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

@article{Woody2018PositiveCI,
  title={Positive cardiac inotrope omecamtiv mecarbil activates muscle despite suppressing the myosin working stroke},
  author={Michael S Woody and M. Greenberg and Bipasha Barua and D. Winkelmann and Y. Goldman and E. Ostap},
  journal={Nature Communications},
  year={2018},
  volume={9}
}
Omecamtiv mecarbil (OM) is a positive cardiac inotrope in phase-3 clinical trials for treatment of heart failure. [...] Key Result Here we show, via single-molecule, biophysical experiments on cardiac myosin, that OM suppresses myosin’s working stroke and prolongs actomyosin attachment 5-fold, which explains inhibitory actions of the drug observed in vitro. OM also causes the actin-detachment rate to become independent of both applied load and ATP concentration.Expand
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