Discovery of highly selective inhibitors of human fatty acid binding protein 4 (FABP4) by virtual screening.
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.
Cai
Haiyan
H
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Yan
Guirui
G
Zhang
Xiaodong
X
Gorbenko
Olena
O
Wang
Heyao
H
Zhu
Weiliang
W
D050197:Atherosclerosis / Q000188:drug therapy; D001665:Binding Sites; D003198:Computer Simulation; D003920:Diabetes Mellitus / Q000188:drug therapy; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical / Q000379:methods; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D006801:Humans; D009154:Mutation; D009765:Obesity / Q000188:drug therapy; D009930:Organic Chemicals / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding / Q000235:genetics; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
C493408:FABP3 protein, human; C493410:FABP4 protein, human; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D009930:Organic Chemicals