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

Authors :
Damaskinaki, Foteini-Nafsika
Moran, Luis A.
Garcia, Angel
Kellam, Barrie
Watson, Steve P.
Source :
Platelets. 2021, Vol. 32 Issue 6, p744-752. 9p.
Publication Year :
2021

Abstract

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
09537104
Volume :
32
Issue :
6
Database :
Academic Search Index
Journal :
Platelets
Publication Type :
Academic Journal
Accession number :
151582621
Full Text :
https://doi.org/10.1080/09537104.2020.1863939