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. 2020 Sep;374(3):438–451. doi: 10.1124/jpet.120.265868

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Fig. 2. — Preincubation time-dependent inhibition of CYP17A1 by abiraterone and D4A. Semilogarithmic plots illustrate time- and concentration-dependent inhibition of CYP17A1 by (A and B) abiraterone or (E and F) D4A using progesterone and 17α-hydroxypregnenolone as probe substrates for 17α-hydroxyprogesterone and dehydroepiandrosterone formation, respectively. The relationship between the observed first-order rate constants for the onset of inhibition ( values determined from (A, B, E, and F) and inhibitor concentration was further investigated in (C, D, G, and H), and data were subsequently fitted to eq. 3a to calculate the forward ( and reverse isomerization constants via nonlinear regression analysis. Goodness of fits (R²) for (C, D, G, and H) were determined to be 0.984, 0.984, 0.986, and 0.996, respectively. Each point in the semilogarithmic plots represents the mean ± S.D. of triplicate determinations.

Inline graphic — Preincubation time-dependent inhibition of CYP17A1 by abiraterone and D4A. Semilogarithmic plots illustrate time- and concentration-dependent inhibition of CYP17A1 by (A and B) abiraterone or (E and F) D4A using progesterone and 17α-hydroxypregnenolone as probe substrates for 17α-hydroxyprogesterone and dehydroepiandrosterone formation, respectively. The relationship between the observed first-order rate constants for the onset of inhibition ( values determined from (A, B, E, and F) and inhibitor concentration was further investigated in (C, D, G, and H), and data were subsequently fitted to eq. 3a to calculate the forward ( and reverse isomerization constants via nonlinear regression analysis. Goodness of fits (R²) for (C, D, G, and H) were determined to be 0.984, 0.984, 0.986, and 0.996, respectively. Each point in the semilogarithmic plots represents the mean ± S.D. of triplicate determinations.