期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 23, 期 5, 页码 976-984出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2015.01.020
关键词
Hepatitis B virus (HBV); Sodium taurocholate cotransporting polypeptide (NTCP); Anti-HBV drug candidate; Autophagy
资金
- Key Projects of the National Science and Technology Pillar Program [2012BAI30B02]
- National Natural Science Foundation of China [81473091, 81102325]
- Shenyang Science and Technology Project [F12-157-9-00]
Sodium taurocholate cotransporting polypeptide (NTCP) is a multiple transmembrane transporter predominantly expressed in the liver, functioning as a functional receptor for HBV. Through our continuous efforts to identify NTCP as a novel HBV target, we designed and synthesized a series of new compounds based on the structure of our previous compound NT-5. Molecular docking and MD simulation validated that a new compound named NTI-007 can tightly bind to NTCP, whose efficacy was also measured in vitro virological examination and cytotoxicity studies. Furthermore, autophagy was observed in NTI-007 incubated HepG2.2.15 cells, and results of q-PCR and Western blotting revealed that NTI-007 induced autophagy through NTCP-APOA1-HBx-Beclin1-mediated pathway. Taken together, considering crucial role of NTCP in HBV infection, NTCP-mediated autophagic pathway may provide a promising strategy of HBV therapy and given efficacy of NTI-007 triggering autophagy. Our study suggests pre-clinical potential of this compound as a novel anti-HBV drug candidate. (C) 2015 Elsevier Ltd. All rights reserved.
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