[HTML][HTML] Myosin modulators: emerging approaches for the treatment of cardiomyopathies and heart failure
SM Day, JC Tardiff, EM Ostap - The Journal of clinical …, 2022 - Am Soc Clin Investig
SM Day, JC Tardiff, EM Ostap
The Journal of clinical investigation, 2022•Am Soc Clin InvestigMyosin 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 …
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 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.
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