Discovery of highly selective inhibitors of human fatty acid binding protein 4 (FABP4) by virtual screening

被引：31

作者：

Cai, Haiyan ^{[1
]}

Yan, Guirui ^{[1
]}

Zhang, Xiaodong ^{[1
]}

Gorbenko, Olena ^{[2
]}

Wang, Heyao ^{[1
]}

Zhu, Weiliang ^{[1
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China

[2] Inst Mol Biol & Genet NASU, Dept Cell Signaling, UA-03143 Kiev, Ukraine

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 12期

关键词：

FABP4; FABP3; Inhibitor; Selectivity; MD studies; Mutation; MOLECULAR-DYNAMICS; ACCURATE DOCKING; MULTIGENE FAMILY; AP2; ATHEROSCLEROSIS; PROGRAMS; GLIDE; AMBER;

D O I：

10.1016/j.bmcl.2010.04.095

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In this study, a series of small molecule inhibitors of human FABP4 were identified through virtual screening. Compound 1 is the most potent hit against FABP4 with a selectivity of more than 144-fold preferences over human FABP3. In addition, MD simulation and mutation studies revealed key residues for inhibitory potency and selectivity, which provides a guideline for further drug design against obesity, diabetes and atherosclerosis. (c) 2010 Elsevier Ltd. All rights reserved.

引用

页码：3675 / 3679

页数：5

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