Journal article
A Refined 3-Dimensional QSAR of Cytochrome P450 2C9: Computational Predictions of Drug Interactions
Journal of medicinal chemistry, Vol.43(15), pp.2789-2796
07/27/2000
Handle:
https://hdl.handle.net/2376/113363
PMID: 10956186
Abstract
A ligand-based model is reported that predicts the K i values for cytochrome P450 2C9 (CYP2C9) inhibitors. This CoMFA model was used to predict the affinity of 14 structurally diverse compounds not in the training set and appears to be robust. The mean error of the predictions is 6 μM. The experimentally measured K i values of the 14 compounds range from 0.1 to 48 μM. Leave-one-out cross-validated partial least-squares gives a q 2 value of between 0.6 and 0.8 for the various models which indicates internal consistency. Random assignment of biological data to structure leads to negative q 2 values. These models are useful in that they establish a pharmacophore for binding to CYP2C9 that can be tested with site-directed mutagenesis. These models can also be used to screen for potential drug interactions and to design compounds that will not bind to this enzyme with high affinity.
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Details
- Title
- A Refined 3-Dimensional QSAR of Cytochrome P450 2C9: Computational Predictions of Drug Interactions
- Creators
- Sreedhara RaoRon AoyamaMichael SchragWilliam F TragerAllan RettieJeffrey P Jones
- Publication Details
- Journal of medicinal chemistry, Vol.43(15), pp.2789-2796
- Academic Unit
- Chemistry, Department of
- Publisher
- American Chemical Society
- Identifiers
- 99900547847301842
- Language
- English
- Resource Type
- Journal article