Repositioning Candidate Details

Candidate ID: R0385
Source ID: DB01050
Source Type: approved
Compound Type: small molecule
Compound Name: Ibuprofen
Synonyms: (±)-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
Molecular Formula: C13H18O2
SMILES: CC(C)CC1=CC=C(C=C1)C(C)C(O)=O
Structure:
DrugBank Description: 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. On 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.
CAS Number: 15687-27-1
Molecular Weight: 206.2808
DrugBank Indication: 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. The 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. Due to its activity against prostaglandin and thromboxane synthesis, ibuprofen has been attributed to alteration of platelet function and prolongation of gestation and labor. As ibuprofen is a widely used medication, the main therapeutic indications are: * 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. * Rheumatoid- and osteo-arthritis - ibuprofen is very commonly used in the symptomatic treatment of inflammatory, musculoskeletal and rheumatic disorders. * Cystic fibrosis - the use of high dosages of ibuprofen has been proven to decrease inflammation and decreasing polymorphonuclear cell influx in the lungs. * 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. * Dental pain - ibuprofen is used to manage acute and chronic orofacial pain. * 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. * Investigational uses - efforts have been put into developing ibuprofen for the prophylaxis of Alzheimer's disease, Parkinson disease, and breast cancer.
DrugBank Pharmacology: 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. The 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. The 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. The administration of ibuprofen in patients with rheumatic diseases has shown to control joint symptoms. Ibuprofen 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. In 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.
DrugBank MoA: 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. Ibuprofen 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.
Targets: 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
Inclusion Criteria: Target associated

Strategy ID Strategy Synonyms Related Targets Related Drugs
S13 Anti-apoptosis hepatocyte apoptosis; hepatic autophagy; apoptosis Pan-caspase inhibitor Emricasan Details
S03 Anti-fibrosis fibrosis Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 Details
S04 Anti-oxidative stress oxidative stress α-tocopherol: antioxidant Vitamin E Details
S05 Anti-inflammatory inflammatory Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; Details

Target ID Target Name GENE Action Class UniProtKB ID Entry Name
T35 Platelet glycoprotein Ib alpha GP1BA inhibitor Enzyme P07359 GP1BA_HUMAN Details
T03 Peroxisome proliferator-activated receptor alpha PPARA agonist Nuclear hormone receptor Q07869 PPARA_HUMAN Details
T05 Peroxisome proliferator-activated receptor gamma PPARG agonist Nuclear hormone receptor P37231 PPARG_HUMAN Details

Diseases ID DO ID Disease Name Definition Class
I15 1290 Bone disease A connective tissue disease that affects the structure or development of bone or causes an impairment of normal bone function. http://en.wikipedia.org/wiki/Bone_disease disease of anatomical entity/ musculoskeletal system disease/connective tissue disease Details