Background:

Omecamtiv mecarbil (CK-1827452) is the first potent cardiac myosin activator that can specifically activate the cardiac myosin S1 domain but not other muscle myosins. In clinical trials, omecamtiv mecarbil has been considered as a promising therapeutic approach to treat systolic heart failure¹.

Omecamtiv mecarbil accelerates the actin-dependent P_irelease from cardiac myosin S1 domain, thus increases the rate of transition from weakly actin-bound state to strongly actin-bound state (EC₅₀= 2.3 μM)¹.

At the concentration of 200nM, omecamtiv mecarbil was reported to remarkably increase the contractility of adult rat cardiac myocytes without influencing calcium transient. In vivo, Omecamtiv mecarbil has been shown to improve cardiac function without changing myocardial oxygen consumption in both beagle dogs and Sprague-Dawley rats under isoflurane anesthesia¹.

参考文献:
1. Malik FI1, Hartman JJ, Elias KA, Morgan BP, Rodriguez H, Brejc K, Anderson RL, Sueoka SH, Lee KH, Finer JT, Sakowicz R, Baliga R, Cox DR, Garard M,Godinez G, Kawas R, Kraynack E, Lenzi D, Lu PP, Muci A, Niu C, Qian X, Pierce DW, Pokrovskii M, Suehiro I, Sylvester S, Tochimoto T, Valdez C, Wang W,Katori T, Kass DA, Shen YT, Vatner SF, Morgans DJ. Cardiac myosin activation: a potential therapeutic approach for systolic heart failure. Science. 2011 Mar 18;331(6023):1439-43.