Citation: Xiang Honggang, Chen Yanmei, Zhang Jifa, Zhang Jin, Pan Dabo, Liu Bo, Ouyang Liang. Discovery of a novel sodium taurocholate cotransporting polypeptide (NTCP) inhibitor: Design, synthesis, and anti-proliferative activities[J]. Chinese Chemical Letters, ;2020, 31(6): 1422-1426. doi: 10.1016/j.cclet.2020.03.017 shu

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

Xiang Honggang ^a,1 ,
Chen Yanmei ^a,1 ,
Zhang Jifa ^a,1 ,
Zhang Jin ^a ,
Pan Dabo ^b,*, ,
Liu Bo ^a,*, ,
Ouyang Liang ^a,*,

a.
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Collaborative Innovation Center for Biotherapy, Chengdu 610041, China
b.
Institute of Traditional Chinese Medicine & Natural Products, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China

pandabo05@163.com

liubo2400@163.com

ouyangliang@scu.edu.cn

Received Date: 17 January 2020
Revised Date: 5 March 2020
Accepted Date: 6 March 2020
Available Online: 6 March 2020

Figures(4)

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 cycle. Besides, 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 therapy. Herein, 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 vitro. Additionally, CETSA assay, molecular docking, and MD simulation validated that B7 could bind to NTCP. Furthermore, 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 cells. Taken together, our study identified B7 as a novel NTCP inhibitor with anti-proliferation activities which might provide a new opportunity for HCC therapy.
- Sodium taurocholate cotransporting,
- polypeptide,
- (NTCP),
- Hepatocellular carcinoma (HCC),
- HBV infection,
- NTCP inhibitor,
- Apoptosis
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