CYP inhibition, direct

CYP activity is measured by incubating the test compound with human liver microsomes and a cocktail of CYP-specific substrates (1A2, 2B6, 2C8, 2C9, 2D6, 2C19 and 3A) in the presence of NADPH. Direct inhibition is observed as reduced level of CYP-specific metabolite formation in the incubations compared to solvent samples (IC50 determination).
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Test concentrations: 6

Time points: 1

Replicates: 2

Positive controls

UPLC/MS/MS analysis

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Direct inhibition as % inhibition or as IC50 for each CYP, tentative Ki values

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Excel report
(full report available per request)

Background

Inhibition of cytochrome P450 (CYP) enzymes by a new chemical entity (NCE) may decrease the metabolism of co-medicated drugs. We offer assays for individual enzymes as well as a cocktail approach to determine inhibition towards multiple enzymes in the same incubation. Liver microsomes are recommended for high-throughput screenings and for mechanistic approach. In addition, CYP inhibition evaluation can be conducted using pooled hepatocytes, for compounds where hepatocytes are a better suited model.

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