Discovery of 1,8-acridinedione derivatives as novel GCN5 inhibitors via high throughput screening
文献类型：期刊论文
| 作者 | Xiong, Huan1,6; Han, Jie2; Wang, Jun2,3; Lu, Wenchao2,4; Wang, Chen2,4; Chen, Yu2,4; Lian, Fulin2; Zhang, Naixia2 ; Liu, Yu-Chih5; Zhang, Chenhua5
|
| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2018-05-10 |
| 卷号 | 151页码:740-751 |
| 关键词 | Epigenetics Histone acetyltransferase GCN5 High throughput screening 1,8-Acridinedione derivative |
| ISSN号 | 0223-5234 |
| DOI | 10.1016/j.ejmech.2018.02.005 |
| 文献子类 | Article |
| 英文摘要 | The general control nonrepressed protein 5 (GCN5) plays a crucial role in many biological processes. Dysregulation of GCN5 has been closely related to various human diseases, especially cancers. Hence, the exploitation of small molecules targeting GCN5 is essential for drug design and academic research. Based on the amplified luminescent proximity homogeneous assay screen methodology, we performed high throughput screening and discovered a novel GCN5 inhibitor DC_G16 with 1,8-acridinedione scaffold. Structure optimization led to the identification of a highly potent inhibitor, namely DC_G16-11 with the half-maximal inhibitory concentration (IC50) value of 6.8 mu M. The binding between DC_G16-11 and GCN5 was demonstrated by NMR and SPR with a K-D of 4.2 mu M. It could also inhibit proliferation and induce cell cycle arrest and apoptosis in cancer cells while it presented minimal effects on normal cells. Herein, DC_G16-11 could be applied as a validated chemical probe for GCN5-related biological function research and presented great potential for clinical disease treatment. (C) 2018 Elsevier Masson SAS. All rights reserved. |
| WOS关键词 | HISTONE ACETYLTRANSFERASE GCN5 ; SMALL-MOLECULE INHIBITOR ; GLUCOSE-METABOLISM ; CHEMICAL BIOLOGY ; ACETYLATION ; TRANSCRIPTION ; P300 ; PCAF ; H3 ; PGC-1-ALPHA |
| 资助项目 | National Natural Science Foundation of China[81625022] ; National Natural Science Foundation of China[21472208] ; National Natural Science Foundation of China[81430084] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020361] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000432640900050 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279762]  |
| 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 药物化学研究室 |
| 通讯作者 | Lu, Wencong; Luo, Cheng; Zhou, Bing |
| 作者单位 | 1.Shanghai Univ, Dept Chem, Coll Sci, 99 Shangda Rd, Shanghai 200444, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China; 3.Nanjing Univ Chinese Med, Jiangsu Key Lab High Technol Res TCM Formulae, 138 Xianlin Rd, Nanjing 210023, Jiangsu, Peoples R China; 4.Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China; 5.Shanghai ChemPartner Life Sci Co Ltd, In Vitro Biol, 5 Bldg,998 Halei Rd, Shanghai 201203, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Xiong, Huan,Han, Jie,Wang, Jun,et al. Discovery of 1,8-acridinedione derivatives as novel GCN5 inhibitors via high throughput screening[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2018,151:740-751. |
| APA | Xiong, Huan.,Han, Jie.,Wang, Jun.,Lu, Wenchao.,Wang, Chen.,...&Zhou, Bing.(2018).Discovery of 1,8-acridinedione derivatives as novel GCN5 inhibitors via high throughput screening.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,151,740-751. |
| MLA | Xiong, Huan,et al."Discovery of 1,8-acridinedione derivatives as novel GCN5 inhibitors via high throughput screening".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 151(2018):740-751. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。