Myosin Activators

Inotropes historically all increased intra-cellular calcium levels and they commonly caused intracellular Ca2+ overload and triggered malignant arrhythmias. The myosin activators, such as Omecamtiv Mecarbil (OM), increase myosin activity and function, and modify acto-myosin interaction through calcium-independent mechanisms. OM is a selective cardiac myosin activator that binds specifically the catalytic domain of cardiac myosin without any significant effect over other types of non-cardiac myosin. It increases the speed of ATP hydrolysis and, therefore, accelerates the transition rate to a strongly bound force-producing state, increases the number of myosin heads that interact with actin filaments and increases the proportion of time they are in a force producing state. OM decreases the inefficient use of non-contractile energy. OM has been studied in 4 phase II clinical trials with more than 1,300 patients with heart failure. The GALACTIC-HF trial is a nearly 8,000 patient HFrEF mortality/morbidity trial which started recruiting in January 2017 and should be completed soon.