometimes associated with Parkinson's disease .\r\n\r\nThere have also been some studies that have prompted the European Medicines Agency to confer orphan designation upon benserazide  hydrochloride as a potential therapy for beta thalassaemia . Although studies are ongoing, no evidence has been formally elucidated as of yet .","When used as a therapy for treating Parkinson's disease, levadopa's specific mechanism of action revolves around its metabolism into dopamine in the body . Unfortunately, the resultant increase in the levels of circulating dopamine in the blood and to various extracerebral tissues can result in a number of side effects like nausea, vomiting, or even cardiac arrhythmias that may diminish patient adherence . A decarboxylase inhibitor like benserazide is consequently an effective compound to combine with levadopa as it is incapable of crossing the blood-brain barrier itself and therefore allows levadopa to elicit its primary action in the central nervous system, but will prevent the formation of dopamine from levadopa in extracerebral tissues - thereby acting to minimize the occurrence of extracerebral side effects .","The combination of levodopa and benserazide is an anti-Parkinsonian agent . Levodopa itself is the metabolic precursor of dopamine. In Parkinson's disease, dopamine is depleted to a large degree in the striatum, pallidum, and substantia nigra in the central nervous system (CNS) . The administration of levodopa to treat the disease is subsequently proposed to facilitate raises in the levels of available dopamine in these areas . The metabolism of levodopa to dopamine occurs via the enzyme dopa decarboxylase, although unfortunately, this metabolism can also occur in extracerebral tissues . As a result, the full therapeutic effect of an administered dose of levodopa may not be obtained if portions of it are catabolized outside of the CNS and various patient adherence diminishing extracerebral side effects due to the extracerebral presence of dopamine like nausea, vomiting, or even cardiac arrhythmias can also happen .\r\n\r\nSubsequently, a peripheral decarboxylase inhibitor like benserazide, which blocks the extracerebral decarboxylation of levodopa, when administered in combination with levodopa has obvious and significant advantages. Such benefits include reduced gastrointestinal side effects, a more rapid and complete response at the initiation of therapy, and a simpler dosing regimen .\r\n\r\nIt is important to note, however, that benserazide is hydroxylated to trihydroxybenzylhydrazine in the intestinal mucosa and the liver , and that as a potent inhibitor of the aromatic amino acid decarboxylase , it is this trihydroxybenzylhydrazine metabolite of benserazide that mainly protects levodopa against decarboxylation to dopamine in the gut and also around the rest of the body outside of the blood-brain barrier .\r\n\r\nRegardless, because Parkinson's disease progresses even with the therapy of levodopa and benserazide, this kind of combined therapy is only ever indicated if it is capable of improving the quality of life and adverse effect profile of using such drugs for Parkinson's patients and there is little to be gained by switching to or starting this combination therapy if patients are already being managed with stable, effective, and well-tolerated levadopa-only therapy .\r\n\r\nFinally, it is also proposed that benserazide hydrochloride may be able to treat beta thalassaemia by maintaining the active expression of the gene for fetal hemoglobin so that constant production of fetal hemoglobin may replace the missing adult hemoglobin variation that is characteristic of patients with the condition, thereby decreasing the need for blood transfusion therapy .","Aromatic-L-amino-acid decarboxylase inhibitor","Therapeutic strategy associated"]
[1463,"DB12808","approved; investigational","small molecule","Trifarotene","Trifarotene","C29H33NO4","CC(C)(C)C1=CC(=CC=C1N1CCCC1)C1=CC(=CC=C1OCCO)C1=CC=C(C=C1)C(O)=O","Trifarotene is a topical retinoid cream used in the treatment of acne vulgaris that was first approved for use in the United States in October 2019. Retinoids are a class of medications structurally and functionally analogous to , though later generation retinoids such as trifarotene and  bear little structural resemblance to vitamin A and are analogous only in function. Trifarotene is considered the first of the \"fourth-generation\" retinoids due to its uniquely selective activity - this selectivity appears to confer improved efficacy and reduced side effects as compared to older, less selective retinoids.","895542-09-3","459.586","Trifarotene is indicated for the topical treatment of acne vulgaris in patients 9 years of age and older.","Trifarotene exerts its effects via agonism at retinoid receptors - these receptors function to alter DNA transcription, resulting in downstream modulation of the expression of various genes involved in acne pathogenesis. It may be associated with skin irritation and should not be applied to cuts, abrasions, or otherwise damaged skin. As trifarotene may result in photosensitivity, patients should be cautioned to avoid excess sun exposure and to use sunscreen and/or protective clothing if exposure is unavoidable.","Trifarotene is a potent and selective agonist of retinoic acid receptor-γ (RAR-γ). It has significantly less activity at RAR-β and RAR-α (16- and 65-fold lower than activity at RAR-γ, respectively), and has no activity at retinoid X receptors (RXRs). Agonism at retinoic acid receptors results in dimerization, and the resulting receptor-ligand dimer binds to specific DNA regulatory sequences (retinoic acid response elements, or RAREs) in the promotor regions of retinoid-responsible genes. Downstream alterations to gene expression induced by binding to these regions is the principle mechanism through which trifarotene exerts its comedolytic, anti-inflammatory, and depigmenting effects. \r\n\r\nLike other retinoids, trifarotene influences the expression of a number of genes involved in retinoid metabolism, epidermal differentiation/proliferation, and epidermal response to stress. In addition, trifarotene appears to modulate retinoid-mediated pathways involved in proteolysis, skin hydration, and cell adhesion - modulation of these additional pathways has not been observed with other retinoids and may therefore be unique to trifarotene.","Retinoic acid receptor gamma agonist; Retinoic acid receptor beta agonist; Retinoic acid receptor alpha agonist","Therapeutic strategy associated"]
[1464,"DB12825","approved; investigational","small molecule","Lefamulin","Lefamulin","C28H45NO5S","[H][C@@]12C(=O)CC[C@]11CCC(C)[C@@]2(C)[C@@H](C[C@@](C)(C=C)[C@@H](O)[C@@H]1C)OC(=O)CS[C@@H]1CC[C@@H](N)C[C@H]1O","Lefamulin is a pleuromutilin antibiotic used for the treatment of bacterial community-acquired pneumonia. A pleuromotilin is a more recently developed type of antibiotic that is derived from the fungus, Pleurotus mutilus. Lefamulin is available in intravenous and oral preparations and was granted FDA approval in August 2019.  This drug is the first semi-synthetic pleuromutilin that has been designed for systemic administration. Lefamulin features a novel mechanism of action that shows benefit against resistant bacteria that cause pneumonia. The chemical structure of lefamulin contains a tricyclic mutilin core that is necessary for some of its antimicrobial activity.","1061337-51-6","507.73","Lefamulin is indicated to treat adults diagnosed with community-acquired bacterial pneumonia (CABP) that is caused by susceptible bacteria. Its use should be reserved for confirmed susceptible organisms or a high probability of infection with susceptible organisms. The list of susceptible bacteria includes Streptococcus pneumoniae, Staphylococcus aureus (methicillin-susceptible), Legionella pneumophila, Haemophilus influenza, Chlamydophila pneumoniae, and Mycoplasma pneumoniae.","Lefamulin demonstrates strong antibacterial activity against several microbes that are found to be common in both acute bacterial skin and skin structure infections as well as community-acquired bacterial pneumonia.   It shows antibacterial activity against gram-positive and atypical microbes (for example, Streptococcus pneumoniae, Legionella pneumophila,  Mycoplasma pneumoniae, Haemophilus influenzae, and Chlamydophila pneumoniae). Lefamulin also exerts activity against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus faecium. It does not treat Pseudomonas aeruginosa infections. During in vitro studies, drug has also has demonstrated activity against Neisseria gonorrhoeae and Mycoplasma genitalium.\r\n\r\n**A note on QT prolongation and Clostridium difficile**\r\n\r\nAccording to the FDA label, lefamulin may have cardiac QT interval prolonging effects and advises against the administration of this drug in patients with diagnosed QT prolongation or ventricular arrhythmias. The administration of lefamulin should also be avoided in patients being administered antiarrhythmic agents and other drugs that prolong the QT interval. As with other antibiotics, the risk of Clostridium difficile associated diarrhea is increased with lefamulin use. Any case of diarrhea should be evaluated for C. difficile.","Lefamulin inhibits prokaryotic ribosomal protein synthesis via its binding to the peptidyl transferase center (PTC) of the ribosomal bacterial 50S subunit. It inhibits protein translation through binding to both the A and P sites of the PTC via four hydrogen bonds, resulting in the interruption of peptide bond formation. Lefamulin's tricyclic mutilin core is the common moiety for binding of all members of its drug class, the pleuromutilins. Although the tricyclic motilin core doesn’t form any hydrogen bonds with the PTC nucleotides, it is stabilized or anchored by hydrophobic and Van der Waals interactions. Lefamulin exerts a selective inhibition of protein translation in eukaryotes, however, does not affect ribosomal translation of eukaryotes. Lefamulin demonstrates a unique induced-fit type of action that closes the binding pocket within a ribosome, conferring close contact of the drug to its target, therefore improving therapeutic efficacy. Because of its mechanism of action that differs from that of other antimicrobials, cross-resistance to other antibiotic classes is less likely.","50S ribosomal protein L22 binder","Indication associated"]
[1465,"DB12831","investigational","small molecule","Gabexate","Gabexate","C16H23N3O4","CCOC(=O)C1=CC=C(OC(=O)CCCCCNC(N)=N)C=C1","Gabexate is a synthetic serine protease inhibitor which has been used as an anticoagulant. It also known to decrease production of inflammatory cytokines. Gabexate has been investigated for use in cancer, ischemia-reperfusion injury, and pancreatitis.","39492-01-8","321.377","No approved indication.","Gabexate bind and inhibits serine proteases in the coagulation cascade to prevent blood clotting. It also prevents proteolytic destruction of IkappaB resulting in suppression of the nuclear factor kappa-B signalling pathway. Ultimately this decreases the production of inflammatory cytokines such as tumor necrosis factor alpha which are produced as a result of NFkappaB activation.","Gabexate inhibits kallikrein, plasmin, and thrombin by binding to their active sites. The inhibition of these components of the coagulation cascade ultimately prevents the formation of fibrin which must be present and polymerized to form a clot. Gabexate decreases the production of inflammatory cytokines by attenuating NFkappaB and c-Jun N-terminal kinase (JNK) pathway activity. The exact mechanism for this is unknown but it is thought that gabexate prevents the proteolyytic destruction of IkappaB which deactivates NFkappaB and interferes with activator protein 1 binding to DNA.","Plasma kallikrein inhibitor; Prothrombin inhibitor; Plasminogen inhibitor","Therapeutic strategy associated"]
[1466,"DB12836","investigational; vet_approved","small molecule","Grapiprant","Grapiprant","C26H29N5O3S","CCC1=NC2=C(C)N=C(C)C=C2N1C1=CC=C(CCNC(=O)NS(=O)(=O)C2=CC=C(C)C=C2)C=C1","Grapiprant, also known as AT-001 and CJ-023, is a drug from the piprant class. These molecules were derived from acylsulfonamide and are characterized to be a novel series of para-N-acylaminomethylbenzoic acid known to be prostaglandin receptor antagonists. This type of molecules is currently in development for veterinary patients. This class of drugs was defined in 2013 by the World Health Organization. \r\n\r\nGrapiprant has been approved in March 2016 by the FDA's Center for Veterinary Medicine as a non-cyclooxygenase inhibiting NSAID for veterinary use.","415903-37-6","491.61","The effects of grapiprant have been investigated in the area of analgesia and anti-inflammation due to the effects that have been reported about this molecule.\r\n\r\nThis molecule has been approved and widely accepted to be used in veterinary for pain reduction in arthritis. In humans, it has been researched to be used in the control of pain and inflammation associated with osteoarthritis.\r\n\r\nThe effect of grapiprant can be explained through the function of prostaglandin E2 (PGE2) which is a key mediator of swelling redness and pain which are classic signs of inflammation. The effect of PGE2 results from its action through four receptor EP1, EP2, EP3 and EP4 from which the EP4 is the primary mediator of PGE2-driven inflammation.","Preclinical studies have shown that grapiprant is very effective to reduce acute and chronic pain and inflammation. The effect of grapiprant seems to be dose-dependent and it is comparable to the effect of rofecoxib and piroxicam.\r\n\r\nThe effects of grapiprant have been reported to be effective in the relief from arthritic pain in canine patients.","Grapiprant is an EP4 prostaglandin receptor antagonist and thus the activity of this drug is thought to be completely related to the selective blockade of this receptor. It binds to human and other mammals EP4 prostaglandin receptor with high affinity without interfering with other prostaglandin pathways which are important for a variety of physiological functions. The binding of grapiprant blocks PGE2 binding and hence its biological effect related to the signaling pain and inflammation cascade.\r\n\r\nGrapiprant has been accepted very greatly in veterinary as its mechanism of action is a targeted approach to pain management by not having any interaction with the production of prostanoids and thus, by not interacting with other prostaglandin receptor pathways.","Prostaglandin E2 receptor EP4 subtype antagonist","Indication associated"]
[1467,"DB12911","approved; investigational","small molecule","Nicoboxil","beta-Butoxyethyl nicotinate; Nicoboxil","C12H17NO3","CCCCOCCOC(=O)C1=CN=CC=C1","Nicoboxil has been investigated for the treatment of Acute Low Back Pain, where it is typically considered an effective and safe therapeutic option. Nevertheless, it is predominantly found paired with nonivamide as a combination topical analgesic product where its proposed mechanism of action as a rubefacient is complementary and ultimately synergistic with nonivamide's capsaicin activity . Such combination topical analgesics are only available for purchase and use (for humans) in some parts of Europe and Asia, like Germany and Australia .\r\n\r\nDespite topical nicoboxil/nonivamide topical analgesic medication being used since the 1950s, recent studies demonstrate continued interest in the medication(s) given its demonstrated efficacy, safety, and capability to be used as an alternative musculoskeletal pain therapy option with less systemic side effects when compared to the oral non-steroidal anti-inflammatory drugs and opioids that may be more typically prescribed .","13912-80-6","223.272","The primary therapeutic use for which nicoboxil is currently indicated for is as an active ingredient in combination with the capsaicinoid nonivamide compound as a topical analgesic for the temporary relief of the pain of rheumatism, arthritis, lumbago, muscular aches, sprains and strains, sporting injuries, and other conditions where local warmth is beneficial .\r\n\r\nNevertheless, most of the available studies regarding the use of nicoboxil and nonivamide topical analgesics focus specifically on their efficacy and safety in treating acute non-specific low back pain, typically finding the combination analgesic to be an effective, safe, and well-tolerated medication for such an indication .","Topical applications consisting of the individual active ingredients of nicoboxil and nonivamide at doses considered to be therapeutic are generally not considered readily available commercially . Subsequently, the pharmacodynamics of nicoboxil are considered useful in commercially available combination products largely because they combine with those of nonivamide to offer a synergistic effect from the unique complementary actions of these two agents .\r\n\r\nSubsequently, nonivamide is a synthetic capsaicin analog with analgesic properties which are assumed to result from the depletion of Substance P in the peripheral nociceptive C-fibres and A-delta nerve fibers upon repetitive topical application . Resultant stimulation of afferent nerve endings in the skin evidently causes a dilatory effect on the surrounding blood vessels accompanied by an intense, long-lasting sensation of warmth associated with the nonivamide use .\r\n\r\nGiven the proposed effect of nonivamide, it is believed that nicoboxil is a vitamin of the B complex  that possesses vasodilating properties facilitated by prostaglandin . The observed hyperaemic increased blood flow effect of nicoboxil occurs earlier and is described as being more intense than the nonivamide hyperaemic effect . Nicoboxil and nonivamide are consequently generally indicated as a combination product because the pharmacodynamics of nicoboxil are considered useful as a complement to those of nonivamide, and vice versa . In essence, both compounds induce vasodilation by different effects and therefore have complementary abilities inducing increased blood flow, thus hastening the hyperaemic skin reaction .","In particular, nicoboxil is considered a rubefacient . However, the specific mechanism of action by which rubefacients like nicoboxil elicit pharmacologic effects has not yet been formally elucidated . Nevertheless, it is generally proposed that rubefacients cause irritation of the skin when applied topically, and are believed to alleviate pain in muscles, joints, tendons, and other musculoskeletal pains in the extremities by counter-irritation . This specific term, 'counter-irritant', derives from the fact that rubefacients can cause a reddening of the skin by causing the blood vessels of the skin to dilate, which gives a soothing feeling of warmth . In essence, the term largely refers to the notion that irritation of the sensory nerve endings alters or offsets pain in the underlying muscle or joints that are innervated by the same nerves .\r\n\r\nIn fact, the vasodilation effect of rubefacients like nicoboxil has been considered the result of nerve conduction mechanisms as early as the late 1950s when certain studies demonstrated that the concomitant application of xylocaine could counteract or prevent the vasolidator response to rubefacients in 50% of such related experiments .",null,"Indication associated"]
[1468,"DB12942","approved; investigational","small molecule","Lactitol",null,"C12H24O11","OC[C@H](O)[C@@H](O)[C@H](O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O)[C@H](O)CO","Lactitol, also known as 4-β-D-galactopyranosyl-D-glucitol, is a sugar alcohol synthesized from . It is used in food manufacturing as a nutritive sweetener and is approximately 35% as sweet as table sugar (i.e. ). Clinically, lactitol has been investigated for use as an osmotic laxative and, along with other non-absorbable disaccharides such as , in the treatment of hepatic encephalopathy in patients with cirrhosis.\r\n\r\nPizensy, an oral lactitol powder for solution, was approved by the FDA for use in chronic idiopathic constipation in February 2020.","585-86-4","344.3124","Lactitol is indicated for the treatment of chronic idiopathic constipation in adults.","Lactitol helps to facilitate bowel movements by drawing water into the gastrointestinal tract. The oral administration of lactitol may reduce the absorption of concomitant medications - other oral medications should be administered at least 2 hours before or 2 hours after lactitol.","Lactitol is an osmotic laxative - it exerts its pharmacologic effect by creating a hyperosmotic environment within the small intestine. The osmotic effect generated by lactitol draws water into the small intestine, which loosens stools and ultimately facilitates bowel movements.",null,"Indication associated"]
[1469,"DB12960","investigational","small molecule","INCB-9471",null,"C30H40F3N5O2","CCO[C@@H]1CC2=CC(=CC=C2[C@H]1N1CCN(C[C@@H]1C)C1(C)CCN(CC1)C(=O)C1=C(C)N=CN=C1C)C(F)(F)F","INCB-9471 is a novel, orally available CCR5 antagonist that is part of a new class of drugs to treat HIV/AIDS. It is a potent, selective inhibitor of the HIV-1 virus.","869769-98-2","559.678",null,null,"INCB-9471 is an antagonist of CCR5. It works through a different mechanism of action than currently marketed oral antiviral drugs. Rather than fighting HIV inside a patient's white blood cells, it prevents the virus from entering uninfected cells by blocking its predominant entry route, the CCR5 co-receptor.","C-C chemokine receptor type 5","Target associated"]
[1470,"DB12961","investigational","small molecule","Leukotriene B4","LTB4","C20H32O4","CCCCC\\C=C/C[C@@H](O)\\C=C\\C=C\\C=C/[C@@H](O)CCCC(O)=O","Leukotriene B4 has been used in trials studying the treatment of HIV Infections.","71160-24-2","336.4657",{"$nulls":3},"Leukotriene B4 receptor 1; Leukotriene B4 receptor 2; Peroxisome proliferator-activated receptor alpha activator","Target associated"]
[1471,"DB12965","approved; investigational","small molecule","Silver","Colloidal silver; Nanosilver; Silver colloidal; Silver nanoparticles; Silver, colloidal","Ag","[Ag]","Silver (Ag) is a chemical element that belongs in the family of transition metals in the periodic table. It has a high electrical conductivity, thermal conductivity, and reflectivity. Silver exists as a pure elemental form, alloy with other metals, and mineral. Having critical roles in various applications inducing chemical and industrial fields, silver compounds have also been used in the field of medicine for centuries due to their broad-spectrum biological actions. Silver nanoparticles especially have been widely used in industrial, household, and healthcare-related products due to their potent antimicrobial activity.  and  have been used as topical antibacterial agents for the treatment of skin infections, while  has also been valued for topical burn treatment . Silver and its compounds have been used in trials studying the management of dental caries since the 1800s, and they may be found in dental pastes as an active ingredients. However, some drawbacks of dental use of silver compounds include tooth discolouration and pulp irritation .","7440-22-4","107.8682","Indicated for the treatment of acne for topical use or the management of dental caries for dental use.","Silver exhibits a broad-spectrum antimicrobial activity. Silver ions were shown to mediate an effective antibacterial action against _Streptococcus mutans_, one of major bacteria present in the human oral cavity and one of etiological microorganism of dental caries . A study reported a dose-dependent antimicrobial activity of silver nanoparticles against MRSA and non-MRSA bacteria . Silver nanoparticles were also shown to mediate antibacterial activity against Gram-positive _S. aureus_ and Gram-negative _E. coli_ by inhibiting the growth .  \r\n\r\nIn experimental dinitrochlorobenzene-induced inflammatory models in porcine or murine skin, topical application of silver nitrate and nanocrystalline silver were shown to exert anti-inflammatory effects associated with lymphocyte apoptosis, decreased expression of pro-inflammatory cytokines, and reduced gelatinase activity . In a rat model of ulcerative colitis, orally or intracolonically administered nanocrystalline silver were shown to suppress matrix metalloproteinase (MMP-9), tumour necrosis factor (TNF), and interleukin-β (IL-β) and IL-12 .","The majority of released silver ions precipitate with chloride or phosphate anions or bind to albumins, macroglobulins, or tissue debris . While bound silver ions do not exert antibacterial actions, they may potentially play a role in silver toxicity in case of chronic exposure . Silver ions mediate antibacterial effects via disrupting the bacterial, fungal, and protozoal cell membranes; they bind to disulphide in membrane proteins, readily allowing penetration through the membranes and intracellular absorption via pinocytosis . They may also bind to negatively-charged peptidoglycans in the cell wall via electrostatic interactions, leading to disruption of membrane transport function and loss of structural integrity . Silver ions also bind to and oxidize sulphydryl groups (SH) in bacterial cytoplasmic enzymes to aberrate their function in metabolic processes. Silver nanoparticles may cause an increase in reactive oxygen species (ROS) inside the microbial cells leading to metal-induced oxidative stress and cell damage . They also modulate cellular signal system via inhibition of phosphorylation of essential bacterial proteins to eventually cause cell death . It is also reported that silver ions also attach to guanine in bacterial DNA, which inhibits DNA replication . While it is not fully understood, the mode of action of silver compounds in preventing and arresting dental caries is thought to involve inhibition of the demineralization process in addition to cytoplasmic and membrane function perturbation mentioned above . Silver compounds may directly interact with hydroxyapatite, a major tooth component .","Metallothionein binder; Ceruloplasmin binder; Serum albumin binder; Alpha-2-macroglobulin binder","Therapeutic strategy associated"]
[1472,"DB13007","approved; investigational","biotech","Enfortumab vedotin","Enfortumab vedotin; enfortumab vedotin-ejfv",null,null,"Enfortumab vedotin is an antibody-drug conjugate used in the treatment of patients with advanced, treatment-resistant urothelial cancers. It is comprised of a fully human monoclonal antibody targeted against Nectin-4 and a microtubule-disrupting chemotherapeutic agent, monomethyl auristatin E (MMAE), joined by a protease-cleavable link. It is similar to , another antibody conjugated with MMAE that targets CD-30 instead of Nectin-4.\r\n\r\nThe clinical development of enfortumab vedotin was the result of a collaboration between Astellas Pharma and Seattle Genetics and it was first approved for use in the United States in December 2019 under the brand name Padcev<sup>TM</sup>.","1346452-25-2",null,"Enfortumab vedotin is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor, and a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced, or metastatic setting.","Enfortumab vedotin is an anti-cancer agent that destroys tumor cells by inhibiting their ability to replicate. Patients with moderate to severe hepatic impairment should not use enfortumab vedotin - although it has not been studied in this population, other MMAE-containing antibody-drug conjugates have demonstrated increased rates of adverse effects in patients with moderate-severe hepatic impairment. Enfortumab vedotin may also cause significant hyperglycemia leading, in some cases, to diabetic ketoacidosis, and should not be administered to patients with a blood glucose level >250 mg/dl.","Enfortumab vedotin is an antibody-drug conjugate comprised of multiple components. It contains a fully human monoclonal antibody directed against Nectin-4, an extracellular adhesion protein which is highly expressed in urothelial cancers, attached to a chemotherapeutic microtubule-disrupting agent, monomethyl auristatin E (MMAE). These two components are joined via a protease-cleavable linker. Enfortumab vedotin binds to cells expressing Nectin-4 and the resulting enfortumab-Nectin-4 complex is internalized into the cell. Once inside the cell, MMAE is released from enfortumab vedotin via proteolytic cleavage and goes on to disrupt the microtubule network within the cell, arresting the cell cycle and ultimately inducing apoptosis.","Nectin-4 binder&antibody","Therapeutic strategy associated"]
[1473,"DB13037","investigational","biotech","Namilumab","MT203; Namilumab",null,null,"Namilumab has been used in trials studying the treatment of Plaque Psoriasis and Rheumatoid Arthritis.","1206681-39-1",{"$nulls":3},"Namilumab is a human antibody which neutralizes the activity of granulocyte/macrophage colony stimulating factor (GM-CSF), which has potential applications in the treatment of various inflammatory and autoimmune diseases, such as rheumatoid arthritis, psoriasis, or multiple sclerosis.",null,"Therapeutic strategy associated"]
[1474,"DB13142","approved","small molecule","Calcium glubionate anhydrous","(D-gluconato)(lactobionato)calcium; Calcium D-gluconate lactobionate; Calcium glubionate anhydrous; Glubionate calcium","C18H32CaO19","OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(=O)O[Ca]OC(=O)[C@H](O)[C@@H](O)[C@H](O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O)[C@H](O)CO","Calcium glubionate (or glubionate calcium) is a mineral supplement to prevent or treat low blood calcium levels in people who do not get enough calcium from their diets.","97635-31-9","592.513","Calcium glubionate is indicated to treat conditions caused by low calcium levels such as bone loss (osteoporosis), weak bones (osteomalacia/rickets), decreased activity of the parathyroid gland (hypoparathyroidism), and a certain muscle disease (latent tetany). It may also be used in certain patients to make sure they are getting enough calcium (e.g., women who are pregnant, nursing, or postmenopausal, people taking certain medications such as phenytoin, phenobarbital, or prednisone).",null,"Essential for nervous, muscular, and skeletal systems. Maintain cell membrane and capillary permeability. Act as an activator in the transmission of nerve impulses and contraction of cardiac, skeletal, and smooth muscle. Essential for bone formation and blood coagulation.",null,"Indication associated"]
[1475,"DB13145","approved; investigational","small molecule","Nedaplatin","(glycolato-O,O')diammineplatinum(II); CDGP; cis-Diammine (glycolato)platinum; cis-diammine(glycolato)platinum; cis-Diammine(glycolato)platinum(II); Nedaplatin","C2H8N2O3Pt","[H][N]([H])([H])[Pt]1(OCC(=O)O1)[N]([H])([H])[H]","Nedaplatin is a second generation platinum analog . It is less nephrotoxic than  but has proven equally effective. It was approved for use in Japan in 1995.","95734-82-0","303.181","Used in the treatment of non-small cell lung cancer, small cell lung cancer, oesophygeal cancer, and head and neck cancers .","Nedaplatin damages DNA and induces cell death in cancer cells . It also functions as a radiosensitizer, increasing the susceptibility of the affected cells to radiation therapy .","As a platinum analog, nedaplatin likely works similarly to  on which the following mechanistic description is based. Once it has entered the cell it is hydrolyzed to its active form which complexes with water molecules . This form binds to to nucleophiles in the cytoplasm such as glutathione and other cyteine rich proteins resulting in an overall increase in oxidative stress as the cell loses antioxidant proteins. It also binds to purine nucleotides in the DNA. The active form allows for two binding interactions to form cross-links between these nucleotides. High mobility group proteins-1 and -2 induce apoptosis in response to guanine cross-links and their binding serves to shield the cross-linked DNA from repair mechanisms. The mismatch repair (MMR) protein complex also recognizes the distortion caused by platinum complexes and attempts to repair the DNA. This results in single strand breaks when the MMR complex attempts to remove the platinum cross-link. The MMR complex induces apoptosis after the repair attempt has failed. The single strand break in DNA makes it easier to form lethal double strand breaks with radiation treatment thus creating the radiosensitizing effect of nedaplatin .","Glutathione ligand; DNA ligand","Therapeutic strategy associated"]
[1476,"DB13149","approved","biotech","Protein S human","Protein S; Protein S (human); Vitamin K-dependent protein S",null,null,"Protein S human is a vitamin K-dependent plasma glycoprotein which has antcoagulant properties . It serves as a negative feedback mechanism in the coagulation cascade.",null,null,"For use in the emergency reversal of coagulation factor deficiency in patients recieving vitamin K antagonist therapy . Protein S is administered as part of a cocktail containing several other coagulation factors.","Protein S acts as an anticoagulant serves as a negative feedback mechanism in the coagulation cascade .","Thrombin converts protein C to activated protein C (APC) . Protein S functions as a cofactor for APC and together they proteolytically cleave factor Va and VIIIa  . This inhibits the activities of the prothrombinase and tenase complexes respectively and leads to a reduction in thrombin generation. The reduction in thrombin generation suppresses the coagulation cascade preventing additional clotting from occuring. Protein S is suggested to inhibit factors Va and Xa through protein-protein interactions  . Protein S is also suggested to inhibit production of factor Xa by the tenase complex by competing for binding to phospholipids via its gamma-carboxyglutamic acid domain.\r\n\r\nProtein S is thought to exert an anti-inflammatory effect in addition to its anticoagulant properties. The protein S-C4b-binding protein complex is believed to bind to phosphotidylserines on the cell membranes of apoptotic cells and interact with macrophages, signalling them to phagocytose the cell before it can rupture .","Coagulation factor V antagonist; Coagulation factor X antagonist; Vitamin K-dependent protein C cofactor","Therapeutic strategy associated"]
[1477,"DB13153","approved; experimental","small molecule","Levomenol","(-)-alpha-Bisabolol; alpha-(-)-bisabolol; alpha-bisabolol; Bisabolol; Kamillosan; Levomenol; α-(−)-bisabolol","C15H26O","[H][C@@]1(CCC(C)=CC1)[C@@](C)(O)CCC=C(C)C","Bisabolol, or more formally α-(−)-bisabolol or also known as levomenol, (-)-alpha-Bisabolol is found in fats and oils. (-)-alpha-Bisabolol is isolated from essential oil of Matricaria chamomilla (German chamomile) (-)-alpha-Bisabolol belongs to the family of Sesquiterpenes. These are terpenes with three consecutive isoprene units.","23089-26-1","222.372","Levomenol has been known to elicit a number of potentially beneficial pharmacological effects, including anti-irritant, anti-inflammatory, and anti-microbial actions. Bisabolol is also demonstrated to enhance the percutaneous absorption of certain molecules","Levomenol is an anti-inflammatory and natural moisturizing agent that has been found to diminish the signs of photodamage, reduce pruritus, and ameliorate skin texture and elasticity.",null,null,"Therapeutic strategy associated"]
[1478,"DB13155","approved","small molecule","Esculin","6-(beta-D-Glucopyranosyloxy)-7-hydroxy-2H-1-benzopyran-2-one; 6-(beta-D-Glucopyranosyloxy)-7-hydroxy-cumarin; 6,7-Dihydroxycoumarin 6-glucoside; 6,7-Dihydroxycoumarin-6-O-glucoside; Aesculin; Esculetin 6-O-glucoside; esculetin 6-β-D-glucoside; Esculoside","C15H16O9","OC[C@H]1O[C@@H](OC2=C(O)C=C3OC(=O)C=CC3=C2)[C@H](O)[C@@H](O)[C@@H]1O","Esculin is found in barley. Vitamin C2 is generally considered a bioflavanoid, related to vitamin P esculin is a glucoside that naturally occurs in the horse chestnut (Aesculus hippocastanum), California Buckeye (Aesculus californica) and in daphnin (the dark green resin of Daphne mezereum). Esculin belongs to the family of Glycosyl Compounds. These are carbohydrate derivatives in which a sugar group is bonded through its anmoeric carbonA to another group via a C-, S-,N-,O-, or Se- glycosidic bond.","531-75-9","340.284","As medication, esculin is sometimes used as a vasoprotective agent.\r\nEsculin is also used in a microbiology laboratory to aid in the identification of bacterial species (especially Enterococci and Listeria), as all strains of Group D Streptococci hydrolyze æsculin in 40% bile.","Topically applied Esculine increases the “capillary density” (the number of capillaries open to flow per surface unit) and improves the morphological aspect of the smallest blood vessels.","The main activities of Esculine focus on capillary protection, as it improves capillary permeability and fragility. It is reported to inhibit catabolic enzymes such as hyaluronidase and collagenase, thus preserving the integrity of the perivascular connective tissue. Esculine also showed good antioxidant properties, protecting triglycerides against auto-oxidation at high temperatures . The antioxidant property might as well explain some of the anti-inflammatory activity of the product, making it a suitable product for after sun treatments, for example.","Androgen receptor agonist","Therapeutic strategy associated"]
[1479,"DB13158","approved","small molecule","Clobetasone","Clobetasone","C22H26ClFO4","[H][C@]1(C)C[C@@]2([H])[C@]3([H])CCC4=CC(=O)C=C[C@]4(C)[C@@]3(F)C(=O)C[C@]2(C)[C@@]1(O)C(=O)CCl","Clobetasone is a corticosteroid that is often employed topically as a treatment for a variety of conditions such as eczema, psoriasis, various forms of dermatitis, and also for certain ophthalmologic conditions. Topical clobetasone butyrate has shown minimal suppression of the Hypothalamic-pituitary-adrenal axis.","54063-32-0","408.89","In dermatology, topical clobestasone butyrate helps to reduce the itchiness and erythema associated with eczema and dermatitis.\r\nIn ophthalmology, clobetasone butyrate 0.1% eye drops have been shown to be safe and effective in the treatment of dry eyes in Sjögren's Syndrome.","Topical corticosteroid like clobetasone are synthetic derivatives of cortisone which produce anti-inflammatory, antiproliferative, immunosuppressive and vasoconstrictor effects when applied to the skin.","Topically applied clobeyasone are thought to bind with cytoplasmic receptors in the dermal and intradermal cells and to induce inhibitory proteins, thus leading to decreased activity of prostaglandins, kinins, histamine, liposomal enzymes and other endogenous mediators of inflammation. Topical corticosteroids inhibit the migration of macrophages and leukocytes into areas of inflamed skin by reversing vascular dilation and permeability, resulting in decreased erythema, edema and pruritus.","Glucocorticoid receptor agonist","Therapeutic strategy associated"]
[1480,"DB13163","approved; experimental","small molecule","Terpin hydrate","cis-p-methane-1,8-diol monohydrate; cis-terpin hydrate; Terpin cis-form hydrate; Terpin hydrate; Terpin monohydrate; Terpinene hydrate; Terpinol hydrate","C10H22O3","O.CC(C)(O)[C@H]1CC[C@@](C)(O)CC1","Terpin hydrate is an expectorant, commonly used to loosen mucus and ease congestion in patients presenting with acute or chronic bronchitis, and related pulmonary conditions. It is derived from sources such as turpentine, oregano, thyme and eucalyptus. It was popular in the United States since the late nineteenth century, but was removed from marketed medications in the 1990s after FDA stated that \"based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients\". Elixirs of terpin hydrate are still available to patients as prescription medications to be prepared by specialty compounding pharmacies.","2451-01-6","190.283","Terpin hydrate is used in the treatment of acute and chronic bronchitis, pneumonia, bronchiectasis, chronic obstructive pulmonary disease, infectious and inflammatory diseases of the upper respiratory tract.","It acts to facilitate the removal of mucus from the respiratory tract. It prevents the exacerbation of excessive mucus production and secretion due to airway bacterial or viral infections, asthma or chronic bronchitis. Expectorants like terpin hydrate change mucus consistency and make coughing more productive.","Terpin hydrate improves mucociliary function by working directly on the bronchial secretory cells in the lower respiratory tract to liquify and facilitate the elimination of bronchial secretionsas well as exerting a weak antiseptic effect on the pulmonary parenchyma. It is thought to increase the amount of fluid in the respiratory tract, which increases the flow and clearance of local irritants and as well as reducing the viscosity of mucus .",null,"Indication associated"]
[1481,"DB13165","experimental","small molecule","Ripasudil","Ripasudil","C15H18FN3O2S","C[C@H]1CNCCCN1S(=O)(=O)C1=C2C(F)=CN=CC2=CC=C1","Ripasudil, as hydrochloride hydrate (K-115), is a specifc Rho-associated coiled-coil containing protein kinase (ROCK) inhibitor used for the treatment of glaucoma and ocular hypertension. It was first approved for treatment in Japan in September 2014. This medication is available in the form of a 0.4% eye drop solution under the brand name Glanatec. Ripasudil is a well tolerated medication that is used when other drugs have been proven to be non-effective or cannot be administered.","223645-67-8","323.39","Ripasudil has been proven to be effective in the twice daily treatment of glaucoma and ocular hypertension. It is currently in studies to be approved for both diabetic retinopathy and diabetic macular oedema. \r","Ripasudil has high intraocular permeability and works by decreasing intraocular pressure (IOP) in a dose-dependent manner and increasing flow facility. The maximum reduction of IOP occurs after 1 to 2 hours.\r","Ripasudil is a highly selective and potent Rho-associated coiled/coil-containing kinase protein (ROCK) inhibitor. Rho-kinase (ROCK) is an effector protein of Rho which binds with Rho to form a Rho/Rho-kinase complex. This complex then regulates many physiological functions including smooth muscle contractions, chemotaxis, neural growth and gene expression. ROCK comes in 2 isoforms: ROCK-1 and ROCK-2 and these two isoforms are distributed widely in our tissues including ocular tissues such as the iris, retina, trabecular meshwork and ciliary muscles. Atypical regulation of ROCK levels is involved in the pathogenesis of diseases such as glaucoma, ocular hypertension, cataracts and other retinal disorders.\r\n\r\nRipasudil acts as very highly selective and potent inhibitor with an IC50 of Ripasudil with ROCK-1 of 0.051 umol/L and with ROCK-2 of 0.019 umol/L. ROCK inhibitors have efficacy in reducing IOP by acting on the trabecular meshwork in the eye directly to increase conventional outflow through the Schlemm’s canal. Ripasudil will inhibit ROCK and induce cytoskeletal changes including the retraction and rounding of cell bodies and cause disruption of actin bundles in this trabecular meshwork. This can reduce the compaction of trabecular meshwork tissue and eventually result in increased aqueous outflow in the eye and reduced resistance to fluid flow.\r\n\r\nThus, Ripasudil is effective by inducing cytoskeletal changes which are depending on ROCK inhibition. Ripasudil decreases IOP by increasing outflow facility along with modulating the behavior of trabecular meshwork cells and Schlemm’s canal endothelial (SCE) cell permeability along with a disruption of the tight junction. \r\n\r\nWhen Ripasudil is used in combination with prostaglandin analogues it results in increased uveoscleral outflow and when used in combination with beta blockers it results in reduced aqueous production. \r","Rho-associated protein kinase 1 inhibitor; Rho-associated protein kinase 2 inhibitor","Indication associated"]
[1482,"DB13167","approved; withdrawn","small molecule","Alclofenac","[4-(allyloxy)-3-chlorophenyl]acetic acid; 3-Chloro-4-(2-propenyloxy)benzeneacetic acid; Alclofenac; Alclophenac","C11H11ClO3","OC(=O)CC1=CC(Cl)=C(OCC=C)C=C1","Alclofenac is a non-steroidal anti-inflammatory drug. It was withdrawn from the market in the United Kingdom in 1979.","22131-79-9","226.66","Alclofenac is indicated in rheumatology, in particular for the treatment of rheumatoid arthritis, ankylosing spondylitis and, as an analgesic, in painful arthritic pathologies.",null,"Alclofenac is an inhibitor of prostaglandin H2 synthase. The inhibition of the enzyme occurs through the reversible block of cyclooxygenase enzyme. Therefore, it prevents the production of inflammatory mediators (and pain) as prostacyclins and prostaglandins.  Aclofenac has the ability to inhibit the biosynthesis  of prostaglandins  which may be an  important  factor in  the action of these drugs, but  in addition,   the  effect  of  these  agents  in  displacing  endogenous anti-inflammatory substances from plasma protein  binding sites is thought  to  be an equally important effect in their mechanism of action","Prostaglandin G/H synthase 2 antagonist","Therapeutic strategy associated"]
[1483,"DB13168","nutraceutical","small molecule","Omega-6 fatty acids","n-6 fatty acids; Omega 6 acids; Omega 6 fatty acids; ω-6 fatty acids",null,null,"Omega-6 fatty acids are polyunsaturated fatty acids with a final carbon-carbon double bond in the n-6 position, that is, the sixth bond, counting from the methyl end. They are a family of fatty acid molecules that act as precursors to potent lipid mediator signalling molecules with either pro-inflammatory and anti-inflammatory effects. Cells involved in the inflammatory response are typically rich in the n-6 fatty acid arachidonic acid, as generally, eicosanoids derived from n-6 PUFA are pro-inflammatory. Arachidonic acid, which is a main precursor of eicosanoids, is an example of omega-6 (n-6) polyunsaturated fatty acids. Vegetable oil is a major dietary sources of omega-6 fatty acids.",null,null,"There are no current pharmacotherapeutic products based on omega-6 fatty acids.","Omega-6 fatty acids mediate pro-inflammatory effects in the cellular level and compete for the same rate-limiting enzymes with omega-3 fatty acids. Arachidonic acid is converted to inflammatory mediators such as omega-6 prostaglandins and leukotriene eicosanoids during the inflammatory cascade. AA-derived eicosanoids are proinflammatory but they have important homeostatic functions in regulating both the promotion and resolution of inflammation in the immune response. It is reported that high intake of n-6 PUFA, along with low intakes of n-3 PUFA, shifts the physiological state to one that is proinflammatory and prothrombotic with increases in vasospasm, vasoconstriction, and blood viscosity and the development of diseases associated with these conditions. Thus maintaining the balance between 2 polyunsaturated fatty acids is critical in inflammatory cascade regulation.","Linoleic acid is the simplest omega-6 fatty acid that can generate longer n-6 polyunsaturated fatty acids such as eicosanoids, endocannabinoids and lipoxins by the insertion of additional double bonds during consecutive elongation and desaturation mechanisms. It gives rise to arachidonic acid (AA) via γ-linolenic acid (GLA, 18:3n-6) and dihomo-γ-linolenic acid (DGLA, 20:3n-6) and the same set of enzymes can also convert AA to EPA and DHA. The initial rate limiting desaturation of LA to GLA is catalysed by the enzyme delta-6-desaturase (FADS2) and elongation of GLA to DGLA by delta-5-desaturase (FADS1) generates AA . AA is also converted to 2-series prostaglandins (PGD2, PGE2, PGF2, PGI2) andthromboxanes (TXA2, TXB2) by COX-2 activity and 4-series leukotrienes (LTA4, LTB4, LTC4, LTD4, LTE4) by 5-LOX activity. Resulting lipid signalling molecules have various pro-inflammatory effects on target tissues and cells; bronchostriction, fever, pain, increased production of inflammatory cytokines such as TNF-alpha and IL-6, platelet aggregation, vasoconstriction, vascular permeability, chemotaxis of leukocytes, and release of reactive oxygen species by granulocytes . \r\nOmega-6 fatty acids activate PPAR to the less extent than omega-3 fatty acids, but a study involving human keratinocytes showed induction of COX-2 expression resulting from PPAR-alpha activation. Omega-6 fatty acids are also reported to directly activate syntaxin-3, a plasma protein membrane that regulates vesicle transport and growth of neurites .",null,"Therapeutic strategy associated"]
[1484,"DB13170","approved; investigational","small molecule","Plecanatide","Guanilib; Plecanatide","C65H104N18O26S4","[H][C@@]12CSSC[C@H](NC(=O)CNC(=O)[C@@]([H])(NC(=O)[C@]([H])(CSSC[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N1)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC2=O)C(C)C)C(C)C)[C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O","Plecanatide is a drug approved in January 2017 by the FDA for the treatment of chronic idiopathic constipation (CIC). It should not be used in children less than six years of age, and should be avoided in patients six years to 18 years of age","467426-54-6","1681.89","Plecanatide stimulates intestinal fluid secretions in the gastrointestinal tract to support regular bowel function. Plecanatide, taken orally once daily, works locally in the upper GI tract to stimulate secretion of intestinal fluid and support regular bowel function.","Food Effect Subjects who received either a low-fat, low calorie (LF-LC) meal or a high fat, high calorie (HF-HC) meal reported looser stools than fasted subjects up to 24 hours after a single dose of 9 mg (3 times the recommended dose). In clinical studies, Plecanatide was administered with or without food.","Guanylate cyclase C (GC-C) agonist\r\nPlecanatide and its active metabolite bind to GC-C and act locally on the luminal surface of intestinal epithelial cells; GC-C activation leads to increased cyclic guanosine monophosphate (cGMP), which, in turn, stimulates secretion of chloride and bicarbonate into the intestinal lumen, mainly by activation of the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel, resulting in increased intestinal fluid and accelerated transit.\r\n In animal models, plecanatide has been shown to increase fluid secretion into the gastrointestinal (GI) tract, accelerate intestinal transit, and cause changes in stool consistency.\r\nIn an animal model of visceral pain, plecanatide reduced abdominal muscle contractions, a measure of intestinal pain. The mechanism has not been studied.","Guanylate cyclase soluble subunit alpha-2 agonist","Therapeutic strategy associated"]
[1485,"DB13174","experimental","small molecule","Rhein",null,"C15H8O6","OC(=O)C1=CC2=C(C(O)=C1)C(=O)C1=C(C=CC=C1O)C2=O","Rhein is an anthraquinone metabolite of rheinanthrone and senna glycoside is present in many medicinal plants including Rheum palmatum, Cassia tora, Polygonum multiflorum, and Aloe barbadensis . It is known to have hepatoprotective, nephroprotective, anti-cancer, anti-inflammatory, and several other protective effects.","478-43-3","284.2204","No approved indication.","**Liver: **Reverses animal models of non-alcoholic fatty liver disease by lowering liver lipids and reducing inflammation . Also reverses and prevents fibrosis in liver injury .\r\n\r\n**Kidney: **Protects against fibrosis in nephropathy models and improves epithelial tight junction function  .\r\n\r\n**Bone and joint:** Decreases inflammation and cartilage destruction and also corrects altered osteoblast acitivity  .\r\n\r\n**Lipid lowering and anti-obesity:** Reduces body weight and fat content, and lowers high density lipoprotein and low density lipoprotein . May prevent adipocyte differentiation .\r\n\r\n**Anti-oxidant/Pro-oxidant**: Reduces levels of reactive oxygen species (ROS) at concentrations of about 2-16 microM but induces the generation of ROS at concentrations of 50 microM and above  .\r\n\r\n**Anti-cancer:** Rhein has been observed to produce DNA damage and suppress DNA repair in cancer cells . It induces apoptosis via ER stress, calcium, and mitochondria mediated pathways . Rhein also prevents cancer cell invasion into systemic circulation by preventing angiogenesis and breakdown of the extracellular matrix . Finally, rhein suppresses the activation of several tumor promoting signalling pathways   .\r\n\r\n**Anti-inflammatory: ** Suppresses the production of pro-inflammatory cytokines such as interleukin-1beta and interleukin-6  .\r\n\r\n**Anti-diabetic: **Lowers plasma glucose and increases survival of islet beta cells in type 2 diabetes mellitus models .\r\n\r\n**Anti-microbial:** Inhibits arylamine N-acteyltransferase and cell growth in Helicobacter pylori . Rhien also appears to be effective against many genotypes of Staphylococcus aureus .\r\n\r\n**Anti-allergenic:** Inhibits production of leukotrienes and the release of histamine from mast cells .","**Liver: **The reversal of non-alcoholic fatty liver disease stems from rhien's lipid lowering and anti-obesity actions which result in an overall decrease in body weight, high density lipoprotein, and low density lipoprotein as well as its anti-inflammatory action . The reversal of hepatic fibrosis is thought to be due to rhien's anti-inflammatory and anti-oxidant action which suppresses the pro-fibrotic signalling from macrophages and further damage from reactive oxygen species respectively . Ultimately this results in reduced expression of alpha-smooth muscle actin (Alpha-SMA) which is indicative of decreased hepatic stellate cell and myofibroblast activation. Rhein also appears to suppress the expression of transforming growth factor-Beta (TGF-Beta) \r\n\r\n**Kidney: **The protection from fibrosis in the kidney also appears to stem from rhien's anti-inflammatory action resulting in less inflammatory cell infiltration along with suppression of alpha-SMA and fibronectin expression . These indicate a reduction in the activation of interstitial fibroblasts which are responsible for excess production of extracellular matrix components. Rhien may also suppress TGF-beta expression in the kidney. The anti-fibrotic mechanism of rhien may involve the upregulation of bone morphogenetic protein 7 and hepatic growth factor . In diabetic nephropathy rhein appears to suppress the expression of integrin-linked kinase leading to a reduction in the matrix metalloproteinase-9/tissue inhibitor of matrix metalloproteinase-1 ratio . The improvement of epithelial tight junction function seems to involve upregulation of zona occludins protein-1 and occludin expression .\r\n\r\n**Bone and joint:**Rhein reduces cartilage destruction by decreasing expression of matrix metalloproteinase (MMP)-1 and -3 as well as upregulating tissue inhibitor of matrix metalloproteinases which serve to reduce the activity of several MMPs . The anti-inflammatory action of rhein reduces the level of interleukin-1beta activity which plays a large role in reduction of extracellular matrix production, MMP activity, and continued inflammation . Rhein reduces abnormal osteoblast synthetic activity through an unknown mechanism .\r\n\r\n**Lipid lowering and anti-obesity: **Rhein is known to bind and inhibit liver X receptor alpha and beta with Kd values of 46.7 microM and 31.97 microM respectively . This decreases the expression of genes such as that of sterol regulatory element binding transcription factor 1 (SREBP1c) and its downstream genes for fatty acid synthase (FAS), steroyl-coenzyme A desaturase 1 (SCD1), and acetyl CoA carboxylase 1 (ACC1). SREBP1c, FAS, SCD1, and ACC1 are all involved in adipogenesis and their suppression results in less fat content. The genes for ABCA1 and ABCG1 are also suppressed. These correspond to cholesterol efflux trasporters and likely explain the reductiion in HDL and LDL seen with rhein. The inhibition of LXR by rhien relieves the inhibition on uncoupling protein 1 expression in brown adipose tissue. The result of this is increased thermogenesis which likely plays a role in the reduction of body weight produced by rhien. Additionally, rhein may downregulate peroxisome proliferator-receptor gamma and its downstream genes to inhibit adipocyte differentiation .\r\n\r\n**Anti-oxidant/Pro-oxidant:** The antoxidant mechanism is unknown. The pro-oxidant action of rhien may involve the inhibition of mitochondrial respiratory complex 1 and subsequent facilitation of NADH and NADPH dependent lipid peroxidation .\r\n\r\n**Anti-cancer:** The exact mechanism of rhein's ability to damage DNA and supress the expression of DNA repair enzymes ADR and MGMT is unknown . The mechanism through which rhien induces ER stress is unknown but likely involves its pro-oxidant properties . Rhein has been observed to produce increases in cytosolic calcium, reductions in mitochondrial membrane potential, and upregulation of pro-apoptotic proteins as well as leakage of cytochrome C which would induce apoptosis via the intrinsic pathway. The reduction of matrix metalloproteinase-9 serves to prevent extra cellular matrix breakdown by cancer cells and hinders their invasion into surrounding tissue . Rhein also decreases vascular endothelial growth factor expression through an unknown mechanism to prevent cancer cells from stimulating agiogenesis. Rhein reduces the activity of the nuclear factor kappa (NFkappaB) pathway by preventing the destruction of IKBalpha  . The activity of the phosphoinositol 3-kinase/Akt pathway is also reduced by rhien . Rhein's inhibition of the mitogen-activated protein kinase pathways (particularly those involving extracellular signal regulated kinase) appears to follow a U-shaped dose response curve. ERK phosphorylation is inhibited at low concentrations of around 3microM but activated at higher concentrations of around 30microM . Furthermore, ERK phosporylation is again inhibited at extremely high concentrations in excess of 100 microM . The suppression of these three pathways is likely involved in the anti-proliferative effects of rhein.\r\n\r\n**Anti-inflammatory:** The mechanism of rhein's anti-inflammatory effect likely involves its inhibition of the NFkappa B pathway which plays a role in the production of many pro-inflammatory cytokines  . Rhein's anti-oxidant activity may also play a role in preventing damage during inflammation.\r\n\r\n**Anti-diabetic:** Rhein is thought to increase islet beta cell survival by suppressing the expression of dynamin-related protein 1 and thereby preventing mitochondrial fission . Rhein's anti-oxidant properties are also thought to play a role in protecting islet beta cells. The reduction in plasma glucose is likely due to increased survival of islet beta cells and subsequent increases in insulin secretion. Rhein's anti-inflammatory action may also serve to reduce insulin resistance.\r\n\r\n**Anti-microbial:** Rhien inhibits H. pylori arylamine N-acetyltransferase in a dose dependent manner . The mechanism of rhein's anti-microbial effect on H. pylori and S. aureus are unknown.\r\n\r\n**Anti-allergenic:** Rhien inhibits 5-lipoxygenase with an IC50 of 13.7microM . Rhien also inhibits mast cell degranulation although the specific mechanism is unknown.","Oxysterols receptor LXR-alpha inhibitor; Oxysterols receptor LXR-beta inhibitor; Arylamine N-acetyltransferase inhibitor; Arachidonate 5-lipoxygenase inhibitor","Therapeutic strategy associated"]
[1486,"DB13178","approved; investigational; withdrawn","small molecule","Inositol","1,2,3,5/4,6-cyclohexanehexol; cis-1,2,3,5-trans-4,6-cyclohexanehexol; Inositol; L-myo-Inositol; Meat sugar; meso-Inositol; myo-inositol","C6H12O6","O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O","Inositol is a collection of nine different stereoisomers but the name is usually used to describe only the most common type of inositol, myo-inositol. Myo-inositol is the cis-1,2,3,5-trans-4,6-cyclohexanehexol and it is prepared from an aqueous extract of corn kernels by precipitation and hydrolysis of crude phytate. These molecules have structural similarities to glucose and are involved in cellular signaling. It is considered a pseudovitamin as it is a molecule that does not qualify to be an essential vitamin because even though its presence is vital in the body, a deficiency in this molecule does not translate into disease conditions. Inositol can be found as an ingredient of OTC products by Health Canada but all current product whose main ingredient is inositol are discontinued. By the FDA, inositol is considered in the list of specific substances affirmed as generally recognized as safe (GRAS).","87-89-8","180.1559","Inositol may be used in food without any limitation. As a drug, inositol is used as a nutrient supplement in special dietary foods and infant formula. As it presents a relevant role in ensuring oocyte fertility, inositol has been studied for its use in the management of polycystic ovaries. Inositol is also being researched for the treatment of diabetes, prevention of metabolic syndrome, aid agent for weight loss, treatment of depression, psychiatric disorder and anxiety disorder and for prevention of cancer.","Inositol can stimulate glucose uptake in skeletal muscle cells which allows the decrease in blood sugar levels. This effect is later seen as a reduction in urine glucose concentration and indicates a decrease in high blood sugar levels.\r\n\r\nIn PCOS, the administration of inositol has produced the remission of symptoms as well as a reduction in male hormone secretion, a regulation of the cholesterol level, and a more efficient fat breakdown which allow to a significant reduction on body mass and appetite.\r\n\r\nIn the cases of infertility, inositol has been proven to increase sperm count and motility, as well as increase the overall quality of oocytes and embryos.\r\n\r\nIn the brain, inositol has been shown to produce an increase in serotonin receptor sensitivity. This activity produces an increase in GABA release. Some of the effects observed in the brain produced a relief in symptoms of anxiety and obsessive-compulsive disorders. In high doses, it has been shown to even reduce panic attacks.\r\n\r\nIn cancer research, inositol has gained interest as it can act as an antioxidant, anti-inflammatory and it seems to enhance immune properties.","The mechanism of action of inositol in brain disorders is not fully understood but it is thought that it may be involved in neurotransmitter synthesis and it is a precursor to the phosphatidylinositol cycle. The change that occurs in the cycle simulates when the postsynaptic receptor is activated but without activating the receptor. This activity provokes a fake activation which regulated the activity of monoamines and other neurotransmitters.\r\n\r\nReports have shown that insulin resistance plays a key role in the clinical development of PCOS. The presence of hyperinsulinemia can induce an excess in androgen production by stimulating ovaries to produce androgens and by reducing the sex hormone binding globulin serum levels. One of the mechanisms of insulin deficiency is thought to be related to a deficiency in inositol in the inositolphosphoglycans. The administration of inositol allows it to act as a direct messenger of the insulin signaling and improves glucose tissue uptake. This mechanism is extrapolated to its functions in diabetes treatment, metabolic syndrome, and weight loss.\r\n\r\nIn cancer, the mechanism of action of inositol is not fully understood. It is hypothesized that the administration of inositol increases the level of lower-phosphate inositol phosphates why can affect cycle regulation, growth, and differentiation of malignant cells. On the other hand, the formation of inositol hexaphosphate after administration of inositol presents antioxidant characteristics by the chelation of ferric ions and suppression of hydroxyl radicals.",null,"Therapeutic strategy associated"]
[1487,"DB13179","approved","small molecule","Troleandomycin","Oleandocetine; Oleandomycin triacetate; Oleandomycin triacetyl ester; Triacetyloleandomycin; Tribiocillina; Troleandomycin","C41H67NO15","CO[C@H]1C[C@H](O[C@H]2[C@H](C)[C@@H](O[C@@H]3O[C@H](C)C[C@@H]([C@H]3OC(C)=O)N(C)C)[C@@H](C)C[C@@]3(CO3)C(=O)[C@H](C)[C@@H](OC(C)=O)[C@@H](C)[C@@H](C)OC(=O)[C@@H]2C)O[C@@H](C)[C@@H]1OC(C)=O","A macrolide antibiotic that is similar to erythromycin.","2751-09-9","813.9684","For the treatment of bacterial infection.","Troleandomycin, like other macrolide antibiotics, inhibits bacterial protein synthesis to prevent growth.","As a macrolide, troleandomycin binds to the 50S subunit of the bacterial ribosome . This binding inhibits translocation of tRNA along the A, P, and E sites of the ribosome. With tRNA unable to move from site to site, amino acids cannot be deposited onto the polypeptide chain leading to failure of protein synthesis. Bacterial cell growth and duplication is inhibited without the ability to generate the necessary proteins.","50S ribosomal protein L32 inhibitor; 50S ribosomal protein L4 inhibitor; Nuclear receptor subfamily 1 group I member 2 activator","Indication associated"]
[1488,"DB13191","nutraceutical","small molecule","Phosphocreatine","Creatine phosphate; Creatine phosphic acid; Creatine-P; Fosfocreatine; N-(N-phosphonoamido)sarcosine; N-(Phosphonoamidino)sarcosine; N-phosphocreatine; N-Phosphorylcreatine; phosphorylcreatine","C4H10N3O5P","CN(CC(O)=O)C(=N)NP(O)(O)=O","Phosphocreatine - or creatine phosphate - is the phosphorylated form of creatine. It is primarily found endogenously in the skeletal muscles of vertebrates where it serves a critical role as a rapidly acting energy buffer for muscle cell actions like contractions via its ability to regenerate adenosine triphosphate (ATP) from adenosine diphosphate (ADP).","67-07-2","211.1131","Phosphocreatine is a naturally occuring substance that is found predominantly in the skeletal muscles of vertebrates. Its primary utility within the body is to serve in the maintanence and recycling of adenosine triphosphate (ATP) for muscular activity like contractions.\r\n\r\nGiven this utility of phosphocreatine to recycle ATP, the most plausible therapeutic potentials for its use involve conditions caused by energy shortage or by increased energy requirements - such as in ischemic stroke and other cerebrovascular diseases. It is important to note however that relatively little clinical research has been done to significantly further the evidence for any such indications, although it is administered intravenously for cardiovascular conditions in some countries.\r\n\r\nAdditionally, because phosphocreatine is not regulated as a controlled substance it is taken as a supplement by some professional athletes as a means to perhaps increase short bursts of muscle strength or energy for professional athletics.","Creatine is a naturally occurring chemical within the body and is primarily stored in skeletal muscle in both free and phosphorylated forms. Phosphocreatine is the name given to the phosphorylated form of creatine. Additionally, phosphocreatine can also be found in other areas of the body like the kidneys, liver, and brain. In fact, most *in vivo* synthesis of creatine occurs in the liver where amidine groups from arginine are transfered to glycine with the help of the glycine transaminidase enzyme to form guanidinoacetic acid. This acid is then methylated with the methyl group of S-adenosylmethionine via guanidinoacetate methyltransferase to generate creatine. The synthesized creatine is transported to storage sites in skeletal muscle via the bloodstream.\r\n\r\nThe phosphorylation of creatine is reversible in both a forwards and backwards reaction. That is, while phosphocreatine is capable of anaerobically donating a phosphate group to adenosine diphosphate (ADP) to regenerate ATP, at the same time excess ATP can be dephosphorylated during periods of low muscle activity to convert creatine to phosphocreatine. This dual activity in synthesizing phosphocreatine from excess levels of ATP during rest and use of phosphocreatine to regenerate ATP during high activity demonstrates the crucial utility of phosphocreatine in acting as an energy buffer in body mucle cells. \r\n\r\nPhosphocreatine's fast regeneration of ATP is considered a coupled reaction - in essence, the energy released from transferring a donating a phosphate group from phosphocreatine is used to regenerate ATP. Phosphocreatine consequently plays an essential role in body tissues that have high, fluctuating energy requirments like muscle and brain tissues.","Adenosine triphosphate (ATP) is the primary source of chemical energy that body muscles use to perform contractions. During such contraction processes, ATP molecules are depleted as they undergo hydrolysis reactions and become adenosine diphosphate (ADP). To maintain homeostasis in muscle activity, the ATP supply of muscles must be regenerated regularly.\r\n\r\nPhosphocreatine occurs naturally within the body and is capable of regenerating ATP by transferring a high-energy phosphate from itself to ADP, resulting in the formation of ATP and creatine. This kind of regeneration of ATP with phosphocreatine typically occurs within seconds of intense muscular or neuronal effort, acting as a quickly accessible reserve of high-energy phosphates for the recycling of ATP in body muscle tissues. ATP recycling from phosphocreatine is in fact known as the quickest form of ATP regeneration.","Guanidinoacetate N-methyltransferase product of; Sodium- and chloride-dependent creatine transporter 1; Creatine kinase M-type ligand; Creatine kinase U-type, mitochondrial ligand; Creatine kinase S-type, mitochondrial ligand; Creatine kinase B-type ligand","Indication associated"]
[1489,"DB13345","approved; experimental","small molecule","Dihydroergocristine","9,10-dihydroergocristine; DHEC","C35H41N5O5","[H][C@@]12CCCN1C(=O)[C@H](CC1=CC=CC=C1)N1C(=O)[C@](NC(=O)[C@H]3CN(C)[C@]4([H])CC5=CNC6=CC=CC(=C56)[C@@]4([H])C3)(O[C@@]21O)C(C)C","Dihydroergocristine is part of the ergoloid mixture products. It is a semisynthetic ergot alkaloid and thus, it is characterized by a structural skeleton formed by an alkaloid ergoline. To know more about ergoloid mixtures, please visit .","17479-19-5","611.743","Dihydroergocristine is used in some countries such as Brasil as a single agent for the treatment of cerebral and peripheric vascular events. To know more about dihydroergocristine as part of the ergoloid mesylate mixture, please visit .","Dihydroergocristine has been shown to present effect on memory and cognition. This activity in the brain is been reported by an increase in glutathione in age-related brain states. The reported effect on serotonin and adrenergic receptors has also been correlated to an inhibition of platelet aggregation. It has also been reported that individuals exposed to dihydroergocristine may present an amphoteric vasoregulating activity either hypotensive in hypertensive individuals or hypertensive in hypotensive individuals. This action is performed by promoting a dilating action in the contracted arteries and a tonic action in the dilated arteries and arterioles. The vasoregulating effect causes an increase in cerebral blood flow and oxygen consumption by the brain, which correlates with the brain protective function of dihydroergocristine. In Alzheimer studies, dihydroergocristine reduced the amyloid-beta levels in different cell types. To know more about dihydroergocristine as part of the ergoloid mesylate mixture, please visit .","Dihydroergocristine mechanism of action seems to be related to a noncompetitive antagonistic activity in the serotonin receptors as well as a double partial agonist/antagonist activity in dopaminergic and adrenergic receptors. In Alzheimer studies, dihydroergocristine act as a direct inhibitor of γ-secretase.","Serotonin Receptors antagonist; Beta adrenergic receptor antagonist&agonist; Alpha adrenergic receptor antagonist&agonist; Dopamine receptor antagonist&agonist","Therapeutic strategy associated"]
[1490,"DB13346","approved; withdrawn","small molecule","Bufexamac","2-(p-Butoxyphenyl)-acetohydroxamic acid; 4-Butoxy-N-hydroxybenzeneacetamide; 4-Butoxyphenylacetohydroxamic acid; Bufexamac; Bufexamic acid; p-Butoxyphenylacetohydroxamic acid","C12H17NO3","CCCCOC1=CC=C(CC(=O)NO)C=C1","Bufexamac is a non-steroidal anti-inflammatory drug (NSAID) under the market name Droxaryl, Malipuran, Paraderm and Parfenac. It is typically administered topically for the treatment of subacute and chronic eczema of the skin, including atopic eczema and other inflammatory dermatoses, as well as sunburn and other minor burns, and itching. It has also been used in suppositories in combination with local anaesthetics indicated for haemorrhoids. The use of bufexamac has been discontinued in Canada and the United States, which may be due to undetermined clinical efficacy and a high prevalence of contact sensitization . Bufexamac was also withdrawn by the EMA in April 2010.","2438-72-4","223.272","Indicated for the treatment of various skin conditions, such as atopic eczema and other inflammatory dermatoses.","Bufexamac is a topically-active anti-inflammatory agent that inhibits the cyclooxygenase enzyme. In cutaneous and deep experimental inflammation, topical administration of bufexamac exerted a dose-related anti-inflammatory effect . In guinea pigs, bufexamax was shown to be more active than topical acetylsalicylic acid 5% or phenylbutazone 5% in delaying the local increase in temperature resulting from UV exposure . Bufexamac is unlikely to have any effect on wound healing .","The full mechanism of action is unclear. It is proposed that bufexamac acts similarly to other non-steroidal anti-inflammatory drugs to inhibit prostaglandin biosynthesis _in vitro_, via inhibiting cyclo-oxygenase (COX) enzymes . Systematically administered bufexamac may accumulate preferentially in the adrenal cortex of rats and may play a role in adrenal stimulation; however its topical anti-inflammatory action is likely to be independent of this effect .","Prostaglandin G/H synthase 1 inhibitor; Prostaglandin G/H synthase 2 inhibitor; Histone deacetylase 6 inhibitor; Histone deacetylase 10 inhibitor","Therapeutic strategy associated"]
[1491,"DB13501","approved; withdrawn","small molecule","Bendazac","Bendazac","C16H14N2O3","OC(=O)COC1=NN(CC2=CC=CC=C2)C2=CC=CC=C12","Bendazac is an oxyacetic acid . Despite possessing anti-inflammatory, anti-necrotic, choleretic, and anti-lipidemic characteristics, most research has revolved around studying and demonstrating the agent's principal action in inhibiting the denaturation of proteins - an effect that has primarily proven useful in managing and delaying the progression of ocular cataracts . Bendazac, however, has since been withdrawn or discontinued in various international regions due to its capability or risk for eliciting hepatotoxicity  in patients although a small handful of regions may continue to have the medication available for purchase and use either as a topical anti-inflammatory/analgesic cream or eye drop formulation.","20187-55-7","282.299","Prior to the withdrawal of bendazac from various international regions of use due to concerns for hepatotoxicity  the chemical had demonstrated potential usefulness predominantly as the prescription medication bendazac lysine for the indication of managing the level of vision in patients with mild to moderate cataracts to facilitate delaying the need for surgical intervention .\r\n\r\nElsewhere bendazac may still be available in a limited capacity as a non-prescription topical cream product for treating conditions like local pain, inflammation, dermatitis, eczema, pruritis, hives, insect bites, burns, erythema, and others  - although such products may also be facing general discontinuation .","Bendazac principally demonstrates an antidenaturant action on proteins . This effect has been shown to inhibit the denaturation of various proteins like ocular lens proteins by heat, ultraviolet radiation, free radicals, and other chemicals . The medication may be administered to patients via a number of different formulations, including orally as the lysine salt, as eye drops, or even topical applications for the skin .\r\n\r\nSome preliminary studies have suggested that an apparent improvement of the blood-retinal barrier had been observed in diabetic patients using bendazac lysine 500 mg three times a day for three to six months . Moreover, the use of topical bendazac has also been shown to demonstrate anti-inflammatory effects in animal models and clinical studies to effectively treat varied dermatoses, especially those involving a necrotic component .\r\n\r\nAdditionally, bendazac has also demonstrated choleretic and antilipidaemic activities that have resulted in substantial reductions in beta/alpha lipoprotein ratio, and total lipid, total cholesterol, and triglyceride levels in patients with dyslipidaemia using oral bendazac lysine 500 mg three times daily . The medication has also elicited the inhibition of phytohaemagglutinin induced lymphocyte transformation in vitro .","Bendazac seems to elicit an anticataract action by inhibiting the denaturation of ocular lens proteins, although the precise mechanisms by which this action occurs has not yet been formally elucidated - despite there being many proposed mechanisms . In particular, the denaturation of lens proteins may in part be prevented by inhibiting the binding of certain chemicals like cyanates or sugars and 5-hydroxybendazac - the major metabolite of bendazac - has been shown to be capable of inhibiting the glycosylation of lens proteins by sugars like galactose or glucose-6-phosphate in a dose-dependent manner . Moreover, the apparent ability for administered bendazac to elicit free radical scavenger activities due to interactions with protein molecules suggests that the medication may also be able to prevent the oxidation of lens proteins by free radicals in the development of cataracts . Furthermore, bendazac may also be capable of reducing the sulfhydryl group oxidation of lens proteins by the saliva, serum, or urine from patients with cataracts following single dose administration and reduce biological liquid oxidant activity (BLOA) in doing so .\r\n\r\nOtherwise, it is believed that bendazac also possesses non-steroidal anti-inflammatory actions, as well as analgesic, antipyretic, and platelet-inhibitory effects  These effects may be accounted for in part by the substance's capability to inhibit prostaglandin synthesis by inhibiting cyclooxygenase activity in converting arachidonic acid to cyclic endoperoxides - the precursors of prostaglandins .","Free radicals blocker; Prostaglandin G/H synthase 1; Prostaglandin G/H synthase 2","Therapeutic strategy associated"]
[1492,"DB13615","approved; experimental","small molecule","Mifamurtide","Mifamurtide","C59H110N6NaO20P","O.[Na+].CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCCNC(=O)[C@H](C)NC(=O)CC[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](C)O[C@@H]([C@H](O)[C@H](O)CO)[C@@H](NC(C)=O)C=O)C(N)=O)OC(=O)CCCCCCCCCCCCCCC","Mifamurtide is an immunomodulator with antitumor activity via activation of macrophages and monocytes. Also called L-MTP-PE, mifamurtide may be a liposomal form of of the active ingredient MTP-PE, which is a synthetic, less pyrogenic, and longer-acting derivative of muramyl dipeptide (MDP). MDP is a motif present in all gram-positive and gram-negative bacterial walls that is recognized by different signalling molecules and activators such as nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) and toll-like receptors present in macrophages and monocytes. The overall result of MDP recognition leads to the production of proinflammatory cytokines and promotion of bactericidal and tumoricidal effects . As a liposomal formulation, mifamurtide demonstrates an enhanced tumoricidal effect and improved safety profile .\r\n\r\nMifamurtide is marketed in Europe as Mepact for intravenous infusion. It is administered as an adjuvant therapy to postoperative combination chemotherapy in pediatric, adolescent or adult patients with high-grade, resectable, non-metastatic osteosarcoma after macroscopically complete surgical resection. In the US, it is currently under investigation that holds orphan drug status for the treatment of osteosarcoma .\r\n\r\nOsteosarcoma is the most common primary malignant bone tumor that usually arises in the metaphyses of long bone in children and adolescents . The standard therapy for osteosarcoma is comprised of macroscopic surgical resection and multi-agent chemotherapy consisting of doxorubicin, cisplatin, high-dose methotrexate with leucovorin rescue, and ifosfamide . While about 90% of patients with newly diagnosed osteosarcoma may achieve complete remission from first-line therapies, the prognosis is still poor for patients with non-metastatic osteosarcoma with lower 5-year event-free survival. In a large, randomized, open-label, multicenter, phase III trial, the treatment of mifamurtide in conjunction with three- or four-drug combination chemotherapy (doxorubicin, cisplatin, and high-dose methotrexate with, or without, ifosfamide) was associated with significant improvement in survival rates and good tolerance . The adverse events (AEs) associated with mifamurtide were generally mild to moderate in severity .","838853-48-8","1277.515","Indicated in children, adolescents and young adults for the treatment of high-grade, resectable, non-metastatic osteosarcoma after macroscopically complete surgical resection, typically in combination with post-operative multi-agent chemotherapy .","Mifamurtide stimulates the innate immunity by activating monocytes and macrophages. Within hours following administration of mifamurtide in healthy adults or patients with osteosarcoma NOS, elevated plasma levels of proinflammatory molecules, such as TNF-α, IL-6, and IL-1β, and other indicators of immune stimulation like C-reactive protein and neopterine were observed . _In vivo_ administration of mifamurtide in rat and mouse model resulted in inhibition of tumour growth of lung metastasis, skin and liver cancer, and fibrosarcoma . In addition, increased disease-free survival rate was demonstrated when mifamurtide was given as an adjuvant in dog models of osteosarcoma and hemangiosarcoma. Administration of mifamurtide was associated with transient neutropenia, usually when used in conjunction with chemotherapy. Pronounced inflammatory responses are uncommon .","It was discovered that tumor necrosis could be promoted by factors released by the host’s immune system (e.g. macrophages) in response to the endotoxins or bacterial products . Mifamurtide is referred to as MTP-PE or L-MTP-PE (in case of the liposomal formulation), which is a fully synthetic derivative of muramyl dipeptide (MDP), which is a motif within the peptidoglycan polymer in the cell wall of bacteria. \r\n\r\nMDP stimulates the immune system by being recognized by different pattern recognition molecules and receptors, such as nucleotide-binding oligomerization domain (NOD) 2 receptor and toll-like receptor (TLR). Similarly, mifamurtide acts as a ligand for TRL4 and NOD2. Involved in the innate immunity, NOD2 is an intracellular MDP sensor that is primarily expressed on monocytes, dendritic cells, and macrophages. It possesses an amino-terminal caspase recruitment domain, which is required to trigger nuclear factor-kappaB (NF-κB) signaling . Activation of intracellular signaling transduction pathway NF-κB can promote inflammation and release of antimicrobial peptides, resulting in the production of pro-inflammatory cytokines like interleukin-1β (IL-1β), interleukin-6 (IL-6), and TNF-α, and other molecules such as chemokines and adhesion molecules . Upon binding to TLR4, mifamurtide may activate extracellular-signal-regulated kinase 1/2 (ERK 1/2), nuclear factor-kappa B (NF-κB) and adaptor protein (AP)-1 . Mifamurtide may also activate NLRP3, which is an essential component of the inflammasome, a protein complex that promotes the cleavage of procaspase 1 into its active form. Active caspase 1 further activates pro-inflammatory cytokines like IL-1β . Furthermore, mifamurtide induces the expression of adhesion molecules including lymphocyte function-associated antigen (LFA)-1, intracellular adhesion molecule (ICAM)-1, and human leukocyte antigen (HLA)-DR . Mifamurtide may interact with interferon (IFN)-γ to up-regulate tumoricidal activity .\r\n\r\nUpon intravenous administration, lipophilic mifamurtide is selectively phagocytosed by monocytes and macrophages followed by subsequent degradation of liposomal vesicles by the phagocytic cells. Then, MTP-PE is released into the cytosol where it interacts with Nod2 and activates the macrophages and monocytes . Mifamurtide exerts a tumoricidal action via the same signalling pathway as MDP but with greater superiority because the lipophilic properties of MTP-PE cause higher cell uptake via passive transfer through the cytoplasmic membrane . Incorporation of MTP-PE into liposomal structures allows better safety profile and more efficient distribution to the liver, spleen, and lungs after intravenous administration .","Toll-like receptor 4 ligand; Nucleotide-binding oligomerization domain-containing protein 2 ligand","Therapeutic strategy associated"]
[1493,"DB13749","approved; investigational","small molecule","Magnesium gluconate","Magnesium (as gluconate); Magnesium D-gluconate (1:2) dihydrate; Magnesium D-gluconate (1:2) hydrate; Magnesium gluconate; Magnesium gluconate,dihydrate","C12H26MgO16","O.O.[Mg++].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O","Magnesium gluconate is a magnesium salt of gluconate. It demonstrates the highest oral bioavailability of magnesium salts  and is used as a mineral supplement. Magnesium is ubiquitous in the human body, and is naturally present in many foods, added to other food products, available as a dietary supplement and used as an ingredient in some medicines (such as antacids and laxatives) .\r\n\r\nAlthough magnesium is available in the form of sulphates, lactate, hydroxide, oxide and chloride, only magnesium gluconate is recommended for magnesium supplementation as it appears to be better absorbed and causes less diarrha .\r\n\r\nThis drug has been studied in the prevention of pregnancy-induced hypertension, and has displayed promising results . In addition, it has been studied for its effects on premature uterine contractions .","59625-89-7","450.629","Magnesium gluconate is a mineral supplement which is used to prevent and treat low levels of magnesium. Magnesium is very important for the normal physiologic functioning of cells, nerves, muscles, bones, and the heart. Generally, a well-balanced diet provides the necessary amounts of magnesium for homeostasis. However, certain conditions causing chronic magnesium deficiency may decrease levels of magnesium. These conditions include treatment with diuretics, a poor diet, alcoholism, or other medical conditions (e.g., severe diarrhea/vomiting, stomach/intestinal absorption problems, poorly controlled diabetes) .","Magnesium is a cofactor in over 300 enzyme systems that regulate a variety of biochemical reactions in the body, including protein synthesis, muscle and nerve function, blood glucose control, and blood pressure regulation. Magnesium is necessary for energy production, oxidative phosphorylation, and glycolysis . \r\n\r","Replaces deficient circulating levels of magnesium .\r\n\r\nBy competing with calcium for membrane binding sites and by stimulating calcium sequestration by sarcoplasmic reticulum, magnesium helps in the maintenance of a low resting intracellular free calcium ion concentration, which is essential in various cellular functions. The electrical properties of membranes and their permeability characteristics are also affected by magnesium .\r\n\r\nMagnesium is essential to many enzymatic reactions in the body, serving as a cofactor in protein synthesis and in carbohydrate metabolism .\r\n\r\nMagnesium contributes to the structural development of bone and is also essential in the synthesis of DNA, RNA, and the antioxidant glutathione. Magnesium also plays an important role in the active transport of calcium and potassium ions across cell membranes, a process which is important to nerve impulse conduction, muscle contraction, and normal heart rhythm .\r\n\r\nIn addition to the above, magnesium is an essential mineral required for the regulation of body temperature, nucleic acid and protein synthesis, and in preserving nerve and muscle cell electrical potentials.  Magnesium supplementation during pregnancy may help to reduce fetal growth restriction and pre-eclampsia, as well to increase birth weight .",null,"Indication associated"]
[1494,"DB13751","approved; experimental","small molecule","Glycyrrhizic acid","18-beta-Glycyrrhizic acid; Glizigen; Glycyrrhizin","C42H62O16","[H][C@@]12C[C@](C)(CC[C@]1(C)CC[C@]1(C)C2=CC(=O)[C@]2([H])[C@@]3(C)CC[C@H](O[C@H]4O[C@@H]([C@@H](O)[C@H](O)[C@H]4O[C@@H]4O[C@@H]([C@@H](O)[C@H](O)[C@H]4O)C(O)=O)C(O)=O)C(C)(C)[C@]3([H])CC[C@@]12C)C(O)=O","Glycyrrhizic acid is extracted from the root of the licorice plant; _Glycyrrhiza glabra_. It is a triterpene glycoside with glycyrrhetinic acid that possesses a wide range of pharmacological and biological activities. When extracted from the plant, it can be obtained in the form of ammonium glycyrrhizin and mono-ammonium glycyrrhizin. Glycyrrhizic acid has been developed in Japan and China as a hepatoprotective drug in cases of chronic hepatitis. From January 2014, glycyrrhizic acid as part of the licorice extract was approved by the FDA as an existing food sweetener. It was approved by Health Canada to be used in over-the-counter products but all the products are currently on the status canceled post marketed.","1405-86-3","822.942","Glycyrrhizic acid is widely applied in foods as a natural sweetener. As a therapeutic agent, is has been used in a vast variety of formulations as it is reported to be anti-inflammatory, anti-ulcer, anti-allergic, antioxidant, anti-tumor, anti-diabetic and hepatoprotective. Due to this properties, its indications have been: treatment of premenstrual syndrome, treatment of viral infections, anti-lipidemic and antihyperglycemic. It is also known to be used as a remedy for peptic ulcer and other stomach diseases.","Glycyrrhizic acid was reported to present antiallergic, antiviral and anti-inflammatory activities as well as improvements in glucose tolerance. \r\n\r\nThe effect of glycyrrhizic acid in metabolic syndrome generates a significant decrease in blood glucose, fasting blood glucose and mean serum insulin concentration.","Glycyrrhizic acid can be found in the alpha and beta forms. The alpha form is predominant in the liver and duodenum and thus, it is thought that the anti-inflammatory liver effect of this drug are mainly due to the action of this isomer. Glycyrrhizic acid anti-inflammatory effect is generated via suppression of TNF alpha and caspase 3. It also inhibits the translocation of NFkB into the nuclei and conjugates free radicals. Some studies have shown a glycyrrhizic-driven inhibition of CD4+ T cell proliferation via JNK, ERK and PI3K/AKT.\r\n\r\nThe antiviral activity of glycyrrhizic acid includes the inhibition of viral replication and immune regulation. The antiviral activity of glycyrrhizic acid seems to be of a broad spectrum and be able to cover several different viral types such as vaccinia virus, herpes simplex virus, Newcastle disease virus and vesicular stomatitis virus.\r\n\r\nThe effect of glycyrrhizic acid on metabolism is thought to be related to its inhibitory activity towards 11-beta-hydroxysteroid dehydrogenase type 1 which in turn decreases the activity of hexose-6-phosphate dehydrogenase. On the other hand, some studies have shown a potential lipoprotein lipase induction in non-hepatic tissues and thus it is suggested to enhance dyslipidemic conditions.","Corticosteroid 11-beta-dehydrogenase isozyme 1 antagonist; Tumor necrosis factor antagonist; Caspase-3 antagonist; Nuclear factor NF-kappa-B translocation inhibitor; Lipoprotein lipase inducer","Therapeutic strategy associated"]
[1495,"DB13783","approved; investigational","small molecule","Acemetacin","Acemetacin; indometacin carboxymethyl ester; indometacin glycolic ester; indomethacin carboxymethyl ester; indomethacin glycolic ester","C21H18ClNO6","COC1=CC2=C(C=C1)N(C(=O)C1=CC=C(Cl)C=C1)C(C)=C2CC(=O)OCC(O)=O","Acemetacin is a carboxymethyl ester of indometacin. It is a potent non-steroidal anti-inflammatory drug, derived from the indol-3-acetic acid, whose activity is thought to be mainly through its active metabolite indomethacin. In clinical trials, acemetacin exhibits a better gastric tolerability compared to its active metabolite indometacin. It was developed by E. Merck and Company in Germany as an attempt to provide a safer drug but other than the amelioration on the gastrointestinal effects, the metabolism of acetamicin led to the formation of indomethacin and it kept the same side effects.","53164-05-9","415.83","Acemetacin is not FDA, Canada or EMA approved, but in the countries where it is marketed it is indicated for the symptomatic treatment of pain and swelling in acute inflammation of the joints in rheumathoid arthritis, osteoarthritis, low back pain and post-surgical pain. It is also indicated for the treatment of chronic inflammation of the joints in presence of rheumatoid arthritis, treatment of ankylosing spondylitis, treatment of irritation in the joints and spinal column caused by degenerative disorders, treatment of inflammatory soft-tissue rheumatism syndrome and painful swelling and inflammation caused by injury.","The effect of acemetacin causes a weak reduction of prostaglandin synthesis which generates an anti-inflammatory and analgesic effect. The weak inhibition of prostaglandin reduces significantly the damage caused in the mucous membrane of the gastrointestinal tract. Studies have shown that acemetacin strongly inhibits the release of histamine from mast cells and the generation of hyperthermia. Acemetacin effect also causes changes in systolic and diastolic blood pressure as well as inhibition of platelet aggregation.","Acemetacin is a non-selective inhibitor of the production of pro-inflammatory mediators derived from the action of the enzyme COX. COX is essential for the synthesis of prostaglandin E2 and F2 which are molecules derived from fatty acids and stored in the cell membrane. Acetometacine is metabolized and forms its major metabolite indometacin which is also a non-selective inhibitor of COX and exhibits the capacity to inhibit the motility of polymorphonuclear leukocytes and decreased cerebral flow by modulating the nitric oxide pathway and vasoconstriction.","Prostaglandin G/H synthase 1 antagonist; Prostaglandin G/H synthase 2 antagonist","Therapeutic strategy associated"]
[1496,"DB13854","approved; investigational","small molecule","Gamolenic acid","(6,9,12)-linolenic acid; (6Z,9Z,12Z)-Octadecatrienoic acid; (Z,Z,Z)-6,9,12-octadecatrienoic acid; 18:3 (n-6); 6-cis,9-cis,12-cis-octadecatrienoic acid; 6,9,12-Octadecatrienoic acid; all-cis-6,9,12-octadecatrienoic acid; gamma-Linolenic acid; gamoleic acid; Gamolenic acid; GLA; γ-linolenic acid","C18H30O2","CCCCC\\C=C/C\\C=C/C\\C=C/CCCCC(O)=O","Gamolenic acid, or gamma-linolenic acid (γ-Linolenic acid) or GLA, is an essential fatty acid (EFA) comprised of 18 carbon atoms with three double bonds  that is most commonly found in human milk and other botanical sources . It is an omega-6 polyunsaturated fatty acid (PUFA) also referred to as 18:3n-6; 6,9,12-octadecatrienoic acid; and cis-6, cis-9, cis-12- octadecatrienoic acid . Gamolenic acid is produced minimally in the body as the delta 6-desaturase metabolite of . It is converted to , a biosynthetic precursor of monoenoic prostaglandins such as PGE1. While Gamolenic acid is found naturally in the fatty acid fractions of some plant seed oils ,  and  are rich sources of gamolenic acid. Evening primrose oil has been investigated for clinical use in menopausal syndrome, diabetic neuropathy, and breast pain, where gamolenic acid is present at concentrations of 7-14% . Gamolenic acid may be found in over-the-counter dietary supplements. Gamolenic acid is also found in some fungal sources and also present naturally in the form of triglycerides . Various clinical indications of gamolenic acid have been studied, including rheumatoid arthritis, atopic eczema, acute respiratory distress syndrome, asthma, premenstrual syndrome, cardiovascular disease, ulcerative colitis, ADHD, cancer, osteoporosis, diabetic neuropathy, and insomnia.","506-26-3","278.4296","Indicated as a dietary supplement for over-the-counter uses.","Gamolenic acid is converted to PGE1, which exhibits anti-inflammatory, antithrombotic, antiproliferative, and lipid-lowering effects . PGE1 also induces smooth muscle relaxation and vasodilation. Gamolenic acid is an essential component of membrane phospholipids, including the mitochondrial membrane, where it enhances the the integrity and the fluidity of the membrane . \r\n\r\n**Bone and joint health:** In a pilot study of women with a mean age of 79.5 years and senile osteoporosis, the use of gamolenic acid in combination with calcium and eicosapentaenoic acid was associated with an increase in femoral bone density and lumbar spine density in comparison to placebo, where there were no observable changes . In clinical studies of patients with rheumatoid arthritis, treatment with gamolenic acid-containing oils resulted in an improvement in symptoms, measured by joint tenderness counts and scores, joint swelling scores, physician global assessment, and pain . \r\n\r\n**Inflammation:** A study demonstrated that oral administration of gamolenic acid suppressed human T-cell proliferation and activation by interfering with early events in the TcR/CD3-receptor–mediated signal transduction cascade . \r\n\r\n**Atherosclerosis:** In ApoE genetic knock-out mice, dietary gamolenic acid was shown to reduce the average medial layer thickness of the vessel wall and reduces the size of atherosclerotic lesions . \r\n\r\n**Diabetic complications:** In a clinical trial of patients with mild diabetic neuropathy or distal diabetic neuropathy, treatment with gamolenic acid was associated with improved symptoms in hot and cold threshold, sensation, tendon reflexes, and muscle strength . GLA ameliorated the inflammatory profile in diabetic nephropathy in rat studies . \r\n\r\n**Cancer:** In three human tumor cell lines (the neuroblastoma CHP-212, the tubal carcinoma TG, and the colon carcinoma SW-620), gamolenic acid elicited cytotoxic effects in tumours by blocking cell proliferation following incorporation into malignant cells . In both clinical and animal studies of breast cancer, gamolenic acid, in combination with tamoxifen, down-regulated the expression of estrogen receptors . \r\n\r\n**Skin disorders:** In an open study of patients with atopic dermatitis, which is a disorder related to a deficiency of delta-6-desaturase and inefficient conversion of linoleic acid to gamolenic acid, daily administration of gamolenic acid was associated with a significant increase in plasma GLA and DGLA levels in combination with an improvement of clinical signs of atopic dermatitis .  \r\n\r\n**Respiratory disorders:** In patients with acute lung injury or acute respiratory distress syndrome, gamolenic acid was shown to reduce cytokine production and neutrophil recruitment into the lung . In patients with atopic asthma, gamolenic acid blocked _ex vivo_ synthesis of leukotrienes from whole blood and isolated neutrophils compared to the placebo group .","Once gamolenic acid (GLA) is absorbed and converted to dihomo-gamolenic acid (DGLA), circulating DGLA fatty acids are converted to several lipid mediators with predominantly anti-inflammatory properties, such as prostaglandin-E1 (PGE1) and 15-HETrE. The anti-inflammatory effects of DGLA are attributed to both the anti-inflammatory properties of DGLA-derived metabolites and the ability of DGLA and its products to compete with arachidonic acid (AA) in the synthesis of pro-inflammatory potent eicosanoid products, such as prostaglandins, thromboxane and leukotrienes . Both PGE1 and 15-HETrE are known to suppress inflammation, promote vasodilation, lower blood pressure, inhibit smooth muscle cell proliferation, inhibit platelet aggregation, and exert anti-neoplastic activities . PGE1 is a potent vasodilator that binds to surface receptors on smooth muscle cells, increasing intracellular cAMP . PGE1 is binds to G protein coupled surface PGE (EP) receptors and prostacyclin (IP) receptors as a natural ligand . \r\n\r\nGLA is proposed to enhance calcium absorption, reduce excretion and increase calcium deposition in bone . It is proposed that GLA may suppress tumor growth _in vivo_ by increasing the expression of E-cadherin, a cell-to-cell adhesion molecule that acts as a suppressor of metastasis. Another possible mechanism of tumour suppression is that GLA also reduces tumor-endothelium adhesion, which is a key factor in the establishment of distant metastases, partly by improving gap junction communication within the endothelium . By targeting the inflammatory process involved in the pathogenesis of diabetic nephropathy, GLA inhibits the expression of inflammatory mediators that tend be elevated in diabetes, intracellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1), thereby attenuates the recruitment and infiltration of monocytes or macrophages .",null,"Therapeutic strategy associated"]
[1497,"DB13873","approved","small molecule","Fenofibric acid",null,"C17H15ClO4","CC(C)(OC1=CC=C(C=C1)C(=O)C1=CC=C(Cl)C=C1)C(O)=O","Fenofibric acid is a lipid-lowering agent that is used in severe hypertriglyceridemia, primary hyperlipidemia, and mixed dyslipidemia. It works to decrease elevated low-density lipoprotein cholesterol, total cholesterol, triglycerides, apolipoprotein B, while increasing high-density lipoprotein cholesterol. Due to its high hydrophilicity and poor absorption profile, prodrug ,, and other conjugated compounds of fenofibric acid, such as choline fenofibrate, have been developed for improved solubility, gastrointestinal absorption, and bioavailability, and more convenient administration.","42017-89-0","318.75","For use as an adjunctive therapy to diet to: (a) reduce triglyceride levels in adult patients with severe hypertriglyceridemia, and (b) reduce elevated total cholesterol, low-density-lipoprotein (LDL-C), triglycerides, and apolipoprotein B, and to increase high-density-lipoprotein (HDL-C) in adult patients with primary hypercholesterolemia or mixed dyslipidemia (Fredrickson Types IIa and IIb).","Various clinical studies have shown that elevated levels of total cholesterol, low-desnsity-lipoprotein (LDL-C), and apolipoprotein B (apo B) - an LDL membrane complex - are associated with human atherosclerosis . Concurrently, decreased levels of high-density-lioprotein (HDL-C) and its transport complex, apolipoproteins apo AI and apo AII, are associated with the development of atherosclerosis . Furthermore, epidemiological investigations demonstrate that cardiovascular morbidity and mortality vary directly with the levels of total cholesterol, LDL-C, and triglycerides, and inversely with the level of HDL-C .\r\n\r\nFenofibric acid, the active metabolite of fenofibrate, subsequently produces reductions in total cholesterol, LDL-C, apo B, total triglycerides, and triglyceride rich lipoprotein (VLDL) in treated patients . Moreover, such treatment with fenofibrate also results in increases in HDL-C and apo AI and apo AII .","Having performed clinical studies with in vivo transgenic mice and in vitro human hepatocyte cultures, it is believed that the principal mechanism of action of fenofibric acid is demonstrated through its capability to activate peroxisome proliferator receptor alpha (PPAR-alpha) .\r\n\r\nBy activating PPAR-alpha, fenofibric acid increases lipolysis and the elimination of triglyceride-rich particles from plasma by actuating lipoprotein lipase and reducing production of apoprotein C-III, which acts as an inhibitor of lipoprotein lipase activity . The resultant decrease in triglycerides causes an alteration in the size and composition of low-density-lipoprotein from small, dense particles to large, buoyant ones . The size of these larger low-density-lipoprotein particles have a greater affinity for cholesterol receptors and are therefore catabolized more rapidly . Additionally, fenofibric acid's activation of PPAR-alpha also induces an increase in the synthesis of apoproteins apo A-I, apo A-II, and high-density-lipoprotein .\r\n\r\nMoreover, the use of fenofibric acid can also act to reduce serum uric acid levels in ordinary or hyperuricemic individuals by increasing the urinary excretion of uric acid .","Peroxisome proliferator-activated receptor alpha agonist; Matrix metalloproteinase-25 unknown; Peroxisome proliferator-activated receptor gamma; Peroxisome proliferator-activated receptor delta unknown; Nuclear receptor subfamily 1 group I member 2 partial agonist","Target associated"]
[1498,"DB13891","approved; experimental","biotech","Crotalus scutulatus antivenin","Crotalus scutulatus immune fab antivenin (ovine)",null,null,"Crotalus scutulatus antivenin is derived and purified immunoglobulin fragments obtained from other domestic animals such as sheep previously immunized with Crotalus scutulatus (also known as the _Mojave rattlesnake_ ). \r\n\r\nThe final purified antivenin product is obtained by mixing other different monospecific snake antivenins and isolating the antivenin of interest through fractionation and chromatography techniques. It is intravenously administered to limit systemic toxicity , , .\r\n\r\nCROFAB (crotalidae polyvalent immune fab (ovine))is a sheep-derived antivenin used for the management of adult and pediatric patients with North American crotalid envenomation , which includes the Crotalus scutulatus snake (Mojave snake).\r\n\r\nMojave rattlesnakes inhabit desert areas of the southwestern United States and central Mexico. Specimens with type A venom, which cause a different pattern of injury than other rattlesnakes, have been reported in southern California, Nevada, Utah, Arizona, Texas, and New Mexico .\r\n\r\nSince it was approved by the Food and Drug Administration in October 2000, crotalidae poyvalent immune Fab (CroFab) has largely replaced previously used crotaline antivenom. CroFab is more specifically tailored for crotalids of North America and is less allergenic than whole immunoglobulin antivenoms .",null,null,"CROFAB is indicated for the management of adult and pediatric patients with North American crotalid envenomation. The term crotalid is used to describe the Crotalinae subfamily (formerly known as Crotalidae) of venomous snakes which includes rattlesnakes, copperheads and cottonmouths/water moccasins .","Acts as an antivenin, relieving symptoms of envenomation from Crotalinae family of snakes, and preventing lethal consequences of snake evenomation .\r\n\r\nThe Crotalidae family produces venoms which are generally necrolytic and hemolyzing to tissues. Hemorrhagins in crotalid venom is toxic to the blood vessels and therefore cause hemorrhage and edema at the wound site, in addition to systemic hemorrhage and shock. Significant anemia is observed due to hemolysis and extravasation of blood due to damaged vessels. Disseminated intravascular coagulation (DIC) has been observed in some cases. The most frequent initial clinical pathological changes include echinocytosis, thrombocytopenia, leukocytosis and prolonged activated clotting time. In general, edema and erythema along with fang marks (_Crotalidae _family) may be seen at the site of bite although it is tough to identify due to thick hair coat in animals .\r\n\r\nPatients sustaining rattlesnake envenomation often develop thrombocytopenia, the etiology of which is not clear. It has been shown thatCrotaline Fab antivenom improved platelet aggregation in an in vitro model of platelet dysfunction induced by venom from C. scutulatus .","\r\nCROFAB is a venom-specific Fab fragment of immunoglobulin G (IgG) that works by binding and neutralizing venom toxins, facilitating their redistribution away from target tissues and their elimination from the body",null,"Therapeutic strategy associated"]
