MYH7

Cell biology

Cardiac muscle

Biology

Myosin light-chain kinase

Cardiology

Biochemistry

Contractility

Heart failure

Bioinformatics

Myosin

Internal medicine

Pharmacology

Cardiomyopathy

Medicine

Journal of Clinical Investigation

Myosin modulators are a novel class of pharmaceutical agents that are being developed to treat patients with a range of cardiomyopathies. The therapeutic goal of these drugs is to target cardiac myosins directly to modulate contractility and cardiac power output to alleviate symptoms that lead to heart failure and arrhythmias, without altering calcium signaling. In this Review, we discuss two classes of drugs that have been developed to either activate (omecamtiv mecarbil) or inhibit (mavacamten) cardiac contractility by binding to β-cardiac myosin (MYH7). We discuss progress in understanding the mechanisms by which the drugs alter myosin mechanochemistry, and we provide an appraisal of the results from clinical trials of these drugs, with consideration for the importance of disease heterogeneity and genetic etiology for predicting treatment benefit.

Myosin modulators: emerging approaches for the treatment of cardiomyopathies and heart failure