TABLE 5

Parsing rationale for substrate and inhibitors

CategoryClearance/P450-GloClassificationParsing Rationale
1+/+SubstrateExhibiting activity in both assays, the compound is a clear ligand for the enzyme(s). It is unclear whether the parent, product, or both are responsible for the inhibition.
2−/+InhibitorThe compound is able to inhibit the enzyme metabolism of a probe substrate but is not itself cleared, indicating that the parent molecule is an effective inhibitor.
3−/−NoncompetitorThe lack of activity in both assays signifies either that binding does not occur or that the interaction does not generate a catalytically competent or inhibitory complex.
4+/−SubstrateAlthough a clear substrate, the binding kinetics of the parent compound and its metabolites do not preclude the concomitant metabolism of the P450-Glo probe.