Rapid mRNA Induction Screen

Rapid mRNA Induction Screen

Published:  06 February 2015

A Rapid High Content Cytochrome P450 (CYP) mRNA Induction Screen for Early Drug Development

Cytochrome P450 (CYP) enzymes play an important role in the oxidative metabolism of many drugs. Consequently, inhibition or induction of these enzymes by perpetrator drugs can result in alterations in the clearance of a victim drug that is metabolized by CYP pathways (i.e. drug-drug interactions; DDIs). The induction of CYP enzymes, which results in elevated CYP expression levels, can lead to an increase in the clearance of a victim drug resulting in potential loss of drug efficacy. Thus, characterizing a new drug's CYP induction potential early in drug development can lead to better and safer drug design. In the present study, we developed a rapid CYP induction screen evaluating up to 10 compounds in one assay (at three concentrations, with an additional positive control) with the fold change of CYP3A4 mRNA expression levels measured as an endpoint.