[1499,"DB13906","experimental","biotech","Aloe vera leaf","Aloe; Aloe (aloe barbadensis); Aloe barbadensis leaf; Aloe barbadensis leaf extract; Aloe barbadensis leaf juice; Aloe barbadensis leaf juice powder; Aloe barbadensis leaf powder; Aloe barbadensis leaf water; Aloe folii extractus (aloe vera); Aloe folium (aloe vera); Aloe herba (aloe vera); Aloe leaf extract; Aloe vera; Aloe vera dry leaf juice; Aloe vera extract; Aloe vera leaf extract; Aloe vera leaf exudate; Aloe vera leaf juice; Aloe vera leaf mucilage; Aloe vera leaf powder; Aloe vera mucilage; Aloes; Aloes (aloe barbadensis); Barbatos aloe leaf; Curacao aloe leaf; Ghrita kumari leaf; Kanyasara; Lu hui (aloe vera); Lu hui ye; Luhui (aloe barbadensis)",null,null,"Aloe describes a genus including over 500 species of flowering succulent plants that grow in the Southern peninsula and various islands. Aloe vera, or _Aloe barbadensis miller_, is the most common species of Aloe that is cultivated for agricultural and medical purposes. It is a perennial succulent xerophyte with elongated leaves that contain a clear gel. While aloe vera has a long history of commercial uses, it is still widely used in cosmetic, food and pharmaceutical products. The use of aloe vera in constipation, inflammatory disorders, cancer, ulcer, and diabetes has also been investigated . The active constituents of aloe vera include polysaccharides with protective effects on skin, as they exhibit antioxidant and anti-inflammatory properties . Common active polysaccharides include glucomannans, polymannose, and acemannan, or b-(1–4)-acetylated polymannose . Acemannan and other modified polysaccharides are responsible in preventing suppression of contact hypersensitivity or immune suppression induced by external factors such as irradiation .","8001-97-6",null,"Indicated for use as a topical agent to soothe sensitive skin and to relieve symptoms of various skin conditions, including contact or atopic dermatitis, eczema, dermatitis and acne urticata, first- and second-degree burns, radiation dermatitis, and sunburn.","Aloe polysaccharides mediate antioxidant and anti-inflammatory actions, as well as immunoregulatory activities. Various studies indicate that aloe polysaccharides possess effective free radical scavenging activity _in vitro_, and produce potent antioxidant potential during oxidative stress _in vivo_ . According to the findings of studies _in vitro_ and _in vivo_, aloe polysaccharides exhibit radioprotective activity. Treatment with acemmanan, which is a common aloe polysaccharide, on CH3 mice with radiation-induced skin reactions resulted in reduced signs of those reactions . Studies suggest that aloe polysaccharides may evidently attenuate tumor growth in mice . Treatment of aloe polysaccharides in Vero cells as well as in the in vivo zebrafish model led to protective effects against AAPH-indued oxidative stress resulting from accumulation of free radical species and improved cell viability .","It is suggested that aloe polysaccharides mediate skin-protectant effects in damaged skin, induced by internal or other external factors such as radiation, via inhibiting apoptosis of normal cell lines _in vitro_ and thrombocytes _in vivo_ . Following irradiation, aloe polysaccharides block the upregulation of pro-apoptotic p53, Bax, and Bad while blocking downregulating anti-apoptotic Bcl-2 . _In vivo_, aloe polysaccharides may act as a scavenger for oxygen free radicals including DPPH, alkyl radicals, superoxides, and singlet oxygen and hydroxyl radicals that may also be generated by superoxides . Hydrogen peroxide, which is a weak initiate lipid peroxidation, may also be effectively scavenged by aloe polysaccharides . In a Fenton reaction system, aloe polysaccharides demonstrated a concentration-dependent scavenging activity against hydroxyl radical that were generated during the reaction . Aloe polysaccharides may also compete with oxygen to react with nitric oxide (NO), thereby inhibiting the generation of nitrite and peroxynitrite anions that act as free radicals . \r\n\r\nFindings from a study investigating the effects of aloe polysaccharides on doxorubicin-induced oxidative stress suggest that aloe polysaccharides mediate potent antioxidant actions _in vivo_ . Doxorubicin, known to generate reactive oxygen species such as superoxide and hydroxy radicals, was administered to albino rats. This led to myocardial oxidative stress and cardiac injury accompanied by leakage of LDH and CPK from cardiac myocytes and to serum due to lipid peroxidation of cardiac membranes, reduced levels of antioxidant coenzyme GSH, and increased levels of SOD from a compensatory and combative mechanism of oxidative stress . Treatment with aloe polysaccharides resulted in a significant decrease in serum LDH and CPK levels, indicating that aloe polysaccharides are capable in stabilizing cardiac membranes from peroxidative damage. Restored levels of endogenous GSH and SOD in a dose-dependent manner were also observed with the treatment of aloe polysaccharides, suggesting that aloe polysaccharides exhibit potent antioxidant properties .\r\n\r\nIn a study of rats with open cutaneous back wounds, treatment with aloe polysaccharides decreased the levels of matrix metalloproteinase-3 (MMP-3) and induced tissue inhibitors of matrix metalloproteinase-2 (TIMP-2) during the early stage of wound repair, resulting in decreased collagen breakdown and increased preservation of collagen content in the injured area . A study proposes that acemannan, a common aloe polysaccharide, stimulates BMSC proliferation, ALPase activity, expression of VEGF, BMP-2, OPN, BSP, and mineralization leading to osteoblast differentiation and bone formation during socket healing .","Free radicals chelator","Therapeutic strategy associated"]
[1500,"DB13908","approved","small molecule","Amylmetacresol","5-methyl-2-pentylphenol; 6-amyl-m-cresol; 6-n-amyl-m-cresol; 6-n-pentyl-m-cresol; 6-pentyl-m-cresol; Amyl metacresol; Amylmetacresol","C12H18O","CCCCCC1=CC=C(C)C=C1O","Amylmetacresol is an antiseptic available in Canada over-the-counter in a number of lozenges for the treatment of sore throat and minor mouth infections , .  Amylmetacresol is often combined with dichlorobenzyl alcohol and menthol in the commonly used sore throat lozenges, known as Strepsils .\r\n\r\nThe acute sore throat (pharyngitis) is one of the most common conditions for which children are seen in the primary care setting. Pharyngitis is normally caused by viruses and proves benign and self-limiting. Clinically proven, over-the-counter throat lozenges offer rapid and effective relief of acute sore throat symptoms, and are increasingly important in the management of this condition .","1300-94-3","178.275","Sore throat, minor mouth and throat infections , , .","The mixture of amylmetacresol throat lozenge medications markedly reduces the infectivity of certain infectious viruses in the throat and in cough droplets, thus reducing opportunities for person-to-person transmission .    In addition, it relieves symptoms of sore throat/irritation of the throat , .\r\n\r\nAmylmetacresol is thought to inhibit the inflammatory and pain mediators that are involved in the inflammation of the mouth and throat mucous membranes, as well as the sore throat .","The mechanism of virucidal action is not fully elucidated, however it is suggested that denaturation of external protein spikes, a pH-induced rearrangement of the tertiary structure of attachment proteins, or a selective effect on viral lipid membranes/protein–lipid interaction is responsible for this action .\r\n\r\nAmylmetacresol is an antibacterial and antiviral agent, and blocks voltage-gated Na channels in a local anesthetic-like manner .","Sodium channel protein type 2 subunit alpha antagonist","Therapeutic strategy associated"]
[1501,"DB13915","approved","biotech","Axicabtagene ciloleucel","Autologous T cells transduced with retroviral vector encoding an anti-CD-19 CD28/CD3-zeta chimeric antigen receptor; Axicabtagene ciloleucel",null,null,"Axicabtagene ciloleucel is a chimeric antigen receptor (CAR) T cell therapy for the treatment of Diffuse large B-cell lymphoma (DLBCL), which is a type of a non-Hodgkin lymphoma (NHL). It is the second cell-based gene therapy that is FDA-approved but the first in the treatment of large B-cell lymphoma in adult patients. Uniquely, axicabtagene ciloleucel utilizes each patient’s own immune system where each dose of the drug consists of the patient's genetically modified T-cells that were previously collected. The modified version of the T-cell expresses a new gene that targets and kills the lymphoma cells and is infused back into the patient. \r\n\r\nDiffuse large B-cell lymphoma (DLBCL) is the most common type of NHL in adults that mostly originates from the lymph nodes but can initiate outside of the lymphatic system. Lymphoma cells appear to be much larger in size than normal lymphocytes. In a multicenter clinical trial, the patients who were treated with axicabtagene ciloleucel achieved the complete remission rate of 51%. \r\n \r\nDeveloped by Kite Pharma, Inc., it was approved on October 18th, 2017 by the FDA as an intravenously infused anticancer therapy and is marketed under the brand name Yescarta.",null,null,"Indicated for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.","The levels of cytokines, chemokines and other blood molecules were measured over a 4-week interval after the drug infusion. There were transient elevations of chemokines such as IL-6, IL-8, IL-10, IL-15, TNF-α, IFN-γ, and sIL2Rα where the peak elevation was reached within the first 14 days after infusion, and the levels gradually returned to baseline within 28 days . It is likely that axicabtagene ciloleucel may lead to B cell aplasia, or low numbers of B cells or absent B cells, as expected by other chimeric anntigen receptor T-cell therapies.","The CD 19 antigen is a 95 kDa integral membrane glycoprotein expressed on lymphocytes of the B-cell lineage but noton pluripotent stem cell. While this antigen is ubiquitously expressed on B lymphocyte lineage, the expression of this Ig protein is downregulated during terminal differentiation of premature and mature B cells into plasma cells . In blood disorders, however, the expression CD19 is maintained in in B-lineage cells that has undergone neoplastic transformation . Thus CD19 plays a critical role in clinical oncolgy as it aids in the diagnosis of blood cancers such as leukemias and lymphomas and serves as a therapeutic target for immunotherapies.\r\n\r\nAxicabtagene ciloleucel is a CD19-directed genetically modified autologous T cell immunotherapy that binds to CD19-expressing cancer cells and normal B cells. First, the patient's own peripheral blood mononuclear cells are obtained. The T cells are then harvested and genetically modified ex vivo by retroviral transduction to express a chimeric antigen receptor (CAR) comprising a murine anti-CD19 single chain variable fragment (scFv) linked to CD28 and CD3-zeta co-stimulatory domains . These anti-CD19 CAR T cells are expanded and infused back into the patient. \r\n\r\nOnce the modified CAR T cells recognize the CD19-expressing target cells, the CD28 and CD3-zeta co-stimulatory domains activate downstream signaling cascades that lead to T-cell activation, proliferation, acquisition of effector functions and secretion of inflammatory cytokines and chemokines . These events lead to elimination of the target cells.","B-lymphocyte antigen CD19 antibody","Therapeutic strategy associated"]
[1502,"DB13919","experimental","small molecule","Candesartan","2-ethoxy-1-(p-(o-1H-tetrazol-5-ylphenyl)benzyl)-7-benzimidazolecarboxylic acid; Candesartan","C24H20N6O3","CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC1=CC=C(C=C1)C1=CC=CC=C1C1=NN=NN1","Candesartan is an angiotensin-receptor blocker (ARB) that may be used alone or with other agents to treat hypertension. It is available as a prodrug in the form of .","139481-59-7","440.454",{"$nulls":3},"Type-1 angiotensin II receptor antagonist","Target associated"]
[1503,"DB13931","approved","small molecule","Netarsudil","(4-((1S)-1-(Aminomethyl)-2-(isoquinolin-6-ylamino)-2-oxoethyl)phenyl)methyl 2,4- dimethylbenzoate; Netarsudil","C28H27N3O3","CC1=CC(C)=C(C=C1)C(=O)OCC1=CC=C(C=C1)[C@@H](CN)C(=O)NC1=CC=C2C=NC=CC2=C1","A Rho kinase inhibitor with norepinephrine transport inhibitory activity that reduces production of aqueous\r\n\r\nAs of December 18, 2017 the FDA approved Aerie Pharmaceutical's Rhopressa (netarsudil ophthalmic solution) 0.02% for the indication of reducing elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Acting as both a rho kinase inhibitor and a norepinephrine transport inhibitor, Netarsudil is a novel glaucoma medication in that it specifically targets the conventional trabecular pathway of aqueous humour outflow to act as an inhibitor to the rho kinase and norepinephrine transporters found there as opposed to affecting protaglandin F2-alpha analog like mechanisms in the unconventional uveoscleral pathway that many other glaucoma medications demonstrate.","1254032-66-0","453.542","Netarsudil is indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension .","Aqueous humour flows out of the eye via two pathways: 1) the conventional trabecular pathway and 2) the unconventional uveoscleral pathway. And, although it has been shown that the conventional trabecular pathway accounts for most aqueous outflow due to various pathologies, most medications available for treating glaucoma target the uveoscleral pathway for treatment and leave the diseased trabecular pathway untreated and unhindered in its progressive deterioration and dysfunction .\r\n\r\nNetarsudil is subsequently a novel glaucoma medication that is both a rho kinase and norepinephrine transport (NATs)s inhibitor that specifically targets and inhibits rho kinase and NATS found in the conventional trabecular pathway while many of its contemporaries offer therapy that focuses on cell and muscle tissue remodelling \r","The medical condition glaucoma is a leading cause of progressive visual impairment and blindness across the world with primary open-angle glaucoma (POAG) being the major type of glaucoma .\r\n\r\nElevated intraocular pressure (IOP) resulting from increased resistance to aqueous humor outflow is considered a major risk for the development and progression of POAG, but various clinical studies have demonstrated that the reduction and tight control of IOP can delay or prevent POAG and the vision loss associated with it. Ordinary physiological IOP results from aqueous humor produced by the ocular ciliary body and its outflow through two main outflow pathways: the conventional (trabecular) and the unconventional (uveoscleral) pathways .\r\n\r\nUnder ordinary physiological conditions, diagnostic tracers have shown that the conventional trabecular pathway accounts for up to 90% of aqueous humor outflow. Through this pathway, aqueous humor drains from the anterior chamber sequentially through the uveal and corneoscleral meshwork beams, juxtacanalicular connective tissue (JCT) region, and inner wall (IW) endothelial cells of Schlemm's canal (SC) until finally entering the lumen of SC. From there aqueous humor drains into the collector channels, intravascular plexus, epscleral veins, and finally into the blood circulation .\r\n\r\nIn glaucomatous eyes, elevated IOP is the result of abnormally increased resistance to aqueous outflow in the conventional trabecular pathway due to apparent increases in the contractile tone and stiffness of the trabecular pathway meshwork (TM), changes in extracellular matrix composition, and/or a decrease in the conductance of the IW endothelial cells of SC .\r\n\r\nSubsequently, as a rho kinase inhibitor, the novelty of netarsudil lies in its ability or specificity to apply its mechanism of action directly and specifically at the diseased TM of the conventional trabecular outflow pathway. In particular, rho kinases are serine/threonine kinases that function as important downstream effectors of Rho GTPase. Such activity in the TM and SC drives actomysin contraction, promotes extracellular matrix production, and increases cell stiffness. Acting as an inhibitor of rho kinase, netarsudil consequently reduces cell contraction, decreases the expression of fibrosis-related proteins, and reduces cell stiffness in the TM and SC cells. As a result, netarsudil has been able to demonstrate increases in trabecular outflow facility, increases in the effective filtration area of the TM, cause expansion of the TM tissue, and dilate episcleral veins .\r\n\r\nFurthermore, netarsudil is also believed to possess inhibitory action against the norepinephrine transporter (NET). Such inhibition of the NET prevents reuptake of norepinephrine at noradrenergic synapses, which results in an increase in the strength and duration of endogenous norepinephrine signaling. As a consequence of this enhanced signaling, norepinephrine-induced vasoconstriction that can reduce blood flow to the ciliary body may subsequently be responsible for a mechanism in which the formation of aqueous humor may be delayed, prolonged, or reduced as well .","Rho-associated protein kinase 1 inhibitor; Rho-associated protein kinase 2 inhibitor; Sodium-dependent noradrenaline transporter inhibitor","Therapeutic strategy associated"]
[1504,"DB13944","approved","small molecule","Testosterone enanthate","Testosterone enanthate; Testosterone heptanoate","C26H40O3","[H][C@@]12CC[C@H](OC(=O)CCCCCC)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C","Testosterone enanthate is an esterified variant of testosterone that comes as an injectable compound with a slow-release rate.  This slow release is achieved by the presence of the enanthate ester functional group attached to the testosterone molecule. This testosterone derivative was first approved on December 24, 1953.\r\n\r\nIn 2017, about 6.5 million retail prescriptions for testosterone therapy were filled . The majority of the prescriptions written were for injectable (66%) and topical (32%) testosterone products. As recent as 1 October 2018, the US FDA approved Antares Pharma Inc.'s Xyosted - a subcutaneous testosterone enanthate product for once-weekly, at-home self-administration with an easy-to-use, single dose, disposable autoinjector . As the first subcutaneous autoinjector product designed for testosterone replacement therapy, this innovative formulation removes transfer concerns commonly associated with testosterone gels and potentially reduces the need for in-office/in-clinic injection procedures that may inconvenience patients with frequent visits to the clinic .","315-37-7","400.594","Testosterone enanthate in males is indicated as a replacement therapy in conditions associated with a deficiency or absence of endogenous testosterone. Some of the treated conditions are 1) primary hypogonadism, defined as testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome or orchidectomy; 2) hypogonadotropic hypogonadism due to an idiopathic gonadotropin or luteinizing hormone-releasing hormone deficiency or due to a pituitary-hypothalamic injury from tumors, trauma or radiation, in this case it is important to accompany the treatment with adrenal cortical and thyroid hormone replacement therapy; 3) to stimulate puberty in patients with delayed puberty not secondary to a pathological disorder. If the conditions 1 and 2 occur prior to puberty, the androgen replacement therapy will be needed during adolescent years for the development of secondary sexual characteristics and prolonged androgen treatment might be needed it to maintain sexual characteristics after puberty.\r\n\r\nIn females, testosterone enanthate is indicated to be used secondarily in presence of advanced inoperable metastatic mammary cancer in women who are from one to five years postmenopausal. It has also been used in premenopausal women with breast cancer who have benefited from oophorectomy and are considered to have a hormone-responsive tumor.\r\n\r\nTestosterone enanthate injections that are currently formulated for subcutaneous use are specifically indicated only for primary hypogonadism and hypogonadotropic hypogonadism . The use of such formulations is limited because the safety and efficacy of these subcutaneous products in adult males with late-onset hypogonadism and males less than 18 years old have not yet been established . Moreover, subcutaneously administered testosterone enanthate is indicated only for the treatment of men with hypogonadal conditions associated with structural or genetic etiologies, considering the medication could cause blood pressure increases that can raise the risk of major adverse cardiovascular events like non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death .","Administration of ester derivatives of testosterone as testosterone enanthate generates an increase in serum testosterone to levels reaching 400% from the baseline within 24 hours of administration. These androgen levels remain elevated for 3-5 days after initial administration. Continuous administration of testosterone enanthate shows a significant suppression of dihydrotestosterone, serum PSA, HDL and FSH, as well as a slight increase in serum estradiol. The levels of dihydrotestosterone and FSH can remain suppressed even 14 days after treatment termination. There are no changes in mood and sexual activity by the presence of testosterone enanthate.","The effects of testosterone in humans and other vertebrates occur by way of two main mechanisms: by activation of the androgen receptor (directly or as DHT), and by conversion to estradiol and activation of certain estrogen receptors. Free testosterone (T) is transported into the cytoplasm of target tissue cells, where it can bind to the androgen receptor, or can be reduced to 5&alpha;-dihydrotestosterone (DHT) by the cytoplasmic enzyme 5&alpha;-reductase. DHT binds to the same androgen receptor even more strongly than T, so that its androgenic potency is about 2.5 times that of T. The T-receptor or DHT-receptor complex undergoes a structural change that allows it to move into the cell nucleus and bind directly to specific nucleotide sequences of the chromosomal DNA. The areas of binding are called hormone response elements (HREs), and influence transcriptional activity of certain genes, producing androgen effects.\r\n\r\nSuch activities are useful as endogenous androgens like testosterone and dihydrotestosterone are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics . These effects include the growth and maturation of the prostate, seminal vesicles, penis, and scrotum; the development of male hair distribution, such as facial, pubic, chest, and axillary hair; laryngeal enlargement, vocal cord thickening, and alterations in body musculature and fat distribution .\r\n\r\nMale hypogonadism, a clinical syndrome resulting from insufficient secretion of testosterone, has two main etiologies . Primary hypogonadism is caused by defects of the gonads, such as Klinefelter’s syndrome or Leydig cell aplasia, whereas secondary hypogonadism is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH) .","Androgen receptor agonist; Estrogen receptor alpha; Mineralocorticoid receptor","Indication associated"]
[1505,"DB13949","approved","small molecule","Ferric cation","FE (III) ION; Fe(III); Ferric ion; iron(3+)","Fe","[Fe+3]","Iron is a transition metal with a symbol Fe and atomic number 26. By mass, it is the most common element on Earth. Iron is an essential element involved in various metabolic processes, including oxygen transport, deoxyribonucleic acid (DNA) synthesis, and energy production in electron transport . Resulting from inadequate supply of iron to cells due to depletion of stores, iron deficiency is the most common nutritional deficiency worldwide, particularly affecting children, women of childbearing age, and pregnant women . Iron deficiency may be characterized without the development of anemia, and may result in functional impairments affecting cognitive development and immunity mechanisms, as well as infant or maternal mortality if it occurs during pregnancy . The main therapeutic preparation of iron is , and iron-sucrose may also be given intravenously .\r\n\r\nIron exists in two oxidation states: the ferrous cation (Fe2+) and ferric cation (Fe3+). Non-haem iron in food is mainly in the ferric state, which is the insoluble form of iron, and must be reduced to the ferrous cation for absorption . Ferric citrate (tetraferric tricitrate decahydrate) is a phosphate binder indicated for the control of serum phosphorus levels in patients with chronic kidney disease on dialysis.","20074-52-6","55.845","For the control of serum phosphorus levels in patients with chronic kidney disease on dialysis, as ferric citrate.","When Fe3+ is converted to soluble Fe2+, it primarily exists in the circulation in the complex forms bound to protein (hemoprotein) as heme compounds (hemoglobin or myoglobin), heme enzymes, or nonheme compounds (flavin-iron enzymes, transferring, and ferritin) . Once converted, Fe2+ serves to support various biological functions. Iron promotes the synthesis of oxygen transport proteins such as myoglobin and hemoglobin, and the formation of heme enzymes and other iron-containing enzymes involved in electron transfer and redox reactions . It also acts as a cofactor in many non-heme enzymes including hydroxylases and ribonucleotide reductase . Iron-containing proteins are responsible in mediating antioxidant actions, energy metabolism, oxygen sensing actions, and DNA replication and repair . Saturation of transferrin from high concentrations of unstable iron preparations may elevate the levels of weakly transferrin-bound Fe3+, which may induce oxidative stress by catalyzing lipid peroxidation and reactive oxygen species formation .","Iron is incorporated into various proteins to serve biological functions as a structural component or cofactor. Once ferric or ferrous cation from intestinal enterocytes or reticuloendothelial macrophages is bound to circulating transferrin, iron-transferrin complex binds to the cell-surface transferrin receptor (TfR) 1, resulting in endocytosis and uptake of the metal cargo. Internalized iron is transported to mitochondria for the synthesis of heme or iron-sulfur clusters, which are integral parts of several metalloproteins . Excess iron is stored and detoxified in cytosolic ferritin . Internalized Fe2+ exported across the basolateral membrane into the bloodstream via Fe+2 transporter ferroportin, which is coupled by reoxidation to Fe3+ via membrane-bound ferroxidase hephaestin or ceruloplasmin activity . Fe+3 is again scavenged by transferrin which maintains the ferric iron in a redox-inert state and delivers it into tissues .\r\n\r\nFe3+ participates in the autoxidation reaction, where it can be chelated by DNA. It mainly binds to the backbone phosphate group, whereas at higher metal ion content, the cation binds to both guanine N-7 atom and the backbone phosphate group .","Iron(3+)-hydroxamate-binding protein FhuD binder; Transferrin receptor protein 1 agonist","Therapeutic strategy associated"]
[1506,"DB13973","approved; investigational","biotech","Remestemcel-L","Adult human mesenchymal stem cells; Allogeneic human mesenchymal stem cell; Remestemcel-L",null,null,"Remestemcel-L is a third-party, off-the-shelf suspension of ex-vivo cultured adult human mesenchymal stem cells intended for intravenous infusion. The mesenchymal stem cells are derived from the bone marrow of unrelated and human leukocyte antigen (HLA)–unmatched healthy adult donors and have the ability to differentiate into different tissue cells. It was approved for use in Canada in May 2012 as Prochymal for the management of refractory acute Graft versus Host Disease (aGvHD) in children who are unresponsive to systemic steroid therapies, with the approval conditional upon further trials being conducted.\r\n\r\naGvHD is a T-cell mediated disease that occurs after allogeneic hematopoietic stem cell transplant and is a reaction of donor immune cells against host tissues  developed by 30-80% of the recipients . aGvHD is often characterized by the presence of inflammatory cascades through signalling of activated T cells. While systemic corticosteroids and other immunosuppressive agents are commonly used as first-line treatments to manage aGvHD, about 30-50% of patients with aGvHD experience inadequately control of disease with first-line therapies, putting them in a risk for poor outcomes and creating a significant clinical challenge . It is estimated that the patients with the most severe forms of refractory aGvHD that do not respond to steroid therapy have expected one-year survival rates of only 5% to 30% . Human mesenchymal stem cells (hMSCs) serve to down-regulate inflammatory responses and produce anti-inflammatory cytokines and growth factors to promote tissue repair . In clinical studies, patients treated with remestemcel-L demonstrated an improvement in their aGvHD and improved survival rates at subsequent days following intravenous infusion . Based on its tolerability and safety profile, remestemcel-L is a promising alternative to second-line immunosuppressive agents .",null,null,"Indicated for in the management of acute Graft versus Host Disease (aGvHD) in pediatric patients. Acute GvHD should be refractory to treatment with systemic corticosteroid therapy and/or other immunosuppressive agents. Remestemcel-L may be used for Grades C and D of the disease in any organ. Remestemcel-L may also be used in the management of Grade B aGvHD involving any visceral organ, including the GI tract and the liver, but excluding skin.","Remestemcel-L exerts an immunomodulatory effects both in vivo and vitro by suppressing the proliferative activity of allogenic T  lymphocytes. In vitro, there was evidence of tissue protection and tissue repair effects, through reduction of pro-inflammatory cytokines and secretion of factors. There were no signs of electrocardiogram disturbances, changes in hemoglobin saturation, heart rate, or respiration rate with intravenous administration of remestemcel-L.","**Pathogenesis of acute graft versus host disease:** Acute graft versus host disease (aHvGD) occurs in recipients of allogenic stem cell transplantation and is characterized by differentiation and activation of alloreactive T lymphocytes. aGvHD is associated with tissue injury in various organs such as the liver, skin and intestinal mucosa . Acute GvHD can be summarized in a three-step process: conditioning phase, donor T-Cell activation, and cellular and inflammatory effector phase . The first phase involves the tissue damage induced by conditioning regimen (irradiation and chemotherapy) and production of inflammatory factors such as cytokines and adhesion molecules . The expression of MHC antigens and adhesion molecules is recognized by donor T cells. These donor T cells are activated in phase 2, resulting in subsequent proliferation, differentiation and secretion of cytokines including IL-2 and IFN-γ . These cytokines enhance T-cell expansion, induce cytotoxic T cells (CTL) and natural killer (NK) cell responses and facilitate the production of TNF-α and IL-1 by monocular phagocytes . Inflammatory cytokines promotes the production of inflammatory chemokines, thus recruits effector cells into target organs and initiates phase 3 of the disease . Phase 3 involves cascades of cell-mediated cytotoxicity and signalling of multiple inflammatory effectors , leading to amplification of local tissue injury and further promotion of an inflammatory response . \r\n\r\n**Mechanism of action of remestemcel-L:** Human mesenchymal stem cells (hMSCs), or remestemcel-L, are derived from the bone marrow are capable of differentiation into cells derived from the mesoderm germ layer, such as osteocyte, adipocyte and chondrogenic cells . Once administered, they migrate to the site of inflammation to reduce the production of pro-inflammatory cytokines. It has been demonstrated that hMSCs secrete a wide range of bioactive molecules, such as growth factors, cytokines, and chemokines, that mediate regenerative and anti-apoptotic actions . Some molecules released by hMSCs include PGE2 and IL-10 for anti-inflammatory effects, or TGFβ1 and HLA-G5 for suppression of T cell proliferation . There is evidence that hMSCs interact with natural killers cells, monocytes, macrophages, effector T cells and regulatory T cells to shift their pro-inflammatory Th1 cytokine secretion profile to an anti-inflammatory Th2 cytokine profile . hMSCs also suppress NK cell proliferation and disrupts the migration, maturation, and antigen presentation of dendritic cells that differentiated from monocytes . In a mouse model of ischemia, remestemcel-L have been shown to stimulate the growth of new blood vessels, which is a process crucial to tissue repair, through secretion of factors such as VEGF. Overall, hMSCs exert immunomodulatory actions to inhibit inflammatory responses in aGvHD.",null,"Therapeutic strategy associated"]
[1507,"DB13975","experimental","biotech","Black cohosh","Black cohosh; Black snakeroot; Cimicifuga racemosa; Cimicifuga racemosa rhizome; Cimicifuga racemosa root; Cimicifuga racemosa root with rhizome; Cimicifugae rhizoma; Fairy candle root; Rattleroot",null,null,"Black cohosh (_Actaea racemosa_ or _Cimicifuga racemosa_), a member of the buttercup family, is a perennial plant which native to North America. Historical names for this plant include snakeroot, black bugbane, rattleweed, macrotys, and rheumatism weed. Black cohosh has a long history of use. Native Americans used it for its purported benefits in treating musculoskeletal pain, fever, cough, pneumonia, sluggish labor, and menstrual irregularities. European settlers were said to use black cohosh as a tonic to support female reproductive health.\r\n\r\nHormone replacement therapy (HRT) is the standard treatment for early symptoms in post-menopausal women, however, increases the risk of stroke, heart diseases, as well as breast cancer in older women. Various studies have shown that the number of post-menopausal women using hormone replacement therapy is currently low and that the effects of hormone replacement therapy in reducing menopausal symptoms are not as positive as expected. For these reasons, there has been a trend toward using alternative therapies to relieve menopausal symptoms.\r\n\r\nBlack cohosh has been associated with serious safety concerns. Results from studies suggest that C. racemosa possesses a central activity instead of a hormonal effect.\r\n\r\nThe American College of Obstetrics and Gynecology guidelines on the use of botanicals, such as black cohosh, for the management of menopausal symptoms the use of for up to six months, especially in treating the symptoms of sleep and mood disturbance, and hot flushes.",null,null,"Treatment of menopausal symptoms and menstrual dysfunction .","This agent is purported to relieve some of the vasomotor symptoms of menopause, including hot flashes and night sweats.\r\n\r\nA 2012 Cochrane review analyzed 16 randomized clinical trials on the effectiveness of black cohosh in reducing menopausal symptoms, including hot flushes, night sweats, vaginal dryness, and numerous combinations of symptoms which were measured by validated rating scales. There is currently insufficient evidence to support the use of black cohosh for menopausal symptoms. The studies were quite heterogeneous in design, duration, type and amount of black cohosh used, and main findings.\r\n\r\nA 2016 systematic review and meta-analysis of randomized clinical trials analyzed four studies of herbal and plant-based therapies that included black cohosh to treat menopausal symptoms. It was suggested that composite and specific phytoestrogen supplementations were associated with small reductions in the incidence of hot flashes and vaginal dryness, however, no significant reduction in night sweats.","Although the mechanism by which black cohosh relieves menopausal symptoms is unknown, several hypotheses have been made. It is believed to act through the following mechanisms/effects:\r\n\r\n 1) as a selective estrogen receptor modulator\r\n 2) through serotonergic pathways\r\n 3) as an antioxidant\r\n 4) on inflammatory pathways\r\n\r\nThe primary active component of the black cohosh root is believed to be the _terpene glycoside_ fraction, including _actein_ and _cimifugoside_. The triterpenes are one of the most ubiquitous and diverse groups of plant natural products. They are classified as complex molecules that are beyond the reach of chemical synthesis in the laboratory. Simple triterpenes are constituents of surface waxes and specialized plant membranes and may possibly serve as signaling molecules. More complex glycosylated triterpenes (also known as saponins) provide protection against pathogens and pests. The rhizome (stem portion of the plant) also contains other potentially biologically active substances, including alkaloids, flavonoids, and tannins. The therapeutic activity of black cohosh was initially believed to be the activation of estrogen receptors; however, more recent studies show that although some components of the extract bind to at least one subtype of estrogen receptor, the receptor binding produces very little (if any) estrogenic effect, and may selectively block some of the effects.\r\n\r\nAn early study reported that treatment with black cohosh leads to a decrease in luteinizing hormone (LH) levels consistent with its purported estrogenic effect. Despite this, more recent studies have shown no effect on levels of LH, follicle-stimulating hormone (FSH), or prolactin. To this day it is unclear whether black cohosh exerts its effect via estrogen receptors or through another mechanism.\r\n\r\nOne study observed that while the most prominent _triterpene_ in black cohosh, known as _23-epi-26-deoxyactein_, inhibits cytokine-induced nitric oxide production in brain microglial cells, the complete black cohosh extract demonstrated to enhance this pathway. A variety of activities have been reported for black cohosh and its compounds, however, the absorption and tissue distribution of these compounds is not known.\r\n\r\n_Cimicifuga racemosa_ (black cohosh) is used most often to treat symptoms occurring during menopause. However, in recent years, several concerns regarding its safety have been voiced.",null,"Therapeutic strategy associated"]
[1508,"DB14001","approved; nutraceutical; vet_approved","small molecule","alpha-Tocopherol succinate","(+)-alpha-Tocopheryl succinate; alpha-Tocopheryl acid succinate; alpha-Tocopheryl succinate; alpha-Vitamin E succinate; d-alpha-Tocopherol acid succinate; Tocopheryl acid succinate,D-alpha; Vitamin E hemisuccinate; Vitamin E succinate","C33H54O5","[H][C@@](C)(CCCC(C)C)CCC[C@@]([H])(C)CCC[C@]1(C)CCC2=C(C)C(OC(=O)CCC(O)=O)=C(C)C(C)=C2O1","Alpha-tocopherol is the primary form of vitamin E that is preferentially used by the human body to meet appropriate dietary requirements. In particular, the RRR-alpha-tocopherol (or sometimes called the d-alpha-tocopherol stereoisomer) stereoisomer is considered the natural formation of alpha-tocopherol and generally exhibits the greatest bioavailability out of all of the alpha-tocopherol stereoisomers. Moreover, manufacturers typically convert the phenol component of the vitamin to esters using acetic or succinic acid, making a compound such as alpha-tocopherol succinate more stable and easier to use in vitamin supplements .\r\n\r\nAlpha-tocopherol succinate is subsequently most commonly indicated for dietary supplementation in individuals who may demonstrate a genuine deficiency in vitamin E. Vitamin E itself is naturally found in various foods, added to others, or used in commercially available products as a dietary supplement. The recommended dietary allowances (RDAs) for vitamin E alpha-tocopherol are: males = 4 mg (6 IU) females = 4 mg (6 IU) in ages 0-6 months, males = 5 mg (7.5 IU) females = 5 mg (7.5 IU) in ages 7-12 months, males = 6 mg (9 IU) females = 6 mg (9 IU) in ages 1-3 years, males = 7 mg (10.4 IU) females = 7 mg (10.4 IU) in ages 4-8 years, males = 11 mg (16.4 IU) females = 11 mg (16.4 IU) in ages 9-13 years, males = 15 mg (22.4 IU) females = 15 mg (22.4 IU) pregnancy = 15 mg (22.4 IU) lactation = 19 mg (28.4 IU) in ages 14+ years . Most individuals obtain adequate vitamin E intake from their diets; genuine vitamin E deficiency is considered to be rare.\r\n\r\nNevertheless, vitamin E is known to be a fat-soluble antioxidant that has the capability to neutralize endogenous free radicals. This biologic action of vitamin E consequently continues to generate ongoing interest and study in whether or not its antioxidant abilities may be used to help assist in preventing or treating a number of different conditions like cardiovascular disease, ocular conditions, diabetes, cancer and more. At the moment, however, there exists a lack of formal data and evidence to support any such additional indications for vitamin E use.\r\n\r\nMoreover, although it is generally believed that alpha-tocopherol succinate would naturally demonstrate such general vitamin E-tocopherol pharmacodynamics after undergoing a logical de-esterification in the gut , there is ongoing research that proposes that the alpha-tocopherol succinate compound itself is capable of eliciting anti-cancer  and inflammation mediation  activities that are unique from the alpha-tocopherol form and other alpha-tocopherol esters .","4345-03-3","530.79","The primary health-related use for which alpha-tocopherol succinate is formally indicated is as a dietary supplement for patients who demonstrate a genuine vitamin E deficiency. At the same time, vitamin E deficiency is generally quite rare but may occur in premature babies of very low birth weight (< 1500 grams), individuals with fat-malabsorption disorders (as fat is required for the digestive tract to absorb vitamin E), or individuals with abetalipoproteinemia - a rare, inherited disorder that causes poor absorption of dietary fat - who require extremely large doses of supplemental vitamin E daily (around 100 mg/kg or 5-10 g/day) . In all such cases, alpha-tocopherol is largely the preferred form of vitamin E to be administered.\r\n\r\nElsewhere, vitamin E's chemical profile as a fat-soluble antioxidant that is capable of neutralizing free radicals in the body continues to generate ongoing interest and study regarding how and whether or not the vitamin can help prevent or delay various chronic diseases associated with free radicals or other potential biological effects that vitamin E possesses like cardiovascular diseases, diabetes, ocular conditions, immune illnesses, cancer, and more . None of these ongoing studies have yet to elucidate any formally significant evidence, however .\r\n\r\nSimilarly, more effective clinical trials are necessary to confirm what has only been accrued as preliminary data when it comes to studies proposing the demonstration of alpha-tocopherol succinate's capability to act as an anti-cancer therapy or as a regulator of inflammation .","Of the eight separate variants of vitamin E, alpha-tocopherol is the predominant form of vitamin E in human and animal tissues, and it has the highest bioavailability . This is because the liver preferentially resecretes only alpha-tocopherol by way of the hepatic alpha-tocopherol transfer protein (alpha-TTP); the liver metabolizes and excretes all the other vitamin E variants, which is why blood and cellular concentrations of other forms of vitamin E other than alpha-tocopherol are ultimately lower .\r\n\r\nFurthermore, the term alpha-tocopherol generally refers to a group of eight possible stereoisomers which is often called all-rac-tocopherol for being a racemic mixture of all eight stereoisomers . Of the eight stereoisomers, the RRR-alpha-tocopherol - or sometimes referred to as the d-alpha-tocopherol - stereoisomer is the naturally occurring form of alpha-tocopherol that is perhaps best recognized by the alpha-TTP  and has been reported to demonstrate approximately twice the systemic availability of all-rac-tocopherol .\r\n\r\nAs a result, often times (but certainly not always) the discussion of vitamin E - at least within the context of using the vitamin for health-related indications - is generally in reference to the use of RRR- or d-alpha-tocopherol.\r\n\r\nSubsequently, without further evidence to suggest otherwise, alpha-tocpherol succinate is generally believed to undergo a logical de-esterification in the gastrointestinal tract before being subsequently absorbed as free tocopherol .","Without further evidence to suggest otherwise, alpha-tocpherol succinate is generally believed to undergo a logical de-esterification in the gastrointestinal tract before being subsequently absorbed as free tocopherol . The free alpha-tocopherol is therefore available and capable of the following activities.\r\n\r\nVitamin E's antioxidant capabilities are perhaps the primary biological action associated with alpha-tocopherol. In general, antioxidants protect cells from the damaging effects of free radicals, which are molecules that consist of an unshared electron . These unshared electrons are highly energetic and react rapidly with oxygen to form reactive oxygen species (ROS) . In doing so, free radicals are capable of damaging cells, which may facilitate their contribution to the development of various diseases . Moreover, the human body naturally forms ROS when it converts food into energy and is also exposed to environmental free radicals contained in cigarette smoke, air pollution, or ultraviolet radiation from the sun . It is believed that perhaps vitamin E antioxidants might be able to protect body cells from the damaging effects of such frequent free radical and ROS exposure .\r\n\r\nSpecifically, vitamin E is a chain-breaking antioxidant that prevents the propagation of free radical reactions . The vitamin E molecule is specifically a peroxyl radical scavenger and especially protects polyunsaturated fatty acids within endogenous cell membrane phospholipids and plasma lipoproteins . Peroxyl free radicals react with vitamin E a thousand times more rapidly than they do with the aforementioned polyunsaturated fatty acids . Furthermore, the phenolic hydroxyl group of tocopherol reacts with an organic peroxyl radical to form an organic hydroperoxide and tocopheroxyl radical . This tocopheroxyl radical can then undergo various possible reactions: it could (a) be reduced by other antioxidants to tocopherol, (b) react with another tocopheroxyl radical to form non-reactive products like tocopherol dimers, (c) undergo further oxidation to tocopheryl quinone, or (d) even act as a prooxidant and oxidize other lipids .\r\n\r\nIn addition to the antioxidant actions of vitamin E, there have been a number of studies that report various other specific molecular functions associated with vitamin E . For example, alpha-tocopherol is capable of inhibiting protein kinase C activity, which is involved in cell proliferation and differentiation in smooth muscle cells, human platelets, and monocytes . In particular, protein kinase C inhibition by alpha-tocopherol is partially attributable to its attenuating effect on the generation of membrane-derived dialglycerol, a lipid that facilitates protein kinase C translocation, thereby increasing its activity .\r\n\r\nIn addition, vitamin E enrichment of endothelial cells downregulates the expression of intercellular cell adhesion molecule (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), thereby decreasing the adhesion of blood cell components to the endothelium .\r\n\r\nVitamin E also upregulates the expression of cytosolic phospholipase A2 and cyclooxygenase-1 . The increased expression of these two rate-limiting enzymes in the arachidonic acid cascade explains the observation that vitamin E, in a dose-dependent fashion, enhanced the release of prostacyclin, a potent vasodilator and inhibitor of platelet aggregation in humans .\r\n\r\nFurthermore, vitamin E can inhibit platelet adhesion, aggregation, and platelet release reactions . The vitamin can also evidently inhibit the plasma generation of thrombin, a potent endogenous hormone that binds to platelet receptors and induces aggregation of platelets . Moreover, vitamin E may also be able to decrease monocyte adhesion to the endothellium by downregulating expression of adhesion molecules and decreasing monocyte superoxide production .\r\n\r\nGiven these proposed biological activities of vitamin E, the substance continues to generate ongoing interest and studies in whether or not vitamin E can assist in delaying or preventing various diseases with any one or more of its biologic actions. For instance, studies continue to see whether vitamin E's ability to inhibit low-density lipoprotein oxidation can aid in preventing the development of cardiovascular disease or atherogenesis .\r\n\r\nSimilarly, it is also believed that if vitamin E can decrease the chance of cardiovascular disease then it can also decrease the chance of related diabetic disease and complications . In much the same way, it is also believed that perhaps the antioxidant abilities of vitamin E can neutralize free radicals that are constantly reacting and damaging cellular DNA . Furthermore, it is also believed that free radical damage does contribute to protein damage in the ocular lens - another free radical-mediated condition that may potentially be prevented by vitamin E use . Where it is also suggested that various central nervous system disorders like Parkinson's disease, Alzheimer's disease, Down's syndrome, and Tardive Dyskinesia possess some form of oxidative stress component, it is also proposed that perhaps vitamin E use could assist with its antioxidant action .\r\n\r\nThere have also been studies that report the possibility of vitamin E supplementation can improve or reverse the natural decline in cellular immune function in healthy, elderly individuals .\r\n\r\nAs of this time, however, there is either only insufficient data or even contradicting data (where certain doses of vitamin E supplementation could even potentially increase all-cause mortality)  on which to suggest the use of vitamin E could formally benefit in any of these proposed indications.\r\n\r\nFurthermore, there are ongoing studies that demonstrate alpha-tocopherol succinate's unique possession of capabilities that allow it to induce differentiation, inhibit proliferation and apoptosis in cancer cells, enhance the growth-inhibitory effect of ionizing radiation, hyperthermia, and some chemotherapeutic agents and biological response modifiers on tumor cells, all the while protecting normal cells against any adverse effects . Despite being able to demonstrate such effects on animal and human cells in culture, the value of these effects has not drawn significant attention from researchers and clinicians and nor has the specific mechanisms of action been elucidated . Additionally, other studies have also shown that alpha-tocopherol succinate seemingly possesses an ability exclusive from other tocopherol esters to inhibit and minimize prostaglandin E2 production in human lung epithelial cells . Considering increased prostaglandin E2 production has been observed frequently in lung cancer patients, there may be another avenue in which alpha-tocopherol succinate may be able to treat lung cancer . Nevertheless, the possibility of such activity requires further elucidation.","SEC14-like protein 3; SEC14-like protein 2; Nuclear receptor subfamily 1 group I member 2; Protein kinase C beta type; Arachidonate 5-lipoxygenase; Protein kinase C alpha type; Diacylglycerol kinase; Lung epithelial cells","Therapeutic strategy associated"]
