ArticleNature communications2017
Mechanistic and structural basis for activation of cardiac myosin force production by omecamtiv mecarbil.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
133 citing papers in PubMed, 2 syntheses or guidelines pooled it, 204 citations in OpenAlex.
- Differential cardiovascular benefits of SGLT2 inhibitors, sacubitril/valsartan, omecamtiv mecarbil, and vericiguat across heart failure phenotypes: a systematic review and meta-analysis.Frontiers in pharmacology · 2026Pooled it
- Safety and efficacy of omecamtiv mecarbil for heart failure: A systematic review and meta-analysis.Indian heart journalPooled it
- Determining properties of human-induced pluripotent stem cell-derived cardiomyocytes using spatially resolved electromechanical metrics.The Journal of physiology · 2026Article
- Substrate-Dependent Pro- and Antiarrhythmic Action of Omecamtiv Mecarbil at the Ventricular and Atrial Level: Insights from a Langendorff-Perfused Rabbit Heart Model.Cardiovascular toxicology · 2026Article
- Desmoplakin Loss Leads to PKC- and Src-Mediated Contractile Dysfunction in Cardiomyocytes.Circulation research · 2026Article
- Insights from electromechanical simulations to assess omecamtiv mecarbil efficacy in heart failure.The Journal of physiology · 2026Article
- The E525K β-Myosin Mutation Causes Hypocontractility in Cardiomyocytes Without Altering Loaded Crossbridge Cycling.bioRxiv : the preprint server for biology · 2026Article
- 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
- Emerging Mechanisms and Therapeutic Strategies in Dilated Cardiomyopathy.Biomedicines · 2026Review
- Diffusion Tensor CMR Assessment of the Microstructural Response to Dobutamine Stress in Health and Comparison With Patients With Recovered Dilated Cardiomyopathy.Circulation. Cardiovascular imaging · 2026Observational
- Structural Biology of Actin: Interplay Between Molecular Assembly, Conformational Polymorphism and ATPase.Sub-cellular biochemistry · 2026Review
- 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
- Article
- Dual Modulation of Cardiac Ion Pumps: A Small-Molecule SERCA2a SUMOylation Enhancer Also Inhibits the NaBiomedicines · 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
- Tailored therapeutics for cardiomyopathies.Nature reviews. Cardiology · 2025Review
- Theoretical treatment of tension transients in muscle following sudden changes in orthophosphate concentration: implications for energy transduction.Journal of muscle research and cell motility · 2025Article
73 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
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Omecamtiv mecarbil is a selective, small-molecule activator of cardiac myosin that is being developed as a potential treatment for heart failure with reduced ejection fraction. Here we determine the crystal structure of cardiac myosin in the pre-powerstroke state, the most relevant state suggested by kinetic studies, both with (2.45 Å) and without (3.10 Å) omecamtiv mecarbil bound. Omecamtiv mecarbil does not change the motor mechanism nor does it influence myosin structure. Instead, omecamtiv mecarbil binds to an allosteric site that stabilizes the lever arm in a primed position resulting in accumulation of cardiac myosin in the primed state prior to onset of cardiac contraction, thus increasing the number of heads that can bind to the actin filament and undergo a powerstroke once the cardiac cycle starts. The mechanism of action of omecamtiv mecarbil also provides insights into uncovering how force is generated by molecular motors.Omecamtiv mecarbil (OM) is a cardiac myosin activator that is currently in clinical trials for heart failure treatment. Here, the authors give insights into its mode of action and present the crystal structure of OM bound to bovine cardiac myosin, which shows that OM stabilizes the pre-powerstroke state of myosin.
Indexed as
Identifiers
What OpenQuestion holds
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.