Division of Cardiovascular Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Department of Biomedical Engineering, University of Arizona, Tucson, Arizona, USA.
J Clin Invest. 2022 Mar 1;132(5). doi: 10.1172/JCI148557.
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.
肌球蛋白调节剂是一类新型的药物制剂，正在被开发用于治疗多种心肌病患者。这些药物的治疗目标是直接靶向心肌肌球蛋白，调节收缩性和心输出量，以缓解导致心力衰竭和心律失常的症状，而不改变钙信号。在这篇综述中，我们讨论了两类已被开发出来的药物，它们通过与β-心脏肌球蛋白（MYH7）结合来激活（omecamtiv mecarbil）或抑制（mavacamten）心脏收缩性。我们讨论了药物改变肌球蛋白机械化学的机制方面的进展，并对这些药物的临床试验结果进行了评估，同时考虑了疾病异质性和遗传病因对预测治疗效果的重要性。
