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Pharmacophore modeling and virtual screening for the discovery of new fatty acid amide hydrolase inhibitors.
- Source :
- Acta Pharmaceutica Sinica B; Jun2011, Vol. 1 Issue 1, p27-35, 9p
- Publication Year :
- 2011
-
Abstract
- Abstract: A predictive pharmacophore model has been generated from a series of diverse fatty acid amide hydrolase (FAAH) inhibitors and the optimal pharmacophore model applied in virtual screening. The pharmacophore model was based on a training set of 21 compounds carefully selected from the published literatures. The optimal model Hypo-1 included four features (two hydrogen-bond acceptor units, one aromatic hydrophobic unit and one aromatic ring unit) and two excluded volumes. Cross-validation of the model confirmed that Hypo-1 was not generated by chance correlation. A large test set of 55 compounds showed that Hypo-1 performed well in classifying highly active and less active FAAH inhibitors. Superimposition analysis of the FAAH X-ray crystal structure and the pharmacophore Hypo-1 further validated the adequacy of the model. Virtual screening generated a total of 976 hits from the Zinc Natural Products database, a hit rate of 1.04% and enrichment of 83.89. The acceptable hit rate further supports the use of Hypo-1 as a 3D query tool for virtual screening. [Copyright &y& Elsevier]
- Subjects :
- FATTY acids
AMIDES
HYDROLASES
ENZYME inhibitors
HYDROGEN bonding
NATURAL products
Subjects
Details
- Language :
- English
- ISSN :
- 22113835
- Volume :
- 1
- Issue :
- 1
- Database :
- Supplemental Index
- Journal :
- Acta Pharmaceutica Sinica B
- Publication Type :
- Academic Journal
- Accession number :
- 65424480
- Full Text :
- https://doi.org/10.1016/j.apsb.2011.04.003