[1509,"DB14002","approved; nutraceutical; vet_approved","small molecule","D-alpha-Tocopherol acetate","(+)-alfa-tocopherol acetate; alpha-tocopheryl acetate, D-; D-alpha tocoferil acetate; D-alpha tocopheryl acetate; D-alpha-Tocopheryl acetate; RRR-alpha-tocopheryl acetate; Vitamin E acetate, D-","C31H52O3","CC(C)CCC[C@@H](C)CCC[C@@H](C)CCC[C@]1(C)CCC2=C(C)C(OC(C)=O)=C(C)C(C)=C2O1","Alpha-tocopherol is the primary form of vitamin E that is preferentially used by the human body to meet appropriate dietary requirements. In particular, the RRR-alpha-tocopherol (or sometimes called the d-alpha-tocopherol stereoisomer) stereoisomer is considered the natural formation of alpha-tocopherol and generally exhibits the greatest bioavailability out of all of the alpha-tocopherol stereoisomers. Moreover, RRR-alpha-tocopherol acetate is a relatively stabilized form of vitamin E that is most commonly used as a food additive when needed .\r\n\r\nAlpha-tocopherol acetate is subsequently most commonly indicated for dietary supplementation in individuals who may demonstrate a genuine deficiency in vitamin E. Vitamin E itself is naturally found in various foods, added to others, or used in commercially available products as a dietary supplement. The recommended dietary allowances (RDAs) for vitamin E alpha-tocopherol are: males = 4 mg (6 IU) females = 4 mg (6 IU) in ages 0-6 months, males = 5 mg (7.5 IU) females = 5 mg (7.5 IU) in ages 7-12 months, males = 6 mg (9 IU) females = 6 mg (9 IU) in ages 1-3 years, males = 7 mg (10.4 IU) females = 7 mg (10.4 IU) in ages 4-8 years, males = 11 mg (16.4 IU) females = 11 mg (16.4 IU) in ages 9-13 years, males = 15 mg (22.4 IU) females = 15 mg (22.4 IU) pregnancy = 15 mg (22.4 IU) lactation = 19 mg (28.4 IU) in ages 14+ years . Most individuals obtain adequate vitamin E intake from their diets; genuine vitamin E deficiency is considered to be rare.\r\n\r\nNevertheless, vitamin E is known to be a fat-soluble antioxidant that has the capability to neutralize endogenous free radicals. This biologic action of vitamin E consequently continues to generate ongoing interest and study in whether or not its antioxidant abilities may be used to help assist in preventing or treating a number of different conditions like cardiovascular disease, ocular conditions, diabetes, cancer and more. At the moment however, there exists a lack of formal data and evidence to support any such additional indications for vitamin E use.","58-95-7","472.7428","_In addition to any following information, owing to d-alpha-Tocopherol acetate's closely related chemical nature with alpha-Tocopherol acetate, please also refer to the drug information page for alpha-Tocopherol acetate for further data._\r\n\r\nVitamin E, known for its antioxidant activities, is protective against cardiovascular disease and some forms of cancer and has also demonstrated immune-enhancing effects. It may be of limited benefit in some with asthma and rheumatoid arthritis. It may be helpful in some neurological diseases including Alzheimer's, some eye disorders including cataracts, and diabetes and premenstrual syndrome. It may also help protect skin from ultraviolet irradiation although claims that it reverses skin aging, enhances male fertility and exercise performance are poorly supported. It may help relieve some muscle cramps.","_In addition to any following information, owing to d-alpha-Tocopherol acetate's closely related chemical nature with alpha-Tocopherol acetate, please also refer to the drug information page for alpha-Tocopherol acetate for further data._\r\n\r\nVitamin E has antioxidant activity. It may also have anti-atherogenic, antithrombotic, anticoagulant, neuroprotective, antiviral, immunomodulatory, cell membrane-stabilizing and antiproliferative actions. Vitamin E is a collective term used to describe eight separate forms, the best-known form being alpha-tocopherol. Vitamin E is a fat-soluble vitamin and is an important antioxidant. It acts to protect cells against the effects of free radicals, which are potentially damaging by-products of the body's metabolism. Vitamin E is often used in skin creams and lotions because it is believed to play a role in encouraging skin healing and reducing scarring after injuries such as burns. There are three specific situations when a vitamin E deficiency is likely to occur. It is seen in persons who cannot absorb dietary fat, has been found in premature, very low birth weight infants (birth weights less than 1500 grams, or 3&frac12; pounds), and is seen in individuals with rare disorders of fat metabolism. A vitamin E deficiency is usually characterized by neurological problems due to poor nerve conduction. Symptoms may include infertility, neuromuscular impairment, menstrual problems, miscarriage and uterine degradation. Preliminary research has led to a widely held belief that vitamin E may help prevent or delay coronary heart disease. Antioxidants such as vitamin E help protect against the damaging effects of free radicals, which may contribute to the development of chronic diseases such as cancer. It also protects other fat-soluble vitamins (A and B group vitamins) from destruction by oxygen. Low levels of vitamin E have been linked to increased incidence of breast and colon cancer.","_In addition to any following information, owing to d-alpha-Tocopherol acetate's closely related chemical nature with alpha-Tocopherol acetate, please also refer to the drug information page for alpha-Tocopherol acetate for further data._\r\n\r\nAlthough all forms of Vitamin E exhibit antioxidant activity, it is known that the antioxidant activity of vitamin E is not sufficient to explain the vitamin's biological activity. <br/>Vitamin E's anti-atherogenic activity involves the inhibition of the oxidation of LDL and the accumulation of oxLDL in the arterial wall. It also appears to reduce oxLDL-induced apoptosis in human endothelial cells. Oxidation of LDL is a key early step in atherogenesis as it triggers a number of events which lead to the formation of atherosclerotic plaque. In addition, vitamin E inhibits protein kinase C (PKC) activity. PKC plays a role in smooth muscle cell proliferation, and, thus, the inhibition of PKC results in inhibition of smooth muscle cell proliferation, which is involved in atherogenesis. <br/>Vitamin E's antithrombotic and anticoagulant activities involves the downregulation of the expression of intracellular cell adhesion molecule(ICAM)-1 and vascular cell adhesion molecule(VCAM)-1 which lowers the adhesion of blood components to the endothelium. In addition, vitamin E upregulates the expression of cytosolic phospholipase A2 and cyclooxygenase (COX)-1 which in turn enhances the release of prostacyclin. Prostacyclin is a vasodilating factor and inhibitor of platelet aggregation and platelet release. It is also known that platelet aggregation is mediated by a mechanism involving the binding of fibrinogen to the glycoprotein IIb/IIIa (GPIIb/IIIa) complex of platelets. GPIIb/IIIa is the major membrane receptor protein that is key to the role of the platelet aggregation response. GPIIb is the alpha-subunit of this platelet membrane protein. Alpha-tocopherol downregulates GPIIb promoter activity which results in reduction of GPIIb protein expression and decreased platelet aggregation. Vitamin E has also been found in culture to decrease plasma production of thrombin, a protein which binds to platelets and induces aggregation. A metabolite of vitamin E called vitamin E quinone or alpha-tocopheryl quinone (TQ) is a potent anticoagulant. This metabolite inhibits vitamin K-dependent carboxylase, which is a major enzyme in the coagulation cascade.<br/>The neuroprotective effects of vitamin E are explained by its antioxidant effects. Many disorders of the nervous system are caused by oxidative stress. Vitamin E protects against this stress, thereby protecting the nervouse system. <br/>The immunomodulatory effects of Vitamin E have been demonstrated in vitro, where alpha-tocopherol increases mitogenic response of T lymphocytes from aged mice. The mechanism of this response by vitamin E is not well understood, however it has been suggested that vitamin E itself may have mitogenic activity independent of its antioxidant activity. <br/>Lastly, the mechanism of action of vitamin E's antiviral effects (primarily against HIV-1) involves its antioxidant activity. Vitamin E reduces oxidative stress, which is thought to contribute to HIV-1 pathogenesis, as well as to the pathogenesis of other viral infections. Vitamin E also affects membrane integrity and fluidity and, since HIV-1 is a membraned virus, altering membrane fluidity of HIV-1 may interfere with its ability to bind to cell-receptor sites, thus decreasing its infectivity.","SEC14-like protein 3; SEC14-like protein 2; Nuclear receptor subfamily 1 group I member 2; Protein kinase C beta type; Arachidonate 5-lipoxygenase; Protein kinase C alpha type","Therapeutic strategy associated"]
[1510,"DB14003","approved","small molecule","alpha-Tocopherol acetate","Tocopherol acetate; Tocopherol acetate, unspecified; Tocopheryl acetate; Vitamin E (alpha tocopherol acetate); Vitamin E acetate; Vitamin E acetate, unspecified form",null,null,"Alpha-tocopherol is the primary form of vitamin E that is preferentially used by the human body to meet appropriate dietary requirements. In particular, the RRR-alpha-tocopherol (or sometimes called the d-alpha-tocopherol stereoisomer) stereoisomer is considered the natural formation of alpha-tocopherol and generally exhibits the greatest bioavailability out of all of the alpha-tocopherol stereoisomers. Moreover, RRR-alpha-tocopherol acetate is a relatively stabilized form of vitamin E that is most commonly used as a food additive when needed .\r\n\r\nAlpha-tocopherol acetate is subsequently most commonly indicated for dietary supplementation in individuals who may demonstrate a genuine deficiency in vitamin E. Vitamin E itself is naturally found in various foods, added to others, or used in commercially available products as a dietary supplement. The recommended dietary allowances (RDAs) for vitamin E alpha-tocopherol are: males = 4 mg (6 IU) females = 4 mg (6 IU) in ages 0-6 months, males = 5 mg (7.5 IU) females = 5 mg (7.5 IU) in ages 7-12 months, males = 6 mg (9 IU) females = 6 mg (9 IU) in ages 1-3 years, males = 7 mg (10.4 IU) females = 7 mg (10.4 IU) in ages 4-8 years, males = 11 mg (16.4 IU) females = 11 mg (16.4 IU) in ages 9-13 years, males = 15 mg (22.4 IU) females = 15 mg (22.4 IU) pregnancy = 15 mg (22.4 IU) lactation = 19 mg (28.4 IU) in ages 14+ years . Most individuals obtain adequate vitamin E intake from their diets; genuine vitamin E deficiency is considered to be rare.\r\n\r\nNevertheless, vitamin E is known to be a fat-soluble antioxidant that has the capability to neutralize endogenous free radicals. This biologic action of vitamin E consequently continues to generate ongoing interest and study in whether or not its antioxidant abilities may be used to help assist in preventing or treating a number of different conditions like cardiovascular disease, ocular conditions, diabetes, cancer and more. At the moment however, there exists a lack of formal data and evidence to support any such additional indications for vitamin E use.","7695-91-2",null,"The primary health-related use for which alpha-tocopherol acetate is formally indicated is as a dietary supplement for patients who demonstrate a genuine vitamin E deficiency. At the same time, vitamin E deficiency is generally quite rare but may occur in premature babies of very low birth weight (< 1500 grams), individuals with fat-malabsorption disorders (as fat is required for the digestive tract to absorb vitamin E), or individuals with abetalipoproteinemia - a rare, inherited disorder that causes poor absorption of dietary fat - who require extremely large doses of supplemental vitamin E daily (around 100 mg/kg or 5-10 g/day) . In all such cases, alpha-tocopherol is largely the preferred form of vitamin E to be administered.\r\n\r\nElsewhere, vitamin E's chemical profile as a fat-soluble antioxidant that is capable of neutralizing free radicals in the body continues to generate ongoing interest and study regarding how and whether or not the vitamin can help prevent or delay various chronic diseases associated with free radicals or other potential biological effects that vitamin E possesses like cardiovascular diseases, diabetes, ocular conditions, immune illnesses, cancer, and more . None of these ongoing studies have yet to elucidate any formally significant evidence, however .","Of the eight separate variants of vitamin E, alpha-tocopherol is the predominant form of vitamin E in human and animal tissues, and it has the highest bioavailability . This is because the liver preferentially resecretes only alpha-tocopherol by way of the hepatic alpha-tocopherol transfer protein (alpha-TTP); the liver metabolizes and excretes all the other vitamin E variants, which is why blood and cellular concentrations of other forms of vitamin E other than alpha-tocopherol are ultimately lower .\r\n\r\nFurthermore, the term alpha-tocopherol generally refers to a group of eight possible stereoisomers which is often called all-rac-tocopherol for being a racemic mixture of all eight stereoisomers . Of the eight stereoisomers, the RRR-alpha-tocopherol - or sometimes referred to as the d-alpha-tocopherol - stereoisomer is the naturally occurring form of alpha-tocopherol that is perhaps best recognized by the alpha-TTP  and has been reported to demonstrate approximately twice the systemic availability of all-rac-tocopherol .\r\n\r\nAs a result, often times (but certainly not always) the discussion of vitamin E - at least within the context of using the vitamin for health-related indications - is generally in reference to the use of RRR- or d-alpha-tocopherol.","Vitamin E's antioxidant capabilities are perhaps the primary biological action associated with alpha-tocopherol. In general, antioxidants protect cells from the damaging effects of free radicals, which are molecules that consist of an unshared electron . These unshared electrons are highly energetic and react rapidly with oxygen to form reactive oxygen species (ROS) . In doing so, free radicals are capable of damaging cells, which may facilitate their contribution to the development of various diseases . Moreover, the human body naturally forms ROS when it converts food into energy and is also exposed to environmental free radicals contained in cigarette smoke, air pollution, or ultraviolet radiation from the sun . It is believed that perhaps vitamin E antioxidants might be able to protect body cells from the damaging effects of such frequent free radical and ROS exposure .\r\n\r\nSpecifically, vitamin E is a chain-breaking antioxidant that prevents the propagation of free radical reactions . The vitamin E molecule is specifically a peroxyl radical scavenger and especially protects polyunsaturated fatty acids within endogenous cell membrane phospholipids and plasma lipoproteins . Peroxyl free radicals react with vitamin E a thousand times more rapidly than they do with the aforementioned polyunsaturated fatty acids . Furthermore, the phenolic hydroxyl group of tocopherol reacts with an organic peroxyl radical to form an organic hydroperoxide and tocopheroxyl radical . This tocopheroxyl radical can then undergo various possible reactions: it could (a) be reduced by other antioxidants to tocopherol, (b) react with another tocopheroxyl radical to form non-reactive products like tocopherol dimers, (c) undergo further oxidation to tocopheryl quinone, or (d) even act as a prooxidant and oxidize other lipids .\r\n\r\nIn addition to the antioxidant actions of vitamin E, there have been a number of studies that report various other specific molecular functions associated with vitamin E . For example, alpha-tocopherol is capable of inhibiting protein kinase C activity, which is involved in cell proliferation and differentiation in smooth muscle cells, human platelets, and monocytes . In particular, protein kinase C inhibition by alpha-tocopherol is partially attributable to its attenuating effect on the generation of membrane-derived dialglycerol, a lipid that facilitates protein kinase C translocation, thereby increasing its activity .\r\n\r\nIn addition, vitamin E enrichment of endothelial cells downregulates the expression of intercellular cell adhesion molecule (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), thereby decreasing the adhesion of blood cell components to the endothelium .\r\n\r\nVitamin E also upregulates the expression of cytosolic phospholipase A2 and cyclooxygenase-1 . The increased expression of these two rate-limiting enzymes in the arachidonic acid cascade explains the observation that vitamin E, in a dose-dependent fashion, enhanced the release of prostacyclin, a potent vasodilator and inhibitor of platelet aggregation in humans .\r\n\r\nFurthermore, vitamin E can inhibit platelet adhesion, aggregation, and platelet release reactions . The vitamin can also evidently inhibit the plasma generation of thrombin, a potent endogenous hormone that binds to platelet receptors and induces aggregation of platelets . Moreover, vitamin E may also be able to decrease monocyte adhesion to the endothellium by downregulating expression of adhesion molecules and decreasing monocyte superoxide production .\r\n\r\nGiven these proposed biological activities of vitamin E, the substance continues to generate ongoing interest and studies in whether or not vitamin E can assist in delaying or preventing various diseases with any one or more of its biologic actions. For instance, studies continue to see whether vitamin E's ability to inhibit low-density lipoprotein oxidation can aid in preventing the development of cardiovascular disease or atherogenesis .\r\n\r\nSimilarly, it is also believed that if vitamin E can decrease the chance of cardiovascular disease then it can also decrease the chance of related diabetic disease and complications . In much the same way, it is also believed that perhaps the antioxidant abilities of vitamin E can neutralize free radicals that are constantly reacting and damaging cellular DNA . Furthermore, it is also believed that free radical damage does contribute to protein damage in the ocular lens - another free radical-mediated condition that may potentially be prevented by vitamin E use . Where it is also suggested that various central nervous system disorders like Parkinson's disease, Alzheimer's disease, Down's syndrome, and Tardive Dyskinesia possess some form of oxidative stress component, it is also proposed that perhaps vitamin E use could assist with its antioxidant action .\r\n\r\nThere have also been studies that report the possibility of vitamin E supplementation can improve or reverse the natural decline in cellular immune function in healthy, elderly individuals .\r\n\r\nAs of this time however, there is either only insufficient data or even contradicting data (where certain doses of vitamin E supplementation could even potentially increase all-cause mortality)  on which to suggest the use of vitamin E could formally benefit in any of these proposed indications.","Free radicals binder","Therapeutic strategy associated"]
[1511,"DB14004","approved; investigational","biotech","Tildrakizumab","Tildrakizumab; tildrakizumab-asmn",null,null,"Tildrakizumab is a high-affinity, humanized, IgG1 κ antibody targeting interleukin 23 p19 that shows promise in the evolution of treatment strategy in chronic plaque psoriasis .\r\n\r\nThe Food and Drug Administration (FDA) approved ILUMYA (tildrakizumab-asmn) for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy in March 2018. The approved recommended dosage of ILUMYA is a subcutaneous injection of 100 mg at Weeks 0, 4, and every 12 weeks thereafter .\r\n\r\nA study was performed on the pharmacokinetics of this drug on various ethnicities. The pharmacokinetics of tildrakizumab were similar in Japanese, Caucasian, and Chinese subjects .","1326244-10-3",null,"Moderate-severe plaque psoriasis , .","Tildrakuzimab is a targeted immunomodulator that decreases inflammation by inhibiting the action of various cytokines associated with plaque psoriasis, thus relieving its symptom of scaly plaques , .","This drug selectively binds interleukin (IL)-23 p19 subunit of cytokine IL-23 and neutralizes its function IL-23 regulates Th17 cells and is a powerful activator of keratinocyte proliferation . Targeting IL-23p19 alone has been found to be a promising treatment approach in patients with moderate-to-severe chronic plaque psoriasis.  Upon administration, downregulation of Th17 and Th22 cell responses occur .\r\n\r\nIL-23 is a naturally occurring cytokine that is involved in inflammatory and immune responses. Tildrakizumab inhibits the release of proinflammatory cytokines and chemokines .","Interleukin-23 antagonist","Therapeutic strategy associated"]
[1512,"DB14006","approved; nutraceutical","small molecule","Choline salicylate","Choline salicylate","C12H19NO4","C[N+](C)(C)CCO.OC1=CC=CC=C1C([O-])=O","Choline salicylate is an anti-inflammatory pain reliever agent that is related to aspirin. It is used to decrease swelling and to treat mild-moderate pain. It is used to treat arthritis in both children and adults. This medicine can also be used for fever .\r\n\r\nCholine Salicylate is the choline salt of salicylic acid, used as an analgesic, antipyretic and antirheumatic. It relieves mild to moderate pain and reduce fever and inflammation or swelling. Choline salicylate is effective in the treatment of gout, rheumatic fever, rheumatoid arthritis and muscle injuries .\r\n\r\nThis drug is also a main ingredient in teething gels to relieve pains associated with tooth growth in the infant population .  The UK government has regulated its use, due to toxicity in those under 16 years of age.  Topical oral salicylate gels are no longer indicated for people younger than 16 years for pain associated with infant teething, orthodontic devices, cold sores, or mouth ulcers .","2016-36-6","241.287","The oral gel is indicated for the relief of pain and discomfort of common mouth ulcers, cold sores, denture sore spots, infant teething and mouth ulcers, and sore spots due to orthodontic devices in children .\r\n\r","This is an anti-inflammatory and antipyretic medication , .\r\n\r\nIf is often used in oral gel form for the relief of pain, discomfort, and inflammation caused by common mouth ulcers, cold sores, denture and sore spots, as well as mouth ulcers, and sore spots because of orthodontic devices .","Choline salicylate relieves pain by inhibition of prostaglandin synthesis and reduces fever by acting on the hypothalamus heat-regulating center. It also inhibits the generation of impulses through the inhibition of cyclooxygenase enzyme (COX) , .  \r\n\r\nCyclooxygenase is involved in the production of prostaglandins, in response to injury and after various other stimuli. The prostaglandins promote pain, swelling, and inflammation. The choline salicylate decreases inflammation and pain by reducing the production of these prostaglandins in the area of the mouth it is applied to .","Choline-phosphate cytidylyltransferase B product of; Acetylcholinesterase product of; Choline-phosphate cytidylyltransferase A product of; Phospholipase D2 product of; Cholinesterase product of; Phospholipase D1 product of; Neuronal acetylcholine receptor subunit alpha-7","Therapeutic strategy associated"]
[1513,"DB14009","experimental; investigational","biotech","Medical Cannabis","Cannabis; Cannabis indica; Cannabis indica top; Cannabis sativa subsp. indica top; Cannabis sativa subsp. indica top extract; Hashish top; Marihuana; Marijuana; Marijuana top",null,null,"The use of the plant species _Cannabis sativa_ and _Cannabis indica_, popularly known as marijuana, has gained popularity in recent years for the management of a wide variety of medical conditions as a wave of legalization in North America has changed public and medical opinion on its use. Consequently, an expanding body of evidence has begun to emerge that has demonstrated its potential usefulness in the management of conditions such as chronic pain, spasticity, inflammation, epilepsy, and chemotherapy-induced nausea and vomiting among many others. This area of research is controversial and has been heavily debated, however, due to concerns over risks of addiction, long-term health effects, and Cannabis' association with schizophrenia.\r\n\r\nFrom a pharmacological perspective, Cannabis' diverse receptor profile explains its potential application for such a wide variety of medical conditions. Cannabis contains more than 400 different chemical compounds, of which 61 are considered cannabinoids, a class of compounds that act upon cannabinoid receptors of the body . Tetrahydrocannabinol (THC) and  (CBD) are two types of cannabinoids found naturally in the resin of the marijuana plant, both of which interact with the cannabinoid receptors that are found throughout the body. Although THC and CBD have been the most studied cannabinoids, there are many others identified to date including cannabinol (CBN), cannabigerol (CBG),  (CBDV), and  (THCV) that have been shown to modify the physiological effects of cannabis . \r\n\r\nWhile both CBD and THC are used for medicinal purposes, they have different receptor activity, function, and physiological effects. THC and CBD are converted from their precursors, tetrahydrocannabinolic acid-A (THCA-A) and cannabidiolic acid (CBDA), through decarboxylation when unfertilized female cannabis flowers are activated either through heating, smoking, vaporization, or baking. While cannabis in its natural plant form is currently used \"off-label\" for the management of many medical conditions, THC is currently commercially available in synthetic form as , as purified isomer as , or in a 1:1 formulation with CBD from purified plant extract as .\r\n\r\nCannabinoid receptors are utilized endogenously by the body through the endocannabinoid system, which includes a group of lipid proteins, enzymes, and receptors that are involved in many physiological processes. Through its modulation of neurotransmitter release, the endocannabinoid system regulates cognition, pain sensation, appetite, memory, sleep, immune function, and mood among many others. These effects are largely mediated through two members of the G-protein coupled receptor family, cannabinoid receptors 1 and 2 (CB1 and CB2). CB1 receptors are found in both the central and peripheral nervous systems, with the majority of receptors localized to the hippocampus and amygdala of the brain. Physiological effects of using cannabis make sense in the context of its receptor activity as the hippocampus and amygdala are primarily involved with regulation of memory, fear, and emotion. In contrast, CB2 receptors are mainly found peripherally in immune cells, lymphoid tissue, and peripheral nerve terminals .\r\n\r\nThe primary psychoactive component of Cannabis, delta 9-tetrahydrocannabinol (Δ9-THC), demonstrates its effects through weak partial agonist activity at Cannabinoid-1 (CB1R) and Cannabinoid-2 (CB2R) receptors. This activity results in the well-known effects of smoking cannabis such as increased appetite, reduced pain, and changes in emotional and cognitive processes. In contrast to THC's weak agonist activity, CBD has been shown to act as a negative allosteric modulator of the cannabinoid CB1 receptor, the most abundant G-Protein Coupled Receptor (GPCR) in the body . Allosteric regulation is achieved through the modulation of receptor activity on a functionally distinct site from the agonist or antagonist binding site, which is therapeutically important as direct agonists are limited by their psychomimetic effects while direct antagonists are limited by their depressant effects . \r\n\r\nThere is further evidence that CBD also activates 5-HT1A serotonergic and TRPV1–2 vanilloid receptors, antagonizes alpha-1 adrenergic and µ-opioid receptors, inhibits synaptosomal uptake of noradrenaline, dopamine, serotonin and gaminobutyric acid and cellular uptake of anandamide, acts on mitochondria Ca2 stores, blocks low-voltage-activated (T-type) Ca2 channels, stimulates activity of the inhibitory glycine-receptor, and inhibits activity of fatty amide hydrolase (FAAH) .\r\n\r\nDue to the differences in receptor profile between CBD and THC, these cannabinoids are understandably used to treat different conditions. Furthermore, when combined with THC, CBD has been shown to modulate THC's activity, resulting in differences in pharmacological effect between \"strains\", or chemovars, of the Cannabis plant which are bred to contain different concentrations of CBD and THC. For example, strains containing a high proportion of CBD have been shown to reduce the psychosis- and anxiety-inducing effects of THC . Reliably studying the effects of Cannabis is complicated by the large variety of available strains and by the numerous other compounds that Cannabis contains such as terpenes, flavonoids, phenols, amino acids, and fatty acids among many others that have shown potential to modulate the plant's pharmacological effect .",{"$nulls":3},"The primary psychoactive component of Cannabis, delta 9-tetrahydrocannabinol (Δ9-THC), demonstrates its effects through weak partial agonist activity at Cannabinoid-1 (CB1R) and Cannabinoid-2 (CB2R) receptors. This activity results in the well-known effects of smoking cannabis such as increased appetite, reduced pain, and changes in emotional and cognitive processes.\r\n\r\nIn contrast to THC's weak agonist activity, CBD has been shown to act as a negative allosteric modulator of the cannabinoid CB1 receptor, the most abundant G-Protein Coupled Receptor (GPCR) in the body . There is further evidence that CBD also activates 5-HT1A serotonergic and TRPV1–2 vanilloid receptors, antagonizes alpha-1 adrenergic and µ-opioid receptors, inhibits synaptosomal uptake of noradrenaline, dopamine, serotonin and gaminobutyric acid and cellular uptake of anandamide, acts on mitochondria Ca2 stores, blocks low-voltage-activated (T-type) Ca2 channels, stimulates activity of the inhibitory glycine-receptor, and inhibits activity of fatty amide hydrolase (FAAH) .",null,"Cannabinoid receptor 1 negative modulator; Cannabinoid receptor 2; G-protein coupled receptor 12 inverse agonist; Glycine receptor subunit alpha-1; Glycine receptor (alpha-1/beta); Glycine receptor subunit alpha-3; N-arachidonyl glycine receptor; G-protein coupled receptor 55; 5-hydroxytryptamine receptor 1A; 5-hydroxytryptamine receptor 2A; Neuronal acetylcholine receptor subunit alpha-7; Delta-type opioid receptor; Mu-type opioid receptor; Peroxisome proliferator-activated receptor gamma; Transient receptor potential cation channel subfamily V member 1; Voltage-dependent T-type calcium channel subunit alpha-1G; Voltage-dependent T-type calcium channel subunit alpha-1H; Voltage-dependent T-type calcium channel subunit alpha-1I; Transient receptor potential cation channel subfamily A member 1; Transient receptor potential cation channel subfamily M member 8; Transient receptor potential cation channel subfamily V member 2; Transient receptor potential cation channel subfamily V member 3; Transient receptor potential cation channel subfamily V member 4; Voltage-dependent anion-selective channel protein 1; N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D inhibitor; N-acylethanolamine-hydrolyzing acid amidase inhibitor; Arylalkylamine N-acetyltransferase inhibitor; Phospholipase A2 inhibitor&inducer; Superoxide dismutase [Cu-Zn] inhibitor; Fatty-acid amide hydrolase 1 inhibitor; Catalase inhibitor; Quinone oxidoreductase inhibitor; Sphingomyelin phosphodiesterase inducer; Glutathione peroxidase 1 inducer; Glutathione reductase, mitochondrial inducer; 3-hydroxy-3-methylglutaryl-coenzyme A reductase inducer; Indoleamine 2,3-dioxygenase 1 inhibitor; Prostaglandin G/H synthase 1 inhibitor; Prostaglandin G/H synthase 2 inhibitor; Steroid 17-alpha-hydroxylase/17,20 lyase inhibitor; Acetyl-CoA acetyltransferase, mitochondrial inhibitor","Target associated"]
[1514,"DB14011","investigational","small molecule","Nabiximols","Nabiximols","C42H60O4","[H][C@]1(CCC(C)=C[C@@]1([H])C1=C(O)C=C(CCCCC)C=C1O)C(C)=C.[H][C@@]12CCC(C)=C[C@@]1([H])C1=C(O)C=C(CCCCC)C=C1OC2(C)C","Nabiximols (tradename Sativex®) is a whole plant extract from the Cannabis species _Cannabis sativa L._ that has been purified into the active components CBD (cannabidiol) and THC (delta-9-tetrahydrocannabinol). For trademark purposes, purified CBD is branded as Nabidiolex®, while THC is purified as the product Tetrabinex®. Sativex® is available in a 1:1 formulation of THC:CBD as an oro-mucosal pump spray used for treatment of neuropathic pain from Multiple Sclerosis (MS) and for intractable cancer pain. Although still largely debated, Cannabis has been shown to have analgesic, anticonvulsant, muscle relaxant, anxiolytic, neuroprotective, anti-oxidant, and anti-psychotic activity . \r\n\r\nFrom a pharmacological perspective, Cannabis' diverse receptor profile explains its potential application for such a wide variety of medical conditions. Cannabis contains more than 400 different chemical compounds, of which 61 are considered cannabinoids, a class of compounds that act upon cannabinoid receptors of the body . Tetrahydrocannabinol (THC) and cannabidiol (CBD) are two types of cannabinoids found naturally in the resin of the marijuana plant, both of which interact with the cannabinoid receptors found in the human body. While both CBD and THC are used for medicinal purposes, they have different receptor activity, function, and physiological effects. While cannabis in its natural plant form is currently used \"off-label\" for the management of many medical conditions, THC is currently commercially available in synthetic form as , as purified isomer as , or in a 1:1 formulation with CBD from purified plant extract as .\r\n\r\nThe primary psychoactive component of Cannabis, delta 9-tetrahydrocannabinol (Δ9-THC), demonstrates its effects through weak partial agonist activity at Cannabinoid-1 (CB1R) and Cannabinoid-2 (CB2R) receptors. This activity results in the well-known effects of smoking cannabis such as increased appetite, reduced pain, and changes in emotional and cognitive processes. In contrast to THC's weak agonist activity, CBD has been shown to act as a negative allosteric modulator of the cannabinoid CB1 receptor, the most abundant G-Protein Coupled Receptor (GPCR) in the body . Allosteric regulation is achieved through the modulation of receptor activity on a functionally distinct site from the agonist or antagonist binding site. The negative allosteric modulatory effects of CBD are therapeutically important as direct agonists are limited by their psychomimetic effects while direct antagonists are limited by their depressant effects . \r\n\r\nIn Canada, Sativex® has received a Notice of Compliance (NOC) for use as an as adjunctive treatment for symptomatic relief of spasticity in patients with multiple sclerosis (MS) who have not responded adequately to other therapy and who demonstrate meaningful improvement during an initial trial of therapy. \r\n\r\nSativex® has also received a Notice of Compliance with Conditions (NOC/c) for use as an adjunctive treatment for the symptomatic relief of neuropathic pain in adult patients with multiple sclerosis (MS) and as adjunctive analgesic treatment in adult patients with advanced cancer who experience moderate to severe pain during the highest tolerated dose of strong opioid therapy for persistent background pain.","56575-23-6","628.938","In Canada, Sativex has received a Notice of Compliance (NOC) for use as an as adjunctive treatment for symptomatic relief of spasticity in patients with multiple sclerosis (MS) who have not responded adequately to other therapy and who demonstrate meaningful improvement during an initial trial of therapy. \r\n\r\nSativex has also received a Notice of Compliance with Conditions (NOC/c) for use as an adjunctive treatment for the symptomatic relief of neuropathic pain in adult patients with multiple sclerosis (MS) and as adjunctive analgesic treatment in adult patients with advanced cancer who experience moderate to severe pain during the highest tolerated dose of strong opioid therapy for persistent background pain. \r\n\r\nMarketing authorisations with conditions reflect the promising nature of the clinical evidence and the need for confirmatory studies to verify the clinical benefit. Patients should be advised of the conditional nature of the authorizations with conditions.","The principal pharmacological effects of THC include analgesic, muscle relaxant, antiemetic, appetite stimulant and psychoactive effects. CBD has analgesic, anticonvulsant, muscle relaxant, anxiolytic, neuroprotective, anti-oxidant and anti-psychotic activity.","The primary psychoactive component of Cannabis, delta 9-tetrahydrocannabinol (Δ9-THC), demonstrates its effects through weak partial agonist activity at Cannabinoid-1 (CB1R) and Cannabinoid-2 (CB2R) receptors. This activity results in the well-known effects of smoking cannabis such as increased appetite, reduced pain, and changes in emotional and cognitive processes. In contrast to THC's weak agonist activity, CBD has been shown to act as a negative allosteric modulator of the cannabinoid CB1 receptor, the most abundant G-Protein Coupled Receptor (GPCR) in the body . Allosteric regulation is achieved through the modulation of receptor activity on a functionally distinct site from the agonist or antagonist binding site. The negative allosteric modulatory effects of CBD are therapeutically important as direct agonists are limited by their psychomimetic effects while direct antagonists are limited by their depressant effects . \r\n\r\nThere is further evidence that CBD also activates 5-HT1A serotonergic and TRPV1–2 vanilloid receptors, antagonizes alpha-1 adrenergic and µ-opioid receptors, inhibits synaptosomal uptake of noradrenaline, dopamine, serotonin and gaminobutyric acid and cellular uptake of anandamide, acts on mitochondria Ca2 stores, blocks low-voltage-activated (T-type) Ca2 channels, stimulates activity of the inhibitory glycine-receptor, and inhibits activity of fatty amide hydrolase (FAAH) .","Cannabinoid receptor 1; Cannabinoid receptor 2; G-protein coupled receptor 12 inverse agonist; Glycine receptor subunit alpha-1; Glycine receptor (alpha-1/beta); Glycine receptor subunit alpha-3; N-arachidonyl glycine receptor; G-protein coupled receptor 55; 5-hydroxytryptamine receptor 1A; 5-hydroxytryptamine receptor 2A; Neuronal acetylcholine receptor subunit alpha-7; Delta-type opioid receptor; Mu-type opioid receptor; Peroxisome proliferator-activated receptor gamma; Transient receptor potential cation channel subfamily V member 1; Voltage-dependent T-type calcium channel subunit alpha-1G; Voltage-dependent T-type calcium channel subunit alpha-1H; Voltage-dependent T-type calcium channel subunit alpha-1I; Transient receptor potential cation channel subfamily A member 1; Transient receptor potential cation channel subfamily M member 8; Transient receptor potential cation channel subfamily V member 2; Transient receptor potential cation channel subfamily V member 3; Transient receptor potential cation channel subfamily V member 4; Voltage-dependent anion-selective channel protein 1; Prostaglandin G/H synthase 1 inhibitor; Prostaglandin G/H synthase 2 inhibitor; Acetyl-CoA acetyltransferase, mitochondrial inhibitor; Steroid 17-alpha-hydroxylase/17,20 lyase inhibitor; 3-hydroxy-3-methylglutaryl-coenzyme A reductase stimulator; Glutathione reductase, mitochondrial stimulator; Glutathione peroxidase 1 stimulator; Indoleamine 2,3-dioxygenase 1 inhibitor; Arylalkylamine N-acetyltransferase inhibitor; Cytochrome P450 1B1 inhibitor; Cytochrome P450 3A5 inhibitor; Cytochrome P450 2D6 substrate&inhibitor; Cytochrome P450 1A2 inhibitor; Cytochrome P450 1A1 inhibitor; Cytochrome P450 3A7 inhibitor; Quinone oxidoreductase inhibitor; Catalase inhibitor; Fatty-acid amide hydrolase 1 inhibitor&inducer; Superoxide dismutase [Cu-Zn] inhibitor; N-acylethanolamine-hydrolyzing acid amidase inhibitor","Target associated"]
[1515,"DB14012","approved; investigational","biotech","Burosumab","Burosumab; Burosumab (genetical recombination); burosumab-twza",null,null,"Burosumab (KRN23) is an entirely human monoclonal IgG1 antibody that binds excess fibroblast growth factor 23 (FGF23) and has been successfully tested in clinical trials in children with X-linked hypophosphatemic rickets .  \r\n\r\nThe U.S. Food and Drug Administration approved Crysvita (burosumab) in April 2018. This is the first drug approved to treat adults and children ages 1 year and older with X-linked hypophosphatemia (XLH), which is a rare, inherited form of rickets. X-linked hypophosphatemia causes low circulating levels of phosphorus in the blood. It causes impaired bone growth and development in children and adolescents and issues with bone mineralization throughout a patient’s life  .\r\n\r\nXLH is a serious disease which affects about 3,000 children and 12,000 adults in the United States. Most children with XLH suffer from bowed or bent legs, short stature, bone pain and severe dental pain. Some adults with this condition suffer from persistent, unrelenting discomfort and complications, such as joint pain, impaired mobility, tooth abscesses and hearing loss .","1610833-03-8",null,"This drug is indicated for the treatment of X-linked hypophosphatemia with radiological evidence of bone disease in children of 1 year of age and older and adolescents with growing skeletons .","This drug has the ability to reduce the loss of phosphate, to improve pathologically low serum phosphate concentrations and other metabolic changes, as well as to reduce the severity of rickets as seen radiographically . In summary, this drug works to support of bone mineralization .","Burosumab is a recombinant human monoclonal antibody (IgG1) that both binds to and inhibits the actions of fibroblast growth factor 23 (FGF23). By inhibiting this growth factor, burosumab increases the tubular reabsorption of phosphate from the kidney and thus increases serum concentration of 1, 25 dihydroxy-Vitamin D .  This form of vitamin D enhances intestinal absorption of phosphate and calcium, supporting bone mineralization .\r\n\r","Fibroblast growth factor 23 antagonist","Indication associated"]
[1516,"DB14034","experimental","small molecule","Darglitazone","Darglitazone","C23H20N2O4S","CC1=C(CCC(=O)C2=CC=C(CC3SC(=O)NC3=O)C=C2)N=C(O1)C1=CC=CC=C1",null,"141200-24-0","420.48",{"$nulls":3},"Peroxisome proliferator-activated receptor gamma agonist","Target associated"]
[1517,"DB14059","experimental; investigational","small molecule","SC-236",null,"C16H11ClF3N3O2S","NS(=O)(=O)C1=CC=C(C=C1)N1N=C(C=C1C1=CC=C(Cl)C=C1)C(F)(F)F","SC-236 is a potent, selective, orally active inhibitor of cyclooxygenase-2 (COX-2)  that has been studied in cancer therapy , lower back pain , and inflammation , ,, .","170569-86-5","401.79",null,null,"This drug is a selective inhibitor of the COX-2 enzyme , . COX-2 is expressed in the brain, in the kidney, in bone, and likely in the female reproductive system . Its expression at other sites is increased during inflammation, experimentally, in response to mitogenic stimuli. Growth factors, phorbol esters, and interleukin (IL)-1 stimulate the expression of COX-2 in fibroblasts, while endotoxin serves the same function in monocytes/macrophages .\r\n\r\nSC-236 works also directly through suppressing the nuclear translocation of RelA/p65, a transcription factor. SC-236 directly targets proteins that facilitate the nuclear translocation of NF-κB, an inflammatory signaling pathway , .","Cyclooxygenase 2 inhibitor; Nuclear factor NF-kappa-B complex inhibitor","Therapeutic strategy associated"]
[1518,"DB14487","approved; investigational","small molecule","Zinc acetate","Acetic acid, zinc salt; Dicarbomethoxyzinc; Zinc acetate anhydrous; Zinc diacetate; Zinc(II) acetate","C4H6O4Zn","[Zn++].CC([O-])=O.CC([O-])=O",null,"557-34-6","183.497","Zinc can be used for the treatment and prevention of zinc deficiency/its consequences, including stunted growth and acute diarrhea in children, and slowed wound healing. It is also utilized for boosting the immune system, treating the common cold and recurrent ear infections, as well as preventing lower respiratory tract infections .  \r\n\r","Zinc is involved in various aspects of cellular metabolism. It has been estimated that approximately 10% of human proteins may bind zinc, in addition to hundreds of proteins that transport and traffic zinc. It is required for the catalytic activity of more than 200 enzymes, and it plays a role in immune function wound healing, protein synthesis, DNA synthesis, and cell division. Zinc is an essential element for a proper sense of taste and smell and supports normal growth and development during pregnancy, childhood, and adolescence. It is thought to have antioxidant properties, which may be protective against accelerated aging and helps to speed up the healing process after an injury; however, studies differ as to its effectiveness. Zinc ions are effective antimicrobial agents even if administered in low concentrations .\r\n\r\nStudies on oral zinc for specific conditions shows the following evidence in various conditions :\r\n\r\n**Colds:** Evidence suggests that if zinc lozenges or syrup are taken within 24 hours after cold symptoms start, the supplement may shorten the length of colds. The use intranasal zinc has been associated with the loss of the sense of smell, in some cases long-term or permanently .\r\n\r\n**Wound healing:** Patients with skin ulcers and decreased levels of zinc may benefit from oral zinc supplements . \r\n\r\n**Diahrrea**: Oral zinc supplements can reduce the symptoms of diarrhea in children with low levels of zinc, especially in cases of malnutrition .\r","**Zinc has three primary biological roles**: _catalytic_, _structural_, and _regulatory_. The catalytic and structural role of zinc is well established, and there are various noteworthy reviews on these functions. For example, zinc is a structural constituent in numerous proteins, inclusive of growth factors, cytokines, receptors, enzymes, and transcription factors for different cellular signaling pathways. It is implicated in numerous cellular processes as a cofactor for approximately 3000 human proteins including enzymes, nuclear factors, and hormones .\r\n\r\nZinc promotes resistance to epithelial apoptosis through cell protection (cytoprotection) against reactive oxygen species and bacterial toxins, likely through the antioxidant activity of the cysteine-rich metallothioneins .\r\n\r\nIn HL-60 cells (promyelocytic leukemia cell line), zinc enhances the up-regulation of A20 mRNA, which, via TRAF pathway, decreases NF-kappaB activation, leading to decreased gene expression and generation of tumor necrosis factor-alpha (TNF-alpha), IL-1beta, and IL-8 .\r\n\r\nThere are several mechanisms of action of zinc on acute diarrhea. Various mechanisms are specific to the gastrointestinal system: zinc restores mucosal barrier integrity and enterocyte brush-border enzyme activity, it promotes the production of antibodies and circulating lymphocytes against intestinal pathogens, and has a direct effect on ion channels, acting as a potassium channel blocker of adenosine 3-5-cyclic monophosphate-mediated chlorine secretion. Cochrane researchers examined the evidence available up to 30 September 2016 .\r\n\r\nZinc deficiency in humans decreases the activity of serum _thymulin_ (a hormone of the thymus), which is necessary for the maturation of T-helper cells. T-helper 1 (Th(1)) cytokines are decreased but T-helper 2 (Th(2)) cytokines are not affected by zinc deficiency in humans .\r\n\r\nThe change of _Th(1)_ to _Th(2)_ function leads to cell-mediated immune dysfunction. Because IL-2 production (Th(1) cytokine) is decreased, this causes decreased activity of natural-killer-cell (NK cell) and T cytolytic cells, normally involved in killing viruses, bacteria, and malignant cells . \r\n\r\nIn humans, zinc deficiency may lead to the generation of new CD4+ T cells, produced in the thymus. In cell culture studies (HUT-78, a Th(0) human malignant lymphoblastoid cell line), as a result of zinc deficiency, nuclear factor-kappaB (NF-kappaB) activation, phosphorylation of IkappaB, and binding of NF-kappaB to DNA are decreased and this results in decreased Th(1) cytokine production .\r\n\r\nIn another study, zinc supplementation in human subjects suppressed the gene expression and production of pro-inflammatory cytokines and decreased oxidative stress markers . In HL-60 cells (a human pro-myelocytic leukemia cell line), zinc deficiency increased the levels of TNF-alpha, IL-1beta, and IL-8 cytokines and mRNA. In such cells, zinc was found to induce A20, a zinc finger protein that inhibited NF-kappaB activation by the tumor necrosis factor receptor-associated factor pathway. This process decreased gene expression of pro-inflammatory cytokines and oxidative stress markers .\r\n\r\nThe exact mechanism of zinc in acne treatment is poorly understood. However, zinc is considered to act directly on microbial inflammatory equilibrium and facilitate antibiotic absorption when used in combination with other agents. Topical zinc alone as well as in combination with other agents may be efficacious because of its anti-inflammatory activity and ability to reduce P. acnes bacteria by the inhibition of P. acnes lipases and free fatty acid levels .","B1 bradykinin receptor; Methylated-DNA--protein-cysteine methyltransferase; Fructose-bisphosphate aldolase A; Elongation factor 1-alpha 1; Alpha-enolase; Glyceraldehyde-3-phosphate dehydrogenase, testis-specific; Nucleoside diphosphate kinase A; Protein disulfide-isomerase; Protein disulfide-isomerase A3; Peroxiredoxin-1; Phosphoserine phosphatase; Triosephosphate isomerase; Elongation factor Tu, mitochondrial; Estrogen receptor alpha; Interleukin-3; Metallothionein-2; Copper chaperone for superoxide dismutase; Histone deacetylase 1; Histone deacetylase 4; DNA-3-methyladenine glycosylase; Semenogelin-1; Superoxide dismutase [Cu-Zn]; Histone deacetylase 8; Apoptosis regulatory protein Siva; Glycine receptor subunit alpha-1; E3 ubiquitin-protein ligase Mdm2; Insulin; Utrophin; Aspartoacylase; Protein S100-A8; Protein S100-A9; Matrix metalloproteinase-9; Tumor protein p73; Protein S100-A2; Cellular tumor antigen p53; Metallothionein-3; Programmed cell death protein 6; DAN domain family member 5; Metallothionein-1A; Alpha-1B-glycoprotein; Alpha-2-macroglobulin; Angiotensinogen; Alpha-2-HS-glycoprotein; Serum amyloid P-component; Apolipoprotein A-I; Apolipoprotein A-II; Apolipoprotein A-IV; Apolipoprotein B receptor; Apolipoprotein E; Apolipoprotein L1; Complement C1q subcomponent subunit B; Complement C1q subcomponent subunit C; Complement C1r subcomponent; Complement C1s subcomponent; Complement C3; Complement C4-B; C4b-binding protein alpha chain; C4b-binding protein beta chain; Complement C5; Lys-63-specific deubiquitinase BRCC36; Complement component C8 alpha chain; Complement component C8 beta chain; Complement component C8 gamma chain; Complement factor B; Complement factor H; Complement factor I; Clusterin; Ceruloplasmin; Carboxypeptidase N catalytic chain; Carboxypeptidase N subunit 2; Dermcidin; Desmoplakin; Coagulation factor XII; Coagulation factor XIII B chain; Prothrombin; Ficolin-3; Fibrinogen alpha chain; Fibronectin; Gelsolin; Hemoglobin subunit alpha; Hemoglobin subunit beta; Haptoglobin-related protein; Hornerin; Insulin-like growth factor-binding protein complex acid labile subunit; Ig alpha-1 chain C region; Ig mu chain C region; Immunoglobulin kappa variable 1-17; Ig kappa chain V-III region GOL; Immunoglobulin lambda variable 3-21; Inter-alpha-trypsin inhibitor heavy chain H1; Inter-alpha-trypsin inhibitor heavy chain H2; Inter-alpha-trypsin inhibitor heavy chain H3; Inter-alpha-trypsin inhibitor heavy chain H4; Immunoglobulin J chain; Junction plakoglobin; Plasma kallikrein; Kininogen-1; Keratin, type II cytoskeletal 1; Keratin, type I cytoskeletal 10; Keratin, type I cytoskeletal 14; Keratin, type I cytoskeletal 16; Keratin, type II cytoskeletal 2 epidermal; Keratin, type II cytoskeletal 5; Keratin, type II cytoskeletal 6A; Keratin, type I cytoskeletal 9; Alpha-1-acid glycoprotein 2; N-acetylmuramoyl-L-alanine amidase; Serum paraoxonase/arylesterase 1; Pregnancy zone protein; Protein S100-A7; Selenoprotein P; Alpha-1-antitrypsin; Alpha-1-antichymotrypsin; Kallistatin; Corticosteroid-binding globulin; Heparin cofactor 2; Sex hormone-binding globulin; Serotransferrin; Transthyretin; Vitronectin; Amyloid-like protein 1; Amyloid-like protein 2; Amyloid beta A4 protein; Poly [ADP-ribose] polymerase 1","Therapeutic strategy associated"]
[1519,"DB14502","approved","small molecule","Sodium phosphate, dibasic","Dibasic sodium phosphate anhydrous; Dibasic sodium phosphate, anhydrous; Disodium acid phosphate; Disodium hydrogen monophosphate; Disodium hydrogen phosphate; Disodium hydrogen phosphate, anhydrous; disodium hydrogenphosphate; Disodium phosphate; Phosphoric acid, disodium salt, anhydrous; Phosphoric acid, sodium salt (1:2); Sodium phosphate dibasic; Sodium phosphate, dibasic; Sodium phosphate, dibasic (anhydrous); Sodium phosphate, dibasic anhydrous; Sodium phosphate, dibasic, anhydrous; Sodium phosphate,dibasic,anhydrous","HNa2O4P","[Na+].[Na+].OP([O-])([O-])=O",null,"7558-79-4","141.9588","Used to treat constipation or to clean the bowel before a colonoscopy .","Sodium phosphate inceases fecal water content to increase mobility through the large intestine .","Sodium phosphate is thought to work by increasing the amount of solute present in the intestinal lumen thereby creating an osmotic gradient which draws water into the lumen .",null,"Indication associated"]
[1520,"DB14503","approved","small molecule","Sodium phosphate, monobasic, unspecified form",{"$nulls":6},"Used to treat constipation or to clean the bowel before a colonoscopy .","Sodium phosphate inceases fecal water content to increase mobility through the large intestine .","Sodium phosphate is thought to work by increasing the amount of solute present in the intestinal lumen thereby creating an osmotic gradient which draws water into the lumen .",null,"Indication associated"]
