ArticleNature communications2024
Omecamtiv mecarbil and Mavacamten target the same myosin pocket despite opposite effects in heart contraction.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Immature and mature myocardium in the pathophysiology of hypertrophic cardiomyopathy.Journal of molecular and cellular cardiology plus · 2026Review
- Structure-Function Relationship as the Foundation for Cardiac Myosin Inhibition in Hypertrophic Cardiomyopathy.Circulation · 2026Article
- The hypertrophic cardiomyopathy mutation G768R makes cardiac myosin a high duty ratio motor.bioRxiv : the preprint server for biology · 2026Article
- 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
- A Covalent Allosteric Molecular Glue Suppresses NRF2-Dependent Cancer Growth.Cancer discovery · 2026Article
- Myosin Filaments of Vertebrate Skeletal and Cardiac Muscle are Highly Similar, but not Identical.bioRxiv : the preprint server for biology · 2026Article
- Nonmuscle α-Actinin-4 Couples Sarcomere Function to Cardiac Remodeling.Circulation research · 2026Article
- Cardiac Myosin Activators in Heart Failure: Experimental Advances Amid Clinical Uncertainty.Drug design, development and therapy · 2026Review
- Mavacamten for Obstructive Hypertrophic Cardiomyopathy: Targeting Sarcomeric Hypercontractility with Demonstrated Long-Term Safety and Efficacy-A Narrative Review.Journal of clinical medicine · 2025Review
- S165F mutation-induced Junctophilin-2 autoinhibition impairs CaCommunications biology · 2025Article
- Cryo-EM Reveals How Cardiomyopathy Therapeutic Drugs Modulate the Myosin Motors of the Heart.bioRxiv : the preprint server for biology · 2025Article
- Understanding hypertrophic cardiomyopathy and its regulation by myosin drugs.Protein science : a publication of the Protein Society · 2025Article
- Hypertrophic cardiomyopathy mutations Y115H and E497D disrupt the folded-back state of human β-cardiac myosin allosterically.Nature communications · 2025Article
- Comparative mechanistic analysis of danicamtiv and omecamtiv mecarbil's in vivo cardiac effects.The Journal of general physiology · 2025Article
- Dynamics of β-cardiac myosin between the super-relaxed and disordered-relaxed states.The Journal of biological chemistry · 2025Article
- Mechanistic insights into effects of the cardiac myosin activator omecamtiv mecarbil from mechanokinetic modelling.Frontiers in physiology · 2025Article
- The order of things: phosphate release or the power stroke, which does actomyosin do first?Frontiers in physiology · 2025Review
- Interacting myosin head dynamics and their modification by 2'-deoxy-ADP.Biophysical journal · 2024Article
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9 authors.
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Abstract
Inherited cardiomyopathies are common cardiac diseases worldwide, leading in the late stage to heart failure and death. The most promising treatments against these diseases are small molecules directly modulating the force produced by β-cardiac myosin, the molecular motor driving heart contraction. Omecamtiv mecarbil and Mavacamten are two such molecules that completed phase 3 clinical trials, and the inhibitor Mavacamten is now approved by the FDA. In contrast to Mavacamten, Omecamtiv mecarbil acts as an activator of cardiac contractility. Here, we reveal by X-ray crystallography that both drugs target the same pocket and stabilize a pre-stroke structural state, with only few local differences. All-atom molecular dynamics simulations reveal how these molecules produce distinct effects in motor allostery thus impacting force production in opposite way. Altogether, our results provide the framework for rational drug development for the purpose of personalized medicine.
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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.