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Citations to this article

Myosin modulators: emerging approaches for the treatment of cardiomyopathies and heart failure
Sharlene M. Day, … , Jil C. Tardiff, E. Michael Ostap
Sharlene M. Day, … , Jil C. Tardiff, E. Michael Ostap
Published March 1, 2022
Citation Information: J Clin Invest. 2022;132(5):e148557. https://doi.org/10.1172/JCI148557.
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Review Series Article has an altmetric score of 21

Myosin modulators: emerging approaches for the treatment of cardiomyopathies and heart failure

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Abstract

Myosin modulators are a novel class of pharmaceutical agents that are being developed to treat patients with a range of cardiomyopathies. The therapeutic goal of these drugs is to target cardiac myosins directly to modulate contractility and cardiac power output to alleviate symptoms that lead to heart failure and arrhythmias, without altering calcium signaling. In this Review, we discuss two classes of drugs that have been developed to either activate (omecamtiv mecarbil) or inhibit (mavacamten) cardiac contractility by binding to β-cardiac myosin (MYH7). We discuss progress in understanding the mechanisms by which the drugs alter myosin mechanochemistry, and we provide an appraisal of the results from clinical trials of these drugs, with consideration for the importance of disease heterogeneity and genetic etiology for predicting treatment benefit.

Authors

Sharlene M. Day, Jil C. Tardiff, E. Michael Ostap

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Total citations by year

Year: 2025 2024 2023 2022 Total
Citations: 5 13 14 5 37
Citation information
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Citations to this article (37)

