Therapeutic Potential of Cardiac Myosin Activators for the Treatment of Heart Failure

Heart failure (HF) is one of the serious and leading threats to human lives with increasing incidence throughout the world. Presently available therapeutic agents for treatment of heart failure patients have serious safety issues and efficacy limitations. Therefore, an urgent need for the development of novel and efficient therapeutic agents against heart failure continues to be a challenge for clinicians globally. During the last decade a novel class of myosin activators which act as positive inotropic drugs have attracted the interest of clinicians. These compounds act by the modulation of activity of myosin motor proteins through their interaction with chemo-mechanical actin-myosin cross bridge cycle. Myosin activators have been found to enhance the cardiac contractions without increasing the requirement of oxygen. The present review demonstrates the role of myosin activators as therapeutic agents for the treatment of heart failure. Myosin activators generally act through chemo-mechanical actin-myosin crossbridge cycle by the modulation of myosin motor protein activity. Omecamtiv mecarbil is the first reported myosin activator that has shown promising results during clinical trials by increasing the LV ejection fraction and systolic ejection time without inducing any major harmful side effects. Danicamtiv is the second reported direct myosin activator that binds to the myosin molecule of cardiomyocytes. It has been found to be more selective in binding with cardiac myosin in preference to the skeletal or smooth muscle myosin compared to omecamtiv mecarbil. Novel urea based scaffold with flexible spacers have also been synthesized as selective cardiac myosin activator for the treatment of systolic heart failure. Thus, myosin activators have great therapeutic potential as novel class of positive inotropic drugs for the treatment of heart failure patients.