Effective Virtual Screening Strategy toward heme-containing proteins: Identification of novel IDO1 inhibitors
文献类型：期刊论文
| 作者 | Zou, Yi2,3; Hu, Yue4; Ge, Shushan3; Zheng, Yingbo3; Li, Yuezhen1; Liu, Wen4; Guo, Wenjie4; Zhang, Yihua3; Xu, Qiang4; Lai, Yisheng3 |
| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2019-12-15 |
| 卷号 | 184页码:23 |
| ISSN号 | 0223-5234 |
| 关键词 | IDO1 Heme T cell Cancer immunotherapy Virtual screening Drug design Molecular dynamics simulation |
| DOI | 10.1016/j.ejmech.2019.111750 |
| 通讯作者 | Guo, Wenjie(guowj@nju.edu.cn) ; Xu, Qiang(molpharm@163.com) ; Lai, Yisheng(yslai@cpu.edu.cn) |
| 英文摘要 | Developing small molecules occupying the heme-binding site using computational approaches remains a challenging task because it is difficult to characterize heme-ligand interaction in heme-containing protein. Indoleamine 2,3-dioxygenase 1 (IDO1) is an intracellular heme-containing dioxygenase which is associated with the immunosuppressive effects in cancer. With IDO1 as an example, herein we report a combined virtual screening (VS) strategy including high-specificity heme-binding group (HmBG)-based pharmacophore screening and cascade molecular docking to identify novel IDO1 inhibitors. A total of four hit compounds were obtained and showed proper binding with the heme iron coordinating site. Further structural optimization led to a promising compound S18-3, which exerted potent anti-tumor efficacy in BALB/c mice bearing established CT26 tumors by activating the host's immune system. These results suggest that S18-3 merits further study to assess its potential for the intervention of cancer. Furthermore, our study also unveils a novel in silico-based strategy for identifying potential regulators for hemeproteins within short timeframe. (C) 2019 Elsevier Masson SAS. All rights reserved. |
| WOS关键词 | INDOLEAMINE 2,3-DIOXYGENASE 1 ; RATIONAL DESIGN ; DRUG DISCOVERY ; MECHANISM ; INDOLEAMINE-2,3-DIOXYGENASE ; PHARMACOPHORE ; EXPRESSION ; BINDING ; POTENT ; 3-DIOXYGENASE |
| 资助项目 | National Natural Science Foundation of China[21772233] ; National Natural Science Foundation of China[81730100] ; National Natural Science Foundation of China[21807104] ; National Natural Science Foundation of China[81922067] ; Postgraduate Research & Practice Innovation Program of Jiangsu Province[KYCX18_0790] ; Fundamental Research Funds for the Central Universities[YK2017121107] ; Fundamental Research Funds for the Central Universities[6204070087] ; Fundamental Research Funds for the Central Universities[020814380114] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| WOS记录号 | WOS:000501660900021 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/282174]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Guo, Wenjie; Xu, Qiang; Lai, Yisheng |
| 作者单位 | 1.China Pharmaceut Univ, Sch Sci, Dept Organ Chem, Nanjing 211198, Jiangsu, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China 3.China Pharmaceut Univ, Ctr Drug Discovery, State Key Lab Nat Med, Jiangsu Key Lab Drug Discovery Metab Dis, Nanjing 210009, Jiangsu, Peoples R China 4.Nanjing Univ, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Jiangsu, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zou, Yi,Hu, Yue,Ge, Shushan,et al. Effective Virtual Screening Strategy toward heme-containing proteins: Identification of novel IDO1 inhibitors[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2019,184:23. |
| APA | Zou, Yi.,Hu, Yue.,Ge, Shushan.,Zheng, Yingbo.,Li, Yuezhen.,...&Lai, Yisheng.(2019).Effective Virtual Screening Strategy toward heme-containing proteins: Identification of novel IDO1 inhibitors.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,184,23. |
| MLA | Zou, Yi,et al."Effective Virtual Screening Strategy toward heme-containing proteins: Identification of novel IDO1 inhibitors".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 184(2019):23. |
入库方式： OAI收割
来源：上海药物研究所
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