ArticleThe Journal of biological chemistry2017
A small-molecule modulator of cardiac myosin acts on multiple stages of the myosin chemomechanical cycle.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers, 2 of them syntheses that pooled it.
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Who cites it
123 citing papers in PubMed, 2 syntheses or guidelines pooled it, 220 citations in OpenAlex.
- Efficacy and safety of cardiac myosin inhibitors for symptomatic hypertrophic cardiomyopathy: a meta-analysis of randomized controlled trials.Frontiers in cardiovascular medicine · 2024Pooled it
- The effect of mavacamten on echocardiographic parameters, cardiac function and biomarkers in hypertrophic cardiomyopathy patients, a systematic review and meta-analysis.Indian heart journalPooled it
- Long-Term Safety and Efficacy of Mavacamten in Symptomatic Obstructive Hypertrophic Cardiomyopathy: Interim Results of the PIONEER-OLE Study.Journal of the American Heart Association · 2024Trial
- Real-World Effectiveness of Mavacamten in Canada: Insights from the MAVEN Study.Cardiology and therapy · 2026Article
- Mavacamten's Dose-Time Dynamics and Predictive Factors in Hypertrophic Obstructive Cardiomyopathy Cardiac Remodeling.Echocardiography (Mount Kisco, N.Y.) · 2026Article
- Mavacamten in Chinese Patients with Obstructive Hypertrophic Cardiomyopathy: Patient-Reported Health Status Analysis up to 78 Weeks in the EXPLORER-CN Study.Cardiology and therapy · 2026Article
- Mavacamten inhibits myosin activity by stabilizing the myosin interacting-heads motif and stalling motor force generation.Science advances · 2026Article
- Myosin Filaments of Vertebrate Skeletal and Cardiac Muscle are Highly Similar, but not Identical.bioRxiv : the preprint server for biology · 2026Article
- Mavacamten for Obstructive Hypertrophic Cardiomyopathy: Targeting Sarcomeric Hypercontractility with Demonstrated Long-Term Safety and Efficacy-A Narrative Review.Journal of clinical medicine · 2025Review
- Pharmacological Inhibition of β Myosin II Disrupts Sarcomere Assembly in Human iPSC-Derived Cardiac Myocytes.Cytoskeleton (Hoboken, N.J.) · 2025Article
- Treatment Patterns and Healthcare Resource Utilization Among Patients with Obstructive Hypertrophic Cardiomyopathy in Japan: A Claims Database Study.Cardiology and therapy · 2025Article
- Mavacamten in the Treatment of Obstructive Hypertrophic Cardiomyopathy: from Pathophysiology To Real World Data.Current cardiology reports · 2025Review
- Myosin-binding protein C slows cardiac myofibril relaxation kinetics.The Journal of physiology · 2025Article
- Mavacamten facilitates myosin head ON-to-OFF transitions and shortens thin filament length in relaxed mouse skeletal muscle.Physiological reports · 2025Article
- Current and emerging medical and surgical therapy in hypertrophic cardiomyopathy.Journal of cardiovascular imaging · 2025Review
- Cardiac Myosin Inhibitors in Hypertrophic Cardiomyopathy: From Sarcomere to Clinic.International journal of molecular sciences · 2025Review
- Hypertrophic Cardiomyopathy: Current Perspectives.Reviews in cardiovascular medicine · 2025Review
- Anterior mitral valve leaflet length and response to mavacamten in obstructive hypertrophic cardiomyopathy.European heart journal. Imaging methods and practice · 2025Article
- Aficamten in the treatment of obstructive hypertrophic cardiomyopathy.Future cardiology · 2025Review
- Cardiac myosin inhibitors - a cutting-edge solution for the management of hypertrophic cardiomyopathy: a narrative review.Annals of medicine and surgery (2012) · 2025Review
63 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mavacamten, formerly known as MYK-461 is a recently discovered novel small-molecule modulator of cardiac myosin that targets the underlying sarcomere hypercontractility of hypertrophic cardiomyopathy, one of the most prevalent heritable cardiovascular disorders. Studies on isolated cells and muscle fibers as well as intact animals have shown that mavacamten inhibits sarcomere force production, thereby reducing cardiac contractility. Initial mechanistic studies have suggested that mavacamten primarily reduces the steady-state ATPase activity by inhibiting the rate of phosphate release of β-cardiac myosin-S1, but the molecular mechanism of action of mavacamten has not been described. Here we used steady-state and presteady-state kinetic analyses to investigate the mechanism of action of mavacamten. Transient kinetic analyses revealed that mavacamten modulates multiple steps of the myosin chemomechanical cycle. In addition to decreasing the rate-limiting step of the cycle (phosphate release), mavacamten reduced the number of myosin-S1 heads that can interact with the actin thin filament during transition from the weakly to the strongly bound state without affecting the intrinsic rate. Mavacamten also decreased the rate of myosin binding to actin in the ADP-bound state and the ADP-release rate from myosin-S1 alone. We, therefore, conclude that mavacamten acts on multiple stages of the myosin chemomechanical cycle. Although the primary mechanism of mavacamten-mediated inhibition of cardiac myosin is the decrease of phosphate release from β-cardiac myosin-S1, a secondary mechanism decreases the number of actin-binding heads transitioning from the weakly to the strongly bound state, which occurs before phosphate release and may provide an additional method to modulate myosin function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.