Repositioning Candidate Details
| Candidate ID: | R0020 |
| Source ID: | DB00065 |
| Source Type: | approved |
| Compound Type: | biotech |
| Compound Name: | Infliximab |
| Synonyms: | Infliximab; Infliximab (genetical recombination); Infliximab-abda; Infliximab-axxq; Infliximab-dyyb; Infliximab-qbtx |
| Molecular Formula: | -- |
| SMILES: | -- |
| DrugBank Description: | 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 . Infliximab 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 . There 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. |
| CAS Number: | 170277-31-3 |
| Molecular Weight: | |
| DrugBank Indication: | * 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 * Indicated for reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing **Crohn’s disease**. * 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. * 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**. * Indicated for reducing signs and symptoms in patients with active **ankylosing spondylitis**. * Indicated for reducing signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function in patients with **psoriatic arthritis**. * 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. |
| DrugBank Pharmacology: | 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 {. |
| DrugBank MoA: | 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 . |
| Targets: | Tumor necrosis factor inhibitor |
| Inclusion Criteria: | Therapeutic strategy associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S13 | Anti-apoptosis | hepatocyte apoptosis; hepatic autophagy; apoptosis | Pan-caspase inhibitor | Emricasan | 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 |
| 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 |