Discovery of Novel Cardiac Myosin Modulators Omecamtiv Mecarbil and Aficamten

Impaired myocardial contractility is a fundamental pathophysiological mechanism underlying various cardiac disorders. Two distinct conditions exemplify opposing contractile dysfunction: Heart failure with reduced ejection fraction (HFrEF), characterized by diminished myocardial contractile function, and hypertrophic cardiomyopathy (HCM), where sarcomeric gene mutations result in pathological hypercontractility.

This Flash Talk discusses the development of two novel therapeutic agents targeting these contrasting contractile disorders. Omecamtiv mecarbil, a cardiac myosin activator, augments myocardial performance and demonstrates improved clinical outcomes in HFrEF patients. Conversely, aficamten functions as a cardiac myosin inhibitor, attenuating excessive sarcomeric contractility in HCM patients. Both compounds represent precision-based therapeutic approaches through direct modulation of sarcomeric function.

00:00 Welcome and Introduction
09:52 DH Features
12:10 Presentation
56:00 Q&A

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Recorded on April 24th, 2025, as a Drug Hunter Flash Talk.

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