ArticleCirculation research2023
Danicamtiv Increases Myosin Recruitment and Alters Cross-Bridge Cycling in Cardiac Muscle.
Article in Circulation research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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32 citing papers in PubMed, 46 citations in OpenAlex.
- Hypocalcaemic cardiomyopathy with recurrent heart failure: a natural rechallenge case report with 30-month follow-up.European heart journal. Case reports · 2026Article
- Metabolite-sensitive cross-bridge models of human atria reveal the impact of diabetes on muscle mechanoenergetics.The Journal of physiology · 2026Article
- A primer on the methods of skeletal and cardiac muscle mechanics using permeabilized preparations.The Journal of general physiology · 2026Review
- Emerging Mechanisms and Therapeutic Strategies in Dilated Cardiomyopathy.Biomedicines · 2026Review
- Cardiac Myosin Activators in Heart Failure: Experimental Advances Amid Clinical Uncertainty.Drug design, development and therapy · 2026Review
- Maintenance of Energy Metabolism Is an Integral Part of Plakophilin-2 and Desmosome Functions.JACC. Basic to translational science · 2025Article
- Myosin-binding protein C slows cardiac myofibril relaxation kinetics.The Journal of physiology · 2025Article
- Danicamtiv increases cardiac mechanical efficiency.The Journal of physiology · 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
- ATP directly modulates thick filament structure and function in porcine myocardium.Biophysical journal · 2025Article
- Comparative mechanistic analysis of danicamtiv and omecamtiv mecarbil's in vivo cardiac effects.The Journal of general physiology · 2025Article
- Cardiac myosin inhibitors - a cutting-edge solution for the management of hypertrophic cardiomyopathy: a narrative review.Annals of medicine and surgery (2012) · 2025Review
- Thick-Filament-Based Regulation and the Determinants of Force Generation.Biomedicines · 2025Article
- Bayesian estimation of muscle mechanisms and therapeutic targets using variational autoencoders.Biophysical journal · 2025Article
- Differential effects of myosin activators on myocardial contractile function in nonfailing and failing human hearts.American journal of physiology. Heart and circulatory physiology · 2025Article
- The Genetic Basis of Sudden Cardiac Death: From Diagnosis to Emerging Genetic Therapies.Annual review of medicine · 2025Review
- Identification of key genes for heart failure in dilated cardiomyopathy in different populations.Frontiers in genetics · 2025Article
- What frozen human hearts can tell us about treating heart failure.American journal of physiology. Heart and circulatory physiology · 2025Article
- Bayesian Estimation of Muscle Mechanisms and Therapeutic Targets Using Variational Autoencoders.bioRxiv : the preprint server for biology · 2024Article
- Danicamtiv reduces myosin's working stroke but enhances contraction by activating the thin filament.bioRxiv : the preprint server for biology · 2024Article
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Authors and funding
21 authors at 9 institutions in 5 countries.
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Abstract
backgroundModulating myosin function is a novel therapeutic approach in patients with cardiomyopathy. Danicamtiv is a novel myosin activator with promising preclinical data that is currently in clinical trials. While it is known that danicamtiv increases force and cardiomyocyte contractility without affecting calcium levels, detailed mechanistic studies regarding its mode of action are lacking.
methodsPermeabilized porcine cardiac tissue and myofibrils were used for X-ray diffraction and mechanical measurements. A mouse model of genetic dilated cardiomyopathy was used to evaluate the ability of danicamtiv to correct the contractile deficit.
resultsDanicamtiv increased force and calcium sensitivity via increasing the number of myosins in the ON state and slowing cross-bridge turnover. Our detailed analysis showed that inhibition of ADP release results in decreased cross-bridge turnover with cross bridges staying attached longer and prolonging myofibril relaxation. Danicamtiv corrected decreased calcium sensitivity in demembranated tissue, abnormal twitch magnitude and kinetics in intact cardiac tissue, and reduced ejection fraction in the whole organ.
conclusionsAs demonstrated by the detailed studies of Danicamtiv, increasing myosin recruitment and altering cross-bridge cycling are 2 mechanisms to increase force and calcium sensitivity in cardiac muscle. Myosin activators such as Danicamtiv can treat the causative hypocontractile phenotype in genetic dilated cardiomyopathy.
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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.