TY - JOUR
T1 - Integrin-based therapeutics
T2 - Biological basis, clinical use and new drugs
AU - Ley, Klaus
AU - Rivera-Nieves, Jesus
AU - Sandborn, William J.
AU - Shattil, Sanford
N1 - Publisher Copyright:
© 2016 Macmillan Publishers Limited.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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.
AB - 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.
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U2 - 10.1038/nrd.2015.10
DO - 10.1038/nrd.2015.10
M3 - Review article
C2 - 26822833
AN - SCOPUS:84959369497
SN - 1474-1776
VL - 15
SP - 173
EP - 183
JO - Nature Reviews Drug Discovery
JF - Nature Reviews Drug Discovery
IS - 3
ER -