Discovering novel anti-HCV compounds with inhibitory activities toward HCV NS3/4A protease
文献类型：期刊论文
| 作者 | Yu, Ye; Jing, Jing-feng; Tong, Xian-kun ; He, Pei-lan; Li, Yuan-chao; Hu, You-hong; Tang, Wei; Zuo, Jian-ping
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2014-08 |
| 卷号 | 35期号:8页码:1074-1081 |
| 关键词 | hepatitis C virus NS3/4A protease secreted embryonic alkaline phosphatase (Seap) 2,4-diaminoquinazoline carboxamide telaprevir |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2014.55 |
| 文献子类 | Article |
| 英文摘要 | Aim: To discover novel hepatitis C virus (HCV) inhibitors and elucidate the mechanism of action of the active compounds. Methods: HCV subgenomic replicon-based luciferase reporter cell line was used to screen 1200 synthetic compounds with novel structures. Huh7.5.1 cell line stably transfected with HCV NS3/4A protease reporter was established to investigate the anti-HCV mechanism of the active compounds. The active compounds were further examined in an in vitro HCV infection assay to confirm their anti-HCV activity. Results: After two-round screening in the anti-HCV replicon assay, some 2,4-diaminoquinazoline derivatives and carboxamide analogues were found to possess anti-HCV replicon activities (the IC50 values were less than 5 mu mol/L). Among them, two representative compounds HZ-1157 and LZ-110618-6 inhibited HCV NS3/4A protease with IC50 values of 1.0 and 0.68 mu mol/L, respectively. Furthermore, HZ-1157 and LZ-110618-6 inhibited HCV infection in vitro with 1050 values of 0.82 and 0.11 mu mol/L, respectively. Conclusion: Some 2,4-diaminoquinazoline derivatives and carboxamide analogues have been identified as novel anti-HCV compounds. |
| WOS关键词 | HEPATITIS-C VIRUS ; GENOTYPE 1 INFECTION ; PLUS RIBAVIRIN ; IN-VITRO ; REPLICATION ; TELAPREVIR ; POTENT ; EPIDEMIOLOGY ; BOCEPREVIR ; PROTEINS |
| 资助项目 | Ministry of Science and Technology of PRC (National Basic Research Program of China, 973 Program)[2013CB911104] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:5206242 |
| WOS记录号 | WOS:000340510400010 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276960]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Tong, Xian-kun |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yu, Ye,Jing, Jing-feng,Tong, Xian-kun,et al. Discovering novel anti-HCV compounds with inhibitory activities toward HCV NS3/4A protease[J]. ACTA PHARMACOLOGICA SINICA,2014,35(8):1074-1081. |
| APA | Yu, Ye.,Jing, Jing-feng.,Tong, Xian-kun.,He, Pei-lan.,Li, Yuan-chao.,...&Zuo, Jian-ping.(2014).Discovering novel anti-HCV compounds with inhibitory activities toward HCV NS3/4A protease.ACTA PHARMACOLOGICA SINICA,35(8),1074-1081. |
| MLA | Yu, Ye,et al."Discovering novel anti-HCV compounds with inhibitory activities toward HCV NS3/4A protease".ACTA PHARMACOLOGICA SINICA 35.8(2014):1074-1081. |
入库方式： OAI收割
来源：上海药物研究所
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