Title and authors Publication Year
Mavacamten inhibits myosin activity by stabilising the myosin interacting-heads motif and stalling motor force generation
McMillan SN, Pitts JR, Barua B, Winkelmann DA, Scarff CA
bioRxiv 2025
Phosphorylation of CRYAB induces a condensatopathy to worsen post–myocardial infarction left ventricular remodeling
Islam M, Rawnsley DR, Ma X, Navid W, Zhao C, Guan X, Foroughi L, Murphy JT, Navid H, Weinheimer CJ, Kovacs A, Nigro J, Diwan A, Chang RP, Kumari M, Young ME, Razani B, Margulies KB, Abdellatif M, Sedej S, Javaheri A, Covey DF, Mani K, Diwan A
The Journal of Clinical Investigation 2025
cMyBP-C in hypertrophic cardiomyopathy: gene therapy and small-molecule innovations
Wood PT, Seffrood MM, Colson BA, Stelzer JE
Frontiers in Cardiovascular Medicine 2025
The Genetic Basis of Sudden Cardiac Death: From Diagnosis to Emerging Genetic Therapies.
Dewars ER, Landstrom AP
Annual review of medicine 2025
The role of the troponin T interactions with actin in regulation of cardiac thin filament revealed by the troponin T pathogenic variant Ile79Asn
Risi CM, Landim-Vieira M, Belknap B, Bryant Chase P, Pinto JR, Galkin VE
Journal of molecular and cellular cardiology 2025
The folding of myosin molecules enhances their solubility and mobility within cardiac muscle sarcomeres
Colleen M Kelly, Jody Martin, Michael Previs
JCI Insight 2024
Omecamtiv Mecarbil in the treatment of heart failure: the past, the present, and the future
Zhou S, Liu Y, Huang X, Wu C, Pórszász R
Frontiers in Cardiovascular Medicine 2024
The Expansion of Genetic Testing in Cardiovascular Medicine: Preparing the Cardiology Community for the Changing Landscape.
Reza N, Alford RL, Belmont JW, Marston N
Current Cardiology Reports 2024
Emerging Concepts of Mechanisms Controlling Cardiac Tension: Focus on Familial Dilated Cardiomyopathy (DCM) and Sarcomere-Directed Therapies.
Solaro RJ, Goldspink PH, Wolska BM
Biomedicines 2024
Myosin-Catalyzed ATP Hydrolysis in the Presence of Disease-Causing Mutations: Mavacamten as a Way to Repair Mechanism
Chakraborti A, Tardiff JC, Schwartz SD
The journal of physical chemistry. B 2024
Omecamtiv mecarbil and Mavacamten target the same myosin pocket despite opposite effects in heart contraction
Auguin D, Robert-Paganin J, Réty S, Kikuti C, David A, Theumer G, Schmidt AW, Knölker HJ, Houdusse A
Nature Communications 2024
Mechanisms of a novel regulatory light chain-dependent cardiac myosin inhibitor.
Kooiker K, Gan QF, Yu M, Sa N, Mohran S, Cheng Y, Flint G, Neys S, Gao C, Nissen D, McMillen T, Asencio A, Ma W, Irving TC, Moussavi-Harami F, Regnier M
The Journal of general physiology 2024
Reassessing the unifying hypothesis for hypercontractility caused by myosin mutations in hypertrophic cardiomyopathy.
Spudich JA, Nandwani N, Robert-Paganin J, Houdusse A, Ruppel KM
The EMBO journal 2024
Myosin Isoform-Dependent Effect of Omecamtiv Mecarbil on the Regulation of Force Generation in Human Cardiac Muscle
Scellini B, Piroddi N, Dente M, Pioner JM, Ferrantini C, Poggesi C, Tesi C
International Journal of Molecular Sciences 2024
Subcellular mass spectrometric detection unveils hyperglycemic memory in the diabetic heart.
Zhan J, Zhou Y, Chen Y, Jin K, Chen Z, Chen C, Li H, Wang DW
Journal of diabetes 2024
Miocardiopatias em Crianças e Adolescentes na Era da Medicina de Precisão
Torbey AF, Couto RG, Grippa A, Maia EC, Miranda SA, dos Santos MA, Peres ET, Costa OP, de Oliveira EM, Mesquita ET
Arquivos Brasileiros de Cardiologia 2024
Probing actin‐activated ATP turnover kinetics of human cardiac myosin II by single molecule fluorescence
Berg A, Velayuthan LP, Tågerud S, Ušaj M, Månsson A
Cytoskeleton (Hoboken, N.j.) 2024
Pharmacodynamics of single-dose omecamtiv mecarbil administered intravenously in clinically healthy cats
Ishizaka M, Hsu HH, Miyagawa Y, Takemura N
Open Veterinary Journal 2024
Development and prevention of ischemic contracture (“stone heart”) in the pig heart
Li M, Qin Z, Steen E, Terry A, Wang B, Wohlfart B, Steen S, Arner A
Frontiers in Cardiovascular Medicine 2023
Familial Hypertrophic Cardiomyopathy: Diagnosis and Management
Litt MJ, Ali A, Reza N
Vascular Health and Risk Management 2023
Muscle Mechanics and Thick Filament Activation: An Emerging Two-Way Interaction for the Vertebrate Striated Muscle Fine Regulation
Marcucci L
International journal of molecular sciences 2023
Binding pocket dynamics along the recovery stroke of human β-cardiac myosin.
Akter F, Ochala J, Fornili A
PLoS computational biology 2023
Preserving mitochondria to treat hypertrophic cardiomyopathy: From rare mitochondrial DNA mutation to heart failure therapy?
Abhinav Diwan
Journal of Clinical Investigation 2023
Novelties in the pharmacological approaches for chronic heart failure: new drugs and cardiovascular targets
Correale M, Tricarico L, Croella F, Alfieri S, Fioretti F, Brunetti ND, Inciardi RM, Nodari S
Frontiers in Cardiovascular Medicine 2023
Restoration of Cardiac Myosin Light Chain Kinase Ameliorates Systolic Dysfunction by Reducing Superrelaxed Myosin
Hitsumoto T, Tsukamoto O, Matsuoka K, Li J, Liu L, Kuramoto Y, Higo S, Ogawa S, Fujino N, Yoshida S, Kioka H, Kato H, Hakui H, Saito Y, Okamoto C, Inoue H, Hyejin J, Ueda K, Segawa T, Nishimura S, Asano Y, Asanuma H, Tani A, Imamura R, Komagawa S, Kanai T, Takamura M, Sakata Y, Kitakaze M, Haruta JI, Takashima S
Circulation 2023
Mechanism of small molecule inhibition of Plasmodium falciparum myosin A informs antimalarial drug design.
Moussaoui D, Robblee JP, Robert-Paganin J, Auguin D, Fisher F, Fagnant PM, Macfarlane JE, Schaletzky J, Wehri E, Mueller-Dieckmann C, Baum J, Trybus KM, Houdusse A
Nature Communications 2023
Aficamten: A Breakthrough Therapy for Symptomatic Obstructive Hypertrophic Cardiomyopathy.
Sebastian SA, Padda I, Lehr EJ, Johal G
American journal of cardiovascular drugs : drugs, devices, and other interventions 2023
Mouse Models of Cardiomyopathies Caused by Mutations in Troponin C
Tikunova SB, Thuma J, Davis JP
International journal of molecular sciences 2023
Lactylation regulates cardiac function
Ghosh-Choudhary S, Finkel T
Cell Research 2023
Discovery of a novel cardiac-specific myosin modulator using artificial intelligence-based virtual screening
Parijat P, Attili S, Hoare Z, Shattock M, Kenyon V, Kampourakis T
Nature Communications 2023
Omecamtiv mecarbil and Mavacamten target the same myosin pocket despite antagonistic effects in heart contraction
Auguin D, Robert-Paganin J, Réty S, Kikuti C, David A, Theumer G, Schmidt AW, Knölker HJ, Houdusse A
2023
Functional assays reveal the pathogenic mechanism of a de novo tropomyosin variant identified in patient with dilated cardiomyopathy.
Barrick SK, Garg A, Greenberg L, Zhang S, Lin CY, Stitziel NO, Greenberg MJ
Journal of Molecular and Cellular Cardiology 2023
The Interventricular Septum: Structure, Function, Dysfunction, and Diseases
Triposkiadis F, Xanthopoulos A, Boudoulas KD, Giamouzis G, Boudoulas H, Skoularigis J
Journal of Clinical Medicine 2022
Cardiac Sarcomere Signaling in Health and Disease
Martin AA, Thompson BR, Hahn D, Angulski AB, Hosny N, Cohen H, Metzger JM
International journal of molecular sciences 2022
The Novel Cardiac Myosin Activator Danicamtiv Improves Cardiac Systolic Function at the Expense of Diastolic Dysfunction In Vitro and In Vivo: Implications for Clinical Applications
Ráduly AP, Sárkány F, Kovács MB, Bernát B, Juhász B, Szilvássy Z, Porszász R, Horváth B, Szentandrássy N, Nánási P, Csanádi Z, Édes I, Tóth A, Papp Z, Priksz D, Borbély A
International journal of molecular sciences 2022
Comparative study of binding pocket structure and dynamics in cardiac and skeletal myosin
Antonovic AK, Ochala J, Fornili A
Biophysical Journal 2022
Insights into the Mechanism of the Cardiac Drug Omecamtiv Mecarbil—A Computational Study
Chakraborti A, Tardiff JC, Schwartz SD
The journal of physical chemistry. B 2022

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