Positive cardiac inotrope omecamtiv mecarbil activates muscle despite suppressing the myosin working stroke

Omecamtiv mecarbil (OM) is a positive cardiac inotrope in clinical trials for the treatment of heart failure whose mechanism of action is incompletely understood. Here the authors show that OM inhibits myosin's working stroke and prolongs actomyosin attachment and propose a model that reconcile...

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Autores principales: Michael S. Woody, Michael J. Greenberg, Bipasha Barua, Donald A. Winkelmann, Yale E. Goldman, E. Michael Ostap
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2018
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Acceso en línea:https://doaj.org/article/a390d9a0840145559f69f13c5f0635e6
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Sumario:Omecamtiv mecarbil (OM) is a positive cardiac inotrope in clinical trials for the treatment of heart failure whose mechanism of action is incompletely understood. Here the authors show that OM inhibits myosin's working stroke and prolongs actomyosin attachment and propose a model that reconciles the OM-induced increase in cardiac performance in vivo with the inhibitory actions observed in vitro.