Figure 4. Concentration-dependent inhibition of CYP3A4 by TRAM-34 with LVS as substrate.

Recombinant enzyme CYP3A4, LVS and varying concentrations of TRAM-34 were incubated according to the methods described. Percent control enzyme activity (ordinate) is plotted versus the log of inhibitor concentration (abscissa). The formation of two LVS metabolites (in brackets) by CYP3A4 is shown. All TRAM-34 data points represent the mean ± SEM of 3 experiments performed in duplicate. The TRAM-34 IC₅₀ values were determined by non-linear regression and are shown in parentheses. Ketoconazole (10 µM) inhibited the formation of both metabolites by greater than 85% (not shown).