Drug-like antagonists of P2Y receptors — from lead identification to drug development

Conroy, Sean; Kindon, Nicholas; Kellam, Barrie; Stocks, Michael

Abstract

P2Y receptors are expressed in virtually all cells and tissue types and mediate an astonishing array of biological functions, including platelet aggregation, smooth muscle cell proliferation, and immune regulation. The P2Y receptors belong to the G protein-coupled receptor superfamily and are composed of eight members encoded by distinct genes that can be subdivided into two groups on the basis of their coupling to specific G-proteins. Extensive research has been undertaken to find modulators of P2Y receptors, although to date only a limited number of small-molecule P2Y receptor antagonists have been approved by drug/medicines agencies. This Perspective reviews the known P2Y receptor antagonists, highlighting oral drug-like receptor antagonists, and considers future opportunities for the development of small molecules for clinical evaluation.

Citation

Conroy, S., Kindon, N., Kellam, B., & Stocks, M. (in press). Drug-like antagonists of P2Y receptors — from lead identification to drug development. Journal of Medicinal Chemistry, https://doi.org/10.1021/acs.jmedchem.5b01972

• Journal Article Type: Article
• Acceptance Date: Jul 14, 2016
• Online Publication Date: Jul 14, 2016
• Deposit Date: Aug 2, 2016
• Publicly Available Date: Aug 2, 2016
• Journal: Journal of Medicinal Chemistry
• Print ISSN: 0022-2623
• Electronic ISSN: 1520-4804
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1021/acs.jmedchem.5b01972
• Public URL: https://nottingham-repository.worktribe.com/output/800967
• Publisher URL: http://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.5b01972
• Additional Information: This is the author's version of a submitted work that was subsequently accepted for publication in the Journal of Medicinal Chemistry, c2016 American Chemical Society. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.5b01972
• Contract Date: Aug 2, 2016