Danicamtiv is a cardiac-specific myosin activator.1,2 It activates human cardiac S1 myosin when used at a concentration of 3 ?M but does not activate skeletal or smooth muscle myosin.1 It increases sarcomere activity of isolated porcine left ventricular and atrial myofibrils with 50% active concentration values (AC50s) of 6 and 3.6 ?M, respectively. Danicamtiv (3 ?M) increases calcium sensitivity of isolated porcine skinned left ventricular and atrial fibers. Danicamtiv (2-3 mg/kg) also prolongs systolic ejection time and improves left ventricular ejection fraction and stroke volume in a dog model of heart failure.
1.Voors, A.A., Tamby, J.-F., Cleland, J.G., et al.Effects of danicamtiv, a novel cardiac myosin activator, in heart failure with reduced ejection fraction: experimental data and clinical results from a phase 2a trialEur. J. Heart Fail.22(9)1649-1658(2020) 2.Grillo, M.P., Markova, S., Evanchik, M., et al.Preclinical in vitro and in vivo pharmacokinetic properties of danicamtiv, a new targeted myosin activator for the treatment of dilated cardiomyopathyXenobiotica51(2)222-238(2021)