Danicamtiv reduces myosin's working stroke but activates the thin filament by accelerating actomyosin attachment.

ABSTRACT: Heart failure is a leading cause of death worldwide, and even with current treatments, the 5-y transplant-free survival rate is only ~50 to 70%. As such, there is a need to develop new treatments for patients that improve survival and quality of life. Recently, there have been efforts to develop small molecules for heart failure that directly target components of the sarcomere, including cardiac myosin. Danicamtiv is one of these molecules; however, its direct effects on myosin's single molecule mechanics and kinetics are not well understood. Using optical trapping techniques, stopped flow transient kinetics, and in vitro reconstitution assays, we found that danicamtiv reduces the size of cardiac myosin's working stroke without affecting actomyosin detachment kinetics at the level of indiv

SUBMITTER: Scott B 

PROVIDER: S-EPMC12403133 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature