Binding of CYP2C9 with diverse drugs and its implications for metabolic mechanism.

Article Details

Citation

Wang JF, Yan JY, Wei DQ, Chou KC

Binding of CYP2C9 with diverse drugs and its implications for metabolic mechanism.

Med Chem. 2009 May;5(3):263-70.

PubMed ID
19442216 [ View in PubMed
]
Abstract

Cytochrome P450 2C9 (CYP2C9) is an important member of the cytochrome P450 enzyme superfamily with responsibility for metabolizing many important exogenous and endogenous compounds in many species of microorganisms, plants and animals. CYP2C9 is related to the oxidative of 16% of all therapeutics in current clinical use and has adverse drug effects, such as, enzyme induction and inhibition. In order to understand the metabolic mechanism of various drugs, two crystal structures of CYP2C9 have been studied, and their structural differences and structure-activity relationships with the drugs of Fluoxetine, Ibuprofen, Naproxen, Suprofen, and Mefenamic acid were investigated. By a series of docking studies and MD simulations, the binding pockets of CYP2C9 for the five drugs are explicitly defined that will be very useful for conducting mutagenesis studies, providing insights into the metabolic mechanism, which may be of relevance to the personalized drug.

DrugBank Data that Cites this Article

Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
FluoxetineCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Inhibitor
Details
Mefenamic acidCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Inhibitor
Details
SuprofenCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Inhibitor
Details
Drug Interactions
DrugsInteraction
Fluoxetine
Peginterferon alfa-2b
The serum concentration of Fluoxetine can be decreased when it is combined with Peginterferon alfa-2b.