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Updated: Aug 15, 2026

Characterizing Modulators of Protease-Activated Receptors with a Calcium Mobilization Assay Using a Plate Reader
Published on: May 24, 2024
Discovery of potent orally active thrombin receptor (protease activated receptor 1) antagonists as novel
Samuel Chackalamannil1, Yan Xia, William J Greenlee
1Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA. samuel.chackalaminnil@spcorp.com
Abstract:
Structurally novel thrombin receptor (protease activated receptor 1, PAR-1) antagonists based on the natural product himbacine are described. The prototypical PAR-1 antagonist 55 showed a Ki of 2.7 nM in the binding assay, making it the most potent PAR-1 antagonist reported. 55 was highly active in several functional assays, showed excellent oral bioavailability in rat and monkey models, and showed complete inhibition of agonist-induced ex vivo platelet aggregation in cynomolgus monkeys after oral administration.
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