title: Discovery of highly selective inhibitors of human fatty acid binding protein 4 (FABP4) by virtual screening.
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.
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Cai
authors.forename: Guirui
authors.initials: G
authors.lastname: Yan
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.forename: Olena
authors.initials: O
authors.lastname: Gorbenko
authors.forename: Heyao
authors.initials: H
authors.lastname: Wang
authors.forename: Weiliang
authors.initials: W
authors.lastname: Zhu
mesh_terms: 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
chemical_list: C493408:FABP3 protein, human; C493410:FABP4 protein, human; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D009930:Organic Chemicals