Overcoming challenges in developing small molecule inhibitors for GPVI and CLEC-2

Research output: Contribution to journalArticlepeer-review


  • Foteini-Nafsika Damaskinaki
  • Luis Moran Lara
  • Angel García
  • Barrie Kellam
  • Steve Watson

Colleges, School and Institutes


GPVI and CLEC-2 have emerged as promising targets for long-term prevention of both arterial thrombosis and thrombo-inflammation with a decreased bleeding risk relative to current drugs. However, while there are potent blocking antibodies of both receptors, their protein nature comes with decreased bioavailability, making formulation for oral medication challenging. Small molecules are able to overcome these limitations, but there are many challenges in developing antagonists of nanomolar potency, which is necessary when considering the structural features that underlie the interaction of CLEC-2 and GPVI with their protein ligands. In this review, we describe current small-molecule inhibitors for both receptors and strategies to overcome such limitations, including considerations when it comes to in silico drug design and the importance of complex compound library selection.

Bibliographic note

Funding: This work was supported by the British Heart Foundation [CH03/003]; European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant [766118].


Original languageEnglish
Early online date7 Jan 2021
Publication statusE-pub ahead of print - 7 Jan 2021


  • GPVI, CLEC-2, small molecule inhibitors, platelets, antagonists