Advances in the development of TRPM2 channel inhibitors.

Abstract

The studies on specific transient receptor potential melastatin 2(TRPM2) channel inhibitors can deepen our understanding of the pathological mechanism of related diseases, and discover novel, effective targets for therapeutic drugs. The development of TRPM2 channel inhibitors can be broadly classified into four categories with distinct characteristics: reutilization and structural modification of homologous ion channel modulators to produce a diverse array of TRPM2 channel inhibitors with strong inhibitory effects; TRPM2 channel inhibitors developed on channel gating mechanism with high specificity; inhibitors developed through high-throughput screening with novel chemical structures; inhibitors developed from natural antioxidants with higher safety. In recent years, the application of computer-aided drug design has significantly accelerated the development of TRPM2 channel inhibitors. Several promising compounds such as ZA18, A1 and D9 have been discovered, and it is expected that more potent and selective TRPM2 channel inhibitor scaffolds will be discovered in the future. This article reviews the advances on the studies of TRPM2 channel inhibitors, aiming to provide insights for the further research and clinical application of TRPM2 channel inhibitors.