title: Cytochrome P450 inhibition assays using traditional and fluorescent substrates.
abstract: A key liability in transitioning a new chemical entity (NCE) to a development candidate is NCE-related inhibition (or induction) of cytochrome P450 enzymes, a superfamily of heme-containing oxygenases that are the major route of first-pass metabolism for the majority of marketed drugs. The drawback of a drug/NCE that modulates CYP450 enzyme activity occurs when the compound is co-administered with another drug that relies on the same P450 enzyme for its metabolism. This could result in overdose of the second drug in the case of inhibition, or more rapid metabolism of one or both drugs accompanied by loss of efficacy in the case of enzyme induction. Screening for the inhibition of CYP450 enzymes is now routine in the early stages of evaluating NCEs. This unit describes two inhibition assays using traditional and fluorescent substrates.
authors.affiliation: Surface Logix, Inc., Brighton, Massachusetts, USA.
authors.forename: Elsa
authors.initials: E
authors.lastname: Paradise
authors.forename: Prasoon
authors.initials: P
authors.lastname: Chaturvedi
authors.forename: Elena
authors.initials: E
authors.lastname: Ter-Ovanesyan
mesh_terms: D002851:Chromatography, High Pressure Liquid; D065607:Cytochrome P-450 Enzyme Inhibitors; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005453:Fluorescence; D013379:Substrate Specificity; D053719:Tandem Mass Spectrometry
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors