ArticleNature communications2018
Positive cardiac inotrope omecamtiv mecarbil activates muscle despite suppressing the myosin working stroke.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
102 citing papers in PubMed, 140 citations in OpenAlex.
- Effects of danicamtiv, a novel cardiac myosin activator, in heart failure with reduced ejection fraction: experimental data and clinical results from a phase 2a trial.European journal of heart failure · 2020Trial
- Targeting cardiac myosin in HFrEF: mechanism, clinical evidence, and the role of omecamtiv mecarbil.Journal of cardiothoracic surgery · 2026Review
- The hypertrophic cardiomyopathy mutation G768R makes cardiac myosin a high duty ratio motor.bioRxiv : the preprint server for biology · 2026Article
- Cryo-EM reveals how cardiomyopathy therapeutic drugs modulate the myosin motors of the heart.Science advances · 2026Article
- Molecular and Cellular Determinants of Human Iron Overload Cardiomyopathy.bioRxiv : the preprint server for biology · 2026Article
- A myosin hypertrophic cardiomyopathy mutation disrupts the super-relaxed state and boosts contractility by enhanced actin attachment.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- S2Tag, a novel affinity tag for the capture and immobilization of coiled-coil proteins: Application to the study of human β-cardiac myosin.The Journal of biological chemistry · 2025Article
- Cryo-EM Reveals How Cardiomyopathy Therapeutic Drugs Modulate the Myosin Motors of the Heart.bioRxiv : the preprint server for biology · 2025Article
- Danicamtiv reduces myosin's working stroke but activates the thin filament by accelerating actomyosin attachment.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Delayed phosphate release can highly improve energy efficiency of muscle contraction.Biophysical journal · 2025Article
- Comparative mechanistic analysis of danicamtiv and omecamtiv mecarbil's in vivo cardiac effects.The Journal of general physiology · 2025Article
- Modulation of striated-muscle contractility by a high-affinity myosin-targeting peptide.Biophysical journal · 2025Article
- The elementary step that generates force and sinusoidal analysis in striated muscle fibers.Journal of muscle research and cell motility · 2025Review
- How Omecamtiv Modulates Myosin Motion.Biochemistry · 2025Article
- Review
- Mechanistic insights into effects of the cardiac myosin activator omecamtiv mecarbil from mechanokinetic modelling.Frontiers in physiology · 2025Article
- What frozen human hearts can tell us about treating heart failure.American journal of physiology. Heart and circulatory physiology · 2025Article
- The order of things: phosphate release or the power stroke, which does actomyosin do first?Frontiers in physiology · 2025Review
- Pharmacodynamics of single-dose omecamtiv mecarbil administered intravenously in clinically healthy cats.Open veterinary journal · 2024Article
- Danicamtiv reduces myosin's working stroke but enhances contraction by activating the thin filament.bioRxiv : the preprint server for biology · 2024Article
42 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Omecamtiv mecarbil (OM) is a positive cardiac inotrope in phase-3 clinical trials for treatment of heart failure. Although initially described as a direct myosin activator, subsequent studies are at odds with this description and do not explain OM-mediated increases in cardiac performance. Here we show, via single-molecule, biophysical experiments on cardiac myosin, that OM suppresses myosin's working stroke and prolongs actomyosin attachment 5-fold, which explains inhibitory actions of the drug observed in vitro. OM also causes the actin-detachment rate to become independent of both applied load and ATP concentration. Surprisingly, increased myocardial force output in the presence of OM can be explained by cooperative thin-filament activation by OM-inhibited myosin molecules. Selective suppression of myosin is an unanticipated route to muscle activation that may guide future development of therapeutic drugs.
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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.