ArticleThe Journal of general physiology2021
Mavacamten has a differential impact on force generation in myofibrils from rabbit psoas and human cardiac muscle.
Article in The Journal of general physiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 51 citations in OpenAlex.
- Subsarcomeric regulation of thin and thick filaments in skeletal muscle myofibrils.Proceedings of the National Academy of Sciences of the United States of America · 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
- 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
- Delayed phosphate release can highly improve energy efficiency of muscle contraction.Biophysical journal · 2025Article
- Mechanistic insights into effects of the cardiac myosin activator omecamtiv mecarbil from mechanokinetic modelling.Frontiers in physiology · 2025Article
- Cardiac length-dependent activation driven by force-dependent thick-filament dynamics.Biophysical journal · 2024Article
- Cardiac length-dependent activation driven by force-dependent thick-filament dynamics.Biophysical journal · 2024Article
- Myosin Isoform-Dependent Effect of Omecamtiv Mecarbil on the Regulation of Force Generation in Human Cardiac Muscle.International journal of molecular sciences · 2024Article
- Aficamten reduces cardiac contractility by modifying the actomyosin interaction.Nature cardiovascular research · 2024Article
- Myosin-Catalyzed ATP Hydrolysis in the Presence of Disease-Causing Mutations: Mavacamten as a Way to Repair Mechanism.The journal of physical chemistry. B · 2024Article
- Myosin folding boosts solubility in cardiac muscle sarcomeres.JCI insight · 2024Article
- Increased Chamber Resting Tone Is a Key Determinant of Left Ventricular Diastolic Dysfunction.Circulation. Heart failure · 2023Article
- Discovery of a novel cardiac-specific myosin modulator using artificial intelligence-based virtual screening.Nature communications · 2023Article
- Mavacamten, a precision medicine for hypertrophic cardiomyopathy: From a motor protein to patients.Science advances · 2023Review
- Super relaxed myosins loosen up to different cues in cardiac and skeletal muscle sarcomeres.The Journal of general physiology · 2023Article
- Small molecule drugs to improve sarcomere function in those with acquired and inherited myopathies.American journal of physiology. Cell physiology · 2023Review
- Muscle Mechanics and Thick Filament Activation: An Emerging Two-Way Interaction for the Vertebrate Striated Muscle Fine Regulation.International journal of molecular sciences · 2023Review
- Single-molecule imaging reveals how mavacamten and PKA modulate ATP turnover in skeletal muscle myofibrils.The Journal of general physiology · 2023Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mavacamten (MYK-461) is a small-molecule allosteric inhibitor of sarcomeric myosins being used in preclinical/clinical trials for hypertrophic cardiomyopathy treatment. A better understanding of its impact on force generation in intact or skinned striated muscle preparations, especially for human cardiac muscle, has been hindered by diffusional barriers. These limitations have been overcome by mechanical experiments using myofibrils subject to perturbations of the contractile environment by sudden solution changes. Here, we characterize the action of mavacamten in human ventricular myofibrils compared with fast skeletal myofibrils from rabbit psoas. Mavacamten had a fast, fully reversible, and dose-dependent negative effect on maximal Ca2+-activated isometric force at 15°C, which can be explained by a sudden decrease in the number of heads functionally available for interaction with actin. It also decreased the kinetics of force development in fast skeletal myofibrils, while it had no effect in human ventricular myofibrils. For both myofibril types, the effects of mavacamten were independent from phosphate in the low-concentration range. Mavacamten did not alter force relaxation of fast skeletal myofibrils, but it significantly accelerated the relaxation of human ventricular myofibrils. Lastly, mavacamten had no effect on resting tension but inhibited the ADP-stimulated force in the absence of Ca2+. Altogether, these effects outline a motor isoform-specific dependence of the inhibitory effect of mavacamten on force generation, which is mediated by a reduction in the availability of strongly actin-binding heads. Mavacamten may thus alter the interplay between thick and thin filament regulation mechanisms of contraction in association with the widely documented drug effect of stabilizing myosin motor heads into autoinhibited states.
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