《米兰app官网版下载官方版》 2016, 28(9): 965-977

KCNQ钾通道及其小分子调节剂研究进展

刘　妮1，2，吕　伟1，南发俊1，2*

(1 华东师范大学化学与分子工程学院，上海 200062；2 中国科学院上海药物研究所国家新药筛选中心，上海 201203)

摘　要：摘　要：KCNQ 钾通道是一类电压门控钾离子通道，具有慢激活和不失活的特点，参与调控细胞的正常代谢。KCNQ 钾通道包括KCNQ1~KCNQ5 五个亚型，在心脏、神经元和平滑肌等组织广泛分布，并在调节细胞兴奋性和离子平衡中发挥着重要的生理功能。KCNQ 功能失调导致多种人类疾病，因此被认为是治疗癫痫、心律失常、疼痛、耳聋和认知功能障碍等疾病的重要药物靶点。2011 年，FDa 批准KCNQ 激动剂Retigabine 上市，进一步促进了以KCNQ 为靶点的小分子调节剂的研究。在综述中主要介绍了KCNQ 钾通道小分子调节剂的研究进展。

KCNQ potassium channel and the development of its small molecule modulators

LIU Ni1，2， LÜ Wei1， Nan Fa-Jun1，2*

(1 College of Chemistry and Molecular Engineering， East China Normal University， Shanghai 200062， China; 2 Chinese National Center for Drug Screening， Shanghai Institute of Materia Medica， Chinese Academy of Sciences， Shanghai 201203， China)

Abstract: Abstract: KCNQ channel belongs to voltage-gated potassium channel， characterised by a slow activation and deactivation current， and can regulate the normal metabolism process. KCNQ genes encode five KCNQ channel subunits (KCNQ1-5). Mutations in the KCNQ gene cause dysfunction in KCNQ channel， which leads to LQT1， DFNA2， epilepsy， pain and cognitived impairment etc. Therofore， KCNQ channel can be a therapeutic target to treat the related diseases. In 2011， FDA approved Retigabine for the adjunctive treatment of partial-onset seizures in patients with further promoting the research progress of KCNQ channel modulators. This review mainly introduces the development of KCNQ channel small molecule modulators.