[1521,"DB14507","approved","small molecule","Lithium citrate","Anhydrous lithium citrate; Citric acid, trilithium salt; Lithium citrate (anhydrous); Trilithium citrate","C6H5Li3O7","[Li+].[Li+].[Li+].OC(CC([O-])=O)(CC([O-])=O)C([O-])=O",null,"919-16-4","209.92","Lithium is used as a mood stabilizer, and is used for treatment of depression and mania. It is often used in bipolar disorder treatment.","Although lithium has been used for over 50 years in treatment of bipolar disorder, the mechanism of action is still unknown. Lithium's therapeutic action may be due to a number of effects, ranging from inhibition of enzymes such as glycogen synthase kinase 3, inositol phosphatases, or modulation of glutamate receptors.","The precise mechanism of action of Li+ as a mood-stabilizing agent is currently unknown. It is possible that Li+ produces its effects by interacting with the transport of monovalent or divalent cations in neurons. An increasing number of scientists have come to the conclusion that the excitatory neurotransmitter glutamate is the key factor in understanding how lithium works. Lithium has been shown to change the inward and outward currents of glutamate receptors (especially GluR3), without a shift in reversal potential. Lithium has been found to exert a dual effect on glutamate receptors, acting to keep the amount of glutamate active between cells at a stable, healthy level, neither too much nor too little.  It is postulated that too much glutamate in the space between neurons causes mania, and too little, depression. Another mechanism by which lithium might help to regulate mood include the non-competitive inhibition of an enzyme called inositol monophosphatase.  Alternately lithium's action may be enhanced through the deactivation of the GSK-3B enzyme.  The regulation of GSK-3B by lithium may affect the circadian clock.  GSK-3 is known for phosphorylating and thus inactivating glycogen synthase. GSK-3B has also been implicated in the control of cellular response to damaged DNA. GSK-3 normally phosphorylates beta catenin, which leads to beta catenin degratation. When GSK-3 is inhibited, beta catenin increases and transgenic mice with overexpression of beta catenin express similar behaviour to mice treated with lithium. These results suggest that increase of beta catenin may be a possible pathway for the therapeutic action of lithium.","Inositol monophosphatase 2; Inositol monophosphatase 1; Glycogen synthase kinase-3 beta; Glutamate receptor 3","Indication associated"]
[1522,"DB14512","approved; investigational; vet_approved","small molecule","Mometasone furoate","Mometasone furoate; Mometasone furoate anhydrous","C27H30Cl2O6","[H][C@@]12C[C@@H](C)[C@](OC(=O)C3=CC=CO3)(C(=O)CCl)[C@@]1(C)C[C@H](O)[C@@]1(Cl)[C@@]2([H])CCC2=CC(=O)C=C[C@]12C","Mometasone furoate is a corticosteroid drug that can be used for the treatment of asthma, rhinitis, and certain skin conditions. It has a glucocorticoid receptor binding affinity 22 times stronger than  and higher than many other corticosteroids as well. Mometasone furoate is formulated as a dry powder inhaler, nasal spray, and ointment for its different indications.","83919-23-7","521.429","There are 3 formulations of mometasone furoate with various indications. The inhaler is indicated for prophylaxis of asthma in patients ≥4 years. The nasal spray is indicated for treating nasal symptoms of allergic rhinitis in patients ≥2 years, treating symptoms of nasal congestion from seasonal allergic rhinitis in patients ≥2 years, treating nasal polyps in patients ≥18 years, and prophylaxis of seasonal allergic rhinitis in patients ≥12 years. The ointment is indicated for symptomatic treatment of dermatitis and pruritis in patients ≥2 years.","Mometasone is a synthetic corticosteroid with an affinity for glucocorticoid receptors 22 times higher than that of . Mometasone furoate also has a lower affinity to mineralocorticoid receptors than natural corticosteroids, making it more selective in its action. Mometasone furoate diffuses across cell membranes to activate pathways responsible for reducing inflammation.","In asthma, mometasone is believed to inhibit mast cells, eosinophils, basophils, and lymphocytes. There is also evidence of inhibition of histamine, leukotrienes, and cytokines.\r\n\r\nCorticosteroids diffuse across cell membranes into the cytosol of cells where they bind to glucocorticoid receptors to produce their activity. Mometasone furoate has a particularly high receptor affinity compare to other corticosteroids, 22 times higher than that of . Mometasone furoate binding to a glucocorticoid receptor causes conformational changes in the receptor, separation from chaperones, and the receptor moves to the nucleus. Once at the nucleus, receptors dimerize and bind to a DNA sequence known as the glucocorticoid response element which either increases expression of anti-inflammatory molecules or inhibits expression of pro-inflammatory molecules (such as interleukins 4 and 5). Mometasone furoate also reduces inflammation by blocking transcription factors such as activator-protein-1 and nuclear factor kappa B (NF-kappaB).","Glucocorticoid receptor; Progesterone receptor","Therapeutic strategy associated"]
[1523,"DB14513","approved; experimental; investigational","small molecule","Magnesium","Magnesium metallicum; Magnesium powder; Mg","H2Mg","[MgH2]","Magnesium is classified as an alkaline earth metal and has 2 hydration shells. The element can be found in abundance in the hydrosphere and in mineral salts such as dolomite and magnesium carbonate. \r\n\r\nCommon dietary sources of magnesium include nuts (cashews, peanuts, almonds), beans, bananas, apples, carrots, broccoli, and leafy greens. Magnesium is an important enzyme cofactor and is essential to several metabolic processes. Further, the mineral helps regulate blood pressure and is necessary for RNA, DNA and protein synthesis among several other functions. \r\n\r\nDespite the importance of magnesium and its availability via several food sources, an estimated 56 to 68% of adults who live in developed, western countries do not meet the recommended daily intake (RDI) of magnesium. Several factors and common behaviours reduce the availability of magnesium in the diet such as food processing and cooking vegetables (which are normally a rich source of magnesium).","7439-95-4","26.321","Healthy levels of magnesium can be achieved through a well balanced diet, but if food sources are insufficient, magnesium supplements can be used to prevent and treat magnesium deficiencies.\r\n\r\nIn medicine, various magnesium salts may be used in laxative and antacid products. For example,  is available over-the-counter and may be used to manage occasional constipation.  may be used on its own or with total parenteral nutrition to treat hypomagnesemia.  is also indicated to prevent seizures in pregnant women with pre-eclampsia, and to manage seizures associated with eclampsia.","Magnesium is important for many biochemical processes and is therefore quite common in humans. The majority of magnesium is stored in the bones (>50%), while the remainder is stored in muscle, soft tissue, red blood cells and serum. This is functionally important since the bones behave as a magnesium exchange reservoir and help maintain healthy levels of magnesium.\r\n\r\nMagnesium plays an important role in the regulation of several bodily processes including blood pressure, insulin metabolism, muscular contraction, vasomotor tone, cardiac excitability, nerve transmission and neuromuscular conduction. Disruptions in homeostatic levels of magnesium (often times hypomagnesemia) can impact the nervous system, muscles, or can lead to cardiac abnormalities.\r\n\r","Magnesium is a cofactor for at least 300 enzymes and is important for several functions in the body with some key processes identified below. Enzymes that rely on magnesium to operate help produce energy through oxidative phosphorylation, glycolysis and ATP metabolism. They are also involved in nerve function, muscle contraction, blood glucose control, hormone receptor binding, protein synthesis, cardiac excitability, blood pressure control, gating of calcium channels and transmembrane ion flux.\r\n\r\nThe mitochondrial intracellular space is rich in magnesium, since it is required to produce the active form of ATP (adenosine triphosphate) from ADP (adenosine diphosphate) and inorganic phosphate, and behaves as a counter ion for the energy rich molecule. Additionally, magnesium is essential for ATP metabolism.\r",null,"Indication associated"]
[1524,"DB14533","approved; investigational","small molecule","Zinc chloride","Zinc chloride","Cl2Zn","[Cl-].[Cl-].[Zn++]","Zinc chloride is a solution of ions indicated for use in total parenteral nutrition to maintain zinc levels and prevent deficiency syndromes.\r\n\r\nZinc chloride was granted FDA approval before 26 June 1986.","7646-85-7","136.315","Zinc chloride injections are indicated for use total parenteral nutrition to maintain zinc serum levels and prevent deficiency syndromes.","Zinc is a cofactor in many enzymes and mediates a number of catalytic, structural, and regulatory roles in the body. It has a wide therapeutic index and long duration of action, as most zinc in the body is reabsorbed. Patients should be counselled regarding the risk of administration in patients with severe kidney dysfunction.","Zinc performs catalytic, structural, and regulatory roles in the body. Zinc is a component of approximately 3000 human proteins.\r\n\r\nZinc is cytoprotective against reactive oxygen species mediated apoptosis through the action of metallothioneins.\r\n\r\nIn a promyelocytic leukemia cell line, zinc enhances the up-regulation of A20 mRNA, which, via the TRAF pathway, decreases NF-kappaB activation, leading to decreased gene expression and generation of TNF-α, IL-1β, and IL-8 .\r\n\r\nIn patients with diarrhea, zinc restores mucosal barrier integrity, restores enterocyte brush-border enzyme activity, promotes the production of antibodies, and promotes the production of circulating lymphocytes against intestinal pathogens. Zinc also directly affects ion channels as a potassium channel blocker of cAMP-mediated chlorine secretion.\r\n\r\nZinc deficiency decreases thymulin, inhibiting T-helper cell maturation and decreased Th-1 cytokines like IL-2. Decreased IL-2 decreases the activity of NK cells and CD8+ T cells. Zinc deficiency also leads to the generation of CD4+ T cells, decreased NF-κB activation, decreased phosphorylation of IκB, and decreased binding of NF-κB to DNA.","B1 bradykinin receptor agonist; Methylated-DNA--protein-cysteine methyltransferase stabilization; Fructose-bisphosphate aldolase A ligand; Elongation factor 1-alpha 1 binder; Alpha-enolase binder; Glyceraldehyde-3-phosphate dehydrogenase, testis-specific binder; Nucleoside diphosphate kinase A inhibitor; Protein disulfide-isomerase binder; Protein disulfide-isomerase A3 binder; Peroxiredoxin-1 binder; Phosphoserine phosphatase binder; Triosephosphate isomerase binder; Elongation factor Tu, mitochondrial cofactor; Estrogen receptor alpha binder; Interleukin-3 binder; Metallothionein-2 cofactor; Copper chaperone for superoxide dismutase cofactor; Histone deacetylase 1 cofactor; Histone deacetylase 4 cofactor; DNA-3-methyladenine glycosylase cofactor; Semenogelin-1 cofactor; Superoxide dismutase [Cu-Zn] cofactor; Histone deacetylase 8 cofactor; Apoptosis regulatory protein Siva binder; Glycine receptor subunit alpha-1 inhibitor; E3 ubiquitin-protein ligase Mdm2 binder; Insulin stabilization; Utrophin cofactor; Aspartoacylase cofactor; Protein S100-A8 regulator; Protein S100-A9 regulator; Matrix metalloproteinase-9 binder; Tumor protein p73 chaperone; Protein S100-A2 inactivator&regulator; Cellular tumor antigen p53 chaperone; Metallothionein-3 cofactor; Metallothionein-1A binder; Alpha-2-macroglobulin ligand; Alpha-2-HS-glycoprotein chelator; Apolipoprotein A-I inducer&ligand; Apolipoprotein B receptor inducer; Apolipoprotein E antagonist; Apolipoprotein L1 inhibitor; Complement C1q subcomponent subunit B modulator; Complement C1q subcomponent subunit C modulator; Complement C1r subcomponent modulator; Complement C1s subcomponent modulator; Complement C3 inhibitor&ligand; Complement C4-B modulator; C4b-binding protein alpha chain modulator; C4b-binding protein beta chain modulator; Complement C5 ligand; Lys-63-specific deubiquitinase BRCC36 cofactor; Complement factor H ligand; Clusterin inducer; Ceruloplasmin ligand; Carboxypeptidase N catalytic chain cofactor; Carboxypeptidase N subunit 2 cofactor; Dermcidin stabilization; Fibrinogen alpha chain binder; Fibronectin modulator&ligand; Hemoglobin subunit alpha inducer; Hemoglobin subunit beta inducer; Haptoglobin binder; Insulin-like growth factor-binding protein complex acid labile subunit inducer; Inter-alpha-trypsin inhibitor heavy chain H1 binder; Inter-alpha-trypsin inhibitor heavy chain H2 binder; Inter-alpha-trypsin inhibitor heavy chain H3 binder; Inter-alpha-trypsin inhibitor heavy chain H4 binder; Immunoglobulin J chain component of; Plasma kallikrein inhibitor; Kininogen-1 cofactor; Keratin, type I cytoskeletal 9 ligand; Alpha-1-acid glycoprotein 2 binder; N-acetylmuramoyl-L-alanine amidase binder; Serum paraoxonase/arylesterase 1 inducer; Pregnancy zone protein binder; Protein S100-A7 binder; Selenoprotein P binder; Alpha-1-antitrypsin ligand; Alpha-1-antichymotrypsin binder; Corticosteroid-binding globulin modulator; Heparin cofactor 2 agonist; Sex hormone-binding globulin modulator; Serotransferrin ligand; Transthyretin inducer; Vitronectin inducer; Amyloid-like protein 1 ligand; Amyloid-like protein 2 ligand; Amyloid beta A4 protein ligand; Poly [ADP-ribose] polymerase 1 component of; Apolipoprotein B-100 ligand; Hemopexin ligand; Histidine-rich glycoprotein cofactor; Coagulation factor XI activator; C->U-editing enzyme APOBEC-1 cofactor&chelator; Semenogelin-2 cofactor","Therapeutic strategy associated"]
[1525,"DB14538","experimental; vet_approved","small molecule","Hydrocortisone aceponate","Hydrocortisone aceponate","C26H36O7","[H][C@@]12CC[C@](OC(=O)CC)(C(=O)COC(C)=O)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C",null,"74050-20-7","460.567","For the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses. Also used to treat endocrine (hormonal) disorders (adrenal insufficiency, Addisons disease). It is also used to treat many immune and allergic disorders, such as arthritis, lupus, severe psoriasis, severe asthma, ulcerative colitis, and Crohn's disease.","Hydrocortisone is the most important human glucocorticoid. It is essential for life and regulates or supports a variety of important cardiovascular, metabolic, immunologic and homeostatic functions. Topical hydrocortisone is used for its anti-inflammatory or immunosuppressive properties to treat inflammation due to corticosteroid-responsive dermatoses. Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger a variety of important cardiovascular, metabolic, immunologic and homeostatic effects. Glucocorticoids are distinguished from mineralocorticoids and sex steroids by having different receptors, target cells, and effects. Technically, the term corticosteroid refers to both glucocorticoids and mineralocorticoids, but is often used as a synonym for glucocorticoid. Glucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-alpha, the most important of which is the IL-2. Reduced cytokine production limits T cell proliferation. Glucocorticoids also suppress humoral immunity, causing B cells to express lower amounts of IL-2 and IL-2 receptors. This diminishes both B cell clonal expansion and antibody synthesis. The diminished amounts of IL-2 also leads to fewer T lymphocyte cells being activated.","Hydrocortisone binds to the cytosolic glucocorticoid receptor. After binding the receptor the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes. The anti-inflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. Specifically glucocorticoids induce lipocortin-1 (annexin-1) synthesis, which then binds to cell membranes preventing the phospholipase A2 from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. The cyclooxygenase (both COX-1 and COX-2) expression is also suppressed, potentiating the effect. In other words, the two main products in inflammation Prostaglandins and Leukotrienes are inhibited by the action of Glucocorticoids. Glucocorticoids also stimulate the lipocortin-1 escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines etc.) from neutrophils, macrophages and mastocytes. Additionally the immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding.","Annexin A1; Glucocorticoid receptor; Corticosteroid 11-beta-dehydrogenase isozyme 2; 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1","Therapeutic strategy associated"]
[1526,"DB14539","approved; vet_approved","small molecule","Hydrocortisone acetate","21-O-acetylcortisol; Cortisol 21-acetate; Hydrocortisone 21-acetate; Hydrocortisone acetate","C23H32O6","[H][C@@]12CC[C@](O)(C(=O)COC(C)=O)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C",null,"50-03-3","404.4966","For the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses. Also used to treat endocrine (hormonal) disorders (adrenal insufficiency, Addisons disease). It is also used to treat many immune and allergic disorders, such as arthritis, lupus, severe psoriasis, severe asthma, ulcerative colitis, and Crohn's disease.","Hydrocortisone is the most important human glucocorticoid. It is essential for life and regulates or supports a variety of important cardiovascular, metabolic, immunologic and homeostatic functions. Topical hydrocortisone is used for its anti-inflammatory or immunosuppressive properties to treat inflammation due to corticosteroid-responsive dermatoses. Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger a variety of important cardiovascular, metabolic, immunologic and homeostatic effects. Glucocorticoids are distinguished from mineralocorticoids and sex steroids by having different receptors, target cells, and effects. Technically, the term corticosteroid refers to both glucocorticoids and mineralocorticoids, but is often used as a synonym for glucocorticoid. Glucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-alpha, the most important of which is the IL-2. Reduced cytokine production limits T cell proliferation. Glucocorticoids also suppress humoral immunity, causing B cells to express lower amounts of IL-2 and IL-2 receptors. This diminishes both B cell clonal expansion and antibody synthesis. The diminished amounts of IL-2 also leads to fewer T lymphocyte cells being activated.","Hydrocortisone binds to the cytosolic glucocorticoid receptor. After binding the receptor the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes. The anti-inflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. Specifically glucocorticoids induce lipocortin-1 (annexin-1) synthesis, which then binds to cell membranes preventing the phospholipase A2 from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. The cyclooxygenase (both COX-1 and COX-2) expression is also suppressed, potentiating the effect. In other words, the two main products in inflammation Prostaglandins and Leukotrienes are inhibited by the action of Glucocorticoids. Glucocorticoids also stimulate the lipocortin-1 escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines etc.) from neutrophils, macrophages and mastocytes. Additionally the immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding.","Annexin A1; Glucocorticoid receptor; Corticosteroid 11-beta-dehydrogenase isozyme 2; 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1","Therapeutic strategy associated"]
[1527,"DB14540","approved; vet_approved","small molecule","Hydrocortisone butyrate","11β,21-dihydroxy-17α-butyryloxy-4-pregnene-3,20-dione; 17-O-butyrylcortisol; Cortisol 17-butyrate; H-17-B; Hydrocortisone butyrate; Hydrocortisone-17alpha-butyrate","C25H36O6","[H][C@@]12CC[C@](OC(=O)CCC)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C",null,"13609-67-1","432.557","For the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses. Also used to treat endocrine (hormonal) disorders (adrenal insufficiency, Addisons disease). It is also used to treat many immune and allergic disorders, such as arthritis, lupus, severe psoriasis, severe asthma, ulcerative colitis, and Crohn's disease.","Hydrocortisone is the most important human glucocorticoid. It is essential for life and regulates or supports a variety of important cardiovascular, metabolic, immunologic and homeostatic functions. Topical hydrocortisone is used for its anti-inflammatory or immunosuppressive properties to treat inflammation due to corticosteroid-responsive dermatoses. Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger a variety of important cardiovascular, metabolic, immunologic and homeostatic effects. Glucocorticoids are distinguished from mineralocorticoids and sex steroids by having different receptors, target cells, and effects. Technically, the term corticosteroid refers to both glucocorticoids and mineralocorticoids, but is often used as a synonym for glucocorticoid. Glucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-alpha, the most important of which is the IL-2. Reduced cytokine production limits T cell proliferation. Glucocorticoids also suppress humoral immunity, causing B cells to express lower amounts of IL-2 and IL-2 receptors. This diminishes both B cell clonal expansion and antibody synthesis. The diminished amounts of IL-2 also leads to fewer T lymphocyte cells being activated.","Hydrocortisone binds to the cytosolic glucocorticoid receptor. After binding the receptor the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes. The anti-inflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. Specifically glucocorticoids induce lipocortin-1 (annexin-1) synthesis, which then binds to cell membranes preventing the phospholipase A2 from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. The cyclooxygenase (both COX-1 and COX-2) expression is also suppressed, potentiating the effect. In other words, the two main products in inflammation Prostaglandins and Leukotrienes are inhibited by the action of Glucocorticoids. Glucocorticoids also stimulate the lipocortin-1 escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines etc.) from neutrophils, macrophages and mastocytes. Additionally the immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding.","Annexin A1; Glucocorticoid receptor; Corticosteroid 11-beta-dehydrogenase isozyme 2; 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1","Therapeutic strategy associated"]
[1528,"DB14541","approved; investigational; vet_approved","small molecule","Hydrocortisone cypionate","Cortisol 21-cyclopentanepropionate; Hydrocortisone cipionate","C29H42O6","[H][C@@]12CC[C@](O)(C(=O)COC(=O)CCC3CCCC3)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C",null,"508-99-6","486.649","For the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses. Also used to treat endocrine (hormonal) disorders (adrenal insufficiency, Addisons disease). It is also used to treat many immune and allergic disorders, such as arthritis, lupus, severe psoriasis, severe asthma, ulcerative colitis, and Crohn's disease.","Hydrocortisone is the most important human glucocorticoid. It is essential for life and regulates or supports a variety of important cardiovascular, metabolic, immunologic and homeostatic functions. Topical hydrocortisone is used for its anti-inflammatory or immunosuppressive properties to treat inflammation due to corticosteroid-responsive dermatoses. Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger a variety of important cardiovascular, metabolic, immunologic and homeostatic effects. Glucocorticoids are distinguished from mineralocorticoids and sex steroids by having different receptors, target cells, and effects. Technically, the term corticosteroid refers to both glucocorticoids and mineralocorticoids, but is often used as a synonym for glucocorticoid. Glucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-alpha, the most important of which is the IL-2. Reduced cytokine production limits T cell proliferation. Glucocorticoids also suppress humoral immunity, causing B cells to express lower amounts of IL-2 and IL-2 receptors. This diminishes both B cell clonal expansion and antibody synthesis. The diminished amounts of IL-2 also leads to fewer T lymphocyte cells being activated.","Hydrocortisone binds to the cytosolic glucocorticoid receptor. After binding the receptor the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes. The anti-inflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. Specifically glucocorticoids induce lipocortin-1 (annexin-1) synthesis, which then binds to cell membranes preventing the phospholipase A2 from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. The cyclooxygenase (both COX-1 and COX-2) expression is also suppressed, potentiating the effect. In other words, the two main products in inflammation Prostaglandins and Leukotrienes are inhibited by the action of Glucocorticoids. Glucocorticoids also stimulate the lipocortin-1 escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines etc.) from neutrophils, macrophages and mastocytes. Additionally the immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding.","Annexin A1; Glucocorticoid receptor; Corticosteroid 11-beta-dehydrogenase isozyme 2; 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1","Therapeutic strategy associated"]
[1529,"DB14542","approved; vet_approved","small molecule","Hydrocortisone phosphate","Cortisol 21-phosphate; Hydrocortisone 21-phosphate","C21H31O8P","[H][C@@]12CC[C@](O)(C(=O)COP(O)(O)=O)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C",null,"3863-59-0","442.445","For the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses. Also used to treat endocrine (hormonal) disorders (adrenal insufficiency, Addisons disease). It is also used to treat many immune and allergic disorders, such as arthritis, lupus, severe psoriasis, severe asthma, ulcerative colitis, and Crohn's disease.","Hydrocortisone is the most important human glucocorticoid. It is essential for life and regulates or supports a variety of important cardiovascular, metabolic, immunologic and homeostatic functions. Topical hydrocortisone is used for its anti-inflammatory or immunosuppressive properties to treat inflammation due to corticosteroid-responsive dermatoses. Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger a variety of important cardiovascular, metabolic, immunologic and homeostatic effects. Glucocorticoids are distinguished from mineralocorticoids and sex steroids by having different receptors, target cells, and effects. Technically, the term corticosteroid refers to both glucocorticoids and mineralocorticoids, but is often used as a synonym for glucocorticoid. Glucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-alpha, the most important of which is the IL-2. Reduced cytokine production limits T cell proliferation. Glucocorticoids also suppress humoral immunity, causing B cells to express lower amounts of IL-2 and IL-2 receptors. This diminishes both B cell clonal expansion and antibody synthesis. The diminished amounts of IL-2 also leads to fewer T lymphocyte cells being activated.","Hydrocortisone binds to the cytosolic glucocorticoid receptor. After binding the receptor the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes. The anti-inflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. Specifically glucocorticoids induce lipocortin-1 (annexin-1) synthesis, which then binds to cell membranes preventing the phospholipase A2 from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. The cyclooxygenase (both COX-1 and COX-2) expression is also suppressed, potentiating the effect. In other words, the two main products in inflammation Prostaglandins and Leukotrienes are inhibited by the action of Glucocorticoids. Glucocorticoids also stimulate the lipocortin-1 escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines etc.) from neutrophils, macrophages and mastocytes. Additionally the immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding.","Annexin A1; Glucocorticoid receptor; Corticosteroid 11-beta-dehydrogenase isozyme 2; 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1","Therapeutic strategy associated"]
[1530,"DB14543","approved; vet_approved","small molecule","Hydrocortisone probutate","Hydrocortisone buteprate; Hydrocortisone butyrate propionate; Hydrocortisone probutate","C28H40O7","[H][C@@]12CC[C@](OC(=O)CCC)(C(=O)COC(=O)CC)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C",null,"72590-77-3","488.613","For the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses. Also used to treat endocrine (hormonal) disorders (adrenal insufficiency, Addisons disease). It is also used to treat many immune and allergic disorders, such as arthritis, lupus, severe psoriasis, severe asthma, ulcerative colitis, and Crohn's disease.","Hydrocortisone is the most important human glucocorticoid. It is essential for life and regulates or supports a variety of important cardiovascular, metabolic, immunologic and homeostatic functions. Topical hydrocortisone is used for its anti-inflammatory or immunosuppressive properties to treat inflammation due to corticosteroid-responsive dermatoses. Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger a variety of important cardiovascular, metabolic, immunologic and homeostatic effects. Glucocorticoids are distinguished from mineralocorticoids and sex steroids by having different receptors, target cells, and effects. Technically, the term corticosteroid refers to both glucocorticoids and mineralocorticoids, but is often used as a synonym for glucocorticoid. Glucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-alpha, the most important of which is the IL-2. Reduced cytokine production limits T cell proliferation. Glucocorticoids also suppress humoral immunity, causing B cells to express lower amounts of IL-2 and IL-2 receptors. This diminishes both B cell clonal expansion and antibody synthesis. The diminished amounts of IL-2 also leads to fewer T lymphocyte cells being activated.","Hydrocortisone binds to the cytosolic glucocorticoid receptor. After binding the receptor the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes. The anti-inflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. Specifically glucocorticoids induce lipocortin-1 (annexin-1) synthesis, which then binds to cell membranes preventing the phospholipase A2 from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. The cyclooxygenase (both COX-1 and COX-2) expression is also suppressed, potentiating the effect. In other words, the two main products in inflammation Prostaglandins and Leukotrienes are inhibited by the action of Glucocorticoids. Glucocorticoids also stimulate the lipocortin-1 escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines etc.) from neutrophils, macrophages and mastocytes. Additionally the immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding.","Annexin A1; Glucocorticoid receptor; Corticosteroid 11-beta-dehydrogenase isozyme 2; 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1","Therapeutic strategy associated"]
[1531,"DB14544","approved; vet_approved","small molecule","Hydrocortisone valerate","Cortisol 17-valerate; Hydrocortisone 17-valerate; Hydrocortisone valerate","C26H38O6","[H][C@@]12CC[C@](OC(=O)CCCC)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C",null,"57524-89-7","446.5763","For the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses. Also used to treat endocrine (hormonal) disorders (adrenal insufficiency, Addisons disease). It is also used to treat many immune and allergic disorders, such as arthritis, lupus, severe psoriasis, severe asthma, ulcerative colitis, and Crohn's disease.","Hydrocortisone is the most important human glucocorticoid. It is essential for life and regulates or supports a variety of important cardiovascular, metabolic, immunologic and homeostatic functions. Topical hydrocortisone is used for its anti-inflammatory or immunosuppressive properties to treat inflammation due to corticosteroid-responsive dermatoses. Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger a variety of important cardiovascular, metabolic, immunologic and homeostatic effects. Glucocorticoids are distinguished from mineralocorticoids and sex steroids by having different receptors, target cells, and effects. Technically, the term corticosteroid refers to both glucocorticoids and mineralocorticoids, but is often used as a synonym for glucocorticoid. Glucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-alpha, the most important of which is the IL-2. Reduced cytokine production limits T cell proliferation. Glucocorticoids also suppress humoral immunity, causing B cells to express lower amounts of IL-2 and IL-2 receptors. This diminishes both B cell clonal expansion and antibody synthesis. The diminished amounts of IL-2 also leads to fewer T lymphocyte cells being activated.","Hydrocortisone binds to the cytosolic glucocorticoid receptor. After binding the receptor the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes. The anti-inflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. Specifically glucocorticoids induce lipocortin-1 (annexin-1) synthesis, which then binds to cell membranes preventing the phospholipase A2 from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. The cyclooxygenase (both COX-1 and COX-2) expression is also suppressed, potentiating the effect. In other words, the two main products in inflammation Prostaglandins and Leukotrienes are inhibited by the action of Glucocorticoids. Glucocorticoids also stimulate the lipocortin-1 escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines etc.) from neutrophils, macrophages and mastocytes. Additionally the immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding.","Annexin A1; Glucocorticoid receptor; Corticosteroid 11-beta-dehydrogenase isozyme 2; 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1","Therapeutic strategy associated"]
[1532,"DB14569","approved; investigational","small molecule","Tedizolid","Tedizolid; Torezolid","C17H15FN6O3","CN1N=NC(=N1)C1=NC=C(C=C1)C1=C(F)C=C(C=C1)N1C[C@H](CO)OC1=O","Drug-resistant bacteria, such as methicillin-resistant _Staphylococcus aureus_, vancomycin-resistant _Enterococcus faecium_, and penicillin-resistant _Streptococcus penumoniae_, represent a massive public health threat. Tedizolid is a member of the oxazolidinone class of antibiotics, which includes the previously approved  and is generally effective against multidrug-resistant Gram-positive bacteria. Tedizolid is indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and is generally more effective and more tolerable than .\r\n\r\nTedizolid was approved by the FDA on June 20, 2014, for sale by Cubist Pharmaceuticals as tedizolid phosphate (SIVEXTRO®). This product is currently available as both an oral tablet and as a powder for intravenous injection.","856866-72-3","370.344","Tedizolid is indicated for the treatment of acute bacterial infections of the skin and skin structure (ABSSSI). To prevent drug resistance, tedizolid should only be used for infections that are caused by susceptible bacteria.","Tedizolid is an oxazolidinone antibiotic that works by inhibiting protein synthesis by bacterial ribosomes. However, oxazolidinone antibiotics can also bind to human mitochondrial, but not cytoplasmic, ribosomes. Mitochondrial protein synthesis inhibition is associated with adverse patient effects such as neurological, hematological, and gastrointestinal toxicity, although tedizolid is tolerated better than the related . Alternative therapies should be considered when treating neutropenic patients with ABSSSI. _Clostridium difficile_-associated diarrhea has been reported in patients treated with tedizolid.","Despite renewed efforts to combat the spread of antimicrobial resistance, multidrug-resistant organisms, including gram-positive bacteria such as methicillin-resistant _Staphylococcus aureus_, remain a threat. Oxazolidinones represent a relatively new class of antibacterials inhibiting protein synthesis that is generally capable of overcoming resistance to other bacterial protein synthesis inhibitors.\r\n\r\nProtein synthesis involves the action of ribosomes, multi-subunit complexes composed of both protein and ribosomal RNA (rRNA) substituents. Translocation along the length of a messenger RNA and concomitant protein synthesis involves the action of the A, P, and E sites of the peptidyltransferase centre (PTC), which accepts charged aminoacyl-tRNAs and catalyzes the formation of peptide bonds between them. The bacterial 70S ribosome comprises a small (30S) and a large (50S) subunit.\r\n\r\nEarly studies into the mechanism of action of oxazolidinone antibiotics suggested that they inhibit a step in the initiation of protein synthesis. However, this mechanism was inconsistent with mapped resistance mutations, and later studies involving cross-linking and direct structural determination of the binding site revealed that oxazolidinones, including both  and tedizolid, bind in the A site of the PTC by interacting with the 23S rRNA component. The structural studies also revealed that oxazolidinone binding alters the conformation of a conserved nucleotide in the 23S rRNA (U2585 in _Escherichia coli_), which renders the PTC non-productive for peptide bond formation. Hence, tedizolid exerts its effect through inhibiting bacterial protein synthesis.","23S ribosomal RNA inhibitor","Indication associated"]
[1533,"DB14597","approved; investigational","biotech","Lanadelumab","Lanadelumab; lanadelumab-flyo",null,null,"Lanadelumab, also known as DX-2930, is a human IgG1 monoclonal antibody designed for subcutaneous self-injection. It is a fully human immunoglobulin, k-light-chain made in recombinant Chinese Hamster Ovary cells. The FDA and EU granted the designation of priority review, breakthrough therapy and orphan drug for rare diseases based on the results of the reported clinical trials. Lanadelumab was developed by Shire and FDA approved on August 28, 2018.","1426055-14-2",null,"Lanadelumab is indicated for the prophylaxis treatment to prevent attacks in patients 12 years and older with hereditary angioedema.\r\n\r\nThe hereditary angioedema (HEA) is an autosomal dominant disorder resulted from the presence of C1 deficiency. Some reports have indicated a high prevalence of cases that result from spontaneous mutations which can be inherited. This condition is manifested by attacks of subcutaneous or submucosal edema in the face, larynx, GI tract, limbs or genitalia. From all the types of attacks, the most serious is the laryngeal as it can compromise the airway. The rest of the attacks are accompanied by pain and considerable dysfunction.","In phase 1 studies, the level of kininogen, the substrate of kallikrein, was studied as a marker of kallikrein activity. In patients with C1 deficiency, the level of cleaved kininogen is 4-fold higher when compared with C1-normal individuals. When lanadelumab was administered, the levels of cleaved kininogen were significantly reduced with a dose of 300 and 400 mg of lanadelumab with a maximum reduction at day 22 corresponding with time for maximum concentration. This maximum reduction corresponded with the normal levels of cleaved kininogen. Similarly, the decreases of cleaved kininogen corresponded as well with reductions in the levels of the activated factor XII. \r\n\r\nClinically, the attacks of angioedema completely vanished in the patients receiving a dose of 300 mg of lanadelumab. In other doses such as 400 mg and combo 300/400 mg the attack reduction reached 90%.\r\n\r\nIn phase 3 clinical trials (HELP study, lanadelumab showed an attack rate reduction of over 70% for all three different dose regimes.","Lanadelumab is a plasma kallikrein inhibitor. This enzyme works by cleaving high molecular weight kininogen to generate the pro-inflammatory peptide bradykinin which is a potent vasodilator. The activity of plasma kallikrein is regulated by the activity of C1-inhibitor and thus, the patients that are deficient in C1 are known to be correlated to excessive production of bradykinin which will further lead to fatal angioedema. Hence, lanadelumab occludes the proteolytic active site of plasma kallikrein, preventing the cleavage of kininogen to bradykinin. It is a selective inhibitor as it has been reported that lanadelumab does not bind to prekallikrein or to inhibit any other serine proteases. The activity of lanadelumab works as an additional checkpoint for the patients suffering from C1 deficiency.","Plasma kallikrein inhibitor","Therapeutic strategy associated"]
[1534,"DB14631","approved; vet_approved","small molecule","Prednisolone phosphate","Prednisolone 21-(dihydrogen phosphate); Prednisolone 21-monophosphate; Prednisolone 21-phosphate","C21H29O8P","[H][C@@]12CC[C@](O)(C(=O)COP(O)(O)=O)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)C=C[C@]12C","Prednisolone phosphate is a glucocorticoid similar to  used for its anti-inflammatory, immunosuppressive, anti-neoplastic, and vasoconstrictive effects.\r\n\r\nPrednisolone phosphate was granted FDA Approval on 19 December 1973.","302-25-0","440.429","Prednisolone phosphate is indication to a number of conditions including treat allergic states, dermatologic diseases, edematous states, endocrine disorders, gastrointestinal diseases, hematologic disorders, neoplastic diseases, nervous system, ophthalmic diseases, respiratory diseases, rheumatic disorders.","Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals. Prednisolone has a short duration of action as the half life is 2-4 hours. Corticosteroids have a wide therapeutic window as patients make require doses that are multiples of what the body naturally produces. Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.","The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.\r\n\r\nGlucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10.\r\n\r\nLower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.","Glucocorticoid receptor agonist; Annexin A1 ligand","Therapeutic strategy associated"]
[1535,"DB14635","experimental","small molecule","Curcumin sulfate","Curcumin monosulfate; Curcumin sulphate","C21H20O9S","COC1=CC(\\C=C\\C(=O)CC(=O)\\C=C\\C2=CC=C(OS(O)(=O)=O)C(OC)=C2)=CC=C1O",null,"339286-19-0","448.44","No approved therapeutic indications.","Intravenous application of 25 mg/kg bw curcumin to rats resulted in an increase in bile flow by 80 and 120% . In the rat model of inflammation, curcumin was shown to inhibit edema formation. In nude mouse that had been injected subcutaneously with prostate cancer cells, administration of curcumin caused a marked decrease in the extent of cell proliferation, a significant increase of apoptosis and micro-vessel density . Curcumin may exert choleretic effects by increasing biliary excretion of bile salts, cholesterol, and bilirubin, as well as increasing bile solubility . Curcumin inhibited arachidonic acid-induced platelet aggregation _in vitro_ .","Curcumin acts as a scavenger of oxygen species, such as hydroxyl radical, superoxide anion, and singlet oxygen and inhibit lipid peroxidation as well as peroxide-induced DNA damage . Curcumin mediates potent anti-inflammatory agent and anti-carcinogenic actions via modulating various signalling molecules. It suppresses a number of key elements in cellular signal transduction pathways pertinent to growth, differentiation, and malignant transformation; it was demonstrated _in vitro_ that curcumin inhibits protein kinases, c-Jun/AP-1 activation, prostaglandin biosynthesis, and the activity and expression of the enzyme cyclooxygenase (COX)-2 .","Peroxisome proliferator-activated receptor gamma; Vitamin D3 receptor; Multidrug resistance-associated protein 5; Carbonyl reductase [NADPH] 1; Glutathione S-transferase P","Therapeutic strategy associated"]
[1536,"DB14644","approved","small molecule","Methylprednisolone hemisuccinate","Methylprednisolone hemisuccinate; Methylprednisolone hydrogen succinate; Methylprednisolone succinate","C26H34O8","[H][C@@]12CC[C@](O)(C(=O)COC(=O)CCC(O)=O)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])C[C@H](C)C2=CC(=O)C=C[C@]12C","A water-soluble ester of methylprednisolone used for cardiac, allergic, and hypoxic emergencies.","2921-57-5","474.55",null,"Methylprednisolone sodium succinate (the sodium salt of methylprednisolone hemisuccinate) has the same metabolic and anti-inflammatory actions as methylprednisolone. When given parenterally and in equimolar quantities, the two compounds are equivalent in biologic activity.",null,null,"Therapeutic strategy associated"]
[1537,"DB14669","approved; vet_approved","small molecule","Betamethasone phosphate","Betamethasone 21-(dihydrogen phosphate); Betamethasone 21-phosphate; Betamethasone dihydrogen phosphate","C22H30FO8P","[H][C@@]12C[C@H](C)[C@](O)(C(=O)COP(O)(O)=O)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])CCC2=CC(=O)C=C[C@]12C","Betamethasone phosphate is a prodrug that is rapidly hydrolyzed, providing rapidly accessible  to agonize glucocorticoid receptors. Betamethasone provides greater anti-inflammatory activity than  with less sodium and water retention.\r\n\r\nBetamethasone sodium phosphate was granted FDA approval on 3 March 1965.","360-63-4","472.446","Betamethasone phosphate is indicated intramuscularly to treat allergic states, dermatologic diseases, endocrine disorders, gastrointestinal diseases, hematologic disorders, neoplastic diseases, nervous system conditions, ophthalmic diseases, renal diseases, respiratory diseases, rheumatic disorders, trichinosis with neurologic or myocardial involvement, and tuberculous meningitis with subarachnoid block or impending block. It is also used intra-articularly in the treatment of acute gouty arthritis, acute and subacute bursitis, acute nonspecific tenosynovitis, epicondylitis, rheumatoid arthritis, and synovitis of osteoarthritis. Intralesional betamethasone phospahte is indicated in the treatment of alopecia areata, discoid lupus erythematosus, keloids, lichen planus, lichen simplex chronicus, psoriatic plaques, necrobiosis lipoidica diabeticorum, and localized hypertrophic, infiltrated, inflammatory lesions of granuloma annulare.","Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals. Betamethasone phosphate has a short duration of action as it is rapidly hydrolyzed to betamethasone. Corticosteroids have a wide therapeutic window as patients may require doses that are multiples of what the body naturally produces. Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.","Betamethasone phosphate is a soluble ester prodrug of betamethasone. Betamethasone is rapidly de-esterified, allowing betamethasone to act as an agonist of the glucocorticoid receptor. The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.\r\n\r\nGlucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10.\r\n\r\nLower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.","Glucocorticoid receptor agonist; Annexin A1 agonist","Therapeutic strategy associated"]
[1538,"DB14683","experimental","small molecule","Prezatide copper","CG-copper peptide; Copper tripeptide-1; GHK complex with copper; GHK copper","C14H23CuN6O4","[Cu++].NCCCC[C@H](NC(=O)[C@H](CC1=CN=CN1)NC(=O)CN)C([O-])=O","Prezatide is a tripeptide consisting of glycine, histidine, and lysine which readily forms a complex with copper ions . Prezatide is used in cosmetic products for the skin and hair. It is known to aid wound healing and its potential applications in chronic obstructive pulmonary disease and metastatic colon cancer are currently being investigated.","89030-95-5","402.921","Commonly used in cosmetic products for the skin and hair .","Prezatide in complex with copper improve skin elasticity, density, and firmness, reduces fine lines and wrinkles, reduces photodamage, increases keratinocyte proliferation . Prezatide also displays anti-oxidant and angiogenic effects and appears to modulate tissue remodeling in injury.","Prezatide in complex with copper increases the synthesis and deposition of type I collagen and glycosaminoglycan  . It also increases the expression of matrix metalloproteinase-2 as well as tissue inhibitor of matrix metalloproteinases-1 and -2, suggesting that it plays a role in the modulation of tissue remodeling . It is thought that prezatide's antioxidant activity is due to its ability to supply copper for superoxide dismutase and its anti inflammatory ability due to the blockage the of iron (Fe2+) release during injury . Prezatide also increases angiogenesis to injury sites. The precise mechanisms of these effects are unknown. It is also unknown whether prezatide's effects are due to the action of the tripeptide itself or its ability to localize and transport copper . Prezatide is known to be bound by heparin and heparin sulfate",null,"Therapeutic strategy associated"]
[1539,"DB14684","approved","small molecule","Calcium polycarbophil","Calcium polycarbophil; Polycarbophil calcium; Polycarbophil, calcium",null,null,"Calcium polycarbophil is a stool stabilizer. Based on its chemical structure, it is a synthetic polymer of polyacrylic acid cross-linked with divinyl glycol presenting a calcium atom as a counter-ion. Polycarbophil is used to treat constipation. This drug may also be used to help relieve the symptoms of irritable bowel syndrome or diarrhea.\r\n\r\nLess gas and bloating compared to psyllium laxative products, but can cause heartburn, and belly cramps. It is insoluble in water, dilute acids, and dilute alkali. The material possesses exceptionally high water-binding capacity. is not absorbed, does not interfere with the activity of digestive enzymes or intestinal absorption, possesses satisfactory stability, is physiologically inert, and does not cause gastrointestinal irritation.","126040-58-2",null,"Polycarbophil is used to treat constipation and to help maintain regular bowel movements.","Relieves constipation or diarrhea associated with bowel disorders and acute nonspecific diarrhea.","It is known as a bulk-forming laxative. It increases the bulk in the stool, an effect that helps to cause movement of the intestines. It also works by increasing the amount of water in the stool, making the stool softer and easier to pass.",null,"Indication associated"]
[1540,"DB14731","approved; investigational","biotech","Tagraxofusp","Diphtheria toxin-il-3 fusion protein targeting IL-3 receptor; Tagraxofusp; tagraxofusp-erzs",null,null,"Tagraxofusp is an IL-3 conjugated truncated diphtheria toxin. It is composed by the catalytic and translocation domains of diphtheria toxin fused via Met-His linker to a full-length human IL-3. Tagraxofusp was developed by Stemline Therapeutics Inc and FDA approved on December 21, 2018, as the first therapy for blastic plasmacytoid dendritic cell neoplasm. This drug achieved approval after being designated with the title of breakthrough therapy, priority review, and orphan drug status. Tagraxofusp has been designated as an orphan drug in the EU since November 2015.","2055491-00-2",null,"Tagraxofusp is indicated for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and pediatric patients over 2 years old. This treatment allows an alternative for the previous intense treatment which consisted of intensive chemotherapy followed by bone marrow transplantation.\r\n\r\nBPDCN is a rare hematologic malignancy derived from plasmacytoid dendritic cells. It is characterized by the significantly increased expression of cells expressing CD4/CD56/CD123 and other markers restricted to plasmacytoid dendritic cells and a lack of expression of lymphoid, natural killer or myeloid lineage-associated antigens. A key feature of the malignant cells is the overexpression of CD123, also known as interleukin-3 receptor, and the constant requirement of IL-3 for survival.","In vitro studies showed that BPDCN blasts are ultrasensitive to tagraxofusp by presenting IC50 values in the femtomolar scale. One of the main physiological changes of BPDCN is the presence of elevated interferon alpha and to produce an inflammatory response. In trials with tagraxofusp and following cell depletion, there was observed a significant reduction in the levels of interferon alpha and interleukin 6.\r\n\r\nIn clinical trials, tagraxofusp reported complete remission and complete remission with a skin abnormality not indicative of active disease in 54% of the treated patients.","Tagraxofusp binds to cells expressing the IL-3 receptor and delivers in them the diphtheria toxin after binding. This is very useful as the malignant cells in BPDCN present a particularly high expression of IL-3 receptor (CD123+ pDC). To be more specific, tagraxofusp gets internalized to the IL-3 receptor-expressing cell allowing for diphtheria toxin translocation to the cytosol and followed by the binding to ADP-ribosylation elongation factor 2 which is a key factor for protein translation. Once the protein synthesis is inhibited, the cell goes under a process of apoptosis.\r\n\r\nAs the apoptosis induction requires an active state of protein synthesis, tagraxofusp is not able to perform its apoptotic function in dormant cells.","Interleukin-3 receptor subunit alpha binder; ADP-ribosylation factor-like protein 2 binder","Therapeutic strategy associated"]
[1541,"DB14751","approved","biotech","Mecasermin rinfabate","Mecasermin rinfabate; Mecasermin rinfabate recombinant; rhIGF-I/rhIGFBP-3",null,null,"Mecasermin rinfabate is approved for severe primary insulin-like growth factor (IGF) deficiency or in patients with GH gene deletion who have developed antibodies to growth hormone (GH). Mecasermin rinfabate is similar to  in that both drugs contain recombinant DNA origin insulin-like growth factor 1 (IGF-1). Mecasermin rinfabate however, is already bound to recombinant DNA origin insulin-like growth factor binding protein 3 (IGFBP-3). The binding of IGF-1 to IGFBP-3 is said to extend the half life and reduce the clearance of IGF-1 in patients with growth hormone resistant syndromes and low levels of IGFBP-3 though this may represent <500 patients worldwide.\r\n\r\nMecasermin rinfabate manufactured by Insmed Incorporated under the brand name Iplex was approved by the FDA in 2005. In 2007 Insmed withdrew their application for a marketing authorization with The European Medicines Agency.","478166-15-3",null,"Mecasermin rinfabate was approved for treatment of severe primary insulin-like growth factor (IGF) deficiency or in patients with GH gene deletion who have developed antibodies to growth hormone (GH).\r\nSevere primary IGF-1 deficiency is defined by:\r\n\r\nA) height standard deviation (SD) score less than or equal to 3 SD below normal\r\n\r\nB) basal IGF-1 SD score less than or equal to 3 SD below normal\r\n\r\nC) normal or above normal levels of growth hormone\r\n\r\nIn 2007, Insmed (Mecasermin rinfabate's manufacturer) made an agreement with Tercica (Mecasermin's manufacturer) that Mecasermin would no longer be available for this indication but could be developed for non short stature conditions such as severe insulin resistance, myotonic muscular dystrophy, and HIV associated adipose redistribution syndrome.","Mecasermin rinfabate promotes vertical growth in pediatric patients in a similar fashion to .\r\n\r\n is a biosynthetic (recombinant DNA origin) form of human insulin-like growth factor 1 (IGF-1) designed to replace natural IGF-1 in pediatric patients who are deficient, promoting normalized statural growth. Growth hormones (GH) bind to growth hormone receptors (GHR) in the liver and other tissues, which stimulates the synthesis of IGF-1. In target tissues, IGF-1 activates the IGF-1 receptor, resulting in intracellular signals that stimulate growth . Although many actions of the GH are mediated through IGF-1, the precise roles of GH and IGF-1 have not been fully elucidated. Patients with severe primary IGF-1 deficiency (Primary IGFD) fail to produce adequate levels of IGF-1, due to disruption of the GH pathway used to promote IGF-1 release (possible GH pathway disruptions include mutations in the GHR, post-GHR signaling pathway, and IGF-1 gene defects.\r\n\r\nThe structure of IGFBP-3 remains unsolved.","Mecasermin rinfabate supplies recombinant-DNA-origin IGF-1 (rhIGF-1) bound to recombinant-DNA-origin IGFBP-3. 80% of IGF-1 is naturally bound to IGFBP-3 so the binding of rhIGF-1 to rhIGFBP-3 increases the half life of rhIGF-1 compared to . rhIGF-1 binds to the Type I IGF-1 receptor. This receptor exerts intra-cellular signaling activity in a number of processes involved in statural growth, including mitogenesis in multiple tissue types, chondrocyte growth and division along cartilage growth plates, and increases in organ growth.","Insulin-like growth factor 1 receptor agonist; Insulin receptor; Cation-independent mannose-6-phosphate receptor","Indication associated"]
[1542,"DB14762","approved; investigational","biotech","Risankizumab","Risankizumab; risankizumab-rzaa",null,null,"Risankizumab is a fully humanized IgG1 monoclonal antibody (mAb) that is selective for interleukin 23 (IL-23). On April 23, 2019 it was approved by the FDA (as _SKYRIZI_) for the treatment of moderate-to-severe plaque psoriasis in adults who are clinically considered eligible for systemic therapy or phototherapy for psoriasis. This drug has been commercialized through collaboration between the German pharmaceutical company, Boehringer Ingelheim, and Abbvie.\r\n\r\nPsoriasis is a chronic inflammatory disease of the skin most commonly characterized by raised, red plaques covered with silver scales in cases of plaque psoriasis. There are several subtypes of psoriasis, however, plaque psoriasis is most prevalent. This disease occurs mainly in adults (with a prevalence ranging from 0.91% to 8.5%). Psoriasis has a peak incidence at two age groups: approximately 30–39 years and approximately 60 years of age. Depending on disease severity, psoriasis may have significant effects on quality of life and can lead to embarrassment and negative social consequences. Risankizumab is a promising drug for the relief of plaque psoriasis and has been shown to be effective in managing the above unpleasant symptoms.","1612838-76-2",null,"This drug is for the treatment of moderate-to-severe plaque psoriasis in adults who are eligible to receive systemic therapy or phototherapy based on their disease process.","No formal studies examining pharmacodynamic properties have been completed with risankizumab , however, this drug is expected to relieve symptoms of psoriasis by targeting interleukin 23 (IL-23) and preventing the initiation of the inflammatory cascade that is implicated in psoriasis.","Risankizumab acts to prevent the release of pro-inflammatory cytokines and chemokines that often lead to inflammatory skin symptoms, such as redness, pain, and plaques. Risankizumab binds with a high affinity to the p19 subunit of human interleukin 23 (IL-23) cytokine , thereby preventing its action on the IL-23 receptor. IL-23 is a  cytokine released in the human body that is involved in inflammatory and immune processes, especially in peripheral tissues.\r\n\r\n IL-23 plays a role in polarized type-1 T cell-mediated inflammatory response.  Type-1 T cells are found in very high concentrations in psoriasis-affected skin in addition to the blood of psoriasis patients.  By promoting the action of interferon (IFN)-gamma , type-1 T cells increase the expression of many inflammatory genes that induce inflammatory cascades . Variants of the gene encoding IL-23 p19 subunit and the IL-23 receptor have been recognized as part of the pathogenesis of plaque psoriasis, rendering IL-23 an ideal target for risankizumab therapy.","Interleukin-23 inhibitor","Therapeutic strategy associated"]
[1543,"DB14783","approved; investigational","small molecule","Diroximel fumarate","Diroximel fumarate","C11H13NO6","COC(=O)\\C=C\\C(=O)OCCN1C(=O)CCC1=O","Multiple Sclerosis (MS) is a chronic, debilitating neurological disease that can lead to profound cognitive and physical symptoms, severely affecting quality of life. It is the main cause of neurological disability not caused by trauma in the young adult population of both North America and Europe. Relapsing-remitting forms of MS lead to neurological symptoms that resolve and recur periodically. More than 80% of patients suffering from this disease have relapsing-remitting MS.\r\n\r\nDiroximel fumarate is a new drug from the fumarate class formulated to treat various relapsing forms of MS.  This drug is bioequivalent to (initially manufactured in 2013), but is less likely to cause gastrointestinal side effects, owing to its unique chemical structure. Diroximel fumarate was formulated by Alkermes in collaboration with Biogen, and was approved by the FDA in October 2019 and by the EMA in November 2021.","1577222-14-0","255.226","Diroximel fumarate is indicated for the treatment of relapsing forms of multiple sclerosis (MS) in adults; specifically active secondary progressive disease and clinically isolated syndrome, as well as relapsing-remitting MS.","Diroximel fumarate relieves the neurological symptoms of relapsing MS with less gastrointestinal effects than its bioequivalent counterpart, dimethyl fumarate. It is important to note that diroximel fumarate can cause angioedema, anaphylaxis, hepatotoxicity, flushing, lymphopenia, and Progressive Multifocal Leukoencephalopathy (PML). \r\n\r\nDiscontinue diroximel fumarate immediately if PML is suspected or if anaphylaxis or angioedema occur. Liver function and total bilirubin should be tested prior to initiating diroximel fumarate and during treatment. A complete blood count (CBC) should be obtained prior to starting diroximel fumarate, after the first 6 months of administration, and at subsequent intervals of 6 to 12 months following this period. Suspend treatment if lymphocyte counts are measured to be less than 0.5 × 109/L for more than 6 months.","Currently, the mechanism of action of this drug in MS is not fully understood. Diroximel fumarate is hypothesized to regulate cell signaling pathways, causing beneficial immune and neuroprotective effects. Monomethyl fumarate (MMF) is the active metabolite of diroximel fumarate, and activates the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway in humans. This pathway occurs as a response to oxidative stress in cells.\r\n\r\nIn addition to the above, MMF is a nicotinic acid receptor agonist in the laboratory setting. The relevance of this finding to the treatment of MS is unknown at this time. The mechanism by which this drug leads to less gastrointestinal effects is purported to be due to its lack of a methanol leaving group in its chemical structure, and substitution with inert 2-hydroxyethyl succinimide.","Neuronal acetylcholine receptor subunit alpha-10 agonist","Therapeutic strategy associated"]
[1544,"DB14811","approved; investigational","biotech","Isatuximab","Isatuximab; isatuximab-irfc",null,null,"Isatuximab (formerly SAR650984) is a humanized, IgG1-derived monoclonal antibody (mAb) produced from a Chinese hamster ovary (CHO) cell line. Structurally, isatuximab is comprised of two identical immunoglobulin kappa light chains and two identical immunoglobulin gamma heavy chains. It is a cytolytic antibody targeted against CD38, a glycoprotein found on the surface of some immune cells that is highly expressed by malignant plasma cells in multiple myeloma. Along with , another anti-CD38 mAb, isatuximab constitutes a novel treatment modality for patients with difficult-to-treat multiple myeloma.\r\n\r\nFollowing three consecutive years on the yearly \"Antibodies to watch\" list published in \"mAb\", a peer-reviewed scientific journal dedicated to antibody research, isatuximab was granted Orphan Drug designation and approved on March 2nd, 2020, for the treatment of multiple myeloma. It is manufactured by Sanofi-Aventis U.S. under the brand name Sarclisa.","1461640-62-9",null,"Isatuximab is indicated in combination with  and  for the treatment of multiple myeloma in adults who have received at least two prior therapies including  and a proteasome inhibitor. It is also indicated in combination  and dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy.","Isatuximab results in the apoptosis of malignant plasma cells via inhibition of a surface protein key to their survival and proliferation. It has a relatively long residence time in the body, taking approximately 2 months to clear following the final dose, and may therefore be infused on a weekly or bimonthly schedule. Isatuximab is given in combination with  due to a synergy that exists between the two - isatuximab can induce a depletion in host NK lymphocytes, yet the ADCC effect of anti-CD38 mAbs has been shown to be superior in patient samples with a high ratio of NK to myleoma cells. Pomalidomide, another antineoplastic agent, has the ability to induce and enhance NK lymphocyte activity and thus works synergistically to enhance isatuximab-mediated killing of myeloma cells.\r\n\r\nIsatuximab is formulated as an intravenous infusion and its administration may result in infusion-related reactions characterized most commonly by dyspnea, cough, chills, and nausea. All noted reactions started during the first infusion and 98% resolved on the same day. Reactions may be mitigated by pre-medication with acetaminophen, H2 antagonists, diphenyhdramine, and/or dexamethasone. Patients with grade 1 or 2 reactions may restart the infusion at a slower rate following resolution of symptoms, but patients experiencing a grade 3 or higher reaction (e.g. hypertension, bronchospasm) should discontinue therapy indefinitely.\r\n\r\nIsatuximab can generate false positive results for indirect antglobulin tests (indirect Coombs tests), immunofixation tests, and serum protein electrophoresis.","Multiple myeloma is a blood cancer characterized by an overproduction of malignant plasma cells in the bone marrow. A unique characteristic of myeloma cells is their dense and uniform expression of CD38 surface glycoproteins - these proteins, also expressed in relatively minor quantities on other lymphoid and myeloid cells, have been identified as performing several critical cellular functions, and this, along with their relative abundance on myeloma cells, has made them an attractive target for multiple myeloma treatment. CD38 was first identified as an activation marker, but has subsequently demonstrated roles in adhesion to endothelial CD31 proteins, as an accessory component of the synapse complex, and as an ectoenzyme involved in the metabolism of extracellular NAD+ and cytoplasmic NADP. The products of CD38’s ectoenzymatic activity include the calcium-mobilizing compound adenosine diphosphate ribose (ADPR), which can be further metabolized by CD203a/PC-1 and CD73 to adenosine, an immunosuppressive molecule that may play a role in tumour cell evasion of the immune system.\r\n\r\nIsatuximab is an IgG1-derived monoclonal antibody targeted against CD38 proteins. Its activity against CD38 results in a number of downstream effects, including direct apoptosis of the affected cell and activation of immune mechanisms including antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement dependent cytotoxicity (CDC), all of which result in potent anti-tumour activity. Via allosteric antagonism, isatuximab also inhibits CD38 ectoenzymatic activity, preventing the immunosuppressive effects of its downstream products.\r\n\r\nIsatuximab may also exert its effects via downstream promotion of lysosome-dependent cell death, upregulation of reactive oxygen species, and restoration of antitumor immune effector cell functions.","ADP-ribosyl cyclase 1 binder&antibody","Therapeutic strategy associated"]
[1545,"DB14845","approved; investigational","small molecule","Filgotinib","Filgotinib","C21H23N5O3S","O=C(NC1=NN2C(C=CC=C2C2=CC=C(CN3CCS(=O)(=O)CC3)C=C2)=N1)C1CC1","Rheumatoid arthritis (RA) is a chronic, autoimmune, systemic, and inflammatory disease that causes synovial joint symptoms and can limit range of motion in severe cases. The disease is associated with extra-articular manifestations, progressive disability, and comorbidities including cardiovascular disease and mental disorders. 50-70% of patients with RA are unable to achieve sustained clinical remission despite the availability of several treatments including disease-modifying anti-rheumatic drugs (DMARDS) like , interleukin-6 (IL-6) blockers, and tumor necrosis factor (TNF) inhibitors. New therapeutic developments target other inflammatory pathways implicated in RA including the Janus kinase (JAK) signaling pathway as seen with filgotinib. \r\n\r\nThere are four JAK subtypes which include JAK1, JAK2, JAK3, and tyrosine kinase 2. Non-selective JAK inhibitors like  target JAK1 and JAK3 subtypes with minimal activity at JAK2. In contrast, the newly approved filgotinib is a highly selective JAK1 inhibitor. JAK2 and JAK3 play important roles in both immune and hematologic functions; therefore, selectivity for JAK1 aims to improve the safety profile of filgotinib while maintaining clinical efficacy. Filgotinib is currently reserved for patients who cannot tolerate DMARDs, or who have been unable to achieve remission in response to one or more DMARDs.","1206161-97-8","425.51","Filgotinib is indicated for the treatment of active moderate to severe rheumatoid arthritis alone or in combination with methotrexate. Filgotinib is currently reserved for patients who are unable to tolerate or who have not responded adequately to one or more disease-modifying anti-rheumatic drugs (DMARDS).\r\n\r\nFilgotinib is also indicated for treatment of moderately to severely active ulcerative colitis in adult patients who had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a biologic agent.","In addition to targeted Janus kinase (JAK) 1 inhibition, filgotinib targets pro-inflammatory cytokine signalling by inhibiting IL-6 induced STAT1 phosphorylation. Serum C-reactive protein levels are also reduced in response to filgotinib administration.\r","There are four Janus kinase (JAK) enzymes including JAK1, JAK2, JAK3, and tyrosine kinase 2. JAK1 mediates inflammatory cytokine signaling, while JAK2 and JAK3 are important components of hematologic and immune functions. Filgotinib selectively inhibits JAK1 and is for example nearly 30-fold more selective for JAK1 compared to JAK2. \r\n\r\nThe Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is implicated in several inflammatory pathologies and has been found to be continuously active in patients who have RA. Sustained activation of this pathway contributes to aberrant processes which lead to disease progression including elevated levels of matrix metalloproteinases (MMPs) and reduced cell apoptosis in RA affected synovial tissues. Filgotinib acts on the JAK-STAT pathway by selectively inhibiting JAK1 phosphorylation and preventing STAT activation, which ultimately results in reduced proinflammatory cytokine signaling.","Tyrosine-protein kinase JAK1 inhibitor","Therapeutic strategy associated"]
[1546,"DB14901","approved; investigational","biotech","Inclisiran","ALN-PCSsc; Inclisiran",null,null,"Inclisiran is a long-acting, synthetic small interfering RNA (siRNA) directed against proprotein convertase subtilisin-kexin type 9 (PCSK9), which is a serine protease that regulates plasma low-density lipoprotein cholesterol (LDL-C) levels. By binding to PCSK9 messenger RNA, inclisiran prevents protein translation of PCSK9, leading to decreased concentrations of PCSK9 and plasma concentrations of LDL cholesterol. Lowering circulating plasma LDL-C levels offers an additional benefit of reducing the risk of cardiovascular disease (CVD) and improving cardiovascular outcomes, as hypercholesterolemia is a major known risk factor for CVD. \r\n\r\nOn December 11, 2020, the European Commission (EC) granted authorization for marketing inclisiran as the first and only approved siRNA for the treatment of adults with primary hypercholesterolemia (heterozygous familial and non-familial) or mixed dyslipidemia, alone or in combination with other lipid-lowering therapies. It is marketed under the trade name Leqvio  and is also currently under review by the FDA.","1639324-58-5",null,"Inclisiran is indicated for the treatment of primary hypercholesterolemia (heterozygous familial and non-familial) or mixed dyslipidemia in adults, as an adjunct to diet. \r\n\r\nIt can be used in combination with a statin or statin with other lipid-lowering therapies in patients who cannot reach LDL-C goals with the maximum tolerated dose of a statin. In patients who cannot tolerate statins or in whom a statin is contraindicated, inclisiran can be used as monotherapy or in combination with other lipid-lowering therapies.","Inclisiran is a long-acting small interfering RNA (siRNA) that works to lower plasma LDL-cholesterol (LDL-C) levels. In clinical trials, the reduction of LDL-C levels was observed within 14 days post-dose: mean reductions of LDL-C by 48-51% were observed 30 to 60 days post-dose and reduction of LDL-C levels by 53% persisted after 180 days post-dose. In healthy volunteers, inclisiran reduced PCSK9 levels by 70-80% and LDL-C levels by 27-60%. In a clinical trial consisting of subjects with atherosclerotic cardiovascular disease with or without diabetes, inclisiran reduced LDL-C levels by 28-52%. \r\n\r\nThe long-term effect of inclisiran on cardiovascular outcomes has not yet been elucidated, although reductions in the levels of LDL-C have been associated with a reduction of cardiovascular risk.","Low-density lipoprotein (LDL) receptors expressed on hepatocytes are responsible for the removal of circulating LDL-C from plasma via receptor-mediated endocytosis. Proprotein convertase subtilisin-kexin type 9 (PCSK9) is a serine protease that is mainly produced by hepatocytes. It binds to LDL receptors and targets them for lysosomal degradation, thereby reducing the levels of LDL receptors, attenuating the recycling of LDL receptors, and elevating the levels of circulating plasma LDL-C.\r\n\r\nInclisiran is conjugated to triantennary N-acetylgalactosamine carbohydrates, which can bind to asialoglycoprotein receptors expressed in the liver. Binding to asialoglycoprotein receptors facilitates the uptake of inclisiran into the hepatocytes. Once inside the hepatocyte, inclisiran binds to the RNA-induced silencing complex (RISC), which is a ribonucleoprotein complex that serves as a template for recognizing the target complementary mRNA, activate RNAse, and cleave the target mRNA. Inclisiran incorporated into the RISC allows the drug to cleave PCSK9 mRNA and prevent PCSK9 translation, thus decreasing hepatic production of PCSK9. Less PCSK9 protein available allows more LDL receptors to be recycled to the hepatic membrane for circulating LDL-C uptake.","Proprotein convertase subtilisin/kexin type 9 antisense oligonucleotide","Indication associated"]
[1547,"DB14960","approved","biotech","Somatrogon","Somatrogon",null,null,"Somatrogon is a long-acting recombinant human growth hormone. Growth hormone is a peptide hormone secreted by the pituitary gland that plays a crucial role in promoting longitudinal growth during childhood and adolescence and regulating metabolic function in adulthood. Recombinant growth hormone therapy for growth hormone deficiency and other conditions has been available since 1985, with daily administration being the standard treatment for many years. More recently, longer-acting forms of growth hormone were developed to improve patient adherence and thus, improve the therapeutic efficacy of treatment. Somatrogon was produced in Chinese Hamster Ovary (CHO) cells using recombinant DNA technology. It is a chimeric product generated by fusing three copies of the C-terminal peptide (CTP), or 28 carboxy-terminal residues, from the beta chain of human chorionic gonadotropin (hCG) to the N-terminus and C-terminus of human growth hormone. The glycosylation and the presence of CTPs in the protein sequence prolongs the half-life of somatrogon and allows its once-weekly dosing.\r\n\r\nIn October 2021, Health Canada approved somatrogon under the market name NGENLA as the long-term treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone caused by growth hormone deficiency, marking Canada as the first country to approve this drug. It is available as a once-weekly subcutaneous injection.","1663481-09-1",null,"Somatrogon is indicated for the long-term treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone (growth hormone deficiency).","Somatrogon mimics the physiological actions of endogenous growth hormone, such as cell proliferation, metabolism, and growth. It was also shown to increase the serum concentration of insulin-like growth factor (IGF-1).","Growth hormone is a key hormone that promotes body growth and regulates carbohydrate, protein and lipid metabolism. Somatrogon is a hormone replacement therapy that aims to restore deficient levels of growth hormone (GH). Like endogenous growth hormone, somatrogon binds to the GH receptor, which leads to the binding of JAK2 to GH receptor and activation of JAK2. Activation of JAK2 and phosphorylation of both JAK2 and GHR initiates the recruits various signalling proteins and facilitates multiple signalling pathways responsible for growth and metabolism. One of the activated signalling pathways is the STAT5b signalling pathway, which is critical for the effect of GH on body height.",null,"Therapeutic strategy associated"]
[1548,"DB14962","approved; investigational","biotech","Trastuzumab deruxtecan","fam-trastuzumab deruxtecan-nxki; Trastuzumab deruxtecan",null,null,"Trastuzumab deruxtecan is a HER-2 directed antibody attached to a topoisomerase inhibitor that is approved for use in certain types of metastatic, unresectable breast cancer. It is classified as an antibody-drug conjugate. The cleavable peptide linker used to bind the antibody and drug in this product distinguishes it from other members of its class. Trastuzumab deruxtecan has been granted FDA approval for specific patients with HER-2 positive breast cancer who have failed other treatments.\r\n\r\nPromising results from a clinical trial prompted accelerated FDA approval for this indication on December 20, 2019. Trastuzumab deruxtecan was developed by Daiichi Sankyo in collaboration with AstraZeneca. The continued approval of this drug will depend on the confirmation of its beneficial effects in ongoing clinical trials.","1826843-81-5",null,"Trastuzumab deruxtecan is indicated for the treatment of adult patients with HER-2 positive breast cancer that is unresectable or metastatic and was previously treated with at least 2 anti-HER2-based regimens while the cancer was metastatic.\r\n\r\nContinued approval will depend on the results of clinical trial results confirming its clinical benefit.","Trastuzumab demonstrates antitumor activity against certain types of HER2 positive breast cancer, however, clinical trials are still ongoing to confirm its efficacy.  By exploiting both targeted antibody and cytotoxic effects, trastuzumab deruxtecan can effectively destroy tumors. \r\n\r\nThe FDA label warns of a potential risk for neutropenia, interstitial lung disease/pneumonitis, and left ventricular dysfunction following the use of this drug.","Trastuzumab deruxtecan is a humanized anti-HER2 IgG1 antibody, targeting cancer cause by mutation of the HER2 gene. In addition, the small molecule portion of this drug, deruxtecan (DXd), is a topoisomerase I inhibitor.  It is attached to the antibody by a peptide linker. After trastuzumab deruxtecan binds to HER2 found on malignant cells, it is internalized and linker cleavage occurs through the actions of lysosomal enzymes. After it is released through cleavage, DXd causes targeted DNA damage and apoptosis in cancer cells, due to the ability to cross cell membranes.\r\n\r\nNormally, drugs in this class (antibody-drug conjugates) present a challenge. The monoclonal antibody accurately targets cancer cells, however exert limited killing action. The addition of a cytotoxic agent (a topoisomerase I inhibitor in this case) effectively kills dividing cancer cells, including those in the healthy tissues, leading to various adverse effects.  The peptide linker used to formulate this drug is cleavable, which is unique to other antibody-drug conjugates, allowing for increased efficacy and reduced drug resistance to topoisomerase.","High affinity immunoglobulin gamma Fc receptor I antibody; DNA topoisomerase 1 inhibitor","Therapeutic strategy associated"]
[1549,"DB14967","approved; investigational","biotech","Margetuximab","Margetuximab; margetuximab-cmkb",null,null,"The HER2 oncoprotein, the product of the human _ERBB2_/mouse _neu_ genes, is a member of the HER family of receptor tyrosine kinases that includes the epidermal growth factor receptor (EGFR). Of the various subtypes of breast cancer, HER2-positive breast cancer is characterized by _ERBB2_ overexpression, a higher grade, a more aggressive phenotype, and a worse prognosis compared to HER2-negative cancer. The introduction of  improved patient outcomes in HER2-positive breast cancer, but notably depended substantially on polymorphisms in the FcγRIIIA/CD16A receptor, whereby low affinity 158F CD16A variants are associated with shorter progression-free survival and worse patient outcomes.\r\n\r\nMargetuximab (formerly MGAH22) is an Fc-engineered human/mouse chimeric anti-HER2 IgG1κ monoclonal antibody derived from the same mouse 4D5 clone that  is derived from and is produced in Chinese Hamster Ovary (CHO) culture. Margetuximab binds to the same epitope on the HER2 extracellular domain and induces the same effects as . However, due to its modified Fc region, margetuximab binds with higher affinity to both CD16A variants and exhibits weaker binding to the inhibitory CD32B Fc receptor, resulting in more efficient antibody-dependent cell-mediated cytotoxicity (ADCC) and increased efficacy compared to .\r\n\r\nMargextuximab was granted FDA approval on December 16, 2020, and is currently marketed under the trademark MARGENZA™ by MacroGenics, Inc.","1350624-75-7",null,"Margetuximab is an anti-HER2 monoclonal antibody indicated, in combination with chemotherapy, for the treatment of metastatic HER2-positive breast cancer in adult patients who have received two or more prior anti-HER2 regimens with at least one prior regimen for metastatic disease.","Margetuximab is a chimeric IgG1κ monoclonal antibody (mAb) directed against the extracellular domain of the human epidermal growth factor receptor 2 (HER2) cell-surface protein. Also, margetuximab has an engineered Fc region that alters its affinity for the CD16A and CD32B effector cell receptors resulting in increased antibody-dependent cell-mediated cytotoxicity (ADCC). To date, the exposure-response and time course pharmacodynamic relationships of margetuximab remain incompletely characterized. Although generally well-tolerated, margetuximab carries a risk of infusion-related reactions, including symptoms such as fever, fatigue, nausea, vomiting, headache, tachycardia, hypotension, and cutaneous manifestations such as a rash or urticaria; infusion reactions may require alterations to the infusion or, in serious reactions, discontinuation.","The HER family of transmembrane receptor tyrosine kinases (RTKs) includes the epidermal growth factor receptor (EGFR/HER1), HER2, HER3, and HER4 proteins; HER family members are generally involved in cell proliferation, angiogenesis, cell motility and invasiveness, and resistance to apoptosis. HER2 is an oncoprotein whose overexpression is observed in breast, gastric, and other cancers. HER2 undergoes both ligand-independent homodimerization and ligand-dependent heterodimerization with other HER family members, followed by RTK phosphorylation and induction of downstream oncogenic signalling pathways. EGFR/HER2 dimerization promotes EGFR recycling and prolonged signalling while HER2/HER3 dimerization potently stimulates the downstream PI3K/AKT pathway; HER2 homodimerization directly activates the RAS/MAPK pathway and indirectly activates the PI3K/AKT pathway.\r\n\r\nThe prototypical anti-HER2 therapy is , a monoclonal antibody (mAb) that binds the HER2 extracellular domain.  works through several mechanisms:  binding induces receptor internalization and c-CBL-mediated HER2 degradation; effector cell binding to the Fc region of  through CD16A results in antibody-mediated cell-dependent cytotoxicity (ADCC); finally,  binding dampens HER2 activation, phosphorylation, and subsequent downstream oncogenic signalling.\r\n\r\nDespite demonstrated clinical efficacy,  efficacy is dependent on polymorphisms in CD16A. Effector cells such as natural killer (NK) cells and macrophages bind to mAbs through Fc receptors such as CD16A (FcγRIIIA), CD32A (FcγRIIA), and the inhibitory CD32B (FcγRIIB). CD16A has both high affinity (with valine at position 158; 158V) and low affinity (158F) variants; patients heterozygous or homozygous for the 158F variant have poorer responses to . Margetuximab is derived from the same mouse 4D5 clone as , but with a modified (MGFc0264) Fc region encoding five amino acid substitutions (L235V, F243L, R292P, Y300L, and P396L) to alter Fc receptor binding. Comparatively, margetuximab exhibits increased binding to both the high affinity (K<sub>D</sub> of 89 nM vs 415 nM) and low affinity (K<sub>D</sub> of 161 nM vs 1059 nM) CD16A receptors and decreased binding to the inhibitory CD32B receptor (K<sub>D</sub> of 437 nM vs 52 nM). This, in turn, increases ADCC and anti-tumour effect, especially in cells expressing lower levels of HER2 and in patients with the lower affinity 158F CD16A variant.","Receptor tyrosine-protein kinase erbB-2 antagonist","Therapeutic strategy associated"]
[1550,"DB14999","approved; investigational","biotech","Human interferon beta","Fibroblast interferon; FIF; Interferon beta; Interferon beta (human); Interferon-beta",null,null,"Human interferon beta is a polypeptide used in the management of relapsing forms of Multiple Sclerosis (MS), and was initially approved by the FDA in 1992. Multiple Sclerosis is a devastating neurodegenerative disease that is usually progressive and significantly debilitating with a profound impact on the quality of life. \r\n\r\nInterferon beta is currently being studied as a possible treatment for COVID-19, which results from infection with the novel 2019 SARS-CoV-2 virus. Interferon-beta has been used in the past in clinical studies with other coronaviruses due to its demonstrated activity against the virus causing Middle Eastern Respiratory Syndrome (MERS). It is therefore a potential drug candidate for SARS-CoV-2 based on viral genetic similarity.","74899-71-1",null,"This drug is indicated to treat relapsing forms of Multiple Sclerosis (MS) in adults, which includes clinically isolated syndrome, relapsing-remitting disease, as well as active secondary progressive disease.","Interferon-beta has antiviral and immunomodulatory effects. It reduces demyelination, the main component of Multiple Sclerosis pathophysiology, reducing the clinical frequency of MS attacks and slowing disease progression.\r\n\r\nIn vitro studies have shown that beta interferon reduces the replication of certain coronaviruses in lung tissue. Retrospective studies using combinations of  and beta interferon showed improved survival against MERS-CoV, the virus that causes Middle Eastern Respiratory Syndrome (MERS).","Part of the pathophysiology of MS is immune cell activation in addition to degradation of the blood–brain barrier (BBB), resulting in both neural demyelination and axon injury. Immunomodulating drugs such as interferon-beta decrease the inflammation that results in demyelination of nerves.  Binding of interferon-beta to type 1 interferon receptors induces a series of beneficial transcriptional JAK/STAT pathway changes. This decreases antigen presentation as well as the proliferation of inflammatory T-cells, reducing the inflammation associated with MS. It also changes the expression of cytokine and matrix metalloproteinase (MMP). \r\n\r\n\r\n\r","Interferon alpha/beta receptor 1 binder","Therapeutic strategy associated"]
[1551,"DB15011","approved; investigational","small molecule","Avacopan","Avacopan","C33H35F4N3O2","CC1=CC=C(NC(=O)[C@H]2CCCN([C@H]2C2=CC=C(NC3CCCC3)C=C2)C(=O)C2=C(F)C=CC=C2C)C=C1C(F)(F)F","Anti-neutrophil cytoplasmic (auto)antibody (ANCA)-associated vasculitis (AAV) is a rare (estimated incidence of 3 cases per 100,000 per year) form of \"pauci-immune\" systemic small-vessel vasculitis typified by the presence of ANCAs in the serum. The full spectrum of AAV includes granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), and drug-induced AAV. AAV may be associated with necrotizing and crescentic glomerulonephritis (NCGN). Despite complex pathophysiology, studies over the past ~2 decades have identified a key role for the alternative complement pathway and, in particular, the interaction between the anaphylatoxin fragment C5a and its cognate C5aR receptor in AAV. Avacopan (formerly CCX168) is an allosteric C5aR antagonist indicated for use in AAV.\r\n\r\nAvacopan was granted FDA approval on October 8, 2021, and is currently marketed under the name TAVNEOS by ChemoCentryx, Inc.","1346623-17-3","581.656","Avacopan is indicated for the adjunctive treatment of adult patients with severe active anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (granulomatosis with polyangiitis and microscopic polyangiitis; GPA/MPA) in combination with standard therapy including glucocorticoids. Avacopan does not eliminate the need for glucocorticoids.","Avacopan is a complement 5a receptor (C5aR) antagonist that blocks C5a-induced upregulation of C11b (integrin alpha M) on neutrophils and inhibits C5a-mediated neutrophil activation and migration. Avacopan has been associated with hypersensitivity reactions, including angioedema, and hepatotoxicity, as evidenced by elevated liver transaminases. Likely due to its effect on the complement pathway, avacopan has also been associated with hepatitis B virus reactivation and serious infections, which should be monitored for as appropriate.","Anti-neutrophil cytoplasmic (auto)antibody (ANCA)-associated vasculitis (AAV) is considered a \"pauci-immune\" form of systemic small-vessel vasculitis accompanied by the presence of ANCAs in the serum. The full spectrum of AAV includes granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), and drug-induced AAV. AAV may be associated with necrotizing and crescentic glomerulonephritis (NCGN). Of the various known ANCAs, the major antigens are myeloperoxidase (MPO) and proteinase 3 (PR3/myeloblastin).\r\n\r\nThe pathophysiology giving rise to AAV is complex, though a working model has been proposed. An initial trigger, such as infection, causes differentiation of naive T cells into T<sub>H</sub>17 helper T cells that induce the release from macrophages of pro-inflammatory cytokines (e.g., TNF-α and IL-1β), which prime neutrophils. Concurrently, the anaphylatoxin C5a is produced through activation of the alternative complement pathway, which also primes neutrophils through binding to the C5a receptor (C5aR; CD88). Primed neutrophils undergo physiological changes, including upregulating the display of ANCA antigens on their surface. Circulating ANCAs bind to displayed ANCA antigens on the surface of neutrophils; simultaneously, the Fc region of these ANCAs is recognized by Fcγ receptors on other neutrophils, resulting in excessive neutrophil activation. Activated neutrophils form NETs (neutrophil extracellular traps), which induce tissue damage and vasculitis. MPO/PR3 in NETs induces further ANCA production through dendritic cell- and CD4<sup>+</sup> T cell-mediated activation of B cells, further exacerbating the condition.\r\n\r\nA role for complement was not initially considered in AAV due to a lack of excessive complement or immunoglobulin deposition in AAV lesions. However, extensive molecular studies confirmed a significant role for the alternative complement pathway, acting through C3 and C5, in the pathogenesis of AAV. The C5a fragment, generated by C5 cleavage, can bind to both the C5aR and C5a-like receptor (C5L2) on the surface of neutrophils; C5aR binding is associated with AAV while C5L2 binding has a protective effect. As the alternative complement pathway is self-sustaining in the absence of down-regulation by specific proteins, it is likely a significant driver of AAV. Furthermore, neutrophils activated by C5a release reactive oxygen species, properdin, and other molecules that stimulate the complement pathway leading to the production of more C5a in a vicious cycle.\r\n\r\nAvacopan (CCX168) is a specific C5aR receptor allosteric antagonist that inhibits C5a-mediated neutrophil activation both _in vitro_ and _in vivo_. By inhibiting the C5a/C5aR axis, avacopan should have minimal effects on the formation of the membrane attack complex (which includes C5b) and therefore little effect on the innate immune response in treated patients.","C5a anaphylatoxin chemotactic receptor 1 antagonist","Therapeutic strategy associated"]
[1552,"DB15021","investigational","small molecule","Leriglitazone","Leriglitazone","C19H20N2O4S","CC(O)C1=CN=C(CCOC2=CC=C(CC3SC(=O)NC3=O)C=C2)C=C1","Leriglitazone is under investigation in clinical trial NCT03917225 (A Clinical Study to Evaluate the Effect of MIN-102 on the Progression of Friedreich's Ataxia in Male and Female Patients).","146062-44-4","372.438",{"$nulls":3},"Peroxisome proliferator-activated receptor gamma","Target associated"]
[1553,"DB15044","approved; investigational","biotech","Tafasitamab","Tafasitamab; tafasitamab-cxix",null,null,"Tafasitamab is a humanized, CD19-directed cytolytic monoclonal antibody intended for the treatment of B-cell malignancies. It is produced using recombinant DNA technology in Chinese hamster ovary cells, and contains an IgG1/2 hybrid Fc-domain which has been modified with 2 amino acid substitutions to enhance its cytotoxicity relative to non-engineered anti-CD19 antibodies.\r\n\r\nThe CD19 surface protein is highly expressed on the surface of B-cells, where it appears to play a role in enhancing B-cell receptor signaling. Its relative ubiquity across different stages of B-cell development, including pre-B and mature B-lymphocytes, as well as its presence in several B-cell malignancies (e.g. chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), diffuse large B-cell lymphoma (DLBCL)) has made it a desirable target in the treatment these B-cell malignancies. Tafasatimab is designed to bind to and block the activity of the CD19 surface antigen, which ultimately results in the lysis of B-cells (both healthy and malignant).\r\n\r\nHaving previously received Breakthrough Therapy, Fast Track, and Orphan designations from the FDA, tafasatimab-cxix (Monjuvi®) received an accelerated approval on July 31st, 2020, for the treatment of relapsed or refractory DLBCL in adult patients who cannot receive autologous stem cell transplants. It must be used in combination with , as this combination results in greater efficacy as compared to either agent alone.","1422527-84-1",null,"Tafasitamab is indicated, in combination with , for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified whom are ineligible for autologous stem cell transplant (ASCT).","Tafasitamab induces a reduction in circulating B-cell counts by binding to a surface antigen, CD19, which is important for their survival. Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) experienced a 97% reduction in peripheral blood B-cell counts following 8 days of treatment, with a 100% reduction reached within 16 weeks of treatment.\r\n\r\nTafasitamab can cause infusion-related reactions, particularly during the initial cycles of therapy. Symptoms may include chills, flushing, dyspnea, and hypertension. Patients may be administered premedications (such as , antihistamines, or glucocorticoids) 0.5 - 2 hours prior to infusion to minimize infusion-related reactions. Tafasitamab may also cause significant myelosuppression, and subsequent infection, due to its mechanism of action - patients should undergo monitoring throughout therapy for signs of myelosuppression and/or infection.","The CD19 surface antigen is a protein expressed on the surface of pre-B and mature B-lymphocytes that appears to play a role in enhancing B-cell receptor signaling and is considered integral to their survival. These surface proteins are also highly expressed on several B-cell malignancies, such as chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and diffuse large B-cell lymphoma (DLBCL).\r\n\r\nTafasitamab is a CD19-directed cytolytic monoclonal antibody that, upon binding and blocking the activity of CD19, causes lysis of B-cells. This process is mediated through both direct apoptosis and immune-mediated effector mechanisms, such as antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).","B-lymphocyte antigen CD19 binder&antibody","Therapeutic strategy associated"]
[1554,"DB15090","approved; investigational","biotech","Tezepelumab","AMG 157; AMG-157; MEDI9929; Tezepelumab",null,null,"Asthma is a heterogeneous chronic obstructive respiratory disease with both \"type 2\" (T2) and T2-low endotypes characterized by reduced airflow, chronic inflammation, and airway remodelling. Thymic stromal lymphopoietin (TSLP), an innate pleiotropic IL-2-family cytokine, has emerged as a key upstream regulator of chronic inflammation across asthma endotypes. Blocking the interaction of TSLP with the receptors TSLPR and IL-7Rα improves asthma-associated biomarkers including eosinophil counts and IgE, FeNO, IL-5, and IL-13 levels. As existing asthma treatments such as , , , , and  act on specific downstream mediators of the inflammatory response, they are mostly limited to treating T2 asthma. Conversely, tezepelumab, which targets the upstream master regulator TSLP, has the potential to be effective across asthma endotypes.\r\n\r\nTezepelumab is a human monoclonal IgG2λ antibody directed against TSLP produced in Chinese hamster ovary (CHO) cells by recombinant DNA technology. It was granted FDA approval on December 17, 2021, and is currently marketed under the trademark TEZSPIRE by Amgen/AstraZeneca.","1572943-04-4",null,"Tezepelumab is indicated as an add-on maintenance treatment for patients aged 12 years and older with severe asthma.\r\n\r\nTezepelumab is not indicated for the relief of acute bronchospasm or status asthmaticus.","Tezepelumab is a human monoclonal IgG2λ antibody blocking thymic stromal lymphopoietin (TSLP). Tezepelumab treatment in asthmatic patients improves disease markers, including blood and airway submucosal eosinophils and IgE, FeNO, IL-5, and IL-13 levels. Despite an excellent safety profile, tezepelumab may be associated with hypersensitivity reactions and increased risk of infection, especially by parasitic helminths. Patients receiving tezepelumab should not discontinue systemic or inhaled corticosteroids, and any reduction in these drugs should be performed cautiously.","Asthma is a heterogeneous chronic obstructive respiratory disease characterized by reduced airflow, chronic inflammation, and airway remodelling. Generally, asthma can be divided into \"type 2\" (T2, including allergic and eosinophilic presentations) and T2-low (including neutrophilic and paucigranulocytic presentations) endotypes, each driven by distinct underlying pathways. Thymic stromal lymphopoietin (TSLP) is an innate pleiotropic IL-2-family cytokine distantly related to IL-7; two forms of TSLP exist, with a short isoform (sfTSLP, 60 amino acids long) and a long isoform (lfTSLP, 159 amino acids long). The short isoform appears to be constitutively expressed, especially by lung and gut epithelial cells, while lfTSLP is upregulated in response to proinflammatory stimuli. While the role of sfTSLP is still unclear, lfTSLP has emerged as an upstream alarmin central to the pathophysiology of inflammatory disorders including asthma, atopic rhinitis, chronic obstructive pulmonary disease, eosinophilic esophagitis, and atopic dermatitis.\r\n\r\nUnder normal conditions, lfTSLP interacts with its cognate receptor TSLPR, and IL-7Rα in a ternary complex with three contact sites labelled site I (TSLP:TSLPR), site II (TSLP:IL-7Rα), and site III (TSLPR:IL-7Rα). The assembly of the ternary complex is stepwise, as TSLP does not interact appreciably with IL-7Rα until after it has bound TSLPR. Complementary electrostatic surfaces on TSLP and TSLPR mediate initial high affinity formation of a TSLP:TSLPR complex (_K_<sub>D</sub> of 32 nM and _k_<sub>a</sub> of 1.7 x 10<sup>5</sup> M<sup>-1</sup>s<sup>-1</sup>). This initial binding induces a restructuring of the π-helical turn in the TSLP αA helix and structuring of the AB loop to facilitate binding of TSLP to a hydrophobic patch on IL-7Rα to form the ternary complex (_K_<sub>D</sub> of 29 nM and _k_<sub>a</sub> of 1.23 x 10<sup>5</sup> M<sup>-1</sup>s<sup>-1</sup>). The complete ternary complex is stabilized by additional interactions between TSLPR and IL-7Rα at site III near the transmembrane domain of each receptor.\r\n\r\nFormation of the ternary complex activates JAK1/2, which, through downstream pathways involving STAT3/5, NF-κB, PI3K, and MAPK, induces the expression of Th2 cytokines including IL-4, IL-5, IL-9, and IL-13. TSLP can induce Th2 cytokine production by stimulating dendritic cells and ILC2 cells (primarily in T2 asthma). Furthermore, TSLP has been implicated in steroid resistance of ILC2 cells. In neutrophilic asthma, TSLP induces dendritic cells to drive the development of Th17 cells, which secrete IL-17A to recruit neutrophils and drive inflammation. In paucigranulocytic asthma, TSLP mediates cross-talk between mast cells, smooth muscle cells, and fibroblasts. Hence, despite different underlying pathways, TSLP appears to function as a critical upstream driver across asthma endotypes.\r\n\r\nTezepelumab is a human monoclonal IgG2λ antibody that binds to TSLP with a dissociation constant of 15.8 pM. Specifically, the variable heavy chain domain (V<sub>H</sub>) complementarity determining regions (CDRs) of tezepelumab bind TSLP at the _AB_-loop region and C-terminal region of the αD helix, obstructing the TSLPR binding region while leaving the IL-7Rα binding region unobstructed. As TSLP is incapable of binding IL-7Rα prior to its inclusion in the TSLP:TSLPR dimer, tezepelumab effectively blocks the assembly of the ternary complex and resulting downstream signalling. Furthermore, unlike existing therapies that act on specific downstream effector molecules, targeting TSLP ensures effective upstream blockade and is expected to be efficacious against multiple asthma endotypes.","Thymic stromal lymphopoietin binder&antibody","Therapeutic strategy associated"]
[1555,"DB15091","approved; investigational","small molecule","Upadacitinib","Upadacitinib","C17H19F3N6O","CC[C@@H]1CN(C[C@@H]1C1=CN=C2C=NC3=C(C=CN3)N12)C(=O)NCC(F)(F)F","Upadacitinib is an oral Janus kinase (JAK)1-selective inhibitor and a disease-modifying antirheumatic drug (DMARD) used in the treatment of rheumatoid arthritis to slow down disease progression. Rheumatoid arthritis is a chronic autoimmune inflammatory disease affecting the peripheral joints. It is characterized by synovial inflammation and hyperplasia, autoantibody production, cartilage damage and bone destruction, leading to co-morbidities. Despite a variety of therapeutic agents available for treatment, up to 40% of the patients do not respond to current therapies, including biological therapies. The etiology of the disease is mostly unknown; however, the role of JAK as a driver of immune-mediated conditions was discovered, leading to the use of JAK as therapeutic targets for rheumatoid arthritis. To reduce dose-related toxicity (as seen with some pan-JAK inhibitors) without significantly affecting efficacy, more selective JAK1 inhibitors, upadacitinib and , were developed.\r\n\r\nThe FDA approved Upadacitinib in August 2019 for the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate. In December 2019, it was additionally approved by the European Commission for the same indication in patients with inadequate response or intolerance to one or more DMARDs and can be used as monotherapy or in combination with methotrexate. Upadacitinib is marketed under the brand name RINVOQ™ for oral administration. It is currently being investigated in several clinical trials assessing its therapeutic effectiveness in other inflammatory diseases, such as psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, and atopic dermatitis.","1310726-60-3","380.375","Upadacitinib is indicated for the treatment of moderately to severely active rheumatoid arthritis or active psoriatic arthritis in adult patients who have had an inadequate response or intolerance to one or more disease-modifying anti-rheumatic drugs (DMARDs), such as methotrexate or TNF blockers. For these indications, upadacitinib may be used as monotherapy or in combination with methotrexate.\r\n\r\nUpadacitinib is also indicated for the treatment of active ankylosing spondylitis in adult patients who have an inadequate response to conventional therapy and for the treatment of moderate to severe atopic dermatitis in patients aged 12 years and older who are candidates for systemic therapy.\r\n\r\nCombining upadacitinib with other JAK inhibitors, biologic DMARDs, or other potent immunosuppressive agents is not recommended.","Upadacitinib is a DMARD that works by inhibiting the Janus Kinases (JAKs), which are essential downstream cell signalling mediators of pro-inflammatory cytokines. It is believed that these pro-inflammatory cytokines play a role in many autoimmune inflammatory conditions, such as rheumatoid arthritis. In clinical trials, upadacitinib decreased the activity of pro-inflammatory interleukins, transiently increased the levels of lymphocytes, and insignificantly decreased the levels of immunoglobulins from the baseline.","Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that involves the interplay of several mediators, including the immune cells (mainly T- and B-lymphocytes) and pro-inflammatory cytokines, such as the tumour necrosis factor (TNF), transforming growth factor (TGF), and interleukin 6 (IL-6). The Janus Kinase (JAK) family plays an essential role in the normal physiological functions (such as erythropoiesis), but also the signalling of pro-inflammatory cytokines that are implicated in many immune-mediated diseases. The JAK family consists of four isoforms (JAK1, JAK2, JAK3, and Tyrosine Kinase 2) that each interacts with different cytokine receptors and uniquely associates with the intracellular domains of Type I/II cytokine receptors. JAK1 is primarily involved in the signalling transduction pathways of IL-6, IFN and the common γ -chain cytokines, including IL-2 and IL-15. IL-6 has been closely studied in particular, as it is a major cytokine involved in B- and T-cell differentiation and the acute phase response in inflammation.\r\n\r\nUpon interaction of cytokines with their cytokine receptors, the JAKs mediate the JAK-STAT signal transduction pathway in response to receptor activation. JAKs are tyrosine kinases that cause phosphorylation of several proteins, including cytokine receptors and JAKs themselves. Phosphorylation of JAKs promotes the phosphorylation and activation of the signalling molecules called STATs, leading to their nuclear translocation, binding to DNA promoters, and target gene transcription. JAK1-mediated signalling pathways ultimately promote pro-inflammatory events, such as increased proliferation and survival of immune cells, T cell differentiation, and macrophage activation. Upadacitinib is a selective JAK1 inhibitor that has a negligible effect on JAK3, leading to an improved drug safety profile. Upadacitinib blocks the cellular processes that contribute to the inflammatory conditions in rheumatoid arthritis. In human leukocytes cellular assays, upadacitinib inhibited JAK1/3-induced phosphorylation of STAT3/5 mediated by IL-6/7.","Tyrosine-protein kinase JAK1 inhibitor","Therapeutic strategy associated"]
