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How not to discover a drug - integrins.

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journal contribution
posted on 29.03.2021, 13:37 authored by Dermot CoxDermot Cox
Introduction. Integrins are a family of 24 cell adhesion receptors that play a role in the biggest unmet needs in medicine - cardiovascular disease, immunology and cancer. Their discovery promised huge potential for the pharmaceutical industry.
Areas covered. Over 35-years since their discovery, there is little to show for the hundreds of billions of dollars of investment in anti-integrin drug discovery programmes. In this review the author discusses the reasons for the failure of this promising class of drugs and the future for this class of drugs.
Expert opinion. Within 10-years, there was a plethora of potent, specific anti-integrin molecules and since their discovery, many of these agents have entered clinical trials. The success in discovering these agents was due to recently discovered monoclonal antibody technology. The integrin-recognition domain Arg-Gly-Asp (RGD) provided the basis for discovering small molecule inhibitors to integrins - both cyclic peptides and peptidomimetics. Most agents failed in the Phase III clinical trials and those agents that did make it to the market were plagued with issues of toxicity and limited efficacy and were soon replaced with non-integrin targeting agents. Their failure was due to a combination of poor pharmacokinetics and pharmacodynamics, complicated by the complex pathophysiology of integrins.



This is an Accepted Manuscript of an article published by Taylor & Francis in Expert Opinion on Drug Discovery 2021, available online: http://www.tandfonline.com/ https://doi.org/10.1080/17460441.2020.1819234

Published Citation

Cox D. How not to discover a drug - integrins. Expert Opinion on Drug Discovery. 2021;16(2):197-211.

Publication Date

14 September 2020

PubMed ID



  • School of Pharmacy and Biomolecular Sciences

Research Area

  • Vascular Biology
  • Immunity, Infection and Inflammation


Informa UK Limited


  • Accepted Version (Postprint)