3D-QSAR based pharmacophore modeling and virtual screening for identification of novel G protein-coupled receptor40 agonists

Peng Lu, Yubin Wang, Ping Kai Ouyang, Jin-Xiong She, Mingfang He

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)51-56
Number of pages6
JournalCurrent Computer-Aided Drug Design
Volume11
Issue number1
DOIs
StatePublished - Jul 1 2015
Externally publishedYes

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Quantitative Structure-Activity Relationship
GTP-Binding Proteins
Random Allocation
Hydrogen
Databases
Costs and Cost Analysis

Keywords

  • 3D-QSAR-pharmacophore
  • Discovery studio
  • GPR40 agonists
  • HypoGen
  • Virtual screening

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

3D-QSAR based pharmacophore modeling and virtual screening for identification of novel G protein-coupled receptor40 agonists. / Lu, Peng; Wang, Yubin; Ouyang, Ping Kai; She, Jin-Xiong; He, Mingfang.

In: Current Computer-Aided Drug Design, Vol. 11, No. 1, 01.07.2015, p. 51-56.

Research output: Contribution to journalArticle

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