[1556,"DB15119","approved; investigational","biotech","Ropeginterferon alfa-2b","Ropeginterferon alfa-2b",null,null,"Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia.  has been used for decades to treat PV but requires frequent dosing and is not tolerated by all patients. Ropeginterferon alfa-2b is a next-generation mono-pegylated type I interferon produced from proline-IFN-α-2b in _Escherichia coli_ that has high tolerability and a long half-life. Ropeginterferon alfa-2b has shown efficacy in PV in _in vitro_ and _in vivo_ models and clinical trials.\r\n\r\nRopeginterferon alfa-2b was approved by the FDA on November 12, 2021, and is currently marketed under the trademark BESREMi by PharmaEssentia Corporation.","1335098-50-4",null,"Ropeginterferon alfa-2b is indicated for the treatment of adult patients with polycythemia vera.","Ropeginterferon alfa-2b acts through the interferon-alpha/beta receptor to initiate downstream JAK/STAT signalling leading to its therapeutic effects. Like other interferon alfa products, ropeginterferon alfa-2b may cause various toxicities, including endocrine, cardiovascular, pulmonary, ophthalmologic, dental/periodontal, renal, and dermatological toxicity. In addition, interferon alfa has been associated with hepatotoxicity, including increases in serum ALT, AST, GGT, and bilirubin; ropeginterferon alfa-2b is contraindicated in patients with moderate to severe (Child-Pugh B or C) hepatic impairment. Pancreatitis and colitis, including fatal ulcerative/hemorrhagic/ischemic colitis, have occurred in patients treated with interferon alfa. Significant toxicity of any kind may require treatment discontinuation. Interferon alfa treatment has decreased peripheral blood counts, including thrombocytopenia and leukopenia, and altered lipid levels, including hyperlipidemia, hypertriglyceridemia, and dyslipidemia. Hypersensitivity reactions, including anaphylaxis, may occur; ropeginterferon alfa-2b is contraindicated in hypersensitive patients and those with known hypersensitivity to other interferons. Life-threatening or fatal neuropsychiatric reactions may occur, including in patients without prior history; ropeginterferon alfa-2b is contraindicated in patients with a history of severe psychiatric disorders. Finally, ropeginterferon alfa-2b can cause fetal harm and should be used with caution in females of reproductive potential.","Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), which also includes essential thrombocytopenia and myelofibrosis. PV is characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia. The main driver mutation, _JAK2_ V617F, is present in >95% of PV patients and results in constitutive JAK/STAT signalling; other exon 12 mutations in _JAK2_ may also result in PV. PV results in clonal hematopoietic stem cells, such that they form endogenous erythroid colonies (EECs) _in vitro_.\r\n\r\nInterferon alfa-2b has been used for decades in PV despite the lack of formal approval. Although the mechanism of action is unclear, interferon alfa-2b is known to bind the interferon-alpha/beta receptor (IFNAR) and activate downstream JAK/STAT signalling. The overall result is a series of anti-proliferative, anti-angiogenic, pro-apoptotic, and immunomodulatory effects, including augmenting T-cell, macrophage, and natural killer cells. Interestingly, _in vitro_ studies have revealed that ropeginterferon alfa-2b is specific to some extent for _JAK2_-mutant EECs, a result that is in line with the reduced allelic burden observed in clinical trials. Partial and complete molecular and hematological responses have been achieved with ropeginterferon alfa-2b.","Interferon alpha/beta receptor (IFNAR) binder","Therapeutic strategy associated"]
[1557,"DB15226","approved; investigational","biotech","Dasiglucagon","Dasiglucagon",null,null,"Dasiglucagon is a glucagon analog that acts to increase blood sugar levels. It consists of 29 amino acids similar to endogenous glucagon; however, it contains seven substituted amino acids for improved physical and chemical stability in its drug formulation. In March 2021, the FDA approved dasiglucagon to treat severe hypoglycemia in patients six years and older with diabetes. It is available as a subcutaneous injection marketed as ZEGALOGUE.\r\n\r\nSevere hypoglycemia is an acute, life-threatening medical condition resulting from a profound drop in blood glucose levels. It is characterized by neurological impairment, with manifestations like loss of consciousness and seizure. Hypoglycemia is a common side effect of antidiabetic treatments, most notably insulin and sulfonylureas. Although it tends to be more common in type 1 diabetes mellitus, occurring in about 22% to 46% of patients annually, about 7% to 25% of patients with type 2 diabetes mellitus treated with insulin experience severe hypoglycemia a year. Even with close monitoring of blood glucose levels, it is not always possible to prevent severe hypoglycemic events in patients with diabetes, and children are particularly at risk for experiencing severe hypoglycemia. Treatments for severe hypoglycemia have mostly been limited to intravenous dextrose and different glucagon formulations. The approval of dasiglucagon marks the first glucagon analog approved for severe hypoglycemia treatment that does not require administration by a healthcare professional.","1544300-84-6",null,"Dasiglucagon is an antihypoglycemic agent indicated for the treatment of severe hypoglycemia in pediatric and adult patients with diabetes aged 6 years and above.","Dasiglucagon works to increase blood glucose levels under normal and hypoglycemic conditions. After administration of dasiglucagon in adult patients with type 1 diabetes, the mean glucose increase from baseline at 90 minutes was 168 mg/dL. In pediatric patients with type 1 diabetes aged seven to 17 years, the mean glucose increase at 60 minutes after administration of dasiglucagon was 162 mg/dL.","Dasiglucagon is an analog of glucagon, which is a peptide hormone responsible for increasing blood glucose levels. It has the same mechanism of action as endogenous glucagon by acting as an agonist at glucagon receptors, which are G-coupled receptors expressed throughout the body. Dasiglucagon binds to glucagon receptors in the liver, which activates Gsα and Gq, and consequently, adenylate cyclase. Adenyl cyclase increases intracellular cyclic AMP, which stimulates glycogenolysis and glucogenesis in the liver. As glucose is primarily released from liver glycogen stores, hepatic stores of glycogen are crucial for dasiglucagon to exert its antihypoglycemic effects.","Glucagon receptor agonist","Indication associated"]
[1558,"DB15303","investigational","biotech","Faricimab","Faricimab",null,null,"Retinal vascular diseases (RVDs) such as diabetic macular edema (DME), age-related macular degeneration (AMD), and retinal vein occlusion (RVO) are typically caused by retinal ischemia and subsequent neovascularization (NV). Vascular endothelial growth factor A (VEGF-A) is a well-known mediator of retinal NV, and many currently approved RVD therapies such as  and  solely target VEGF-A. However, another set of factors, the Tie/Ang axis, comprising the transmembrane Tie-2 receptor and its soluble ligands Ang-1 and Ang-2, has been shown to play critical roles in mediating VEGF-A-induced NV. Faricimab is an IgG<sub>1</sub>-derived bispecific antibody capable of simultaneously binding to and depleting VEGF-A and Ang-2, which has been developed to improve therapeutic efficacy, especially in patients that respond poorly to anti-VEGF-A monotherapy.\r\n\r\nFaricimab is under investigation in clinical trial NCT03823287 (A Study to Evaluate the Efficacy and Safety of Faricimab in Participants With Neovascular Age-Related Macular Degeneration (TENAYA)).","1607793-29-2",{"$nulls":3},"The retina is largely avascular to facilitate effective photoreceptor function; rather, the retina is fed by both retinal and choroidal capillary networks, pathologies of which result in retinal and choroidal vascular diseases such as diabetic macular edema (DME), age-related macular degeneration (AMD), and retinal vein occlusion (RVO). One of the underlying causes of retinal vascular diseases (RVDs) is retinal neovascularization (NV), the aberrant growth of new vasculature, usually due to sustained retinal ischemia and mediated primarily by vascular endothelial growth factor A (VEGF-A). VEGF-A is a VEGF family member, which also includes VEGF-B, -C, and -D, whose members signal through the VEGF receptors (VEGFRs) VEGFR-1, -2, and -3 to mediate endothelial and lymphatic growth. Extensive work in animal models of RVD has demonstrated that VEGF-A is necessary but not sufficient in many cases to mediate NV, suggesting that additional factors may be required in deep retinal capillary beds. One such factor has been identified as the angiopoietins Ang-1 and Ang-2 and their cellular receptor Tie-2; Ang-1 is a full Tie-2 agonist whose binding results in Tie-2 phosphorylation and downstream signalling, whereas Ang-2 is a Tie-2 partial agonist/antagonist that inhibits Tie-2 phosphorylation. Ang-1 generally has a protective effect, making endothelial cells less responsive to VEGF-A, while Ang-2 increases VEGF-A-dependent NV and stimulates pericyte apoptosis and breakdown of both the blood-brain and blood-retinal barriers; Ang-2 is upregulated in retinal vascular development and retinal ischemia.\r\n\r\nFaricimab is a bispecific antibody (bsAb) based on human IgG<sub>1</sub> comprising two different heavy and two different light chains capable of simultaneously binding to both VEGF-A and Ang-2 produced using the \"CrossMab\" platform. Faricimab binds VEGF-A and Ang-2 with binding affinities (K<sub>D</sub>) of approximately 3 and 22 nM, respectively; importantly, faricimab does not detectably bind Ang-1. Also, the faricimab Fc region has been modified to reduce binding to FcγR and FcRn receptors. The former virtually eliminates immune-mediated functions such as antibody- and complement-dependent cytotoxicity and antibody-dependent phagocytosis, whereas the latter increases faricimab systemic clearance by reducing FcRn-mediated IgG recycling. Thus, faricimab works by depleting both VEGF-A and Ang-2 to prevent retinal NV in the privileged ophthalmic environment.","Vascular endothelial growth factor A antagonist; Angiopoietin-2 antagonist","Therapeutic strategy associated"]
[1559,"DB15354","approved; investigational","biotech","Evinacumab","Evinacumab; evinacumab-dgnb",null,null,"Evinacumab is a recombinant human IgG4 monoclonal antibody targeted against angiopoietin-like protein 3 (ANGPTL3) and the first drug of its kind. The ANGPTL family of proteins serve a number of physiologic functions - including involvement in the regulation of lipid metabolism - which have made them desirable therapeutic targets in recent years. Loss-of-function mutations in _ANGPTL3_ have been noted to result in hypolipidemia and subsequent reductions in cardiovascular risk, whereas increases in function appear to be associated with cardiovascular risk, and it was these observations that provided a rationale for the development of a therapy targeted against ANGPTL3.\r\n\r\nIn February 2021, evinacumab became the first-and-only inhibitor of ANGPTL3 to receive FDA approval after it was granted approval for the adjunctive treatment of homozygous familial hypercholesterolemia (HoFH) under the brand name \"Evkeeza\". Evinacumab is novel in its mechanism of action compared with other lipid-lowering therapies and therefore provides a unique and synergistic therapeutic option in the treatment of HoFH.","1446419-85-7",null,"Evinacumab is indicated, as an adjunct with other lipid-lowering therapies, for the treatment of familial homozygous hypercholesterolemia (HoFH) in patients 12 years of age and older.","Evinacumab exerts its hypolipidemic and antiatherogenic effects via decreasing circulating levels of triglycerides, HDL-C, and LDL-C, apolipoprotein B, and total cholesterol. It is has a relatively long duration of action that allows for its administration via intravenous injection once-monthly.\r\n\r\nAnimal studies have demonstrated embryo-fetal toxicity - administration to pregnant rabbits during organogenesis resulted in increases in fetal malformations at concentrations lower than those used in humans. For this reason, patients receiving therapy with evinacumab should obtain a pregnancy test prior to beginning therapy and use effective contraception throughout the duration of therapy and for 5 months following the administration of the last dose.","Angiopoetin-like proteins (ANGPTL) are a diverse group of proteins involved in a number of physiological processes, including the regulation of lipoprotein metabolism. Loss-of-function mutations in _ANGPTL3_ and _ANGPTL4_ have been shown to result in hypolipidemia and a reduced risk of coronary artery disease, while increased levels of these proteins appear to be associated with cardiovascular risk. While these observations have made ANGPTLs as a class a desirable target in the treatment of hyperlipidemic disorders, ANGPTL3 is the first to be pharmacologically targeted for the purposes of lipid-lowering therapy. ANGPTL3 is expressed primarily in the liver and acts as an endogenous inhibitor of lipoprotein lipase (LPL) and endothelial lipase (EL) which are responsible, in part, for metabolizing triglycerides (TG) and HDL-C, respectively.\r\n\r\nEvinacumab is monoclonal antibody that binds to and inhibits ANGPTL3, with the resulting disinhibition of LPL and EL reducing the levels of circulating TG and HDL-C. While the mechanism through which evinacumab reduces LDL-C is not entirely clear, this effect is independent of LDL receptor density and is therefore most likely due to the promotion of VLDL processing and upstream clearance of LDL formation.","Angiopoietin-related protein 3 inhibitor&binder&antibody","Indication associated"]
[1560,"DB15442","approved; investigational","small molecule","Trilaciclib","Trilaciclib","C24H30N8O","CN1CCN(CC1)C1=CN=C(NC2=NC3=C(C=C4N3C3(CCCCC3)CNC4=O)C=N2)C=C1","Trilaciclib, or G1T28, is a CDK4 and CDK6 inhibitor, indicated to reduce the incidence of chemotherapy induced myelosuppression in patients before topotecan-containing or platinum and etoposide-containing chemotherapy for extensive stage small cell lung cancer. CDK4 and CDK6 inhibitors have been investigated since the mid 1990s for their use in tumorigenesis and chemotherapy. Trilaciclib was first described in the literature in 2016.\r\n\r\nTrilaciclib was granted FDA approval on 12 February 2021.","1374743-00-6","446.559","Trilaciclib is indicated to reduce the incidence of chemotherapy induced myelosuppression in patients prior to receiving platinum and etoposide-containing or topotecan-containing chemotherapy regimens for extensive-stage small cell lung cancer.","Trilaciclib is indicated to reduce the incidence of chemotherapy induced myelosuppression in patients prior to receiving platinum and etoposide-containing or topotecan-containing chemotherapy regimens for extensive-stage small cell lung cancer. It has a short duration of action of approximately 16 hours, and a narrow therapeutic index. Patients should be counselled regarding the risk of injection site reactions, hypersensitivity, and interstitial lung disease.","Trilaciclib is inhibits cyclin-dependant kinase 4 (CDK4) at a concentration of 1 nmol/L and cyclin-dependent kinase 5 (CDK5) at 4 nmol/L. Inhibition of CDK2, CDK5, and CDK7 is over 1000-fold less at these concentrations and inhibition of CDK9 is 50-fold less.\r\n\r\nCDK4 and CDK5 are expressed in hematopoietic stem cells and progenitor cells. They are capable of phosphorylating and inactivating the retinoblastoma protien; a tumor suppressor. When trilaciclib is given to patients with retinoblastoma protein-null small cell lung cancer, it does not interfere with the intended chemotherapy induced cytotoxicity of cancer cells. Inhibition of CDK4 and CDK5 leads to a reversible pause in the cell cycle in the G1 phase for approximately 16 hours. The temporary cell cycle arrest prevents chemotherapy induced DNA damage in healthy cells, reducing the activity of caspases 3 and 7, which reduces apoptosis of healthy cells.\r\n\r\nOther studies have shown inhibitors of CDK4 and CDK6 enhance T-cell activation, upregulating major histocompatibility complex (MHC) class I and II, and stabilize programmed death-ligand 1 (PD-L1). Together these activities increase T-cell activity, increase antigen presentation, and sensitize cells to immune checkpoint inhibitors.","Cyclin-dependent kinase 4 inhibitor; Cyclin-dependent kinase 6 inhibitor; Cyclin-dependent kinase 9 inhibitor; Cyclin-dependent kinase 2 inhibitor; Cyclin-dependent kinase 5 inhibitor; Cyclin-dependent kinase 7 inhibitor","Therapeutic strategy associated"]
[1561,"DB15444","approved; investigational","small molecule","Elexacaftor","Elexacaftor","C26H34F3N7O4S","C[C@@H]1CN(C2=NC(=CC=C2C(=O)NS(=O)(=O)C2=CN(C)N=C2C)N2C=CC(OCC(C)(C)C(F)(F)F)=N2)C(C)(C)C1","Elexacaftor (previously VX-445) is a small molecule, next-generation corrector of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. It received FDA approval in October 2019 in combination with  and  as the combination product Trikafta<sup>TM</sup>. Elexacaftor is considered a next-generation CFTR corrector as it possesses both a different structure and mechanism as compared to first generation correctors like tezacaftor. While dual corrector/potentiator combination therapy has proven useful in the treatment of a subset of CF patients, their use is typically limited to patients who are homozygous for the _F508del-CFTR_ gene. Elexacaftor, along with , was designed to fill the need for an efficacious CF therapy for patients who are heterozygous for _F508del-CFTR_ and a gene that does not produce protein or produces proteins unresponsive to ivacaftor or tezacaftor. The triple combination product Trikafta<sup>TM</sup>, manufactured by Vertex Pharmaceuticals, is the first product approved for the treatment of CF in individuals who are either homo- _or_ heterozygous for the _F508del-CFTR_  gene - this represents approximately 70-90% of all CF patients.","2216712-66-0","597.66","Elexacaftor, in combination with  and  as the combination product Trikafta<sup>TM</sup>, is indicated for the treatment of cystic fibrosis (CF) in patients 12 years of age and older who have at least one _F508del_ mutation in the CTFR gene.","As a CFTR corrector, elexacaftor works to increase the amount of mature CFTR proteins present on the surface of cells. When used in combination with CFTR potentiators, which enhance the function of cell-surface CFTR proteins, drugs like elexacaftor help to improve a variety of multi-organ cystic fibrosis symptoms, including lung function, nutritional status, and overall quality of life. Trikafta<sup>TM</sup>, the triple combination product containing elexacaftor, may cause elevations in liver transaminases. Liver function testing should be conducted prior to beginning Trikafta, every 3 months for the first year of treatment, and annually thereafter.","Cystic fibrosis (CF) is the result of a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The CFTR proteins produced by this gene are transmembrane ion channels that move sodium and chloride across cell membranes - water follows the flow of chloride ions to the cell surface, which consequently helps to hydrate the surface of the cell and thin the secretions (i.e. mucous) around the cell. Mutations in the CFTR gene produce CFTR proteins of insufficient quantity and/or function, leading to defective ion transport and a build-up of thick mucous throughout the body that causes multi-organ disease involving the pulmonary, gastrointestinal, and pancreatic systems (amongst others). The most common CFTR mutation, the _F508del_ mutation, is estimated to account for 70 to 90% of all CFTR mutations and results in severe processing and trafficking defects of the CFTR protein.\r\n\r\nElexacaftor is a CFTR corrector that modulates CFTR proteins to facilitate trafficking to the cell surface for incorporation into the cell membrane. The end result is an increase in the number of mature CFTR proteins present at the cell surface and, therefore, improved ion transport and CF symptomatology. Elexacaftor is used in combination with tezacaftor, another CFTR corrector with a different mechanism of action, and ivacaftor, a CFTR potentiator that improves the function of CFTR proteins on the cell surface - this multi-faceted, triple-drug approach confers a synergistic effect beyond that seen in typical corrector/potentiator dual therapy regimens.","Cystic fibrosis transmembrane conductance regulator modulator","Therapeutic strategy associated"]
[1562,"DB15456","approved; investigational","small molecule","Vericiguat",null,"C19H16F2N8O2","COC(=O)NC1=C(N)N=C(N=C1N)C1=NN(CC2=CC=CC=C2F)C2=C1C=C(F)C=N2","Vericiguat is a direct stimulator of soluble guanylate cyclase (sGC) used in the management of systolic heart failure to reduce mortality and hospitalizations. A key component of the NO-sGC-cGMP signaling pathway that helps to regulate the cardiovascular system, sGC enzymes are intracellular enzymes found in vascular smooth muscle cells (amongst other cell types) that catalyze the synthesis of cyclic guanosine monophosphate (cGMP) in response to activation by nitric oxide (NO). Cyclic GMP acts as a second messenger, activating a number of downstream signaling cascades that elicit a broad variety of effects, and these diverse cellular effects have implicated deficiencies in its production (primarily due to insufficient NO bioavailability) in the pathogenesis of various cardiovascular diseases. As a direct stimulator of sGC, vericiguat mitigates the need for a functional NO-sGC-cGMP axis and thereby helps to prevent the myocardial and vascular dysfunction associated with decreased sGC activity in heart failure.\r\n\r\nVericiguat was approved by the FDA in January 2021 - developed by Merck under the brand name Verquvo - for use in certain patients with systolic heart failure. Although not the first sGC stimulator to be granted FDA approval ( was approved in 2013 for use in pulmonary hypertension), vericiguat is unique amongst its peers in that modifications to its structure have dramatically decreased its susceptibility to oxidative metabolism, resulting in a relatively long half-life and allowing for once-daily dosing.","1350653-20-1","426.388","Vericiguat is indicated in adults with symptomatic, chronic heart failure and an ejection fraction of <45% to reduce the risk of cardiovascular death and heart failure-related hospitalization following a hospitalization for heart failure or need for outpatient intravenous diuretics.","By directly stimulating the increased production of intracellular cyclic guanosine monophosphate (cGMP), vericiguat causes the relaxation of vascular smooth muscle and vasodilation. Vericiguat has a relatively long half-life (~30h) that allows for once-daily dosing.\r\n\r\nAnimal reproduction studies have demonstrated the potential for embryo-fetal toxicity when vericiguat is administered to pregnant females - defects in major vessel and heart formation, as well as spontaneous abortions/resorptions, were observed when vericiguat was administered to pregnant rabbits during organogenesis. The possibility of pregnancy should be excluded prior to beginning therapy with vericiguat, and adequate contraception should be used throughout therapy and for one month following cessation of treatment.","Heart failure (HF) involves, amongst other morphologic and physiologic changes, the impaired synthesis of nitric oxide (NO) and decreased activity of soluble guanylate cyclase (sGC). Functioning normally, NO binds to sGC and stimulates the synthesis of intracellular cyclic guanosine monophosphate (cGMP), a second messenger involved in the maintenance of vascular tone, as well as cardiac contractility and remodeling. Defects in this pathway are thought to contribute to the myocardial and vascular dysfunction associated with heart failure and are therefore a desirable target in its treatment.\r\n\r\nVericiguat directly stimulates sGC by binding to a target site on its beta-subunit, bypassing the need for NO-mediated activation, and in doing so causes an increase in the production of intracellular cGMP that results in vascular smooth muscle relaxation and vasodilation.","Guanylate cyclase soluble subunit beta-1 stimulator","Indication associated"]
[1563,"DB15495","experimental","small molecule","Rocaglamide",null,"C29H31NO7","COC1=CC=C(C=C1)[C@@]12OC3=C(C(OC)=CC(OC)=C3)[C@]1(O)[C@H](O)[C@@H]([C@H]2C1=CC=CC=C1)C(=O)N(C)C","Rocaglamide, also referred to as rocaglamide-A, is the eponymous member of a class of anti-cancer phytochemicals known as rocaglamides. Rocaglamides are secondary metabolites of the plant genus _Aglaia_, and extracts of the plant have traditionally been used as a form of insect repellant due to its natural insecticidal properties. Reports of _Aglaia_ anti-tumor activity date back as far as 1973, and rocaglamide-A was first isolated in 1982 from the species _A. elliptifolia_. Rocaglamide and a number of its derivatives (e.g. ) are currently being studied for use as chemotherapeutic agents in the treatment of various leukemias, lymphomas, and carcinomas, as well as adjuvant therapy in the treatment of certain chemotherapy-resistant cancers.","84573-16-0","505.567",null,null,"Rocaglamide’s anti-tumor activity is driven primarily via inhibition of protein synthesis in tumor cells. Inhibition of protein synthesis is accomplished via inhibition of prohibitin 1 (PHB1) and prohibitin 2 (PHB2) - these proteins are necessary in the proliferation of cancer cells and are implicated in the Ras-mediated CRaf-MEK-ERK signaling pathway responsible for phosphorylating eIF4E, a key factor in the initiation of protein synthesis. The rocaglamide derivative silvestrol has also been observed to act directly on eIF4A, another translation initiation factor of the eIF4F complex ultimately responsible for initiation of protein synthesis.\r\n\r\nInhibition of protein synthesis has a number of downstream effects. Many of the proteins that are down-regulated in response to protein synthesis inhibition in tumor cells are short-lived proteins responsible for regulation of the cell cycle, such as Cdc25A. Cdc25A is an oncogene that can become overexpressed in certain cancers and lead to unchecked cell growth. In addition to inhibiting its synthesis via the mechanism described above, rocaglamide promotes degradation of Cdc25A via activation of the ATM/ATR-Chk1/Chk2 checkpoint pathway. This pathway is normally activated in response to DNA damage and serves to reduce the expression of proteins responsible for cell cycle progression, thereby inhibiting proliferation of damaged (i.e. tumour) cells. Rocaglamide’s inhibition of protein synthesis also appears to prevent the actions of the transcription factor heat shock factor 1 (HSF1), leading to an increased expression of thioredoxin-interacting protein (TXNIP) which is negatively regulated by HSF1. TXNIP is a negative regulator of cell glucose uptake, and its increased expression blocks glucose uptake and consequently impairs the proliferation of malignant cells.\r\n\r\nRocaglamide also appears to induce apoptosis in tumor cells via activation of the pro-apoptotic proteins p38 and JNK and inhibition of the anti-apoptotic Mcl-1 protein. Similarly, it has been studied as an adjuvant in TRAIL-resistant cancers due to its ability to inhibit the synthesis of c-FLIP and IAP/XIAP - these anti-apoptotic proteins can become elevated in certain cancers, preventing the induction of apoptosis and resulting in resistance to TRAIL-based therapies.","Prohibitin inhibitor; Prohibitin-2 inhibitor","Therapeutic strategy associated"]
[1564,"DB15496","experimental","small molecule","Didesmethylrocaglamide","RocB","C27H27NO7","COC1=CC=C(C=C1)[C@@]12OC3=CC(OC)=CC(OC)=C3[C@]1(O)[C@H](O)[C@@H]([C@H]2C1=CC=CC=C1)C(N)=O","Didesmethylrocaglamide is a naturally-occurring derivative of  and belongs to a class of anti-cancer phytochemicals referred to as \"rocaglamides\" derived from plants of the genus _Aglaia_. While traditionally used for their insecticidal benefits, this class of compounds is now being studied for use as chemotherapeutic agents in the treatment of various leukemias, lymphomas, and carcinomas. Of the known derivatives of rocaglamide, didesmethylrocaglamide appears to carry the most potent anti-tumour activity.",null,"477.513",null,null,"Little research has been conducted specifically regarding didesmethylrocaglamide, but its mechanism of action is likely to be congruent with the rest of the rocaglamide class.\r\n\r\nDidesmethylrocaglamide’s anti-tumor activity, similar to other rocaglamide derivatives, is driven primarily via inhibition of protein synthesis in tumor cells. Inhibition of protein synthesis is accomplished via inhibition of prohibitin 1 (PHB1) and prohibitin 2 (PHB2) - these proteins are necessary in the proliferation of cancer cells and are implicated in the Ras-mediated CRaf-MEK-ERK signaling pathway responsible for phosphorylating eIF4E, a key factor in the initiation of protein synthesis. There is also some evidence that rocaglamides can act directly on eIF4A, another translation initiation factor of the eIF4F complex ultimately responsible for initiation of protein synthesis.\r\n\r\nInhibition of protein synthesis has a number of downstream effects. Many of the proteins that are down-regulated in response to protein synthesis inhibition in tumor cells are short-lived proteins responsible for regulation of the cell cycle, such as Cdc25A. Cdc25A is an oncogene that can become overexpressed in certain cancers and lead to unchecked cell growth. In addition to inhibiting its synthesis via the mechanism described above, rocaglamides promote degradation of Cdc25A via activation of the ATM/ATR-Chk1/Chk2 checkpoint pathway. This pathway is normally activated in response to DNA damage and serves to reduce the expression of proteins responsible for cell cycle progression, thereby inhibiting proliferation of damaged (i.e. tumour) cells. Inhibition of protein synthesis also appears to prevent the actions of the transcription factor heat shock factor 1 (HSF1), leading to an increased expression of thioredoxin-interacting protein (TXNIP) which is negatively regulated by HSF1. TXNIP is a negative regulator of cell glucose uptake, and its increased expression blocks glucose uptake and consequently impairs the proliferation of malignant cells.\r\n\r\nRocaglamides also appear to induce apoptosis in tumor cells via activation of the pro-apoptotic proteins p38 and JNK and inhibition of the anti-apoptotic Mcl-1 protein. Similarly, they have been studied as an adjuvant in TRAIL-resistant cancers due to their ability to inhibit the synthesis of c-FLIP and IAP/XIAP - these anti-apoptotic proteins can become elevated in certain cancers, preventing the induction of apoptosis and resulting in resistance to TRAIL-based therapies.","Prohibitin inhibitor; Prohibitin-2 inhibitor","Therapeutic strategy associated"]
[1565,"DB15566","approved; vet_approved","small molecule","Prednisolone acetate","Prednisolone acetate","C23H30O6","[H][C@@]12CC[C@](O)(C(=O)COC(C)=O)[C@@]1(C)C[C@]([H])(O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)C=C[C@]12C","Prednisolone acetate is a  molecule bound to an acetate functional group by an ester bond.\r\n\r\nPrednisolone acetate was granted FDA approval in 1955.","52-21-1","402.4807","Prednisolone acetate is indicated as an anti-inflammatory or immunosuppressive agent for allergic, dermatologic, gastrointestinal, hematologic, ophthalmologic, nervous system, renal, respiratory, rheumatologic, or infectious conditions. Prednisolone acetate is also indicated in organ transplant patients, as well as endocrine or neoplastic conditions.","Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals. Prednisolone acetate has a short duration of action as the half life is 2-3 hours. Corticosteroids have a wide therapeutic window as patients make require doses that are multiples of what the body naturally produces. Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.","The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.\r\n\r\nGlucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10.\r\n\r\nLower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.","Glucocorticoid receptor agonist","Therapeutic strategy associated"]
[1566,"DB15595","approved","biotech","Ebola Zaire vaccine (live, attenuated)","Ebola Zaire vaccine (live); Ebola Zaire Vaccine (rVSV∆G-ZEBOV-GP, live); Recombinant Vesicular Stomatitis Virus (rVSV) strain Indiana with a deletion of the VSV envelope glycoprotein (G) replaced with the Zaire Ebola Virus (ZEBOV) Kikwit 1995 strain surface glycoprotein (GP)",null,null,"Ebola virus vaccine is a vaccine used to prevent Ebola virus disease caused by _Zaire ebolavirus_ in adults, prevent outbreaks, and reduce the extent of the virus spreading in case of outbreaks. Ebola virus disease, formerly known as Ebola hemorrhagic fever, is a rare but severe and often deadly disease. It is highly contagious: human to human transmission occurs from contact with body fluids from infected patients. It is characterized by fever, headache, myalgia, and gastrointestinal symptoms. These may be accompanied by hypotension and respiratory, kidney and liver failure, as well as internal and external bleeding. In the _Filoviridae_ family, there are five unique Ebolavirus species that are each named after the geographical region where it was first identified. The mortality rate of the Zaire species is about 80%.\r\n\r\nConfirmed outbreaks of Ebola virus disease have been documented since the 1970s, mostly in Sub-Saharan Africa, where Ebola first appeared in 1976 near the Ebola River in Zaire (presently referred to as the Democratic Republic of the Congo) and Sudan. Between 2014 and 2016, Ebola outbreaks occurred in West Africa, leading to more than 11,310 total deaths during this time in Guinea, Liberia, and Sierra Leone. In 2016, this epidemic was exhausted after these countries were declared Ebola-free by 2016, and the World Health Organization (WHO) lifted the Public Health Emergency of International Concern (PHEIC) status on the West Africa Ebola outbreak.\r\n\r\nThe first live, attenuated Ebola virus vaccine was developed by a team of Canadian researchers at Canada’s National Microbiology Laboratory and was later patented by the Canadian government. In non-human primate clinical trials, the vaccine was effective in inducing an immune response against the Ebola viruses. This vaccine was later sold to NewLink Genetics, a biotech company that held the license to the vaccine from 2010 to 2014, although the vaccine was not marketed. In 2014, Merck Inc. signed a licensing agreement with NewLink for further development and marketing. Ervebo, the marketed Ebola virus vaccine by Merck, was first approved by the European Commission in November 2019 after the European Medicines Agency recommended it be licensed. In December 2019, Ervebo was approved by the FDA in the United States. Ervebo consists of an envelope glycoprotein of the Zaire ebolavirus (Kikwit 1995 strain) fused into a vesicular stomatitis virus (VSV) backbone. By introducing the relatively inactive viral protein to the patient, the patient’s immune system learns to recognize and attack the virus if he or she is exposed to it in the future.",null,null,"Ebola Zaire vaccine is indicated for active immunization of individuals 18 years of age or older to protect against Ebola Virus Disease (EVD) caused by _Zaire Ebolavirus_.","Ebola Zaire vaccine protects against the Ebola virus infection and disease by introducing a protein produced by the _Zaire ebolavirus_ and initiating the body's normal immune responses against the virus. In clinical trials consisting of subjects receiving the Ebola virus vaccine, the vaccine virus RNA was detected in the plasma samples of most subjects within the first week after intramuscular injection.","Ebola virus disease occurs when the virus comes into contact with the host tissue and invades the tissue by breaking in the mucosa or skin. Exposure can occur through animal-to-human or human-to-human transmission from blood and other bodily fluids of the virus-infected animal or human. The viral genome then replicates inside the cell, causing gene modulation in host cells - including monocytes, macrophages, and dendritic cells - and promote cell apoptosis, releasing the viral particles to extracellular tissue. The virus can further disseminate the infection by migrating to the regional lymph nodes, liver, and spleen to cause lymphadenopathy, hepatocellular necrosis, and lymphopenia. Ebola virus can cause dysregulation of the host immune system by inducing the host expression and release of pro-inflammatory mediators, including interferons, interleukins (IL-2, IL- 6, IL-8, and IL-10), and tumour necrosis factor α (TNF-α). These inflammatory processes promote endothelial activation and reduced vascular integrity. Furthermore, the release of tissue factors and increased nitric oxide levels lead to disseminated intravascular coagulation (DIC) and hypotension seen in the Ebola virus disease, respectively. The incubation period after the Ebola virus infection is 1-21 days.\r\n\r\nBy introducing the attenuated viral protein to the patient, the Ebola Zaire vaccine elicits strong cellular and antibody responses against the virus. The vaccine produces a long-term immunity and protects the patient from Ebola virus infection and disease when he or she is exposed to  _Zaire ebolavirus_  in the future. However, the relative contributions of innate, humoral and cell-mediated immunity to protection from Zaire ebolavirus is not fully understood.",null,"Therapeutic strategy associated"]
[1567,"DB15598","approved","small molecule","Ferric maltol","Ferric maltol; Iron (III) maltol","C18H15FeO9","[Fe+3].CC1=C([O-])C(=O)C=CO1.CC1=C([O-])C(=O)C=CO1.CC1=C([O-])C(=O)C=CO1","Ferric maltol is an iron(III) atom complexed with 3 maltol molecules to increase the bioavailability compared to iron(II), without depositing it in the duodenum as insoluble ferric hydroxide and phosphate. Ferric maltol has been described in literature since at least the late 1980s as a potential treatment for iron deficiency.\r\n\r\nFerric maltol was granted FDA Approval on 25 July 2019.","33725-54-1","431.154","Ferric maltol is indicated to treat iron deficiency in adults.","Ferric maltol is used to provide supplemental iron to patients with an iron deficiency. It has a wide therapeutic index as patients generally take 30mg twice daily, while concentrations of 20mg/kg may produce toxicity. Patients should be counselled regarding the risk of inflammatory bowel disease flares, iron overload, and accidental ingestion in children.","Ferric maltol dissociates as the iron atom is donated to unknown iron uptake mechanisms, possibly beta 3 integrin or divalent metal transporter 1, in the ileum and duodenum. Once the iron is in circulation, it then associates with transferrin and ferritin.","Integrin beta-3 substrate; Natural resistance-associated macrophage protein 2 substrate","Therapeutic strategy associated"]
[1568,"DB15661","investigational","small molecule","Molnupiravir","Molnupiravir","C13H19N3O7","CC(C)C(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C=C\\C(NC1=O)=N\\O","Molnupiravir (EIDD-2801, MK-4482) is the isopropylester prodrug of . With improved oral bioavailability in non human primates, it is hydrolyzed _in vivo_, and distributes into tissues where it becomes the active 5’-triphosphate form. The active drug incorporates into the genome of RNA viruses, leading to an accumulation of mutations known as viral error catastrophe. Recent studies have shown molnupiravir inhibits replication of human and bat coronaviruses, including SARS-CoV-2, in mice and human airway epithelial cells. A  resistant mutant mouse hepatitis virus has also been shown to have increased sensitivity to N4-hydroxycytidine.\r\n\r\nMolnupiravir was granted approval by the UK's Medicines and Health products Regulatory Agency (MHRA) on 4 November 2021.","2349386-89-4","329.309","and its prodrug molnupiravir are being studied for its activity against a number of viral infections including influenza, MERS-CoV, and SARS-CoV-2.\r\n\r\nMolnupiravir is approved in the UK for reducing the risk of hospitalization and death in mild to moderate COVID-19 cases for patients at increased risk of severe disease (eg. with obesity, diabetes mellitus, heart disease, or are over 60 years old).",null,"Molnupiravir is hydrolyzed _in vivo_ to N4-hydroxycytidine, which is phosphorylated in tissue to the active 5’-triphosphate form, and incorporated into the genome of new virions, resulting in the accumulation of inactivating mutations, known as viral error catastrophe. A  resistant mutant mouse hepatitis virus has also been shown to have increased sensitivity to N4-hydroxycytidine.",null,"Indication associated"]
[1569,"DB15699","approved","biotech","Brexucabtagene autoleucel","Brexucabtagene autoleucel",null,null,"Mantle cell lymphoma is a heterogeneous sub-category of non-Hodgkin's lymphoma that can be classified as either an aggressive nodal or an indolent leukemic non-nodal variant. Despite the introduction of Bruton's tyrosine kinase (BTK) inhibitors such as  and , the prognosis for MCL patients remains poor and those that relapse following BTK inhibitor therapy have few treatment options.\r\n\r\nMore recently, chimeric antigen receptor (CAR) T cell therapies have been developed that modify a patient's own T cells using viral transduction to bind to and destroy cancerous cells. These therapies differ in manufacturing methodology, viral vector, chimeric antigen choice, and the internal co-stimulatory domains of the chimeric antigen. Similar to , brexucabtagene autoleucel employs a murine anti-CD19 single-chain variable fragment (scFv) linked to internal CD28- and CD3ζ-derived co-stimulatory domains. However, the preparation of brexucabtagene autoleucel, previously referred to as KTE-X19, uses a method of T cell enrichment that decreases the prevalence of CD19-expressing tumour cells in the CAR T cell preparation.\r\n\r\nBrexucabtagene autoleucel was granted accelerated approval for the treatment of relapsed and refractory MCL by the FDA on July 24, 2020, and is currently available through Kite Pharma Inc. under the tradename TECARTUS.",null,null,"Brexucabtagene autoleucel is a modified autologous chimeric antigen receptor (CAR) T cell immunotherapy indicated for the treatment of relapsed or refractory mantle cell lymphoma (MCL) in adult patients. It is additionally indicated for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).\r\n\r\nBrexucabtagene autoleucel has been granted accelerated approval based on results from a single-arm, open-label, multicentre clinical trial; continued approval may be contingent on confirmatory trials.","Brexucabtagene autoleucel is an autologous T cell immunotherapy employing a CD19-directed chimeric antigen receptor (CAR) to direct modified T cells to bind to and subsequently destroy cancerous B cells. Like other CAR T cell therapies, brexucabtagene autoleucel has a durable response; in the single-arm ZUMA-2 trial, the median time to peak CAR T cell levels was 15 days, and 60% of assayed patients had detectable levels of CAR T cells at 24 months following the single infusion.\r\n\r\nAs brexucabtagene autoleucel recognizes both normal and cancerous B cells, adverse effects related to B cell depletion are expected, including severe and prolonged cytopenia, severe infections, neurological effects, hypogammaglobulinemia, and the potential to develop secondary malignancies. Patients should be advised not to drive or operate heavy machinery for eight weeks following infusion. Hypersensitivity reactions may occur during infusion.","Mantle cell lymphoma (MCL) is a heterogeneous sub-category of B cell non-Hodgkin's lymphoma typified by overexpression of cyclin D1 and SOX-11 as well as mutations in numerous genes including _TP53_; overall, these changes lead to increased cell growth, apoptosis inhibition, and cell-adhesion-mediated drug resistance. Based on the 2016 World Health Organization guidelines, MCL can be generally subdivided into aggressive nodal and indolent leukemic non-nodal subtypes. Bruton's tyrosine kinase (BTK) inhibitors can be used following a relapse of front-line therapy, but patients who relapse after BTK inhibitor therapy have a poor prognosis.\r\n\r\nChimeric antigen receptors (CARs) are synthetic immunoreceptors that can be introduced into T cells _ex vivo_ using viral transduction and that allow for major histocompatibility complex (MHC)-independent direction of T cells to any cell possessing the complementary antigen. Brexucabtagene autoleucel employs a murine anti-CD19 single-chain variable fragment (scFv) linked to internal CD28- and CD3ζ-derived co-stimulatory domains. Brexucabtagene autoleucel is prepared from the patient's own peripheral blood mononuclear cells using a leukapheresis methodology that excludes CD19-expressing tumour cells to avoid potential activation and exhaustion of CAR T cells during manufacturing. Collected cells are activated with anti-CD3 and anti-CD28 antibodies along with IL-2, transduced with a replication-incompetent retroviral vector, and subsequently expanded prior to infusion.\r\n\r\nOnce infused into the patient, the CAR T cells bind to CD19 antigens on the surface of both normal and cancerous B cells, leading to CAR T cell activation and expansion. Activated CAR T cells secrete cytokines and chemokines including, but not limited to, IL-6, IL-8, IL-10, IL-15, TNF-α, IFN-γ, and soluble IL-2 (sIL2Rα), leading to tumour cell lysis and anti-tumour activity.","B-lymphocyte antigen CD19 binder","Therapeutic strategy associated"]
[1570,"DB15719","approved","biotech","Belantamab mafodotin","Belantamab mafodotin; Belantamab Mafodotin-blmf",null,null,"Belantamab mafodotin, or GSK2857916, is an afucosylated monoclonal antibody that targets B cell maturation antigen conjugated to the microtubule distrupter monomethyl auristatin-F (MMAF).\r\n\r\nBelantamab mafodotin was granted FDA approval on 5 August 2020.","2050232-20-5",null,"Belantamab mafodotin is indicated in the treatment of adults with relapsed or refractory multiple myeloma who have received at least 4 prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent.","Belantamab mafodotin treats multiple myeloma through antibody dependant cell mediated cytotoxicity as well as G2/M cell cycle arrest. It has a narrow therapeutic index due to the incidence of adverse effects, and a long duration of action as it is given every 3 weeks. Patients should be counselled regarding the risk of keratopathy.","Belantamab mafodotin, or GSK2857916, is an afucosylated monoclonal antibody that targets B cell maturation antigen (BCMA) conjugated to the microtubule distrupter monomethyl auristatin-F (MMAF). Afucosylation of the Fc region of monoclonal antibodies enhances binding to the Fc region, which enhances antibody dependant cell mediated cytoxicity.\r\n\r\nBCMA is uniquely expressed on CD138-positive myeloma cells. Targeting BCMA allows belantamab mafodotin to be highly selective in its delivery of MMAF to multiple myeloma cells. Belantamab mafodotin binds to BCMA, is internalised into cells, and releases MMAF.\r\n\r\nThe MMAF payload binds to tubulin, stopping the cell cycle at the DNA damage checkpoint between the G2 and M phases, resulting in apoptosis.","Tumor necrosis factor receptor superfamily member 17 binder","Therapeutic strategy associated"]
[1571,"DB15721","investigational","biotech","Natural Killer Cell","NK Cells",null,null,"Natural Killer (NK) cells originate and differentiate from hematopoietic stem cells through various signalling pathways involving cytokines and interleukins. These cells arise from CD34+ lymphoid progenitors and comprise 10-15% of all lymphocytes in human peripheral blood. Once completely differentiated, NK cells lack B (CD19-) and T(CD3-) lymphocyte markers and carry their unique CD56+ status instead. The two maturate variants of NK cells are CD56dim and CD56bright, which exert cytotoxicity through release of toxic chemicals and cytokine secretion, respectively. NK Cells express features of innate immune responses, and respond to all molecules that appear to be foreign to the body. \r\n\r\nThe most standard and utilized source of NK cells is directly from the peripheral blood of a donor through leukapheresis: a technique where immune cells are separated from red blood cells. Generally, the number of NK cells collected in the peripheral blood mononuclear cell (PBMC) is too low for sufficient potency, and ex vivo expansion is performed. Expansion involves the use of feeder cell line systems or bioreactors to enhance the number of NK cells with desired cytotoxicity. These cells are also purified using cell-separation systems and processing.\r\n\r\nOther techniques involve using umbilical cord blood (UCB) directly; these NK cells have heterogeneous CD56 expression but are considered suitable for immunotherapy. It is also possible to culture UCB CD34+ hematopoietic stem cells (HSCs) under stimulation of IL-2, IL-15, and stem cell factor (SCF) in a system to develop NK cells. \r\n\r\nInduced pluripotent stem cells (iPSCs) and human embryonic stem cells (HESCs) are also used to generate NK cells through a two-step culture method resulting in CD34+ cells.",{"$nulls":4},"The predominant targets of NK cells are ‘stressed’ cells with downregulated expression of class I MHC (MHC-I), a common mechanism used by malignant or virus-infected cells to evade recognition by the body’s immune system. In response to encountering these cells, NK cells release two types of proteins, perforins and granzyme B, which attack the target cell’s membrane, damage its organelles, and trigger apoptosis. NK Cell immunotherapy is an emerging anti-cancer strategy, as these cells are able to exert effects without activating the graft-versus-host disease cascade. In addition, their broad mechanism allows for generally safe administration of NK cells that are not immunologically matched to a patient.",null,"Therapeutic strategy associated"]
[1572,"DB15724","investigational","biotech","Human umbilical cord blood mononuclear cell-conditioned medium","Umbilical Cord Blood Mononuclear Cells Conditioned Medium",null,null,"Transplantation with human umbilical cord blood mononuclear cells (HUCBC) has demonstrated promising results in various disease states. While some of the positive results are credited to HUCBCs’ differentiation potential, the growth factors and cytokines these cells secrete are also implicated. When HUCBCs secrete growth factors and anti-inflammatory cytokines, they are thought to reduce inflammation and associated damage. Thus, the media in which they are cultured is believed to also have therapeutic potential. \r\n \r\nAfter the human umbilical cord mononuclear cells are extracted from the umbilical cord, they are expanded and cultured in Dulbecco’s modified Eagle’s medium. Then, the medium is filtered and separated from the HUCBCs.",{"$nulls":4},"Mononuclear umbilical cord cells have the ability to secrete cytokines, growth factors, interleukins,and chemokines. As many of these factors can have anti-inflammatory, angiogenic, and neuroprotective effects, it is thought that the conditioned media may exert some therapeutic potential related to these effects. \r",null,"Therapeutic strategy associated"]
[1573,"DB15726","investigational","biotech","Human Umbilical Cord Mesenchymal Stem Cells","HUCMSCs; Human Umbilical Cord Wharton’s Jelly-derived Mesenchymal Stem Cells; Mesenchymal Stromal Cells; UC-MSCs; WJ-MSCs; XCEL-UMC-BETA",null,null,"Stem cells obtained from amniotic fluid, the umbilical cord (UC), and placenta are gaining in popularity. Stem cells from the umbilical cord offer several advantages, including: non-invasive collection procedures, more hearty and steady growth than bone-marrow derived stem cells (they can maintain a steady doubling time (DT) over up to 10 passages), higher differentiation capability, and faster self-renewal. These cells express low levels of major histo-compability complex (MHC) class I, and generally lack MHC class II and its co-stimulatory ligands like CD40, CD80, and CD86. Thus, they are characterized with low immunogenicity. The umbilical cord, which starts developing in the fifth week of gestation, contains different compartments where stem cells originate: the cord lining, Wharton’s jelly, and perivascular region. \r\n\r\nUC mesenchymal cells derived from Wharton’s jelly are the most studied and offer more stable and better osteogenic and adipogenic differentiation potentials. The cells are extracted by either the explant or the enzymatic digestion method, though neither method has been characterized as the ‘standard’ thus far. The explant method requires manual mincing of the tissue fragments and results in an inconsistent number of extracted MSCs. In contrast, the enzymatic digestion method uses enzymes to break down the non-required cell fragments, and results in more consistent cell numbers. Regardless of extraction method, the cells are usually expanded in vitro in laboratories using culture systems and bioreactors. \r\n\r\nThe cord lining of the UC is generally isolated with the explant method -- resulting in two kinds of MSCs: cord lining mesenchymal stem cells (CLMC), which are used to aid in burn and diabetic ulcer wound healing, and cord lining epithelial stem cells (CLEC), which are used for persistent corneal epithelial defects and skin improvements.\r\n\r\nCurrently many companies are creating their own version of these stem cells, one of which is by Aspire, who are creating a version named ACT-20.",{"$nulls":4},"General theories of therapeutic action postulate that HUCMSCs can replace damaged cells, inhibit immunological functions through paracrine actions, and promote proliferation of endogenous stem cells through cell-cell communication. HUCMScs are thought to alter immune function through inhibition of Natural Killer Cell, T-cell, and B-cell proliferation along with redirecting monocytes and dendritic cells to less mature states. HUCMSCs are currently investigated for specific cell-based therapies, as they can be differentiated and engrafted for various disease states with low immunogenicity. Such applications include neurodegenerative diseases, spinal cord injury, stroke, and even liver disease. Certain factors secreted by HUCMSCs, such as oxidative stress pathways, are also thought to inhibit tumor growth and even lymphoma cell growth.  These therapies are currently being considered for the treatment of COVID-19. \r",null,"Therapeutic strategy associated"]
