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

Haiyan Cai; Guirui Yan; Xiaodong Zhang; Olena Gorbenko; Heyao Wang; Weiliang Zhu

doi:10.1016/j.bmcl.2010.04.095

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

Bioorg Med Chem Lett. 2010 Jun 15;20(12):3675-9. doi: 10.1016/j.bmcl.2010.04.095. Epub 2010 Apr 24.

Authors

Haiyan Cai¹, Guirui Yan, Xiaodong Zhang, Olena Gorbenko, Heyao Wang, Weiliang Zhu

Affiliation

¹ Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.

PMID: 20471252
DOI: 10.1016/j.bmcl.2010.04.095

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Atherosclerosis / drug therapy
Binding Sites
Computer Simulation*
Diabetes Mellitus / drug therapy
Drug Discovery
Drug Evaluation, Preclinical / methods
Fatty Acid Binding Protein 3
Fatty Acid-Binding Proteins / antagonists & inhibitors*
Fatty Acid-Binding Proteins / chemistry
Fatty Acid-Binding Proteins / genetics
Humans
Mutation
Obesity / drug therapy
Organic Chemicals / chemistry
Organic Chemicals / pharmacology
Protein Binding / genetics
Structure-Activity Relationship
Substrate Specificity

Substances

FABP3 protein, human
FABP4 protein, human
Fatty Acid Binding Protein 3
Fatty Acid-Binding Proteins
Organic Chemicals