HIGH THROUGHPUT REACTIVE OXYGEN SPECIES-BASED CYTOCHROME P450 INHIBITION ASSAY

摘要

A method of screening a candidate compound for an ability to inhibit a cytochrome P450. The method includes the steps of reacting the candidate compound, an indicator compound precursor, a cytochrome P450 substrate, and the cytochrome P450, the cytochrome P450 characterized as having a side reaction associated with metabolic activity of the cytochrome P450 wherein a chemical species capable of reacting with the indicator compound precursor is produced; quantifying the amount of indicator compound produced in the presence of the candidate compound, and comparing the amount of indicator compound produced in the presence of the candidate compound to an amount of indicator produced under identical conditions in the absence of the candidate compound, the comparison indicating the ability of the candidate compound to inhibit the cytochrome P450. Also disclosed is a method for determining an inhibitory potency of a candidate compound for a cytochrome P450.