Discovery of Novel Inhibitors of Indoleamine 2,3-Dioxygenase 1 Through Structure-Based Virtual Screening
文献类型：期刊论文
| 作者 | Zhang, Guoqing1,2; Xing, Jing1,4; Wang, Yulan1,4; Wang, Lihao3; Ye, Yan1,4; Lu, Dong1,4; Zhao, Jihui1,4; Luo, Xiaomin1 ; Zheng, Mingyue1; Yan, Shiying2
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| 刊名 | FRONTIERS IN PHARMACOLOGY
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| 出版日期 | 2018-03-29 |
| 卷号 | 9 |
| ISSN号 | 1663-9812 |
| 关键词 | indoleamine 2, 3-dioxygense IDO1 inhibitor virtual screening molecular docking hit expansion |
| DOI | 10.3389/fphar.2018.00277 |
| 文献子类 | Article |
| 英文摘要 | Indoleamine 2,3-dioxygenase 1 (IDO1) is an intracellular monomeric heme-containing enzyme that catalyzes the first and the rate limiting step in catabolism of tryptophan via the kynurenine (KYN) pathway, which plays a significant role in the proliferation and differentiation of T cells. IDO1 has been proven to be an attractive target for anticancer therapy and chronic viral infections. In the present study, a class of IDO1 inhibitors with novel scaffolds were identified by virtual screening and biochemical validation, in which the compound DC-I028 shows moderate IDO1 inhibitory activity with an IC50 of 21.61 mu M on enzymatic level and 89.11 mu M on HeLa cell. In the following hit expansion stage, DC-I02806, an analog of DC-I028, showed better inhibitory activity with IC50 about 18 mu M on both enzymatic level and cellular level. The structure-activity relationship (SAR) of DC-I028 and its analogs was then discussed based on the molecular docking result. The novel IDO1 inhibitors of DC-I028 and its analogs may provide useful clues for IDO1 inhibitor development. |
| WOS关键词 | ASSAY INTERFERENCE COMPOUNDS ; DRUG DISCOVERY ; LUNG-CANCER ; IDO1 ; TRYPTOPHAN ; THERAPY ; DESIGN ; PAINS ; FOCUS |
| 资助项目 | National Key R&D Program of China[2016YFC1201000] ; Personalized Medicines-Molecular Signature-based Drug Discovery and Development, Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12050201] ; National Natural Science Foundation of China[81773634] ; National Natural Science Foundation of China[81573351] ; National Basic Research Program[2015CB910304] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| 出版者 | FRONTIERS MEDIA SA |
| WOS记录号 | WOS:000428627100001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279836]  |
| 专题 | 药物发现与设计中心 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 | Zheng, Mingyue; Yan, Shiying |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai, Peoples R China; 2.Qingdao Univ, Sch Phys Sci, Qingdao, Peoples R China; 3.East China Univ Sci & Technol, Sch Sci, Shanghai, Peoples R China 4.Univ Chinese Acad Sci, Dept Pharm, Beijing, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Zhang, Guoqing,Xing, Jing,Wang, Yulan,et al. Discovery of Novel Inhibitors of Indoleamine 2,3-Dioxygenase 1 Through Structure-Based Virtual Screening[J]. FRONTIERS IN PHARMACOLOGY,2018,9. |
| APA | Zhang, Guoqing.,Xing, Jing.,Wang, Yulan.,Wang, Lihao.,Ye, Yan.,...&Yan, Shiying.(2018).Discovery of Novel Inhibitors of Indoleamine 2,3-Dioxygenase 1 Through Structure-Based Virtual Screening.FRONTIERS IN PHARMACOLOGY,9. |
| MLA | Zhang, Guoqing,et al."Discovery of Novel Inhibitors of Indoleamine 2,3-Dioxygenase 1 Through Structure-Based Virtual Screening".FRONTIERS IN PHARMACOLOGY 9(2018). |
入库方式： OAI收割
来源：上海药物研究所
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