Discovery and optimization of selective inhibitors of protein arginine methyltransferase 5 by docking-based virtual screening
文献类型：期刊论文
| 作者 | Ye, Yan1,2; Zhang, Bidong1,2; Mao, Ruifeng1; Zhang, Chenhua3; Wang, Yulan1; Xing, Jing1; Liu, Yu-Chih3; Luo, Xiaomin1 ; Ding, Hong1; Yang, Yaxi4
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| 刊名 | ORGANIC & BIOMOLECULAR CHEMISTRY
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| 出版日期 | 2017-05-07 |
| 卷号 | 15期号:17页码:3648-3661 |
| ISSN号 | 1477-0520 |
| DOI | 10.1039/c7ob00070g |
| 文献子类 | Article |
| 英文摘要 | Protein arginine methyltransferase 5 (PRMT5) is a type II PRMT enzyme critical for diverse cellular processes and different types of cancers. Many efforts have been made to discover novel scaffold PRMT5 inhibitors. Herein, we report the discovery of DC_P33 as a hit compound of PRMT5 inhibitor, identified by molecular docking based virtual screening and H-3-labeled radioactive methylation assays. Structure-activity relationship (SAR) analysis was performed on the analogs of DC_P33 and then structural modifications were done to improve its activity. Among the derivatives, the compound DC_C01 displayed an IC50 value of 2.8 mu M, and good selectivity toward PRMT1, EZH2 and DNMT3A. Moreover, DC_C01 exhibited anti-proliferation activities against Z-138, Maver-1, and Jeko-1 cancer cells with EC50 values of 12 mu M, 12 mu M, and 10.5 mu M, respectively. Taken together, these results contribute to the development of specific inhibitors against PRMT5 and cancer therapy. |
| WOS关键词 | REDUCTIVE AMINATION ; CELL-DEATH ; METHYLATION ; PRMT5 ; HISTONE ; GROWTH ; EXPRESSION ; LYMPHOMA ; CANCER ; ASSAY |
| 资助项目 | Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12050201] ; National Basic Research Program[2015CB910304] ; National Natural Science Foundation of China[21210003] ; National Natural Science Foundation of China[81230076] ; National Natural Science Foundation of China[81430084] ; National Natural Science Foundation of China[81625022] ; National Key Research & Development Plan[2016YF1201003] ; Fund of State Key Laboratory of Toxicology and Medical Countermeasures, Academy of Military Medical Science[TMC201505] |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000400868000015 |
| 出版者 | ROYAL SOC CHEMISTRY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272669]  |
| 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 | Luo, Cheng; Zheng, Mingyue |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China; 2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China; 3.Shanghai ChemPartner Co Ltd, 5 Bldg,998 Halei Rd, Shanghai 201203, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Medica, Dept Med Chem, Shanghai 201203, Peoples R China; 5.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ye, Yan,Zhang, Bidong,Mao, Ruifeng,et al. Discovery and optimization of selective inhibitors of protein arginine methyltransferase 5 by docking-based virtual screening[J]. ORGANIC & BIOMOLECULAR CHEMISTRY,2017,15(17):3648-3661. |
| APA | Ye, Yan.,Zhang, Bidong.,Mao, Ruifeng.,Zhang, Chenhua.,Wang, Yulan.,...&Zheng, Mingyue.(2017).Discovery and optimization of selective inhibitors of protein arginine methyltransferase 5 by docking-based virtual screening.ORGANIC & BIOMOLECULAR CHEMISTRY,15(17),3648-3661. |
| MLA | Ye, Yan,et al."Discovery and optimization of selective inhibitors of protein arginine methyltransferase 5 by docking-based virtual screening".ORGANIC & BIOMOLECULAR CHEMISTRY 15.17(2017):3648-3661. |
入库方式： OAI收割
来源：上海药物研究所
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