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Predicting Drug Metabolism by Cytochrome P450 2C9: Comparison with the 2D6 and 3A4 Isoforms
Author(s) -
Rydberg Patrik,
Olsen Lars
Publication year - 2012
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201200160
Subject(s) - cytochrome p450 , gene isoform , drug metabolism , cyp3a4 , cyp2d6 , drug , metabolism , isozyme , cytochrome , computational biology , chemistry , biochemistry , biology , pharmacology , enzyme , gene
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.