Discovery of new non-steroidal FXR ligands via a virtual screening workflow based on Phase shape and induced fit docking

doi:10.1016/j.bmcl.2012.09.045

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 生物技术药物研发中心（筹）

	Discovery of new non-steroidal FXR ligands via a virtual screening workflow based on Phase shape and induced fit docking
	Fu, Jing 3; Si, Pei 1; Zheng, Mingyue2 ; Chen, Lili2 ; Shen, Xu2 ; Tang, Yun 3; Li, Weihua 2,3
刊名	BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
	2012-11-15
卷号	22 期号:22 页码:6848-6853
关键词	FXR Phase shape Docking Ligands Virtual screening
ISSN号	0960-894X
DOI	10.1016/j.bmcl.2012.09.045
文献子类	Article
英文摘要	Farnesol X receptor (FXR) is a member of the metabolic nuclear receptor (NR) superfamily of regulatory proteins. FXR was recognized to be a transcriptional sensor for bile acids, and now it has been shown that activating FXR has important roles in controlling bile acid homeostasis, lipoprotein and glucose metabolism, and hepatic regeneration. For the sake of discovering new, potent non-steroidal FXR ligands, we have established a virtual screening workflow by using Phase Shape and induced fit docking (IFD). Phase shape was performed based on a combination of shape-only and atom types or pharmacophore modes. The results indicated that the pharmacophore mode yielded the best result for our system. The best receptor model was chosen by evaluating the cross-IFD models induced by three crystal structures 3DCT, 3FLI and 3OKI. The Enamine database was screened by the proposed workflow and 50 molecules were selected and purchased for bioassays. Among them, two compounds were found to be the new, potent FXR ligands in cell-based assay. (C) 2012 Elsevier Ltd. All rights reserved.
资助项目	National Natural Science Foundation of China[81173105] ; National Natural Science Foundation of China[30890044] ; National Natural Science Foundation of China[21072059] ; State Key Laboratory of Drug Research[SIMM1106-KF-07] ; Shanghai Committee of Science and Technology[11DZ2260600] ; Foundation of Chinese Academy of Sciences[KSCX2-EW-Q-3] ; 863 project[2012AA0200-308]
WOS关键词	FARNESOID-X-RECEPTOR ; ORPHAN NUCLEAR RECEPTOR ; BILE-ACIDS ; IDENTIFICATION ; POTENT ; ANTAGONISTS ; ACTIVATION ; AGONIST
WOS研究方向	Pharmacology & Pharmacy ; Chemistry
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000310353700013
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277875]
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	Chen, Lili
作者单位	1.Shanghai Normal Univ, Coll Life & Environm Sci, Shanghai 200234, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 3.E China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China
推荐引用方式 GB/T 7714	Fu, Jing,Si, Pei,Zheng, Mingyue,et al. Discovery of new non-steroidal FXR ligands via a virtual screening workflow based on Phase shape and induced fit docking[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2012,22(22):6848-6853.
APA	Fu, Jing.,Si, Pei.,Zheng, Mingyue.,Chen, Lili.,Shen, Xu.,...&Li, Weihua.(2012).Discovery of new non-steroidal FXR ligands via a virtual screening workflow based on Phase shape and induced fit docking.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,22(22),6848-6853.
MLA	Fu, Jing,et al."Discovery of new non-steroidal FXR ligands via a virtual screening workflow based on Phase shape and induced fit docking".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 22.22(2012):6848-6853.