Emergence of small molecule non-RGD-mimetic inhibitors for RGD integrins

Lisa M. Miller, John M. Pritchard, Simon J. F. Macdonald, Craig Jamieson, Allan J. B. Watson

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)


The RGD integrins are recognized therapeutic targets for thrombosis, fibrosis, and cancer, amongst others. Current inhibitors are designed to mimic the tripeptide sequence (arginineglycine-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 2 perspective will discuss the discovery of these non-RGD-mimetic inhibitors, and the progress that has been made in this promising new chemotype.
Original languageEnglish
Pages (from-to)3241-3251
JournalJournal of Medicinal Chemistry
Issue number8
Early online date30 Jan 2017
Publication statusE-pub ahead of print - 30 Jan 2017


  • RGD integrins
  • Therapeutic targets
  • Tripeptide sequence
  • Ligands
  • Non-RGD-mimetic inhibitors
  • Heterodimeric cell adhesion receptors
  • Extracellular matrix


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