The first pharmacophore model for potent G protein-coupled receptor 119 agonist

Eur J Med Chem. 2011 Jul;46(7):2901-7. doi: 10.1016/j.ejmech.2011.04.014. Epub 2011 Apr 13.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Discovery
  • High-Throughput Screening Assays
  • Humans
  • Hydrogen Bonding
  • Hydrophobic and Hydrophilic Interactions
  • Hypoglycemic Agents / chemistry*
  • Molecular Docking Simulation*
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / chemistry
  • Small Molecule Libraries / chemistry*
  • Structure-Activity Relationship
  • User-Computer Interface


  • GPR119 protein, human
  • Hypoglycemic Agents
  • Receptors, G-Protein-Coupled
  • Small Molecule Libraries