Dong Zhoujun, Xiong Baichen, Sun Tianyu, Jiang Ruijia, Feng Feng, Sun Haopeng
Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Bioorg Med Chem. 2025 Oct 1;128:118180. doi: 10.1016/j.bmc.2025.118180. Epub 2025 Apr 4.
Na1.7 has been the most studied ion channel among the 9 subtypes of sodium ion, and it is also one of the popular analgesic targets in recent years. Compared with opioid receptors, because of its advantages of targeting a variety of pain types and being unrelated to addiction, many related inhibitors have been excavated for it, including old drugs and new uses, peptides, and new skeleton small molecules. Some of these inhibitors have reached the second phase of clinical research, and some are still in the laboratory research stage. So far, no exclusive Na1.7 inhibitor has successfully passed the third phase of clinical research and entered the field of vision of patients. This article reviews the action sites and mechanisms of different Na1.7 inhibitors in terms of historical background and related analgesic activities, and also summarizes the related inhibitors that are currently under active development, hoping to provide useful information for the research of new Na1.7 inhibitors.
Na1.7是钠离子9种亚型中研究最多的离子通道，也是近年来热门的镇痛靶点之一。与阿片类受体相比，由于其针对多种疼痛类型且与成瘾无关的优势，已为其挖掘出许多相关抑制剂，包括老药新用、肽类以及新骨架小分子。其中一些抑制剂已进入临床研究二期，一些仍处于实验室研究阶段。迄今为止，尚无独家的Na1.7抑制剂成功通过临床研究三期并进入患者视野。本文从历史背景及相关镇痛活性方面综述了不同Na1.7抑制剂的作用位点及作用机制，还总结了目前正在积极研发的相关抑制剂，希望能为新型Na1.7抑制剂的研究提供有用信息。
