title: 3D-QSAR Based Pharmacophore Modeling and Virtual Screening for Identification of Novel G Protein-Coupled Receptor40 Agonists.
abstract: Pharmacophore models of G protein-coupled receptor40 (GPR40) agonists were developed using Discovery Studio V2.1. One hydrogen bond acceptor and three hydrophobic features, Hypo 1 which was the best hypothesis, had a correlation co-efficient of 0.971, cost difference of 73.041, and RMSD 0.680. This model was validated by test set, Fischer randomization test and decoy set. Subsequently, Hypo 1 was employed as a 3D query to identify potent molecules from chembridge database. 21 compounds were identified with estimated EC50 less than 500 nM. Seven top-scored hit compounds were chosen for further evaluation in FLIPR assay and two compounds were discovered as potent GPR40 agonists.
authors.forename: Peng
authors.initials: P
authors.lastname: Lu
authors.affiliation: Nanjing Sino-USA Cancer Research Center, School of Pharmaceutical Sciences, Nanjing Tech University, No. 5 Xinmofan Road,Nanjing 210009, People's Republic of China. wyb5393@163.com.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Wang
authors.forename: PingKai
authors.initials: P
authors.lastname: Ouyang
authors.forename: Jinxiong
authors.initials: J
authors.lastname: She
authors.forename: Mingfang
authors.initials: M
authors.lastname: He
mesh_terms: D000818:Animals; D016466:CHO Cells; D017076:Computer-Aided Design; D003412:Cricetulus; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism
chemical_list: C473034:FFAR1 protein, human; D043562:Receptors, G-Protein-Coupled