Emergence of Small-Molecule Non-RGD-Mimetic Inhibitors for RGD Integrins

J Med Chem. 2017 Apr 27;60(8):3241-3251. doi: 10.1021/acs.jmedchem.6b01711. Epub 2017 Feb 15.


The RGD integrins are recognized therapeutic targets for thrombosis, fibrosis, and cancer, among others. Current inhibitors are designed to mimic the tripeptide sequence (arginine-glycine-aspartic acid) of the natural ligands; however, the RGD-mimetic antagonists for αIIbβ3 have been shown to cause partial agonism, leading to the opposite pharmacological effect. The challenge of obtaining oral activity and synthetic tractability with RGD-mimetic molecules, along with the issues relating to pharmacology, has left integrin therapeutics in need of a new strategy. Recently, a new generation of inhibitor has emerged that lacks the RGD-mimetic. This review will discuss the discovery of these non-RGD-mimetic inhibitors and the progress that has been made in this promising new chemotype.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Integrins / antagonists & inhibitors*
  • Integrins / chemistry
  • Molecular Mimicry*
  • Oligopeptides / chemistry*


  • Integrins
  • Oligopeptides
  • arginyl-glycyl-aspartic acid