Table 1.
Approved integrin-targeting drugs
| Generic name (brand name; manufacturer) | Chemotype; route of administration | Target; mechanism of action | Indication | Dose185 | Date of regulatory approval |
|---|---|---|---|---|---|
| Lifitegrast (Xiidra; Novartis) | Small molecule; topical | αLβ2 (LFA-1) antagonist; prevents lymphocyte adhesion, thereby reducing T cell-mediated inflammation | Dry eye disease | 1 drop in each eye every 12 h | July 2016 |
| Vedolizumab (Entyvio; Takeda) | Biologic (humanized mAb); i.v. infusion | α4β7 antagonist; inhibits binding to MADCAM1, thereby preventing T cells from homing to the gut | Ulcerative colitis and Crohn’s disease | 300 mg infused over 30 min at weeks 0, 2, 6 and every 8 weeks thereafter | May 2014 |
| Natalizumab (Tysabri; Biogen) | Biologic (humanized mAb); i.v. infusion | Pan-α4 antagonist; inhibits ligand binding to α4β7 and α4β1, thus reducing homing of T cells to the gut (in Crohn’s disease) and across the blood–brain barrier (in multiple sclerosis) | Multiple sclerosis and Crohn’s disease | 300 mg infused over 1 h every 4 weeks | November 2004 |
| Efalizumab (Raptiva; Genentech/Merck Serono) | Biologic (humanized mAb); s.c. injection | αL antagonist; targets lymphocyte-specific αLβ2, preventing lymphocyte activation and migration | Plaque psoriasis | 0.7 mg kg−1 followed by 1 mg kg−1 weekly | October 2003 (withdrawn 2009) |
| Tirofiban (Aggrastat; Medicure & Correvio) | Small molecule; i.v. infusion | αIIbβ3 antagonist, RGD mimetic; prevents platelet aggregation by inhibiting binding to fibrinogen | Acute coronary syndrome and thrombotic cardiovascular events | 25 mg kg−1 followed by 0.15 mg kg−1 min−1 for 18 h | August 1998 |
| Eptifibatide (Integrilin; Takeda, GSK, Merck) | Small molecule (heptapeptide); i.v. injection | αIIbβ3 antagonist, RGD mimetic; prevents platelet aggregation by inhibiting binding to fibrinogen | Acute coronary syndrome and thrombotic cardiovascular events | 180 mg kg−1 followed by 2 mg kg−1 min−1 for up to 72 h | May 1998 |
| Abciximab (ReoPro; Centocor, Inc./Eli Lilly/Janssen Biotech, Inc.) | Biologic (antigen-binding fragment); i.v. injection | Pan-β3 antagonist; inhibits binding of integrin αIIbβ3 to fibronectin, thus preventing platelet aggregation | Acute coronary syndrome and thrombotic cardiovascular events | 0.25 mg kg−1, followed by 10 mg kg−1 min−1 for 12 h | December 1994 |
Successful drugs gaining regulatory approval are tabulated in order of approval date, with most recent first. GSK, GlaxoSmithKline; i.v., intravenous; mAb, monoclonal antibody; MADCAM1, mucosal addressin cell adhesion molecule 1; RGD, Arg–Gly–Asp; s.c., subcutaneous.