Cardiac myosin heavy chain (MHC (with isoforms α-MHC for MYH6 and β-MHC for MYH7))

Cardiac myosin heavy chain is the principal force-generating subunit of the myosin motor protein complex in cardiac muscle, responsible for converting chemical energy from ATP hydrolysis into the mechanical force that drives heart contraction. The protein is a large hexamer comprising two myosin heavy chains (encoded by MYH6 or MYH7, corresponding to α and β isoforms), each associated with regulatory and essential light chains. The α-myosin heavy chain (encoded by MYH6) predominates in human cardiac atria, while the β isoform (MYH7) is more abundant in ventricles but also contributes to atrial contractility. Changes or mutations in these genes are linked to several cardiac diseases, including congenital malformations (e.g., atrial septal defect), cardiomyopathies, and heart failure. Cardiac myosin is a validated therapeutic target, with drugs like omecamtiv mecarbil (activator) and mavacamten (inhibitor) acting directly on myosin to modulate cardiac contractility. The protein carries safety liabilities when targeted, due to its central role in cardiac force generation and disease compensation mechanisms[1][2][8].

Other names

Myosin heavy chain, cardiac muscleMyosin heavy chain alpha isoform (MHC-α)Myosin-6 (for MYH6 gene/isoform)Myosin heavy chain beta isoform (MHC-β)Myosin-7 (for MYH7 gene/isoform)Cardiac myosinCardiac MHC

- Cardiac myosin activators (increase myosin ATPase activity and force generation; e.g., omecamtiv mecarbil)[8] - Cardiac myosin inhibitors (decrease contractility; e.g., mavacamten for hypertrophic cardiomyopathy)[1][8]