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

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Chinese Chemical Letters 2020年第6期31卷 1422-1426,F0003页

作者： Honggang Xiang Yanmei Chen Jifa Zhang jin Zhang Dabo Pan Bo Liu Liang Ouyang State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan UniversityCollaborative Innovation Center for BiotherapyChengdu 610041China Institute of Traditional Chinese Medicine&Natural Products Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs ResearchCollege of PharmacyJinan UniversityGuangzhou 510632China

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.

关键词： Sodium taurocholate cotransporting polypeptide (ntcp) Hepatocellular carcinoma(HCC) HBV infection ntcp inhibitor Apoptosis

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Targeting ntcp for liver disease treatment: A promising strategy

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Journal of Pharmaceutical Analysis 2024年第9期14卷 1267-1281页

作者： Xin Tan Yu Xiang Jianyou Shi Lu Chen Dongke Yu Department of Pharmacy Sichuan Provincial People's HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengdu610072China Personalized Drug Therapy Key Laboratory of Sichuan Province School of MedicineUniversity of Electronic Science and Technology of ChinaChengdu610072China College of Medicine University of Electronic Science and TechnologyChengdu610072China Guanghan People's Hospital GuanghanSichuan618300China

The sodium taurocholate co-transporting polypeptide (ntcp), a bile acids transporter, has been identified as a new therapeutic target for the treatment of liver disease. This paper thoroughly investigates the function of ntcp for regulating bile acid regulation, its correlation with hepatitis B and D infections, and its association with various liver diseases. Additionally, in this review we examine recent breakthroughs in creating ntcp inhibitors and their prospective applications in liver disease treatment. While this review emphasizes the promising potential of targeting ntcp, it concurrently underscores the need for broader and more detailed research to fully understand the long-term implications and potential side effects associated with ntcp inhibition.

关键词： ntcp Bile acids metabolism ntcp inhibitor Viral hepatitis

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