Potent and novel 11 beta-HSD1 inhibitors identified from shape and docking based virtual screening

doi:10.1016/j.bmcl.2011.08.019

	Potent and novel 11 beta-HSD1 inhibitors identified from shape and docking based virtual screening
	Xia, Guangxin 1,2; Xue, Mengzhu 2; Liu, Lin 1; Yu, Jianxin 1; Liu, Haiyan 1; Li, Ping 1; Wang, Jianfa 1; Li, Yanlian 2; Xiong, Bing2 ; Shen, Jingkang 1,2
刊名	BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
	2011-10-01
卷号	21 期号:19 页码:5739-5744
关键词	11 beta-HSD1 inhibitor Virtual screening Docking Shape similarity
ISSN号	0960-894X
DOI	10.1016/j.bmcl.2011.08.019
文献子类	Article
英文摘要	Several potent and novel 11 beta-hydroxysteroid dehydrogenase 1 (11 beta-HSD1) inhibitors were discovered from in silico screening the commercially available Maybridge database. Among them, seven hit compounds showed good affinity, with IC(50) values lower than 100 nM and the best one 3.7 nM. To select the lead for further optimization, computational ADME/T prediction, the CYP3A4 inhibition and 11 beta-HSD1 over 11 beta-HSD2 selectivity test were also performed. Taking all of the above factors into consideration, two promising compounds were selected as lead structures for further development. The employed hierarchical virtual screening protocol not only demonstrates its efficiency, but also provides novel and selective compounds for developing 11 beta-HSD1 inhibitors to protect against metabolic syndrome. (C) 2011 Elsevier Ltd. All rights reserved.
资助项目	Shanghai Postdoctoral Sustentation Fund[07R214213] ; State Key Program of Basic Research of China[009CB918502]
WOS关键词	11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1 ; METABOLIC SYNDROME ; SELECTIVE INHIBITORS ; DISCOVERY ; DISEASE ; DRUGS
WOS研究方向	Pharmacology & Pharmacy ; Chemistry
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000294714400016
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278394]
专题	药物化学研究室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	Xiong, Bing
作者单位	1.Shanghai Pharmaceut Holding Co Ltd, Cent Res Inst, Shanghai 201203, Peoples R China; 2.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	Xia, Guangxin,Xue, Mengzhu,Liu, Lin,et al. Potent and novel 11 beta-HSD1 inhibitors identified from shape and docking based virtual screening[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2011,21(19):5739-5744.
APA	Xia, Guangxin.,Xue, Mengzhu.,Liu, Lin.,Yu, Jianxin.,Liu, Haiyan.,...&Shen, Jingkang.(2011).Potent and novel 11 beta-HSD1 inhibitors identified from shape and docking based virtual screening.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,21(19),5739-5744.
MLA	Xia, Guangxin,et al."Potent and novel 11 beta-HSD1 inhibitors identified from shape and docking based virtual screening".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 21.19(2011):5739-5744.