Discovery of a novel sodium taurocholate cotransporting polypeptide(NTCP) inhibitor: Design, synthesis, and anti-proliferative activities

作     者：Honggang Xiang Yanmei Chen Jifa Zhang jin Zhang Dabo Pan Bo Liu Liang Ouyang Honggang Xiang;Yanmei Chen;Jifa Zhang;Jin Zhang;Dabo Pan;Bo Liu;Liang Ouyang

作者机构：State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityCollaborative Innovation Center for BiotherapyChengdu 610041China Institute of Traditional Chinese Medicine&Natural ProductsGuangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs ResearchCollege of PharmacyJinan UniversityGuangzhou 510632China 

基　　金：supported by National Science and Technology Major Project of the Ministry of Science and Technology of China(No.2018ZX09735005) the National Natural Science Foundation of China(Nos.81922064,81874290,81673290,81803347 and 81903502) the Natural Science Foundation of Guangdong Province(No.2018A030313707) Post-Doctor Research Project,West China Hospital,Sichuan University(No.2019HXBH034) 

出 版 物：《Chinese Chemical Letters》 (中国化学快报（英文版）)

年 卷 期：2020年第31卷第6期

页      码：1422-1426,F0003页

摘      要：Sodium taurocholate cotransporting polypeptide(NTCP)is identified as the functional receptor for HBV entry,which is responsible for upregulated HBV transcription in the HBV life ***,NTCP is also implicated in the progression of HBV-induced hepatocellular carcinoma(HCC).Thereby,NTCP-targeting entry inhibitors are proposed to suppress HBV infection and replication in HBV-induced hepatoma ***,we integrated in silico screening and chemical synthesis to obtain a small-molecule NTCP inhibitor B7,which exhibited moderate anti-proliferative activities against HepG2 cells and anti-HBV activity in ***,CETSA assay,molecular docking,and MD simulation validated that B7 could bind to ***,western blot analysis demonstrated that B7 induced apoptosis with an increased expression of Bax and caspase 3 cleaving as well as a decreasing expression of Bcl-2 in HepG2 *** together,our study identified B7 as a novel NTCP inhibitor with anti-proliferation activities which might provide a new opportunity for HCC therapy.

主 题 词：Sodium taurocholate cotransporting polypeptide (NTCP) Hepatocellular carcinoma(HCC) HBV infection NTCP inhibitor Apoptosis 

学科分类：1007[医学-药学类] 100701[100701] 10[医学] 

核心收录：

D　O　I：10.1016/j.cclet.2020.03.017

馆 藏 号：203888102...