Discovery of highly potent TNF alpha inhibitors using virtual screen
文献类型：期刊论文
| 作者 | Shen, Qi1; Chen, Jing1,2; Wang, Qian2; Deng, Xiaobing3; Liu, Ying1,2; Lai, Luhua1,2,3 |
| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2014-10-06 |
| 卷号 | 85页码:119-126 |
| 关键词 | Tnf Alpha Virtual Screen Small Molecule Inhibitors |
| ISSN号 | 0223-5234 |
| DOI | 10.1016/j.ejmech.2014.07.091 |
| 英文摘要 | Tumor necrosis factor-alpha (TNF alpha) is a validated therapeutic target for various autoimmune disorders such as rheumatoid arthritis and asthma. All TNF alpha inhibitors currently on the market are biologics, making the development of small molecule alternatives in urgent need. However, only a few successful cases of direct TNF alpha antagonization in vitro have been reported. Here, we present the identification of several small molecule candidates able to effectively reduce TNF alpha activity in vitro and in cell assays. Virtual screen targeting TNF alpha dimer was performed on the SPECS database and 101 compounds were selected for experimental testing. Two compounds, 1 and 2, displayed considerable inhibitory activity. Follow-up structure-activity relationship analysis of compound 1 identified 3 molecules with low micromolar cell-level inhibitory activity. Compound 11 showed an IC50 value of 14 mu M, making it among the most potent TNFa small molecule inhibitors reported. These compounds provide new scaffolds for future development of small molecule drugs against TNF alpha. (C) 2014 Elsevier Masson SAS. All rights reserved. |
| 语种 | 英语 |
| WOS记录号 | WOS:000342859700011 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://ir.iccas.ac.cn/handle/121111/51663]  |
| 专题 | 中国科学院化学研究所 |
| 通讯作者 | Lai, Luhua |
| 作者单位 | 1.Peking Univ, Ctr Quantitat Biol, Beijing 100871, Peoples R China 2.Peking Univ, Coll Chem & Mol Engn, State Key Lab Struct Chem Unstable & Stable Speci, BNLMS, Beijing 100871, Peoples R China 3.Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China |
| 推荐引用方式 GB/T 7714 | Shen, Qi,Chen, Jing,Wang, Qian,et al. Discovery of highly potent TNF alpha inhibitors using virtual screen[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2014,85:119-126. |
| APA | Shen, Qi,Chen, Jing,Wang, Qian,Deng, Xiaobing,Liu, Ying,&Lai, Luhua.(2014).Discovery of highly potent TNF alpha inhibitors using virtual screen.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,85,119-126. |
| MLA | Shen, Qi,et al."Discovery of highly potent TNF alpha inhibitors using virtual screen".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 85(2014):119-126. |
入库方式： OAI收割
来源：化学研究所
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