Transient receptor potential melastatin 2 (TRPM2) is a Ca²⁺- permeable nonselective cation channel that is involved in diverse biological functions as a cellular sensor for oxidative stress and temperature. It has been considered a promising therapeutic target for the treatment of ischemia/reperfusion (IR) injury, inflammation, cancer, and neurodegenerative diseases. Development of highly potent and selective TRPM2 inhibitors and validation of their use in relevant disease models will advance drug discovery. In this review, we describe the molecular structures and gating mechanism of the TRPM2 channel, and offer a comprehensive review of advances in the discovery of TRPM2 inhibitors. Furthermore, we analyze the properties of reported TRPM2 inhibitors with an emphasis on how specific inhibitors targeting this channel could be better developed.

瞬时受体电位褪黑素 2 (TRPM2) 是一种 Ca ²⁺- 可渗透的非选择性阳离子通道，作为氧化应激和温度的细胞传感器参与多种生物功能。它被认为是治疗缺血/再灌注 (IR) 损伤、炎症、癌症和神经退行性疾病的有希望的治疗靶点。开发高效和选择性的 TRPM2 抑制剂并验证它们在相关疾病模型中的使用将推动药物发现。在这篇综述中，我们描述了 TRPM2 通道的分子结构和门控机制，并全面回顾了 TRPM2 抑制剂发现的进展。此外，我们分析了已报道的 TRPM2 抑制剂的特性，重点是如何更好地开发针对该通道的特定抑制剂。