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Updated: Sep 7, 2025

Author Spotlight: Developing Parmodulins to Target Protease-Activated Receptors for Inflammation Control
Published on: May 24, 2024
Discovery of Two Novel Antiplatelet Clinical Candidates (BMS-986120 and BMS-986141) That Antagonize
E Scott Priestley1, Jacques Banville2, Daniel Deon2
1Bristol-Myers Squibb Research & Early Development, 3551 Lawrenceville Road, Princeton, New Jersey08540, United States.
Abstract:
Protease-activated receptor 4 (PAR4) is a G-protein coupled receptor that is expressed on human platelets and activated by the coagulation enzyme thrombin. PAR4 plays a key role in blood coagulation, and its importance in pathological thrombosis has been increasingly recognized in recent years. Herein, we describe the optimization of a series of imidazothiadiazole PAR4 antagonists to a first-in-class clinical candidate, BMS-986120 (43), and a backup clinical candidate, BMS-986141 (49). Both compounds demonstrated excellent antithrombotic efficacy and minimal bleeding time prolongation in monkey models relative to the clinically important antiplatelet agent clopidogrel and provide a potential opportunity to improve the standard of care in the treatment of arterial thrombosis.
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