This document describes the development of novel antiplatelet agents that target the EP3 receptor for prostaglandin E2 (PGE2) on platelets. Current antiplatelet drugs like clopidogrel that target the P2Y12 receptor reduce heart attacks and strokes but increase the risk of severe bleeding. The document reports:
1) PGE2 produced in inflamed atherosclerotic plaques activates platelets through the EP3 receptor, similarly to how ADP activates platelets through P2Y12.
2) A selective EP3 antagonist called DG-041 was developed that inhibits PGE2 facilitation of platelet aggregation in vitro and ex vivo without affecting bleeding time in rats, unlike