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Updated: Apr 11, 2026

Quantifying Agonist Activity at G Protein-coupled Receptors
Published on: December 26, 2011
3D-QSAR Based Pharmacophore Modeling and Virtual Screening for Identification of Novel G Protein-Coupled Receptor40
Peng Lu, Yubin Wang1, PingKai Ouyang
1Nanjing 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.
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.
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