Fragment-Based Drug Discovery of 2-Thiazolidinones as Inhibitors of the Histone Reader BRD4 Bromodomain
文献类型：期刊论文
| 作者 | Zhao, Lele ; Cao, Danyan ; Chen, Tiantian ; Wang, Yingqing ; Miao, Zehong ; Xu, Yechun ; Chen, Wuyan ; Wang, Xin ; Li, Yardian ; Du, Zhiyan ; Xiong, Bing ; Li, Jian ; Xu, Chunyan（徐春艳） ; Zhang, Naixia ; He, Jianhua（何建华） ; Shen, Jingkang |
| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2013 |
| 卷号 | 56期号:10页码:CONCATENATE(Sheet1!I134,-Sheet1!J134) |
| ISSN号 | 0022-2623 |
| 英文摘要 | Recognizing acetyllysine of histone is a vital process of epigenetic regulation that is mediated by a protein module called bromodomain. To contribute novel scaffolds for developing into bromodomain inhibitors, we utilize a fragment-based drug discovery approach. By successively applying docking and X-ray crystallography, we were able to identify 9 fragment hits from diffracting more than 60 crystals. In the present work, we described four of them and carried out the integrated lead optimization for fragment 8, which bears a 2-thiazolidinone core. After several rounds of structure guided modifications, we assessed the druggability of 2-thiazolidinone by modulating in vitro pharmacokinetic studies and cellular activity assay. The results showed that two potent compounds of 2-thiazolidinones have good metabolic stability. Also, the cellular assay confirmed the activities of 2-thiazolidinones. Together, we hope the identified 2-thiazolidinone chemotype and other fragment hits described herein can stimulate researchers to develop more diversified bromodomain inhibitors. |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000319650100006 |
| 公开日期 | 2014-06-13 |
| 源URL | [http://ir.sinap.ac.cn/handle/331007/13757]  |
| 专题 | 上海应用物理研究所_中科院上海应用物理研究所2011-2017年 |
| 推荐引用方式 GB/T 7714 | Zhao, Lele,Cao, Danyan,Chen, Tiantian,et al. Fragment-Based Drug Discovery of 2-Thiazolidinones as Inhibitors of the Histone Reader BRD4 Bromodomain[J]. JOURNAL OF MEDICINAL CHEMISTRY,2013,56(10):CONCATENATE(Sheet1!I134,-Sheet1!J134). |
| APA | Zhao, Lele.,Cao, Danyan.,Chen, Tiantian.,Wang, Yingqing.,Miao, Zehong.,...&Shen, Jingkang.(2013).Fragment-Based Drug Discovery of 2-Thiazolidinones as Inhibitors of the Histone Reader BRD4 Bromodomain.JOURNAL OF MEDICINAL CHEMISTRY,56(10),CONCATENATE(Sheet1!I134,-Sheet1!J134). |
| MLA | Zhao, Lele,et al."Fragment-Based Drug Discovery of 2-Thiazolidinones as Inhibitors of the Histone Reader BRD4 Bromodomain".JOURNAL OF MEDICINAL CHEMISTRY 56.10(2013):CONCATENATE(Sheet1!I134,-Sheet1!J134). |
入库方式： OAI收割
来源：上海应用物理研究所
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