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Danicamtiv increases myosin recruitment and alters the chemomechanical cross bridge cycle in cardiac muscle.

Kristina B KooikerSaffie E MohranKyrah L TurnerWeikang MaGalina FlintLin QiChengqian GaoYahan ZhengTimothy S McMillenChristian J MandryckyAmy MartinsonMax Mahoney-SchaeferJeremy C FreemanElijah Gabriela Costales ArenasAn-Yu TuThomas C IrvingMichael A GeevesBertrand C W TannerMichael RegnierJennifer M DavisFarid Mousavi-Harami
Published in: bioRxiv : the preprint server for biology (2023)
Directly augmenting sarcomere function has potential to overcome limitations of currently used inotropic agents to improve cardiac contractility. Myosin modulation is a novel mechanism for increased contraction in cardiomyopathies. Danicamtiv is a myosin activator that is currently under investigation for use in cardiomyopathy patients. Our study is the first detailed mechanism of how Danicamtiv increases force and alters kinetics of cardiac activation and relaxation. This new understanding of the mechanism of action of Danicamtiv can be used to help identify patients that could benefit most from this treatment.
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