Novel (Q)SAR models for prediction of reversible and time-dependent inhibition of cytochrome P450 enzymes.

ABSTRACT: The 2020 FDA drug-drug interaction (DDI) guidance includes a consideration for metabolites with structural alerts for potential mechanism-based inhibition (MBI) and describes how this information may be used to determine whether in vitro studies need to be conducted to evaluate the inhibitory potential of a metabolite on CYP enzymes. To facilitate identification of structural alerts, an extensive literature search was performed and alerts for mechanism-based inhibition of cytochrome P450 enzymes (CYP) were collected. Furthermore, five quantitative structure-activity relationship (QSAR) models were developed to predict not only time-dependent inhibition of CYP3A4, an enzyme that metabolizes approximately 50% of all marketed drugs, but also reversible inhibition of 3A4, 2C9, 2C19 and

SUBMITTER: Faramarzi S 

PROVIDER: S-EPMC11860084 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature