Aficamten CAS# 2364554-48-1

Aficamten (CK-274) is a selective, reversible cardiac myosin inhibitor developed for hypertrophic cardiomyopathy (HCM). In vitro, aficamten inhibits human β-cardiac myosin ATPase activity with low-nanomolar potency (IC₅₀ ≈ 8–15 nM) and reduces actin–myosin cross-bridge formation, leading to decreased sarcomere contractility without affecting skeletal or smooth muscle myosin. In isolated cardiomyocytes, it lowers hypercontractility and normalizes relaxation kinetics. In vivo, aficamten shows dose-dependent negative inotropic effects in rodent and canine models, reducing left ventricular fractional shortening and contractility while preserving heart rate and blood pressure. In transgenic and pressure-overload HCM animal models, chronic dosing reduces left ventricular outflow tract gradients, improves diastolic filling, and attenuates myocardial hypertrophy, supporting its targeted sarcomeric mechanism and favorable cardiac selectivity profile.