Affiliations 

  • 1 Department of Pharmaceutical Sciences, Faculty of Pharmacy, Al-Ahliyya Amman University, 19328, Amman, Jordan; Pharmacological and Diagnostic Research Lab, Al-Ahliyya Amman University, 19328, Amman, Jordan. Electronic address: b.najjar@ammanu.edu.jo
  • 2 Pharmaceutical Design and Simulation (PhDS) Laboratory, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Penang, Malaysia
  • 3 Pharmacological and Diagnostic Research Lab, Al-Ahliyya Amman University, 19328, Amman, Jordan; Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, 19328, Amman, Jordan
  • 4 Faculty of Pharmacy, Al-Ahliyya Amman University, 19328, Amman, Jordan
Eur J Med Chem, 2022 Jan 05;227:113924.
PMID: 34731765 DOI: 10.1016/j.ejmech.2021.113924

Abstract

P2Y12 is a platelet surface protein which is responsible for the amplification of P2Y1 response. It plays a crucial role in platelet aggregation and thrombus formation through an ADP-induced platelet activation mechanism. Despite that P2Y12 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 P2Y12 inhibitors have been made. This review highlights the importance and the role of P2Y12 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 P2Y12 antagonists. Various phytochemical classes might be considered as a corner stone for the discovery of novel P2Y12 inhibitors, whereas a wide range of ring systems can be deliberated as leading scaffolds in that area synthetically and theoretically.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.