P2Y receptor antagonists in thrombosis.
The dual role of P2Y1 and P2Y12 receptors in platelet aggregation by ADP has been firmly established, based on the action of selective inhibitors, gene targeting in mice and human genetic evidence. Both of these receptor subtypes constitute targets for antithrombotic agents, and compounds with a dual action might also be of interest. However, the agents currently on the market (ticlopidine and clopidogrel), or known to be in development (cangrelor, AZD-6140 and prasugrel), all target the P2Y12 receptor. The thienopyridines (ticlopidine, clopidogrel and prasugrel) irreversibly inactivate the P2Y12 receptor via the covalent binding of an active metabolite generated in the liver, while the other compounds are competitive antagonists. Cangrelor, an ATP derivative, is suitable for intravenous perfusion, whereas AZD-6140 is in clinical development as an orally active agent.
Boeynaems
Jean-Marie
JM
Institute of Interdisciplinary Research, School of Medicine and Laboratory of Medical Chemistry, Erasme Hospital, Free University of Brussels, Brussels, B-1070, Belgium. jmboeyna@ulb.ac.be
van Giezen
Hans
H
Savi
Pierre
P
Herbert
Jean-Marc
JM
D000249:Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000077144:Clopidogrel; D006801:Humans; D051379:Mice; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D058919:Purinergic P2 Receptor Antagonists; D013927:Thrombosis / Q000188:drug therapy*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D000249:Adenosine Monophosphate; C117446:cangrelor; D000077144:Clopidogrel; D013988:Ticlopidine