Characterization of a novel non-steroidal glucocorticoid receptor antagonist
文献类型：期刊论文
| 作者 | Li, Qun-Yi3,4; Zhang, Meng3,4; Hallis, Tina M.1; DeRosier, Therese A.1; Yue, Jian-Min4 ; Ye, Yang4; Mais, Dale E.2,3; Wang, Ming-Wei3,4
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| 刊名 | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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| 出版日期 | 2010-01-15 |
| 卷号 | 391期号:3页码:1531-1536 |
| 关键词 | Nuclear receptor Glucocorticoid Antagonist Gluconeogenesis |
| ISSN号 | 0006-291X |
| DOI | 10.1016/j.bbrc.2009.12.117 |
| 文献子类 | Article |
| 英文摘要 | Selective antagonists of the glucocorticoid receptor (GR) are desirable for the treatment of hypercortisolemia associated with Cushing's syndrome, psychic depression, obesity, diabetes, neurodegenerative diseases, and glaucoma. NC3327, a non-steroidal small molecule with potent binding affinity to GR (K-i = 13.2 nM), was identified in a high-throughput screening effort. As a full GR antagonist, NC3327 greatly inhibits the dexamethasone (Dex) induction of marker genes involved in hepatic gluconeogenesis, but has a minimal effect on matrix metalloproteinase 9 (MMP-9), a GR responsive pro-inflammatory gene. Interestingly, the compound recruits neither coactivators nor corepressors to the GR complex but competes with glucocorticoids for the interaction between GR and a coactivator peptide. Moreover, NC3327 does not trigger GR nuclear translocation, but significantly blocks Dex-induced GR transportation to the nucleus, and thus appears to be a 'competitive' GR antagonist. Therefore, the non-steroidal compound, NC3327, may represent a new class of GR antagonists as potential therapeutics for a variety of cortisol-related endocrine disorders. (c) 2009 Elsevier Inc. All rights reserved. |
| WOS关键词 | MECHANISMS ; MODULATORS ; LIGANDS ; RU486 |
| 资助项目 | Ministry of Science and Technology of China[2004CB518902] ; Shanghai Municipality Government[08DZ2291300] ; Invitrogen Corporation[00000000] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Biophysics |
| 语种 | 英语 |
| WOS记录号 | WOS:000274097800043 |
| 出版者 | ACADEMIC PRESS INC ELSEVIER SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278993]  |
| 专题 | 国家新药筛选中心 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 | Wang, Ming-Wei |
| 作者单位 | 1.Invitrogen, Cell Syst Div, Madison, WI USA; 2.MPI Res, Mattawan, MI USA 3.Natl Ctr Drug Screening, Shanghai 201203, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 200031, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Li, Qun-Yi,Zhang, Meng,Hallis, Tina M.,et al. Characterization of a novel non-steroidal glucocorticoid receptor antagonist[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2010,391(3):1531-1536. |
| APA | Li, Qun-Yi.,Zhang, Meng.,Hallis, Tina M..,DeRosier, Therese A..,Yue, Jian-Min.,...&Wang, Ming-Wei.(2010).Characterization of a novel non-steroidal glucocorticoid receptor antagonist.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,391(3),1531-1536. |
| MLA | Li, Qun-Yi,et al."Characterization of a novel non-steroidal glucocorticoid receptor antagonist".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 391.3(2010):1531-1536. |
入库方式： OAI收割
来源：上海药物研究所
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