title: Predicting drug metabolism by cytochrome P450 2C9: comparison with the 2D6 and 3A4 isoforms.
abstract: By the use of knowledge gained through modeling of drug metabolism mediated by the cytochrome P450 2D6 and 3A4 isoforms, we constructed a 2D-based model for site-of-metabolism prediction for the cytochrome P450 2C9 isoform. The similarities and differences between the models for the 2C9 and 2D6 isoforms are discussed through structural knowledge from the X-ray crystal structures and trends in experimental data. The final model was validated on an independent test set, resulting in an area under the curve value of 0.92, and a site of metabolism was found among the top two ranked atoms for 77% of the compounds.
authors.affiliation: Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, Denmark. pry@farma.ku.dk
authors.forename: Patrik
authors.initials: P
authors.lastname: Rydberg
authors.forename: Lars
authors.initials: L
authors.lastname: Olsen
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D018360:Crystallography, X-Ray; D065729:Cytochrome P-450 CYP2C9; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000378:metabolism*
chemical_list: D008024:Ligands; D004364:Pharmaceutical Preparations; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A