Mavacamten, a Novel Therapeutic Strategy for Obstructive Hypertrophic Cardiomyopathy

Zampieri, Mattia; Argirò, Alessia; Marchi, Alberto; Berteotti, Martina; Targetti, Mattia; Fornaro, Alessandra; Tomberli, Alessia; Stefàno, Pierluigi; Marchionni, Niccolò; Olivotto, Iacopo

doi:10.1007/s11886-021-01508-0

Cited by 19 publications

(10 citation statements)

References 33 publications

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“…Table S2 includes a link to ClinicalTrials.gov (https://clinicaltrials.gov/ct2/home, accessed on 9 February 2022), which is a database of clinical studies conducted around the world. For example, recently published phase III reports demonstrate the efficacy and safety of MYK-461 (Mavacamten) in targeting cardiac myosin for the treatment of hypertrophic cardiomyopathy [118][119][120]. Levosimendan targets troponin C with positive inotropic and vasodilatory effects and is being tested in phase III trials [121,122].…”

Section: Actin and Abp As A Drug Targetmentioning

confidence: 99%

Actin-Associated Proteins and Small Molecules Targeting the Actin Cytoskeleton

Gao,

Nakamura

2022

IJMS

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Actin-associated proteins (AAPs) act on monomeric globular actin (G-actin) and polymerized filamentous actin (F-actin) to regulate their dynamics and architectures which ultimately control cell movement, shape change, division; organelle localization and trafficking. Actin-binding proteins (ABPs) are a subset of AAPs. Since actin was discovered as a myosin-activating protein (hence named actin) in 1942, the protein has also been found to be expressed in non-muscle cells, and numerous AAPs continue to be discovered. This review article lists all of the AAPs discovered so far while also allowing readers to sort the list based on the names, sizes, functions, related human diseases, and the dates of discovery. The list also contains links to the UniProt and Protein Atlas databases for accessing further, related details such as protein structures, associated proteins, subcellular localization, the expression levels in cells and tissues, mutations, and pathology. Because the actin cytoskeleton is involved in many pathological processes such as tumorigenesis, invasion, and developmental diseases, small molecules that target actin and AAPs which hold potential to treat these diseases are also listed.

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Section: Actin and Abp As A Drug Targetmentioning

confidence: 99%

Actin-Associated Proteins and Small Molecules Targeting the Actin Cytoskeleton

Gao,

Nakamura

2022

IJMS

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“…This process ultimately leads to sarcomere shortening and muscle contraction. In HCM, most causal genetic variants lead to an increase in actin-myosin cross bridge formation and thus hyperdynamic contraction [ 31 ]. MYH7 (cardiac B-myosin heavy chain) is the predominant myosin isoform expressed in the heart, and MYBPC (myosin-binding protein C) is a modulator of cardiac contraction [ 32 ].…”

Section: Cardiac Myosin Inhibitorsmentioning

confidence: 99%

Contemporary Therapies and Future Directions in the Management of Hypertrophic Cardiomyopathy

et al. 2022

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Hypertrophic cardiomyopathy (HCM) is a genetic disorder caused by pathogenic variants in sarcomeric genes, leading to left ventricular hypertrophy and complex phenotypic heterogeneity. While HCM is the most common inherited cardiomyopathy, pharmacological treatment options have previously been limited and were predominantly directed towards symptom control owing to left ventricular outflow obstruction. These therapies, including beta blockers, calcium channel blockers, and disopyramide, have not been shown to affect the natural history of the disease, which is of particular concern for younger patients who have an increased lifetime risk of experiencing arrhythmias, heart failure, and sudden cardiac death. Increased knowledge of the genetic mechanisms underlying this disease in recent years has led to the development of targeted, potentially disease-modifying therapies for both obstructive and nonobstructive phenotypes that may help to prevent or ameliorate left ventricular hypertrophy. In this review article, we will define the etiology and clinical phenotypes of HCM, summarize the conventional therapies for obstructive HCM, discuss the emerging targeted therapies as well as novel invasive approaches for obstructive HCM, describe the therapeutic advances for nonobstructive HCM, and outline the future directions for the treatment of HCM.

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“…MYH7 p.Val320Met contributes to the increased risk of sudden cardiac death of hypertrophic cardiomyopathy [ 99 ]. It is worth noting that small molecule drugs, such as mavacamten and aficamten, targeting myosin have been employed in clinical trials for treatment of HCM [ 97 , 100 , 101 ]. However, the molecular mechanism by which the gene mutation of myosin mediates the cardiac hypertrophy remains unknown.…”

Section: Abps In Cardiac Hypertrophymentioning

confidence: 99%

Actin-Binding Proteins in Cardiac Hypertrophy

Pan

Wang

Liu

et al. 2022

Cells

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The heart reacts to a large number of pathological stimuli through cardiac hypertrophy, which finally can lead to heart failure. However, the molecular mechanisms of cardiac hypertrophy remain elusive. Actin participates in the formation of highly differentiated myofibrils under the regulation of actin-binding proteins (ABPs), which provides a structural basis for the contractile function and morphological change in cardiomyocytes. Previous studies have shown that the functional abnormality of ABPs can contribute to cardiac hypertrophy. Here, we review the function of various actin-binding proteins associated with the development of cardiac hypertrophy, which provides more references for the prevention and treatment of cardiomyopathy.

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Mavacamten, a Novel Therapeutic Strategy for Obstructive Hypertrophic Cardiomyopathy

Cited by 19 publications

References 33 publications

Actin-Associated Proteins and Small Molecules Targeting the Actin Cytoskeleton

Actin-Associated Proteins and Small Molecules Targeting the Actin Cytoskeleton

Contemporary Therapies and Future Directions in the Management of Hypertrophic Cardiomyopathy

Actin-Binding Proteins in Cardiac Hypertrophy

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