[1574,"DB15729","investigational","biotech","Adipose-Derived Mesenchymal Stem Cells: Autologous or Allogeneic Origins","adMSC; AstroStem-V; CMTAd; HB-adMSCs; HCR040; PSC-04",null,null,"Adipose mesenchymal stem cells (AMSCs) are MSCs derived from adipose tissue, which is more accessible and less painful than stem cells extracted from most other sources. Autologous stem cells are those derived from a patient’s own cells while allogeneic stem cells are derived from that of a donor. Lipoaspiration, also known as liposuction, is a possible method for extraction. This is followed by purification and expansion of the cells in vitro. \r\n\r\nThese AMSCs are multipotent, with the capability of forming different tissues, some of which include bone, muscle, neural, and chondrocyte. This explains why AMSCs have been utilized in repairing craniofacial bone defects. They also have potential in treatment of scarred vocal folds.",{"$nulls":4},"AMSCs have been shown to secrete several growth factors and hyaluronic acid (HA) which balance collagen, with hepatocyte growth factor (HGF) being a major part of those secreted. HGF secreted by AMSCs has been shown, in culture, to attenuate collagen production and fibroblast proliferation. AMSCs also have the ability to produce elastic fibers, something that typically does not appear in a scar environment.\r\n\r\nIn some studies, adipose mesenchymal stem cells have demonstrated anti-inflammatory and chondroprotective properties. Currently, the exact mechanism behind AMSCs is unknown. However, a possible mechanism consists of activation of the cells due to inflammation, with the activated cells then modulating inflammation and cartilage remodeling by prostaglandin E2. The effects for AMSCs seem to also possibly be dose-dependent.\r",null,"Therapeutic strategy associated"]
[1575,"DB15730","investigational","biotech","Placental Mesenchymal Stem Cells","Placental mesenchymal stromal cells; PLX-PAD",null,null,"The placenta serves many purposes, with one of the many being a bank of mesenchymal stem cells (MSCs). It can be obtained relatively easily as medical waste from which MSCs can be non-invasively extracted and without the ethical issues that come with embryonic stem cells. The placental MSCs (pMSCs) are obtained from either the fetal side, which hold chorionic plate-derived MSCs, or the maternal side, which contributes decidual parietalis-dreived MSCs. Although pMSCs have multi-lineage differentiation potential, the fetal-side pMSCs have greater expansion capacity, proliferation and differentiation potential than maternal-side pMSCs. It was also found that fetal-side pMSCs express different surface markers.",{"$nulls":4},"All pMSCs contain therapeutic potential and have been used in medical treatment already as they are an ideal candidate for allogeneic transplantation due to their immunomodulatory properties and low immunogenicity. MSCs secrete growth factors and cytokines during angiogenesis, anti-fibrotic processes, chemotaxis, hematopoiesis induction, immunomodulation, and inhibition of apoptosis, with different levels of secretion between fetal- vs. maternal-side pMSCs. Fetal-side pMSCs secrete a higher level of HGF and VCAM-1 and hold potential in angiogenic therapy, while maternal-side pMSCs have the potential for treatment of critical limb ischemia as they secrete VEGF and Ang-1. \r",null,"Therapeutic strategy associated"]
[1576,"DB15731","investigational","biotech","Allogenic Donor CD362-enriched Human Umbilical Cord-derived Mesenchymal Stem Cells","Allogeneic donor CD362 enriched human umbilical cord-derived mesenchymal stromal cells; ORBCEL C™; Orbcel-C; REALIST ORBCEL-C",null,null,"ORBCEL-C™ is the trade name of a product composed of highly purified stromal cells derived from the human umbilical cord. The isolated cells are expanded in culture and are able to be used allogenically -- meaning that one donor’s cells can be given to other unrelated patients. These cells are CD362 enriched umbilical cord-derived mesenchymal stem cells (UC-MSCs); UC-MSCs share stemness markers with both embryonic stem cells (ESCs) and adult mesenchymal stem cells (MSCs); this feature allows them to be hypoimmunogenic and non-inducible for tumorigenesis.  \r\n\r\nRegarding the modifications of these UC-MSCs, CD362, also known as syndecan-2, is a surface marker identified on MSCs with enhanced clonogenicity and immunomodulatory properties. Enrichment of CD362 expression in MSCs is being investigated for its role in immune modulation of injured tissue.",{"$nulls":4},"The mesenchymal stem cells (MSCs) of ORBCEL-C™ act through release of factors which reduce inflammatory responses, promote blood vessel formation, and have the ability to demonstrate immunomodulatory effects. \r\n\r\nAllogeneic UC-MSCs are also being investigated in orthopedic applications for cartilage and bone regeneration; these UC-MSCs are a valuable allogeneic source of cells as these cells are from a discarded material with virtually unlimited availability. Specifically to orthopedics, UC-MSCs have potential for treatment of chondral and osteochondral lesions, and bone defects as a universal off-the-shelf product. \r",null,"Therapeutic strategy associated"]
[1577,"DB15742","investigational","biotech","MultiStem","Multipotent Adult Progenitor Cells (MAPCs)",null,null,"MultiStem is an intravenously-administered, off-the-shelf proprietary product developed which comprises Multipotent Adult Progenitor Cells (MAPCs). Like mesenchymal stem cells, MAPCs are derived from bone-marrow stroma and are non-hematopoietically adherent. They have immunomodulatory and pro-angiogenic properties while also being mostly non-immunogenic. Additional benefits of MultiStem include their low immunogenicity, meaning they can be administered without tissue matching or concurrent immunosuppressive agents. The cells for creation of the product are isolated from a qualified donor and expanded on a large scale and then frozen until use. After administration, the cells are cleared from the body over time. Currently, MultiStem is being investigated against neurological, inflammatory, immune, and cardiovascular diseases and conditions.",{"$nulls":4},"MultiStem’s main focus is immunological, with MAPCs mainly acting by producing factors regulating the immune system, protecting damaged and injured cells, and also promoting tissue repair and healing. The MAPCs in MultiStem have the ability to express a range of therapeutically relevant proteins and factors with the potential to reduce inflammation, protect damaged or injured tissue, and enhance the formation of new blood vessels in areas of ischemic injury. Immune-wise, it acts to rebalance the immune system, with studies by the company showing that the therapy acts by reducing inflammation (with reduced inflammatory cytokine levels) and lessening activation and migration of the peripheral immune system to the site of injury.  Additionally, this therapy potentially may have therapeutic effects through decreasing activation of the peripheral immune response to the initial injury which then results in reduction of inflammation and thereby means less secondary tissue damage and scarring while also allowing for accelerated repair processes. These cells have also been shown to lessen adverse results of inflammation while reparative immune cells are activated. In summary, there occurs simultaneous upregulation of reparative immune responses and downregulation of proinflammatory processes. \r\n\r\nOutside of immunological applications, MAPCs are also being investigated for ischemic injury treatment and cardiovascular repair. Compared to MSCs, MAPCs have a stronger angiogenic protein release profile while also inducing more extensively developed vasculature in a study. Additionally, MAPCs also hold potential in being a functional cell source for orthopedic applications and to also promote tissue regeneration and healing. Evidence exists that MAPCs can differentiate into cells of mesenchymal lineages which includes bones, bone marrow, cartilage, fat, muscles, and tendon -- giving reason behind the investigating of MAPCs for treatment of bone and cartilage disease. MAPCs, compared to MSCs, also seem to have greater inclination for endothelial differentiation. \r",null,"Therapeutic strategy associated"]
[1578,"DB15745","investigational","biotech","Washed Microbiota Transplantation","WMT",null,null,"Fecal microbiota transplantation (FMT) is effective in enhancing the gut microbiota of patients experiencing a high range of disease states, including Clostridioides difficile (C. diff) infection, Crohn’s disease, and ulcerative colitis. Washed microbiota preparation (WMT) involves a method wherein FMT is used, but the preparation undergoes microfiltration through an automatic purification system combined with repeated centrifugation and suspension. Fecal particles, parasite eggs, fungus and other potentially harmful things are removed. The resulting suspension is shown to decrease FMT-related adverse events.",{"$nulls":4},"WMT delivers a precise dose of enriched microbiota through intraperitoneal injection, oral capsule, nasogastric tube, nasojeunal tube, or anal enema. The transplantation of the materials within the WMT is thought to recolonize the gut bacteria and aid in treating patient pathology associated with disease like Crohn’s, and ulcerative colitis. WMT is being investigated as a rescue therapy for critically ill patients with COVID-19.",null,"Therapeutic strategy associated"]
[1579,"DB15746","investigational","biotech","Recombinant Human Plasma Gelsolin","pGSN; Plasma gelsolin; Rhu-pGSN",null,null,"Plasma gelsolin (pGSN) is a protein found in the blood of healthy individuals which scavenges compounds left over from damaged tissues.",{"$nulls":4},"pGSN also enhances bacterial uptake and death by macrophages. It has positive effects on the immune system as it boosts clearing of pathogens and modulates inflammatory reactions; often pGSN is consumed in both serious infectious and non-infectious conditions. Its physiological effects thus make it a potential candidate for severe acute respiratory syndrome (ARDS) associated with COVID-19, as administration of recombinant protein is thought to supplement depleted levels of pGSN.",null,"Therapeutic strategy associated"]
[1580,"DB15750","investigational","biotech","Trefoil Factor 2","Spasmolytic peptide; TFF2",null,null,"The trefoil factor 2 (TFF2) peptide is a low-molecular weight protein and one of the three trefoil-motif-containing proteins. They are expressed predominantly in gastric tissues with the source for them being predominantly stromal cells, although expression of TFF2 mRNA transcripts also occurs with tissue macrophages. The peptides themselves are most abundant in mucous cells of the gastric mucosa with TFF2 being detected in mucous layers over the tissue.",{"$nulls":4},"TFF2 acts as a regulator of mucosal tissue repair and is a part of epithelial defences, promoting restitution. TFF2 is upregulated in gastric tissue with Helicobacter infections and gastric tissues with inflammatory conditions; its anti-inflammatory actions allow it to down-regulate gastric and colonic inflammation. It has also been proposed that TFF2 is involved with some aspect of immune function. Although there are reports of a number of potential biological roles for TFF, currently, the exact mechanism of action is yet to be elucidated as cell surface receptors for TFFs have not yet been identified. However, a study proposes TFF2 to have a role in the negative regulation of interleukin 1 (IL-1) receptor-mediated signalling.",null,"Therapeutic strategy associated"]
[1581,"DB15751","investigational","biotech","MRx-4DP0004",{"$nulls":3},"MRx-4DP0004 is a lyophilised formulation of the Bifidobacterium breve strain of commensal bacteria. It is a live biotherapeutic derived from the microbiota of a healthy human infant.",{"$nulls":4},"MRx-4DP0004 is an immunomodulatory therapy with anti-viral activity that simultaneously downregulates molecules associated with hyper-inflammatory responses. It reduces neutrophilic and eosinophilic infiltration in the lungs, in addition to a reduction in peribronchiolar and perivascular immunopathology without the side effects associated with immunosuppressants. A study of MRx-4DP0004 also demonstrated specifics of the biotherapeutic increasing lung D4+CD44+ cells and CD4+FoxP3+ cells, decreasing activated CD11b+ dendritic cells, and reducing pro-inflammatory cytokines and chemokines involved in neutrophil migration. MRx-4DP0004 is currently being investigated for severe asthma management, however, the specific mechanism of action is currently unknown.",null,"Therapeutic strategy associated"]
[1582,"DB15753","investigational","biotech","Interferon Gamma","Heberon gamma; IFNγ; Recombinant Interferon Gamma",null,null,"Interferon gamma is a Type 1 inflammatory cytokine and the only type II interferon. It has antitumor properties, antiviral activities, and important immunoregulatory functions. The interferon is primarily produced by activated T lymphocytes and natural killer cells.",{"$nulls":4},"Interferon gamma signals as an antiparallel homodimeric glycoprotein, acting at the complex of interferon gamma receptor 1 (IFNGR1) and IFNGR2 after direct binding to IFNGR1. It activates the JAK/STAT, MAPK, and PI3-Kinase pathways. In addition, Interferon gamma activates macrophages, mediates antiviral and antibacterial immunity, regulates Th1/Th2 balance, and controls cellular proliferation and apoptosis.  It is currently being investigated as an antitumor drug, and a therapy for juvenile rheumatoid arthritis, chemoresistant pulmonary tuberculosis, idiopathic pulmonary fibrosis, and atypical pulmonary mycobacteriosis.\r\n\r\nThis cytokine has been found to have effects such as promotion of host response in antitumor immunity, playing roles in all three phases (elimination, equilibrium, and escape) of cancer immunoediting, directly influencing antiproliferation, apoptosis, and antiangiogenesis on tumor cells, and indirectly influencing antitumor immunity. However, currently there is no approved indication report of using interferon gamma in cancer treatment, indicating that interferon has not yet reached a stage of being a clinically-useful antitumor drug. \r\n\r\nInterferon gamma, when administered in combination with interferon alpha-2-beta as part of the HerberFERON therapy, is found to have synergistic effects, with the potential for more favorable pharmacodynamics than either alone. This synergy between interferon alpha and gamma include antiproliferative effects on several cancers.",null,"Therapeutic strategy associated"]
[1583,"DB15762","approved","biotech","Satralizumab","Humanised anti-IL-6 receptor monoclonal antibody; Sapelizumab; Satralizumab; satralizumab-mwge",null,null,"Satralizumab is a recombinant humanized monoclonal antibody targeted against human interleukin-6 (IL-6) receptors, similar to , which is produced in Chinese hamster ovary cells and based on an IgG2 framework. Satralizumab is used in the treatment of neuromyelitis optica spectrum disorder (NMOSD), a rare autoimmune inflammatory disorder of the central nervous system (CNS) involving demyelinating lesions in the optic nerve, spinal cord, brainstem, and cerebrum. Some of the pro-inflammatory mechanisms involved in NMOSD are thought to be mediated, at least in part, by IL-6, including increased production of anti-aquaporin-4 (AQP4) autoantibodies and increased permeability of the blood-brain barrier, which allows for the passage of pro-inflammatory mediators into the CNS. Satralizumab is thought to exert its therapeutic benefits by blocking IL-6 receptors and, subsequently, these inflammatory responses.\r\n\r\nEnspryng®, a satralizumab formulation developed by Chugai Pharmaceutical and Roche, is uniquely formulated with \"recycling antibody technology\" whereby the association of satralizumab to IL-6 receptors occurs in a pH-dependent manner - this allows satralizumab to bind an IL-6 receptor until it reaches an endosome, after which the drug may dissociate from the receptor and move back into the plasma to act again. This novel mechanism effectively increases the duration of action of satralizumab, as it allows for single drug molecules to interact with multiple endogenous IL-6 receptors prior to elimination.\r\n\r\nSatralizumab was first approved for use in Canada in June 2020 for the treatment of AQP4 antibody-positive patients with NMOSD. It received subsequent approvals in Switzerland and Japan, and was approved for use by the FDA in August 2020, becoming the 3rd treatment to receive FDA approval for NMOSD (after  in June 2019 and  in June 2020).","1535963-91-7",null,"Satralizumab is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive. In Canada, it is also used in adolescent patients for the same indication.","Enspryng®, a satralizumab formulation developed by Chugai Pharmaceutical and Roche, utilizes a novel \"recycling antibody technology\" whereby the association of satralizumab to IL-6 receptors occurs in a pH-dependent manner. Satralizumab-bound IL-6 receptors are taken up into cells and transported into endosomes, a relatively acidic environment in comparison to plasma (pH 5.5-6.0 vs. pH 7.4) - this decrease in pH allows satralizumab to dissociate from the IL-6 receptor and be recycled back into the plasma, where it can bind to another IL-6 receptor and repeat the process. \r\n\r\nSatralizumab has been associated with an increased risk of infection, including serious and potentially fatal infections. It should not be administered to patients with active infections, including localized infections, until the infection resolves, and is contraindicated for use in patients with active hepatitis B or tuberculosis.","Interleukin-6 (IL-6) is a pro-inflammatory cytokine which has been implicated in the pathogenesis of NMOSD. The inflammatory cascade triggered by IL-6 signaling is thought to result in the differentiation of T-cells into pro-inflammatory TH17 cells and the differentiation of B-cells into plasmablasts producing AQP4 autoantibodies. IL-6 may also play a role in increasing the permeability of the blood-brain barrier, thereby allowing penetration of autoantibodies and pro-inflammatory mediators into the central nervous system.\r\n\r\nSatralizumab is a humanized monoclonal antibody targeted against human IL-6 receptors. It binds to soluble and membrane-bound IL-6 receptors and prevents the signaling cascade, and subsequent pro-inflammatory effects, associated with its binding to endogenous IL-6.","Interleukin-6 receptor subunit alpha binder&antibody","Therapeutic strategy associated"]
[1584,"DB15866","investigational","biotech","CK0802","Allogeneic Umbilical Cord Blood Derived Regulatory T-Cells",null,null,"CK0802 is an off-the-shelf product composed of allogeneic umbilical cord blood derived regulatory T-cells (T-Reg cells), which can be used intravenously and without HLA matching. On the surface of these T-Reg cells, T-cell lung homing markers are expressed.",{"$nulls":4},"T-Reg cells engage with antigen-presenting cells lining the alveolar epithelium. This likely results in disarmament and dampening of the cytokine storm — seen with a study where there was a rapid decline in peripheral biomarkers and decreased blood levels of inflammatory cytokines after treatment with CK0802. It is also a possibility that these cells can calm inflammation where it is most active and act discriminately, avoiding general immunosuppression. This therapy is currently being investigated against COVID-19 acute respiratory distress syndrome (ARDS), inflammatory diseases, and autoimmune disorders.",null,"Therapeutic strategy associated"]
[1585,"DB15868","investigational","biotech","Amniotic Epithelial Cells","hAECs; Human Amniotic Epithelial Cells",null,null,"Amniotic epithelial cells (AEC) are multipotent stem-like cells derived from the basement collagenous membrane of the human amnion, the layer of the placenta closest to the fetus. These cells are potential candidates for allogeneic cell therapy and regenerative medicine due to their potential for differentiation and multiplication.",{"$nulls":4},"Amniotic epithelial cells have immunosuppression properties, the likely reason why these cells seem to be resistant to rejection after allotransplantation. Further therapeutic effects of these cells include reported neuroprotection and neuroregeneration properties, attributed to the growth factor secretion by AECs. These cells are being investigated as a therapy against many different conditions, some of which include lung fibrosis, liver fibrosis, multiple sclerosis, congenital metabolic disorders, familial hypercholesterolemia, spinal cord injuries, ophthalmic diseases, and Parkinson’s disease.",null,"Therapeutic strategy associated"]
[1586,"DB15869","investigational","biotech","Platelet Lysate",{"$nulls":3},"Platelet lysate is an acellular compound composed of platelet proteins while also being void of cellular debris, thus making the lysate rich with growth factors. It is extracted through lysis of the plasma membrane of platelets. Because white cell antigens are low in prepared lysate, there is a minimized likelihood of immune responses.",{"$nulls":4},"Platelet lysate plays a role in regeneration through the growth factors it contains, resulting in an increase in cell proliferation and angiogenesis. Nebulized platelet lysate can be administered to the lungs and has applications in treatment of acute lung injuries, chronic obstructive pulmonary disease (COPD), and asthma. Because of the aforementioned diseases that the plasma lysate can treat and its ability to relegate severe inflammatory processes of the respiratory tract, it is currently also being investigated against COVID-19 infection-related acute respiratory syndrome (ARDS).",null,"Therapeutic strategy associated"]
[1587,"DB15890","investigational","biotech","RAPA-501-Allo",{"$nulls":3},"RAPA-501-ALLO is composed of T-cells extracted from healthy volunteers; these cells are then reprogrammed _ex vivo_ in a process that involves de-differentiation and re-differentiation.",{"$nulls":4},"The hybrid TREG and Th2 phenotype of these cells inhibits the inflammatory pathways of COVID-19 through modulation of cytokines and chemokines and cross-regulation of Th1 and Th17 populations. This therapy also has been seen to mediate protection on lung alveolar tissue. The immunomodulation that occurs is in a T-cell receptor independent manner. Currently, RAPA-501-ALLO is being investigated against COVID-19.",null,"Therapeutic strategy associated"]
[1588,"DB16028","investigational","small molecule","Azemiglitazone","Azemiglitazone","C19H17NO5S","COC1=CC=CC(=C1)C(=O)COC1=CC=C(CC2SC(=O)NC2=O)C=C1","Azemiglitazone is under investigation in clinical trial NCT01280695 (A Randomized, Double-blind, Comparator- and Placebo-controlled, Multiple-dose Study to Evaluate the Safety, Tolerability and Efficacy of Three Dose Levels of MSDC-0602 in Type 2 Diabetic Patients).","1133819-87-0","371.41",{"$nulls":3},"Peroxisome proliferator-activated receptor gamma","Target associated"]
[1589,"DB16157","investigational","small molecule","Ensifentrine","Ensifentrine","C26H31N5O4","COC1=C(OC)C=C2C(CCN3C(=O)N(CCNC(N)=O)\\C(C=C23)=N\\C2=C(C)C=C(C)C=C2C)=C1","Ensifentrine is under investigation in clinical trial NCT04535986 (A Phase 3 Clinical Trial to Evaluate the Safety and Efficacy of Ensifentrine in Patients With COPD).","1884461-72-6","477.565",null,null,"Ensifentrine is a dual inhibitor of phosphodiesterase 3 (PDE3) and phosphodiesterase 4 (PDE4); it is also an activator of the cystic fibrosis transmembrane conductance regulator (CFTR). This drug has bronchodilatory and anti-inflammatory properties due to the dual inhibition; it also has mucous viscosity reduction and improved mucociliary clearance effects due to the CFTR activation. Ensifentrine is currently being investigated against COPD, cystic fibrosis, asthma, other respiratory diseases, and COVID-19.",null,"Therapeutic strategy associated"]
[1590,"DB16165","approved; investigational","small molecule","Finerenone","Finerenone","C21H22N4O3","CCOC1=NC=C(C)C2=C1[C@H](C1=CC=C(C=C1OC)C#N)C(C(N)=O)=C(C)N2","Finerenone, or BAY 94-8862, is a mineralocorticoid receptor antagonist indicated to reduce the risk of sustained decline in glomerular filtration rate, end stage kidney disease, cardiovascular death, heart attacks, and hospitalization due to heart failure in adults with chronic kidney disease associated with type II diabetes mellitus. Patients with kidney disease, would originally be given  or  to antagonize the mineraclocorticoid receptor. Spironolactone has low selectivity and affinity for the receptor; it dissociates quickly and can also have effects at the androgen, progesterone, and glucocorticoid receptors. Eplerenone is more selective and has longer lasting effects. More selective nonsteroidal mineralocorticoid antagonists such as , , and finerenone were later developed. So far, finerenone is the only nonsteroidal mineralocorticoid receptor antagonist to be FDA approved.\r\n\r\nFinerenone was granted FDA approval on 9 July 2021.","1050477-31-0","378.432","Finerenone is indicated to reduce the risk of sustained decline in glomerular filtration rate, end stage kidney disease, cardiovascular death, heart attacks, and hospitalization due to heart failure in adults with chronic kidney disease associated with type II diabetes mellitus.","Finerenone is a non-steroidal mineralocorticoid receptor antagonist indicated to reduce the risk of sustained decline in glomerular filtration rate, end stage kidney disease, cardiovascular death, heart attacks, and hospitalization due to heart failure in adults with chronic kidney disease associated with type II diabetes mellitus. It has a moderate duration of action as it is taken once daily, and a wide therapeutic window as patients were given doses from 1.25 mg to 80 mg in clinical trials. Patients should be counselled regarding the risk of hyperkalemia.","Finerenone is a non-steroidal selective mineralocorticoid receptor (MR) antagonist with no significant affinity or activity at androgen, progesterone, estrogen, and glucocorticoid receptors. Animal studies have shown that finerenone binding to the MR reduces inflammation and fibrosis, and phase 2 clinical trials showed a reduction in albuminuria.\r\n\r\nAldosterone is a mineralocorticoid hormone involved in the regulation of blood pressure, sodium reabsorption, and potassium excretion. In 1943, agonism of the MR along with increased salt was shown to be associated with malignant hypertension, which could progress to inflammation and fibrosis of organs.\r\n\r\nBinding of aldosterone, an MR agonist, to the MR causes a conformational change, which dissociates the receptor from inactivating chaperone proteins. The active MR translocates to the nucleus along with a complex of other coactivators to induce transcription of a number of genes. \r\n\r\nFinerenone's binding to the MR prevents binding of MR coactivators, which in turn prevents pro-inflammatory and pro-fibrotic gene transcription.\r\n\r\nClinical trial data shows that blocking the mineralocorticoid receptor reduces mortality and morbidity in patients with chronic severe congestive heart failure with an ejection fraction ≤35%. Patients taking finerenone developed new onset atrial fibrillation or flutter (AFF) with a hazard ratio of 0.71. Finerenone lowered the risk of first onset of kidney failure, a sustained eGFR decrease of ≥40%, or death from a renal cause to a hazard ratio of 0.82. Cardiovascular outcomes including cardiovascular death, nonfatal heart attacks, nonfatal strokes, and hospitalization for heart failure in patients taking finerenone had a hazard ratio of 0.86 in patients with a history of AFF and 0.85 in patients without a history of AFF.","Mineralocorticoid receptor antagonist","Therapeutic strategy associated"]
[1591,"DB16247","investigational","biotech","Nangibotide","Nangibotide",null,null,"Nangibotide is under investigation in clinical trial NCT04055909 (Efficacy, Safety and Tolerability of Nangibotide in Patients With Septic Shock).","2014384-91-7",{"$nulls":3},"Nangibotide targets the immunoreceptor TREM-1 (triggering receptor expressed on myeloid cells-1), and has been explored in treating inflammatory disorders like septic schock. Safety and pharmacokinetics studies have shown Nangibotide to be safe and well-tolerated in humans, while animal septic shock models have shown its ability to restore vascular function and improve survival. As of July 2020, Inotrem is recuriting patients to study Nangibotide's effects on patients with COVID-19 and systemic inflammation (NCT04429334).",null,"Therapeutic strategy associated"]
[1592,"DB16365","investigational","small molecule","Treamid","BDDA; Bisamide derivative of dicarboxylic acid; XC268BG",null,null,"Treamid, also known as bisamide derivative of dicarboxylic acid (BDDA), is a complexing agent that has been found to chelate metal ions, including calcium, copper, iron, magnesium, and zinc. This drug has shown regenerative properties and restoration of the function of various tissues and organs. It is has been investigated in the clinical trials of NCT04428593 (Study to Assess Safety, Tolerability and Pharmacokinetics of Treamid in Healthy Volunteers) and NCT04527354 (Pilot Study to Assess Efficacy and Safety of Treamid in the Rehabilitation of Patients After COVID-19 Pneumonia) by PHARMENTERPRISES.",{"$nulls":4},"In animal studies, treamid displays a positive effect on the capillaries of lungs, exhibits anti-fibrotic activity, and increases the number of endothelial progenitor cells in the lungs of animals with pulmonary fibrosis. Currently, the drug is being investigated against COVID-19.",null,"Therapeutic strategy associated"]
[1593,"DB16366","investigational","biotech","F-652","IL-22 fusion protein",null,null,"F-652 is a recombinant IL-22-Fc fusion protein manufactured in Chinese hamster ovary cells that is composed of 2 human interleukin 22 (IL-22) molecules linked to an immunoglobulin constant region (IgG2-Fc). It is being developed by Evive Biotech (previously known as Generon BioMed Inc).",{"$nulls":4},"F-652 incorporates human interleukin 22’s (IL-22) natural epithelial cell growth-promoting activity as IL-22 plays critical roles in promoting tissue repair and suppressing bacterial infection. F-652 is currently being investigated against acute graft vs host disease, acute alcoholic hepatitis, inflammatory diseases, organ injuries, eventual fatal organ failures, and COVID-19.",null,"Therapeutic strategy associated"]
[1594,"DB16367","approved; investigational","biotech","Autologous peripheral blood-derived CD34+ cells","CD34+ Cells; CLBS119",null,null,"Autologous peripheral blood-derived CD34+ cells, or CLBS119 (a proprietary version being developed by Caladrius Biosciences, Inc.), are hematopoietic stem cells. It is also a cell therapy being investigated by Caladrius Biosciences in the clinical trial NCT04522817 (CLBS119 for Repair of COVID-19 Induced Pulmonary Damage).",{"$nulls":4},"Autologous peripheral blood-derived CD34+ cells have potential tissue repair ability in part due to its anti-inflammatory function which were demonstrated in pre-clinical models, including one of lung inflammation. Due to the pre-programmed tissue repair effects mediated by anti-inflammatory and pro-angiogenic functions of these cells, this cell therapy is currently being investigated against COVID-19-induced lung damage in recovered adult patients that still are experiencing hypoxia and require supplemental oxygen.",null,"Therapeutic strategy associated"]
[1595,"DB16398","investigational","biotech","Efmarodocokin alfa","Efmarodocokin alfa; IL 22-FC; IL-22Fc",null,null,"Efmarodocokin alfa is under investigation in clinical trial NCT04386616 (A Study to Evaluate the Safety and Efficacy of MSTT1041A (Astegolimab) or UTTR1147A in Patients With Severe COVID-19 Pneumonia).","1953227-87-6",{"$nulls":3},"Efmarodocokin alfa is a human IL-22Fc IgG4 fusion protein that activates the IL-22 pathway being investigated for inflammatory diseases. Studies show activation of STAT3 in primary human hepatocytes and human colon cell lines.",null,"Therapeutic strategy associated"]
[1596,"DB16416","investigational","biotech","Vilobelimab","IFX-1; Vilobelimab",null,null,"Vilobelimab is under investigation in clinical trial NCT03895801 (Study of IFX-1 to Replace Steroids in Patients With Granulomatosis With Polyangiitis and Microscopic Polyangiitis).","2250440-41-4",{"$nulls":3},"Vilobelimab is an inhibitor targeting C5a in human plasma which helps markedly alleviate systemic inflammatory responses, and is being investigated in patients with acute lung injury. This neutralizing antihuman antibody acts by blocking the activation of C5a and thereby inhibits granulocyte expression of CD11b.","Complement C5 inhibitor","Therapeutic strategy associated"]
[1597,"DB16447","investigational","small molecule","Thymoquinone","2-Isopropyl-5-methyl-p-benzoquinone; p-Cymene-2,5-dione; p-Mentha-3,6-diene-2,5-dione; Thymoquinon","C10H12O2","CC(C)C1=CC(=O)C(C)=CC1=O","Thymoquinone is a natural compound with widespread protective effects, including anti-oxidative, anti-inflammatory, immunomodulatory, anti-cancer, and anti-microbial.","490-91-5","164.204",null,null,"Thymoquinone is a natural compound with widespread protective effects, including anti-oxidative, anti-inflammatory, immunomodulatory, anti-cancer, and anti-microbial. It is able to induce apoptosis, regulate pro- and anti- apopotitic genes, and inhibit cancer metastasis through JNK and p38 activation. Its anti-inflammatory effects are attributed to its inhibition of inflammatory cytokines and processes, including pathways associated with 5-LO, COX, and PGD2.",null,"Therapeutic strategy associated"]
[1598,"DB16448","investigational","biotech","CD24Fc","Human CD24 and human IgG Fc Fusion Protein",null,null,"CD24Fc is a biological immunomodulator originally developed to address graft-versus-host disease in stem cell transplantation in leukemia patients.",{"$nulls":4},"CD24Fc is a biological immunomodulator originally developed to address graft-versus-host disease in stem cell transplantation in leukemia patients. It has protective abilities against inflammatory mediators and potential to reduce lung pathology associated with pneumonia. The specific mechanisms by which CD24Fc works is currently unknown.",null,"Therapeutic strategy associated"]
[1599,"DB16452","investigational","small molecule","MAS825",{"$nulls":8},"MAS825 is being investigated for applications in inflammatory diseases and oncology. The specific mechanisms of action for this drug are currently unknown.",null,"Therapeutic strategy associated"]
[1600,"DB16522","investigational","small molecule","Sodium copper chlorophyllin","SCC; Sodium copper chlorophyllin",null,null,"Sodium copper chlorophyllin (SCC) is a water-soluble and bright green mixture derived from natural chlorophyll that has potential antimutagenic and antioxidant properties. This compound is used as a food colorant and supplement. \r\n\r\nSCC of the commercial-grade is prepared from a reaction between a crude chlorophyll extract and methanolic sodium hydroxide, followed by replacement of the central magnesium atom with a heavy metal.",{"$nulls":4},"Sodium copper chlorophyllin (SCC) has potential anti-inflammatory, deodorizing, erythropoietic, and antimutagenic activities. It is currently being investigated against COVID-19.",null,"Therapeutic strategy associated"]
[1601,"DB16620","investigational","small molecule","Methopterin","10-methylfolic acid; 10-methylpteroylglutamic acid; alpha-Methopterin; Methopterine; Methotrexate related compound C; N10-methylfolic acid; N10-methylpteroylglutamic acid","C20H21N7O6","CN(CC1=CN=C2N=C(N)NC(=O)C2=N1)C1=CC=C(C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O","Methopterin is thought to have effects on osteoclasts and to inhibit inflammatory bone destruction.","2410-93-7","455.431",null,null,"Methopterin has been shown to inhibit the proliferation, activation, and bone resorption action of osteoclasts, and induce the apoptosis of osteoclasts, likely contributing to the ability of methopterin to inhibit inflammatory bone destruction.",null,"Therapeutic strategy associated"]
[1602,"DB16627","approved; withdrawn","small molecule","Melphalan flufenamide","Melflufen; Melphalan flufenamide; MFF","C24H30Cl2FN3O3","CCOC(=O)[C@H](CC1=CC=C(F)C=C1)NC(=O)[C@@H](N)CC1=CC=C(C=C1)N(CCCl)CCCl","Melphalan flufenamide, also known as melflufen or J1, is a prodrug of . Melphalan flufenamide is more readily uptaken by cells than melphalan, and is cleaved to the active metabolite by aminopeptidases. _In vitro_ models show that melphalan is 10 to hundreds of times more potent than melphalan. The increased potency makes melphalan flufenamide a treatment option for patients with relapsed or refractory multiple myeloma who have attempted at least 4 lines of therapy already.\r\n\r\nMelphalan flufenamide was granted FDA approval on 26 February 2021.. It has since been withdrawn from the market in the wake of the phase 3 OCEAN trial which showed a decrease in overall survival in comparison to standard treatment with  and  despite superior progression-free survival.","380449-51-4","498.42","Melphalan flufenamide is indicated in combination with  to treat adults with relapsed or refractory multiple myeloma who have received ≥4 therapies and are refractory to at least one proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody. The FDA has withdrawn the drug from the market for this indication following phase 3 trial data showing decreased overall survival.","Melphalan flufenamide is an alkylating agent indicated to treat relapsed or refractory multiple myeloma in Melphalan flufenamide has a long duration of action as it is given every 28 days. Patients should be counselled regarding risks of thrombocytopenia, neutropenia, anemia, infections, secondary malignancies, embryo-fetal toxicity.","Melphalan flufenamide is a more lipophilic prodrug of melphalan, which allows it to be more readily uptaken by cells. It is likely taken up into malignant cells by passive diffusion, where it is hydrolyzed by aminopeptidase N. The expression of aminopeptidases, along with other hydrolytic enzymes, is upregulated in many malignant cells, making the hydrolysis reaction to melphalan more favourable in a malignant cell. Increased concentrations of free melphalan in malignant cells leads to rapid irreversible DNA damage and apoptosis, reducing the potential for the development of resistance.\r\n\r\nFree melphalan is an nitrogen mustard derivative alkylating agent. Melphalan attaches alkyl groups to the N-7 position of guanine and N-3 position of adenine, leading to the formation of monoadducts, and DNA fragmenting when repair enzymes attempt to correct the error. It can also cause DNA cross-linking from the N-7 position of one guanine to the N-7 position of another, preventing DNA strands from separating for synthesis or transcription. Finally, melphalan can induce a number of different mutations. While melphalan induces phosphorylation of the DNA damage marker γ-H2AX in melphalan sensitive cells at 6 hours, melphalan flufenamide induces γ-H2AX at 2 hours. Melphalan flufenamide is also able to induce γ-H2AX in melphalan-resistant cells.","DNA cross-linking/alkylation","Therapeutic strategy associated"]
[1603,"DB16629","approved","small molecule","Serdexmethylphenidate","Serdexmethylphenidate","C25H29N3O8","[H][C@@]1(CCCCN1C(=O)OC[N+]1=CC=CC(=C1)C(=O)N[C@@H](CO)C([O-])=O)[C@H](C(=O)OC)C1=CC=CC=C1","Attention Deficit Hyperactivity Disorder (ADHD) is an early-onset neurodevelopmental disorder that often extends into adulthood and is characterized by developmentally inappropriate and impaired attention, impulsivity, and motor hyperactivity. The underlying cause of ADHD is unclear but likely involves dysfunction in dopaminergic and noradrenergic neurotransmission, as evidenced by the clear beneficial effect of CNS stimulants such as  and  that increase extracellular dopamine and norepinephrine levels. Serdexmethylphenidate is a prodrug of the CNS stimulant , a common first-line treatment for ADHD, that is combined with  to provide extended plasma concentrations and therapeutic benefit with once-daily dosing.\r\n\r\nSerdexmethylphenidate was granted FDA approval on March 2, 2021, and is currently marketed as a combination capsule with  under the trademark AZSTARYS™ by KemPharm, Inc.","1996626-29-9","499.52","Serdexmethylphenidate is a prodrug of  that is indicated in combination with  for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients aged six years and older.","Serdexmethylphenidate is a prodrug of the CNS stimulant , which increases extracellular levels of dopamine and norepinephrine in the CNS, leading to altered neurotransmission. As a CNS stimulant, serdexmethylphenidate carries a risk of abuse, misuse, and dependence, which should be monitored. Also, CNS stimulants are associated with increased blood pressure, heart rate, and risk of serious cardiovascular reactions, including stroke, myocardial infarction, and sudden death; patients should be assessed before starting therapy and monitored for cardiovascular abnormalities. Similarly, CNS stimulants may also result in peripheral vasculopathy, including Raynaud's phenomenon. Due to its ability to alter neurological function, serdexmethylphenidate may exacerbate pre-existing psychoses, induce manic episodes in patients with bipolar disorder, or result in newly diagnosable manic or psychotic symptoms. Frequent, sustained, and painful erections, which may require medical attention, have been observed in patients who have been treated for some time with serdexmethylphenidate, often associated with a dose increase. Finally, like other CNS stimulants, serdexmethylphenidate has been associated with weight loss and growth retardation, which may require treatment interruption in serious cases.","Attention Deficit Hyperactivity Disorder (ADHD) is an early-onset neurodevelopmental disorder that often extends into adulthood and is characterized by developmentally inappropriate and impaired attention, impulsivity, and motor hyperactivity. Proper diagnosis is hindered by a lack of biological markers (based on symptoms alone), a spectrum of severity, and frequent comorbidities such as autism spectrum disorder, reading disabilities, developmental coordination disorders, and tic disorders. Although the underlying cause(s) is unclear, dopaminergic, noradrenergic, serotonergic, cholinergic, glutaminergic, and opioid neurotransmission likely plays a role.\r\n\r\nSerdexmethylphenidate is a prodrug of the CNS stimulant (MPH), a common first-line treatment for ADHD. The main effect of MPH is to increase the extracellular levels of dopamine and norepinephrine, which has numerous potential downstream effects. This occurs mainly due to MPH's ability to inhibit the corresponding dopamine and norepinephrine monoamine transporters. Other studies have suggested additional possible MPH functions, including serotonin 5-HT1A receptor agonism, redistribution of vesicular monoamine transporter-2 (VMAT-2), and either direct or indirect activation of α2-adrenergic receptors. Overall, imaging studies reveal that MPH acts to alter brain activity in relevant regions associated with executive function, emotional regulation, reward processing, and working memory.","Sodium-dependent dopamine transporter inhibitor; Sodium-dependent noradrenaline transporter inhibitor; 5-hydroxytryptamine receptor 1A agonist","Therapeutic strategy associated"]
[1604,"DB16648","approved","biotech","Bacillus calmette-guerin substrain russian BCG-I live antigen","Bacillus Calmette-Guérin (BCG) - strain russian BCG-I",null,null,"Bacillus Calmette-Guerin (BCG) substrain Russian BCG-I is a live BCG vaccine administered directly into the bladder for the adjuvant treatment of papillary urothelial cell carcinoma of the bladder. Live BCG vaccines administered intravesically have been a gold standard therapy in the adjuvant treatment of non-muscle-invasive bladder cancers for decades, used after tumor resection, and are thought to work by stimulating a local immune and inflammatory response in the bladder.\r\n\r\nThe live Russian BCG-I substrain of BCG was granted a notice of compliance with conditions by Health Canada in February 2021. It is to be marketed by Verity Pharmaceuticals, under the trade name VERITY-BCG, and manufactured by the Serum Institute of India. It was developed to alleviate Canada's multi-year shortage of BCG vaccine, and is expected to be available by mid-2021.",null,null,"The live BCG vaccine (substrain Russian BCG-I, i.e. VERITY-BCG) is indicated for adjuvant therapy following transurethral resection of a primary or relapsing superficial papillary urothelial cell carcinoma of the bladder in stages Ta (grade 2 or 3) or T1 (grade 1, 2, or 3), without concomitant carcinoma in situ. It may also be used for stage Ta grade 1 papillary tumors, but only when the risk of recurrence is high (>50%).",null,"The precise mechanism through which live BCG vaccines exert antineoplastic activity is unclear. It is likely that instillation of the vaccine into the bladder results in a non-specific immune response, involving both the innate and adaptive immune systems, followed by a local inflammatory response involving a variety of immune cells. BCG itself may exert direct cytotoxic effects on tumor cells, though its primary mechanism of action appears to be via internalization into tumor cells where it stimulates the aforementioned inflammatory pathways.",null,"Therapeutic strategy associated"]
[1605,"DB16665","approved","biotech","Idecabtagene vicleucel","Anti-BCMA CAR T cell; IDE-CEL; Idecabtagene vicleucel",null,null,"Multiple myeloma is a cancer where plasma cells rapidly divide out of control. These cancerous cells generally express the B-cell maturation antigen, while it is rarely expressed on non-cancerous cells. Multiple myeloma is typically treated with an immunomodulatory agent like , a proteasome inhibitor like , or an anti-CD38 monoclonal antibody like .\r\n\r\nIdecabtagene vicleucel, also known as bb2121, is a chimeric antigen receptor (CAR) T-cell therapy like  and . These therapies involve extracting and genetically manipulating T-cells from a patient to express a CAR for a tumor specific antigen. The chimeric antigen receptor of idecabtagene vicleucel includes an anti-B-cell maturation antigen scFv-targeting domain, CD3ζ T-cell activation domain, and 4-1BB costimulatory domain. Idecabtagene vicleucel is indicated as a fifth line treatment of adult patients with relapsed or refractory multiple myeloma.\r\n\r\nIdecabtagene vicleucel was granted FDA approval on 26 March 2021.",null,null,"Idecabtagene vicleucel is indicated to treat adult patients with relapsed or refractory multiple myeloma who have tried at least 4 other lines of therapy, including an immunomodulatory agent, proteasome inhibitor, and anti-CD38 monoclonal antibody.","Idecabtagene vicleucel is a B-cell maturation antigen directed chimeric antigen receptor T-cell therapy indicated to treat relapsed or refractory multiple myeloma. It has a long duration of action as expansion takes place over days. Patients should be counselled regarding the risk of hypersensitivity, infection, prolonged cytopenias, hypogammaglobulinemia, secondary malignancies, and to avoid driving for at least 8 weeks after treatment.","Multiple myeloma is a cancer where plasma cells rapidly divide out of control. These cancerous cells generally express the B-cell maturation antigen, while it is rarely expressed on non-cancerous cells.\r\n\r\nThe chimeric antigen receptor of idecabtagene vicleucel includes an anti-B-cell maturation antigen scFv-targeting domain, CD3ζ T-cell activation domain, and 4-1BB costimulatory domain. The single chain variable fragment (scFv) allows for B-cell maturation antigen specificity of the CAR. The CD23ζ cytoplasmic domain mediates T-cell activation by CD2, a T-cell surface adhesion molecule. 4-1BB enhances cytotoxic T-cell activity as well as the production of interferon-γ.\r\n\r\nIdecabtagene vicleucel binds to B-cell maturation antigen expressing cells. Binding to the target leads to proliferation of idecabtagene vicleucel, secretion of cytokines, and lysis of the targeted cells.","Tumor necrosis factor receptor superfamily member 17 binder","Target associated"]
[1606,"DB16689","investigational","biotech","Tengonermin","NGR-hTNF; Tengonermin",null,null,"Tengonermin, also known as NGR-hTNF, is a vascular-targeting drug. It is a recombinant protein and peptide-targeted agent consisting of the human Tumour Necrosis Factor-α (TNF-α) conjugated with the CNGRCG peptide. This drug works by modifying the tumor microenvironment and increasing intratumoral chemotherapy penetration and T-cell infiltration.\r\n\r\nNGR-hTNF specifically targets angiogenic tumor blood vessels using the NGR motif. Literature demonstrates that NGR-peptides bind to a CD13 isoform, of which expression is restricted to tumor vasculature cells. A study also demonstrated that binding of the NGR-motif to CD13 determined both the homing of NGR-hTNF to tumor vessels and the increase in its antiangiogenic activity.","1960461-99-7",{"$nulls":3},"Tengonermin has highly selective homing to tumor blood vessels due to the NGR peptide portion binding specifically to a CD13 isoform (expressed selectively by endothelial cells of human tumor vessels during neoangiogenesis) which allows it to spare tumor-unrelated human tissues. This drug also increases apoptosis of angiogenic endothelial cells in vivo.  The aforementioned effects significantly contribute to controlling the growth of tumors. Once the drug targets the tumor vasculature, multiple downstream effects occur, mediated by the interaction of both components of the molecule.",null,"Therapeutic strategy associated"]
[1607,"DB16697","investigational","biotech","Glutazumab",{"$nulls":3},"Glutazumab is a novel long-lasting GLP-1/anti-GLP-1R antibody fusion protein exerting anti-diabetic effects.",{"$nulls":5},"Glucagon-like peptide 1 receptor agonist","Target associated"]
[1608,"DB16703","approved; investigational","small molecule","Belumosudil","Belumosudil","C26H24N6O2","CC(C)NC(=O)COC1=CC=CC(=C1)C1=NC2=C(C=CC=C2)C(NC2=CC=C3NN=CC3=C2)=N1","Belumosudil is used in the treatment of chronic graft-versus-host disease (GVHD) and has been investigated for the treatment of pulmonary arterial hypertension. It is an inhibitor of rho-associated coiled-coil-containing protein kinases (ROCK), with significantly more selectivity for ROCK2 as compared to ROCK1 (IC<sub>50</sub> 100 nM vs. 3 μM, respectively). In the treatment of GVHD, a condition in which donor T-cells begin to attack recipient tissues following allogeneic hematopoeitic stem cell transplantation (HSCT), belumosudil helps to resolve immune dysregulation by shifting the balance between Th17 cells and T-regulatory cells, thereby dampening the inflammatory cascade that can occasionally be fatal.\r\n\r\nBelumosudil was first approved by the FDA in July 2021, under the brand name Rezurock, for the treatment of chronic GVHD in patients who have tried and failed at least two prior lines of systemic therapy.","911417-87-3","452.518","Belumosudil is indicated for the treatment of chronic graft-versus-host disease (GVHD) in adult and pediatric patients 12 years of age and older following failure of at least two other lines of systemic therapy.","Belumosudil appears to inhibit several pro-fibrotic and pro-inflammatory processes in order to prevent and treat the damage incurred by graft-versus-host disease. Given its mechanism of action and findings in animal trials, belumosudil is considered to carry embryo-fetal toxicity and may cause significant harm to a developing fetus should a pregnant mother be exposed. Female patients of reproductive potential, or male patients with female partners of reproductive potential, should be advised to use effective contraception during treatment with belumosudil and for one week after the last dose.","Chronic graft-versus-host disease (GVHD) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation in which the transplanted donor T-cells recognize the recipient's tissues as foreign and mount an immune response. During the conditioning regimen prior to stem cell transplantation (e.g. involving irradiation or chemotherapy) the host tissues can become damaged which results in downstream inflammatory responses and the generation of inflammatory mediators like TNF-alpha and IL-1. These cytokines increase the expression of host major histocompatibility (MHC) antigens and adhesion molecules which enhances the ability of mature donor T-cells to recognize these molecules. The activation of these donor T-cells results in the activation of mononuclear phagocytes, whose effector functions are triggered by stimulatory molecules generated by the damage incurred during the conditioning phase of treatment. Activated macrophages and cytotoxic T-lymphocytes begin to directly lyse target cells and/or cause their apoptosis, which eventually leads to local tissue damage and further inflammatory responses.\r\n\r\nBelumosudil is an inhibitor of Rho-associated coiled-coil kinase 2 (ROCK2), a protein that plays a vital role in the pathogenesis of immune and fibrotic diseases. The inhibition of ROCK2 has been shown to resolve immune dysregulation by down-regulating pro-inflammatory Th17 cells and up-regulating regulatory T-cells by manipulating the phosphorylation of STAT3 and STAT5.","Rho-associated protein kinase 2 inhibitor; Rho-associated protein kinase 1 inhibitor","Therapeutic strategy associated"]