KCNQ钾通道及其小分子调节剂研究进展

KCNQ potassium channel and the development of its small molecule modulators

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 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.