Discovery of New Non-Steroidal Farnesoid X Receptor Modulators Through 3D Shape Similarity Search and Structure-Based Virtual Screening
文献类型：期刊论文
| 作者 | Wang, Lei1; Si, Pei2,3; Sheng, Yayun1; Chen, Yingjie1; Wan, Ping2; Shen, Xu3 ; Tang, Yun1; Chen, Lili3; Li, Weihua1
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| 刊名 | CHEMICAL BIOLOGY & DRUG DESIGN
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| 出版日期 | 2015-04 |
| 卷号 | 85期号:4页码:481-487 |
| 关键词 | farnesoid X receptor modulators similarity search virtual screening |
| ISSN号 | 1747-0277 |
| DOI | 10.1111/cbdd.12432 |
| 文献子类 | Article |
| 英文摘要 | As a ligand-activated transcriptional factor, farnesoid X receptor (FXR) has a variety of biological functions, such as biosynthesis of bile acids, metabolism of lipid, and glucose homeostasis, and thus is related to multiple diseases, especially metabolic syndrome. In this study, to discover new FXR modulators, we have designed a strategy by combining 3D shape similarity search and structure-based docking methods. Taking two FXR ligands that we previously reported as the reference molecules, virtual screening was performed against the Enamine database, and finally 59 compounds were selected for bioassay. Among them, four compounds exhibited agonistic or antagonistic activities against FXR in homogeneous time resolved fluorescence assay. Two of them were found to be new, potent FXR antagonists in cell-based assay with IC50 values of 8.39 and 6.53m, respectively. |
| WOS关键词 | BILE-ACID RECEPTOR ; ORPHAN NUCLEAR RECEPTOR ; FXR AGONIST ; GLUCOSE-HOMEOSTASIS ; FEEDBACK-REGULATION ; IDENTIFICATION ; POTENT ; ANTAGONISTS ; LIGANDS ; DERIVATIVES |
| 资助项目 | National Natural Science Foundation of China[81373328] ; National Natural Science Foundation of China[81173105] ; National Natural Science Foundation of China[81373462] ; National Natural Science Foundation of China[91213306] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000351181300008 |
| 出版者 | WILEY-BLACKWELL |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276594]  |
| 专题 | 生物技术药物研发中心（筹） 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 | Li, Weihua |
| 作者单位 | 1.E China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China; 2.Shanghai Normal Univ, Coll Life & Environm Sci, Shanghai 200234, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Lei,Si, Pei,Sheng, Yayun,et al. Discovery of New Non-Steroidal Farnesoid X Receptor Modulators Through 3D Shape Similarity Search and Structure-Based Virtual Screening[J]. CHEMICAL BIOLOGY & DRUG DESIGN,2015,85(4):481-487. |
| APA | Wang, Lei.,Si, Pei.,Sheng, Yayun.,Chen, Yingjie.,Wan, Ping.,...&Li, Weihua.(2015).Discovery of New Non-Steroidal Farnesoid X Receptor Modulators Through 3D Shape Similarity Search and Structure-Based Virtual Screening.CHEMICAL BIOLOGY & DRUG DESIGN,85(4),481-487. |
| MLA | Wang, Lei,et al."Discovery of New Non-Steroidal Farnesoid X Receptor Modulators Through 3D Shape Similarity Search and Structure-Based Virtual Screening".CHEMICAL BIOLOGY & DRUG DESIGN 85.4(2015):481-487. |
入库方式： OAI收割
来源：上海药物研究所
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