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

Nat Rev Drug Discov. 2016 Mar;15(3):173-83. doi: 10.1038/nrd.2015.10. Epub 2016 Jan 29.

Abstract

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 αIIbβ3 integrin are used to prevent thrombotic complications after percutaneous coronary interventions, and compounds targeting the lymphocyte α4β1 and α4β7 integrins have indications in multiple sclerosis and inflammatory bowel disease. New antibodies and small molecules targeting β7 integrins (α4β7 and αEβ7 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / immunology
  • Binding Sites / drug effects
  • Binding Sites / immunology
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / immunology
  • Clinical Trials as Topic / methods
  • Drug Discovery / methods
  • Drug Discovery / trends*
  • Humans
  • Integrins / antagonists & inhibitors*
  • Integrins / immunology
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / immunology

Substances

  • Antibodies, Monoclonal
  • Integrins