ArticleProceedings of the National Academy of Sciences of the United States of America2018
Mavacamten stabilizes an autoinhibited state of two-headed cardiac myosin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers, 1 of them a synthesis that pooled it.
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Who cites it
111 citing papers in PubMed, 1 synthesis or guideline pooled it, 161 citations in OpenAlex.
- Efficacy and Safety of Mavacamten and Aficamten in Obstructive and Nonobstructive Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis.Critical pathways in cardiology · 2026Pooled it
- Evaluating and comparing the signalling and functional landscape of hiPSC-CMs derived from patients with dilated cardiomyopathy.npj biomedical innovations · 2026Article
- Structure-Function Relationship as the Foundation for Cardiac Myosin Inhibition in Hypertrophic Cardiomyopathy.Circulation · 2026Article
- Probing relaxed myosin states in hypertrophic cardiomyopathy by second harmonic-generation microscopy.eLife · 2026Article
- Temperature dependence of activation of thick and thin filaments in skeletal and cardiac muscles.Journal of muscle research and cell motility · 2026Review
- The hypertrophic cardiomyopathy mutation G768R makes cardiac myosin a high duty ratio motor.bioRxiv : the preprint server for biology · 2026Article
- Assaying the myosin super-relaxed state across muscle types, cells and proteins for understanding muscle biology and use in drug discovery.Nature protocols · 2026Review
- The thin line between biochemistry and structure where myosin super relaxed state lies.Biophysical reviews · 2026Review
- Cryo-EM reveals how cardiomyopathy therapeutic drugs modulate the myosin motors of the heart.Science advances · 2026Article
- Mavacamten inhibits myosin activity by stabilizing the myosin interacting-heads motif and stalling motor force generation.Science advances · 2026Article
- Allosteric drugs in biomolecular condensates: ways forward.Drug discovery today · 2026Review
- Myosin Filaments of Vertebrate Skeletal and Cardiac Muscle are Highly Similar, but not Identical.bioRxiv : the preprint server for biology · 2026Article
- A song of heads and tails: myosin II conformational regulation and filament dynamics shape force generation in non-muscle cells.Biophysical reviews · 2026Review
- Mavacamten for Obstructive Hypertrophic Cardiomyopathy: Targeting Sarcomeric Hypercontractility with Demonstrated Long-Term Safety and Efficacy-A Narrative Review.Journal of clinical medicine · 2025Review
- Cryo-EM Reveals How Cardiomyopathy Therapeutic Drugs Modulate the Myosin Motors of the Heart.bioRxiv : the preprint server for biology · 2025Article
- Tailored therapeutics for cardiomyopathies.Nature reviews. Cardiology · 2025Review
- Myosin-binding protein C slows cardiac myofibril relaxation kinetics.The Journal of physiology · 2025Article
- Cardiac Myosin Inhibitors in Hypertrophic Cardiomyopathy: From Sarcomere to Clinic.International journal of molecular sciences · 2025Review
- A FRET assay to monitor different structural states of human β-cardiac myosin including the interacting-heads motif.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- CaBiophysical journal · 2025Article
51 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
We used transient biochemical and structural kinetics to elucidate the molecular mechanism of mavacamten, an allosteric cardiac myosin inhibitor and a prospective treatment for hypertrophic cardiomyopathy. We find that mavacamten stabilizes an autoinhibited state of two-headed cardiac myosin not found in the single-headed S1 myosin motor fragment. We determined this by measuring cardiac myosin actin-activated and actin-independent ATPase and single-ATP turnover kinetics. A two-headed myosin fragment exhibits distinct autoinhibited ATP turnover kinetics compared with a single-headed fragment. Mavacamten enhanced this autoinhibition. It also enhanced autoinhibition of ADP release. Furthermore, actin changes the structure of the autoinhibited state by forcing myosin lever-arm rotation. Mavacamten slows this rotation in two-headed myosin but does not prevent it. We conclude that cardiac myosin is regulated in solution by an interaction between its two heads and propose that mavacamten stabilizes this state.
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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.