CYP Inhibition Assays
CYP inhibition studies are an essential part of drug discovery to evaluate and predict in vivo drug-drug interactions.
Inhibition of cytochrome P450 catalytic activity is a leading mechanism of metabolism-based drug-drug interactions. Many DDI-related pre-clinical/clinical failures to date have been attributed to CYP-related hepatic metabolism. Hence it has become essential to screen compounds in early drug discovery to monitor their in vitro inhibition of the major CYP isoforms and predict their in vivo effects.
Catalytic activities of various CYP isoforms are measured by incubating isoform-specific drug substrates in human liver microsomes in the presence of NADPH. All QDI CYP inhibition assays utilize drug substrates and monitor specific drug metabolites that are recommended by the FDA and EMA.
CYP Inhibition: Standard Assay Conditions (Customizable)
CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 (other isoforms, such as CYP2E1, are available)
Pooled Whole Human Liver Microsomes
CYP1A2-Tacrine (only for RapidFire-MS/MS)
Testing Compound Concentration
0, 0.2, 0.5, 1.3, 3.2, 8, 20, 50 μM
Specific metabolites by LC-MS/MS or RapidFire-MS/MS
IC50, Standard error of IC50, Report
100 μL 50 mM DMSO stock or 1-2 mg solid