Mavacamten

Mavacamten (MYK461) is an orally active modulator of cardiac myosin, with IC₅₀s of 490, 711 nM for bovine cardiac and human cardiac, respectively. IC50 & Target:IC50: 490 nM (bovine cardiac), 711 nM (human cardiac)^[1]. In Vitro:Mavacamten is found to have an IC₅₀ value of 490 nM in the bovine system, 711 nM in the human system, and 2140 nM in the rabbit system, indicating selectivity of >4-fold for cardiac myosin^[1]. In Vivo:Treatment with Mavacamten reduces FS from 52±3% to 38±7%. Treatment with Mavacamten reduces FS from 81±7% to 60±13%, corresponding to a relative reduction of 25%. Across all measurements there is a linear correlation between FS and Mavacamten plasma concentrations with each 100 ng/mL increase in Mavacamten concentration lowering FS by 4.9%^[2]. Mavacamten reduces contractility by decreasing the adenosine triphosphatase activity of the cardiac myosin heavy chain. Chronic administration of Mavacamten suppresses the development of ventricular hypertrophy, cardiomyocyte disarray, and myocardial fibrosis and attenuates hypertrophic and profibrotic gene expression in mice harboring heterozygous human mutations in the myosin heavy chain^[3].