title: The first pharmacophore model for potent G protein-coupled receptor 119 agonist.
abstract: G protein-coupled receptor 119 (GPR119) has emerged as arguably one of the most exciting targets for the treatment of type 2 diabetes mellitus in the new millennium. Pharmacophore models were developed by using Discovery Studio V2.1 with a training set of 24 GPR119 agonists. The best hypothesis consisting of five features, namely, two hydrogen bond acceptors and three hydrophobic features, has a correlation coefficient of 0.969, cost difference of 62.68, RMS of 0.653, and configuration cost of 15.24, suggesting that a highly predictive pharmacophore model was successfully obtained. The application of the model shows great success in predicting the activities of the 25 known GPR119 agonists in our test set with a correlation coefficient of 0.933.
authors.affiliation: Centre of Drug Discovery, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu 210009, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Zhu
authors.forename: Dandan
authors.initials: D
authors.lastname: Huang
authors.forename: Xiaobu
authors.initials: X
authors.lastname: Lan
authors.forename: Chunlei
authors.initials: C
authors.lastname: Tang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Jing
authors.initials: J
authors.lastname: Han
authors.forename: Wenlong
authors.initials: W
authors.lastname: Huang
authors.forename: Hai
authors.initials: H
authors.lastname: Qian
mesh_terms: D055808:Drug Discovery; D057166:High-Throughput Screening Assays; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D007004:Hypoglycemic Agents / Q000737:chemistry*; D062105:Molecular Docking Simulation; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000737:chemistry; D054852:Small Molecule Libraries / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014584:User-Computer Interface
chemical_list: C519854:GPR119 protein, human; D007004:Hypoglycemic Agents; D043562:Receptors, G-Protein-Coupled; D054852:Small Molecule Libraries