Anoctamin家族中钙激活氯离子通道调节剂筛选及应用研究进展  

Research progress in screening and applications of calciumactivated chloride ion channel modulators in Anoctamin family

作　　者：吴明达 洪啟元 兰月娇 姚岚 习诗婷 刘雪莹 高俊涛 郑锴 郝峰 WU Mingda;HONG Qiyuan;LAN Yuejiao;YAO Lan;XI Shiting;LIU Xueying;GAO Juntao;ZHENG Kai;HAO Feng(School of Laboratory Medicine,Jilin Medical College,Jilin 132013,China;School of Public Health,Jilin Medical College,Jilin 132013,China;Jilin Provincial People's Hospital,Changchun 130021,China;School of Medical Technology,Beihua University,Jilin 132013,China;School of Basic Medical Sciences,Jilin Medical College,Jilin 132013,China)

机构地区：[1]吉林医药学院检验学院,吉林吉林132013 [2]吉林医药学院公共卫生学院,吉林吉林132013 [3]吉林省人民医院,吉林长春130021 [4]北华大学医学技术学院,吉林吉林132013 [5]吉林医药学院基础医学院,吉林吉林132013

出　　处：《中国药理学与毒理学杂志》2024年第6期445-454,共10页Chinese Journal of Pharmacology and Toxicology

基　　金：吉林省科技发展计划项目(20220101338JC);吉林省教育厅课题(JJKH20220462KJ);吉林省教育厅课题(JJKH20220473SK);吉林省大学生创新创业项目(S202213706026);吉林省大学生创新创业项目(S202213706019)。

摘　　要：钙激活氯离子通道(CaCC)是一类能通过胞内钙离子激活转运氯离子的通道蛋白,其主要在神经元和肌细胞中参与调节膜电位、细胞内钙平衡和细胞兴奋性等重要的生理作用。Anoctamin(Ano)家族中Ano1是最经典的CaCC,Ano1的靶向调节剂对癌症、囊性纤维化、高血压、腹泻和哮喘等疾病具有潜在治疗作用。自2008年Ano1首次被发现后,先后出现了多种CaCC特异性调节剂的筛选方法,主要包括基于荧光蛋白的高通量初级筛选、电生理膜片钳技术和虚拟筛选,进而发现了多种药理学作用不同的小分子调节剂。本文综述了目前较为主流的筛选方法的原理和优缺点,并对迄今发现的Ano1特异性调节剂的化学结构和潜在的应用进展进行综述。Calcium-activated chloride channels(CaCCs)are a class of channel proteins that trans-port chloride ions activated by intracellular calcium,which play a crucial role in regulating membrane potential,intracellular calcium balance,and cell excitability,particularly in neurons and muscle cells.In the Anoctamin(Ano)family,Ano1 is the most classic CaCC.Targeted modulators of Ano1 have poten-tial therapeutic effects against such diseases as cancer,cystic fibrosis,hypertension,diarrhea,and asthma.Since the discovery of Ano1 in 2008,several methods for screening CaCC-specific modulators have emerged including high-throughput primary screening of fluorescent proteins,electrophysiological patch clamp technique and virtual screening,and identification of small molecule modulators with diverse pharmacological effects.This paper summarizes the principles,advantages and disadvantages of the mainstream screening methods,and reviews the chemical structures and potential applications of Ano1-specific modulators discovered to date.

关 键 词：钙激活氯离子通道 Anoctamin Ano1 Ano2 高通量筛选 特异性调节剂 

分 类 号：R965[医药卫生—药理学] R915[医药卫生—药学]