The mechanically activated Piezo channels, including Piezo1 and Piezo2 in mammals, function as key mechanotransducers for converting mechanical force into electrochemical signals. This review highlights key evidence for the potential of Piezo channel drug discovery. First, both mouse and human genetic studies have unequivocally demonstrated the prominent role of Piezo channels in various mammalian physiologies and pathophysiologies, validating their potential as novel therapeutic targets. Second, the cryo-electron microscopy structure of the 2,547-residue mouse Piezo1 trimer has been determined, providing a solid foundation for studying its structure-function relationship and drug action mechanisms and conducting virtual drug screening. Third, Piezo1 chemical activators, named Yoda1 and Jedi1/2, have been identified through high-throughput screening assays, demonstrating the drugability of Piezo channels. However, the pharmacology of Piezo channels is in its infancy. By establishing an integrated drug discovery platform, we may hopefully discover and develop a fleet of Jedi masters for battling Piezo-related human diseases.

中文翻译：

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利用机械激活的压电通道进行潜在的药理干预。

机械激活的压电通道，包括哺乳动物中的Piezo1和Piezo2，是将机械力转换为电化学信号的关键机械换能器。这篇综述重点介绍了压电通道药物发现潜力的关键证据。首先，小鼠和人类基因研究都明确证明了压电通道在各种哺乳动物生理学和病理生理学中的重要作用，从而验证了它们作为新型治疗靶标的潜力。其次，确定了2547个残基的小鼠Piezo1三聚体的冷冻电子显微镜结构，为研究其结构-功能关系和药物作用机理以及进行虚拟药物筛选提供了坚实的基础。第三，Piezo1化学活化剂，名为Yoda1和Jedi1 / 2，通过高通量筛选测定法已鉴定出，证明了压电通道的可药用性。但是，压电通道的药理学尚处于起步阶段。通过建立一个综合的药物发现平台，我们有望发现并发展一支与绝地动物相关的人类疾病的绝地大师团队。