Molecular modeling aided design of nicotinic acid receptor GPR109A agonists.
Article Details
- CitationCopy to clipboard
Deng Q, Frie JL, Marley DM, Beresis RT, Ren N, Cai TQ, Taggart AK, Cheng K, Carballo-Jane E, Wang J, Tong X, Waters MG, Tata JR, Colletti SL
Molecular modeling aided design of nicotinic acid receptor GPR109A agonists.
Bioorg Med Chem Lett. 2008 Sep 15;18(18):4963-7. doi: 10.1016/j.bmcl.2008.08.030. Epub 2008 Aug 14.
- PubMed ID
- 18760600 [ View in PubMed]
- Abstract
A homology model of the nicotinic acid receptor GPR109A was constructed based on the X-ray crystal structure of bovine rhodopsin. An HTS hit was docked into the homology model. Characterization of the binding pocket by a grid-based surface calculation of the docking model suggested that a larger hydrophobic body plus a polar tail would improve interaction between the ligand and the receptor. The designed compounds were synthesized, and showed significantly improved binding affinity and activation of GPR109A.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Niacin Hydroxycarboxylic acid receptor 2 IC 50 (nM) 130 N/A N/A Details Niacin Hydroxycarboxylic acid receptor 2 EC 50 (nM) 1400 N/A N/A Details