P2Y12 antagonists: Approved drugs, potential naturally isolated and synthesised compounds, and related in-silico studies

P2Y(12) is a platelet surface protein which is responsible for the amplification of P2Y(1) response. It plays a crucial role in platelet aggregation and thrombus formation through an ADP-induced platelet activation mechanism. Despite that P2Y(12) platelets' receptor is an excellent target for developing antiplatelet agents, only five approved medications are currently in clinical use which are classified into thienopyridines and nucleoside-nucleotide derivatives. In the past years, many attempts for developing new candidates as P2Y(12) inhibitors have been made. This review highlights the importance and the role of P2Y(12) receptor as part of the coagulation cascade, its reported congenital defects, and the type of assays which are used to verify and measure its activity. Furthermore, an overview is given of the clinically approved medications, the potential naturally isolated inhibitors, and the synthesised candidates which were tested either in-vitro, in-vivo and/or clinically. Finally, we outline the in-silico attempts which were carried out using virtual screening, molecular docking and dynamics simulations in efforts of designing novel P2Y(12) antagonists. Various phytochemical classes might be considered as a corner stone for the discovery of novel P2Y(12) inhibitors, whereas a wide range of ring systems can be deliberated as leading scaffolds in that area synthetically and theoretically. (C) 2021 Elsevier Masson SAS. All rights reserved.

Automated summary

P2Y(12) is a crucial platelet surface protein involved in platelet aggregation and thrombus formation, making it an excellent target for developing antiplatelet agents. Despite the limited number of approved medications in clinical use, there are ongoing efforts to develop new P2Y(12) inhibitors. Research also includes in-silico attempts to design novel P2Y(12) antagonists.