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

Key Points

  • Integrin antagonists are highly successful drugs for targeting the ligand binding site of αIIbβ3, α4-containing or α4β7 integrins.

  • Antagonists to αIIbβ3 integrin are still being used in patients receiving percutaneous angioplasty but are being replaced in many instances by new classes of anticoagulants and platelet inhibitors.

  • Natalizumab, a monoclonal antibody against α4-containing integrins, is highly successful at treating multiple sclerosis, but can reactivate John Cunningham virus and cause lethal progressive multifocal leukoencephalopathy (PML).

  • Vedolizumab, a monoclonal antibody against α4β7 integrin, and new antibodies against the β7 integrin subunit have not shown any signs of inducing PML.

  • Vedolizumab is safe and effective in the treatment of inflammatory bowel disease and has effectively replaced natalizumab for the treatment of Crohn disease.


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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Figure 1: Integrin families.
Figure 2: Inside-out activation of αIIbβ3 integrin in platelets.
Figure 3: The three integrins, α4β1, α4β7 and αEβ7, that are targeted by therapeutic α4 and β7 antibodies.


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The authors are supported by a grant from the National Institutes of Health (DK108670) and a Biomedical Laboratory Research and Development Vetrans Affairs Merit Review award (1I01BX001051) to J.R.-N., grants from the National Institutes of Health (HL 56595 and HL 78784) to S.S., and grants from the National Institutes of Health (DK091222 and HL078784) to K.L.

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Correspondence to Klaus Ley.

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W.J.S. participates in clinical trials in this area. The other authors declare no competing interests.

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Ley, K., Rivera-Nieves, J., Sandborn, W. et al. Integrin-based therapeutics: biological basis, clinical use and new drugs. Nat Rev Drug Discov 15, 173–183 (2016).

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