靶向Nav1.7的镇痛药物开发:临床试验进展与选择性抑制剂发现

Development of analgesic drugs targeting Nav1.7:advances in clinical trials and discovery of selective inhibitors

电压门控钠离子通道亚型Nav1.7在伤害性感觉神经元中高表达,是多种人类遗传性疼痛综合征的关键致病靶点。近年来,大量研究表明Nav1.7在炎性、神经病理性及伤害性刺激诱发的疼痛中具有重要作用。因此,靶向抑制Nav1.7是新型镇痛药研制的新策略和热点。本文介绍了Nav1.7的结构与功能、在疼痛中的调节作用,重点总结了临床试验中Nav1.7小分子抑制剂的开发进展,并对临床前Nav1.7高专一性抑制剂的开发进行了分析,以期为Nav1.7镇痛药物的开发提供参考。

The voltage-gated sodium channel subtype Navl.7 is highly expressed in nociceptive sensory neurons and is a key pathogenic target in several human hereditary pain syndromes.In recent years,a large number of studies have shown that Nav1.7 plays an important role in inflammatory,neuropathic,and nociceptive pain.Therefore,targeting Navl.7 is a new strategy and hotspot for the development of novel analgesics.This review introduces the structure and function of Navl.7,its regulatory role in pain,highlights the development progress of small-molecule Navl.7 inhibitors in clinical trials,and analyzes the preclinical development of highly specific Nav1.7 inhibitors,with a view to providing reference for the development of Nav1.7 analgesic drugs.