Background: Cytochrome P450 (CYP) enzymes are induced by some therapeutic drugs,
leading to interactions reducing drug plasma concentrations. Recently, an assessment of CYP induction
using messenger RNA (mRNA) levels has shown advantages over measurement of enzymatic activity;
it has a larger dynamic range of induction and enables us to measure the intrinsic induction potential of
time-dependent CYP inhibitors. In order to minimize the late-stage attrition of new chemical entities
(NCE), it is important to evaluate CYP induction potency at mRNA levels in the early stage of drug development.
Objectives: The aim of this study is to establish a new screening method to evaluate induction potency
of CYP1A2, CYP2B6, and CYP3A4 at mRNA levels.
Methods: QuantiGene Plex 2.0 Assay using HepaRG cells.
Results: The results from our new CYP induction assay system corresponded well to the already reported
results obtained by using human hepatocytes. The induction potency was evaluated by calculating
the concentration of test compounds that gives 10% of positive control response (R10), which is
measurable even when full dose-response curves cannot be obtained. Compared with the evaluation of
CYP induction in human hepatocytes, the response at R10 in HepaRG cells suggested the possibility of
exhibiting induction potency for corresponding CYPs. Interestingly, the results with our in-house 109
compounds showed that several compounds induced CYP1A2 or CYP2B6 expression without upregulation
Conclusion: Our developed assay system, as well as the R10 value, is useful for evaluating the CYP induction
potency of NCE in early drug discovery.