Discovery of novel DNA methyltransferase 3A inhibitors via structure-based virtual screening and biological assays
文献类型：期刊论文
| 作者 | Shao, Zhiyuan1; Xu, Pan2; Xu, Wen3; Li, Linjuan2,4; Liu, Shien2; Zhang, Rukang2,4; Liu, Yu-Chih5; Zhang, Chenhua5; Chen, Shijie2; Luo, Cheng2
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| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
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| 出版日期 | 2017-01-15 |
| 卷号 | 27期号:2页码:342-346 |
| 关键词 | Epigenetics DNMT3A inhibitors Virtual screening Molecular docking |
| ISSN号 | 0960-894X |
| DOI | 10.1016/j.bmcl.2016.11.023 |
| 文献子类 | Article |
| 英文摘要 | DNA methyltransferases are involved in diverse biological processes and abnormal methylation patterns play essential roles in cancer initiation and progression. DNA methyltransferase 3A (DNMT3A) acting as a de novo DNA methyltransferase, has gained widespread attention especially in haematological diseases. To date, large numbers of DNMTs inhibitors have been discovered, however, the small molecular inhibitors targeting DNMT3A are still in its infancy. In this study, structure-based virtual screening in combination with biological assays was performed to discovery potent novel DNMT3A inhibitors. Compound 40 and 40_3 displayed comparable in vitro inhibitory activity against DNMT3A with IC50 values of 46.5 mu M and 41 mu M, respectively. Further binding mode analysis suggested these molecules inhibit DNMT3A activity through binding the S-adenosyl-L-methionine (SAM) pocket. Overall, 40 and 40_3 may serve as novel scaffolds for further optimization and small molecular probes for investigating DNMT3A function. (C) 2016 Elsevier Ltd. All rights reserved. |
| WOS关键词 | METHYLATION ; DOCKING ; CANCER ; DNMT3A |
| 资助项目 | Ministry of Science and Technology of China[2015CB910304] ; National Natural Science Foundation of China[21472208] ; National Natural Science Foundation of China[81625022] ; CAS Strategic Priority Research Program[XDA12020304] ; Fund of State Key Laboratory of Toxicology and Medical Countermeasures, Academy of Military Medical Science[TMC201505] |
| WOS研究方向 | Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000392558500043 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/275675]  |
| 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 | Chen, Shijie; Luo, Cheng |
| 作者单位 | 1.Univ Sci & Technol China, Nano Sci & Technol Inst, Suzhou 215123, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China; 3.Fudan Univ, Obstet & Gynecol Hosp, 419 Fangxie Rd, Shanghai 200011, Peoples R China; 4.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China; 5.Shanghai ChemPartner Co LTD, Pudong New Area, Bldg 5,998 Halei Rd,Zhangjiang Hitech Pk, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Shao, Zhiyuan,Xu, Pan,Xu, Wen,et al. Discovery of novel DNA methyltransferase 3A inhibitors via structure-based virtual screening and biological assays[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2017,27(2):342-346. |
| APA | Shao, Zhiyuan.,Xu, Pan.,Xu, Wen.,Li, Linjuan.,Liu, Shien.,...&Luo, Cheng.(2017).Discovery of novel DNA methyltransferase 3A inhibitors via structure-based virtual screening and biological assays.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,27(2),342-346. |
| MLA | Shao, Zhiyuan,et al."Discovery of novel DNA methyltransferase 3A inhibitors via structure-based virtual screening and biological assays".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 27.2(2017):342-346. |
入库方式： OAI收割
来源：上海药物研究所
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