Evaluation of Time-dependent Cytochrome P450 inhibition Using the Fully-validated Area Under the Curve Shift Method

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April 30,2024

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Evaluation of the time-dependent inhibition (TDI) of cytochrome P450 (CYP) enzymesis very important during the drug discovery and development stages. Usually, TDI is studied by measuring the half-maximal inhibitory concentrations (IC₅₀) shift of a compound of interest after 30-min pre-incubation with human liver microsomes in the presence and absence of NADPH.Calculating an IC₅₀ shift is sometimes not available for the compound of interest with weak inhibitory effect o rsolubility limitations.To overcome the seobstacles, we introduce a fully validated quantitative way to assess magnitude of TDI with its cutoff value defined.

Evaluation of Time-dependent Cytochrome P450 inhibition Using the Fully-validated Area Under the Curve Shift Method.jpg

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