In this publication, the authors demonstrated that omecamtiv mecarbil binds to the myosin catalytic domain and acts by an allosteric mechanism to increase the transition rate of myosin into the strongly actin-bound force-generating state. Paradoxically, omecamtiv mecarbil inhibits adenosine 5'-triphosphate (ATP) turnover in the absence of actin, which suggests that it stabilizes an actin-bound conformation of myosin. In animal models, omecamtiv mecarbil increases cardiac function by increasing the duration of ejection without changing the rates of cardiac contraction. The authors concluded that cardiac myosin activation may provide a new therapeutic approach for patients with systolic heart failure.
"This ground-breaking publication underscores the quality and robustness of the science at our company which relates to the mechanics and biology of muscle function and that serves as the basis for our portfolio of drug candidates," stated Robert I. Blum, Cytokinetics' President and Chief Executive Officer. "Over several years, our promising research has now resulted in multiple first-in-class compounds that may address unmet clinical needs in a broad array of indications and medical conditions associated with impaired muscle contractility."
Development Status of Omecamtiv Mecarbil
Omecamtiv mecarbil, a novel cardiac muscle myosin activator, has been the subject of a clinical trials program comprised of multiple Phase I and Phase IIa trials conducted under Cytokinetics' sponsorship. This program was designed to evaluate the safety, tolerability, pharmacodynamic and pharmacokinetic profiles of both intravenous and oral formulations of omecamtiv mecarbil for the potential treatment of heart failure across the continuum of care, in both hospital and outpatient settings. Two Phase IIa clinical trials of omecamtiv mecarbil from this program have been com
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