Cardiac myosin-activator: omecamtiv mecarbil

Cardiac myosin-activator: omecamtiv mecarbil

Cardiac myosin-activator: omecamtiv mecarbil: Cardiac myosin activators improve the systolic function of the left ventricle by activating the force generating protein myosin. They accelerate the transition of the actin myosin complex to the strongly bound configuration from the weakly bound configuration. This is effected through the increase of myosin heads interacting with the actin filaments.  In addition there is reduction in the rate of non productive hydrolysis of adenosine triphosphate. Since these effects are independent of calcium homeostasis, there is no increase in the energy demand or arrhythmogenesis.

Omecamtiv mecarbil which was formerly called CK-1827452 is a novel cardiac myosin activating compound. A recent experimental study by You-Tang Shen, Fady I Malik, Xin Zhao, Christophe Depre, Sunil K Dhar, Patricio Abarzúa, David J Morgans and Stephen F Vatner [1] showed that long term infusion of omecamtiv mecarbil improves left ventricular systolic function in systolic heart failure without progressive desensitization or increased myocardial oxygen consumption, which are the usual disadvantages of conventional inotropic agents. This agent or similar ones may offer novel therapeutic options in systolic heart failure in future.

A phase II clinical trial is evaluated the safety of omecamtiv mecarbil in patients with ischemic cardiomyopathy and angina [2]. The study showed that the drug did not adversely affect exercise capacity at concentrations that improve cardiac function.

References

1. You-Tang Shen, Fady I Malik, Xin Zhao, Christophe Depre, Sunil K Dhar, Patricio Abarzúa, David J Morgans, Stephen F Vatner. Improvement of cardiac function by a cardiac Myosin activator in conscious dogs with systolic heart failure. Circ Heart Fail. 2010 Jul;3(4):522-7.
2. Barry H. Greenberg, Will Chou, Rafael Escandon, Jacqueline H. Lee, Khalil G. Saikali, Fady Malik, Andrew A. Wolff, Tamaz Shaburishvili. Phase II safety study evaluating the novel cardiac myosin activator, CK-1827452, in patients with ischemic cardiomyopathy and angina. J Card Fail. 2009;15:S67–S67.