Myosin modulators: emerging approaches for the treatment of cardiomyopathies and heart failure.
Myosin modulators: emerging approaches for the treatment of cardiomyopathies and heart failure.
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DOI：
10.1172/jci148557
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发表时间：
2022-03-01
期刊：
影响因子：
--
通讯作者：
Ostap EM
中科院分区：
文献类型：
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作者：
Day SM;Tardiff JC;Ostap EM
肌球蛋白调节剂是一类新型的药物，正在开发用于治疗患有一系列心肌病的患者。这些药物的治疗目标是直接靶向心肌肌球蛋白以调节收缩力和心脏功率输出，从而减轻导致心力衰竭和心律失常的症状，而不改变钙信号传导。在这篇综述中，我们讨论了两类药物，它们通过与β-心肌肌球蛋白（MYH 7）结合来激活（Omecamtiv Mecarbil）或抑制（mavacamten）心肌收缩力。我们讨论了药物改变肌球蛋白机械化学机制的进展，并对这些药物的临床试验结果进行了评价，同时考虑了疾病异质性和遗传病因学对预测治疗获益的重要性。
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.