Cardiac myosin is the major target of the autoimmune response in many cases of myocarditis in humans and mice. Omecamtiv mecarbil is a first-in-class cardiac myosin activator.

Omecamtiv mecarbil is the first, selective activator of cardiac myosin. Furthermore, Omecamtiv mecarbil is currently in clinical trials for the treatment of systolic heart failure. Omecamtiv mecarbil is a compound with the potential to treat systolic heart failure in an acute situation through iv administration and acute and chronic systolic heart failure through oral administration.

Omecamtiv mecarbil is a potent, selective activator of cardiac myosin that leads to increases in cardiac function in preclinical models of heart failure. The myosin activator Omecamtiv mecarbil is a pharmacological drug that specifically targets the myosin cross-bridge. Moreover, Omecamtiv mecarbil induces a significant decrease in vitro motility velocity and an increase in the cross-bridge (XB) duty cycle.

Omecamtiv mecarbil improves systolic function in the failing hearts, by enhancing XB-mediated force generation via enhancing the rate of transition of XB’s from the weakly-bound to the strongly-bound state. Omecamtiv mecarbil decreases actomyosin in vitro motility velocity thereby increasing the overall XB duty cycle of the myosin motor. Besides, Omecamtiv mecarbil may be a useful pharmacological approach to normalize hypercontractile XB kinetics in the myocardium. Meanwhile, there is a decreased cMyBP-C expression due to its molecular effects on XB behavior. In addition, Omecamtiv mecarbil specifically targets cardiac muscle myosin and enhances cardiac muscle performance, yet its impact on human cardiac myosin motor function is unclear.

In conclusion, Omecamtiv mecarbil is specific for cardiac myosin and does not alter skeletal or smooth muscle myosin. Omecamtiv mecarbil is currently in clinical trials.

Bradley P Morgan, et al. Discovery of omecamtiv mecarbil the first, selective, small molecule activator of cardiac Myosin. ACS Med Chem Lett. 2010 Aug 20;1(9):472-7.