Integrin-based therapeutics: biological basis, clinical use and new drugs

Integrins are activatable molecules that are involved in adhesion and signalling. Of the 24 known human integrins, 3 are currently targeted therapeutically by monoclonal antibodies, peptides or small molecules: drugs targeting the platelet alpha IIb beta 3 integrin are used to prevent thrombotic complications after percutaneous coronary interventions, and compounds targeting the lymphocyte alpha 4 beta 1 and alpha 4 beta 7 integrins have indications in multiple sclerosis and inflammatory bowel disease. New antibodies and small molecules targeting beta 7 integrins (alpha 4 beta 7 and alpha E beta 7 integrins) and their ligands are in clinical development for the treatment of inflammatory bowel diseases. Integrin-based therapeutics have shown clinically significant benefits in many patients, leading to continued medical interest in the further development of novel integrin inhibitors. Of note, almost all integrin antagonists in use or in late-stage clinical trials target either the ligand-binding site or the ligand itself.