DG-041 was identified as a potent and selective EP3 receptor antagonist that inhibits human platelet aggregation without prolonging bleeding, advancing to clinical trials for atherothrombosis.
Supports EP3 antagonism for antiplatelet development; leaves open translation to human efficacy and safety.
The EP(3) receptor on the platelet mediates prostaglandin E(2) potentiation of thrombogenic coagonists including collagen and adenosine diphosphate (ADP). A pharmacophore driven approach led to the identification of diverse peri-substituted heterocycles as potent and selective EP(3) receptor antagonists. A simultaneous chemical optimization and druglike assessment of prioritized molecules converged on a lead compound 50 (DG-041) that displayed favorable in vitro and functional activities as an inhibitor of human platelet aggregation. This agent is currently in human clinical trials for the treatment of atherothrombosis.
No takes yet. Share an insight, caveat, or question.
Singh et al. (2009) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: