Table 1. Biological characterization of compound 1, 2 and abiraterone in the isolated human CYP17A, in the H295R cell system and their selectivity profiles against other CYPs.
| Compound | Kd [nM]a | Purified CYP17A1 |
H295R system |
Selectivity |
||||
|---|---|---|---|---|---|---|---|---|
| IC50 [nM]c |
IC50 [nM]d |
UV-VIS spectral shift |
||||||
| hydroxylase | lyase | hydroxylasee | lyasef | CYP 3A4 | CYP 2D6 | CYP 21A2 | ||
| 1 | ≪100b | 230 ± 20 | 500 ± 90 | 830 ± 80 | 94 ± 30 | − | − | − |
| 2 | ≪100b | 130 ± 10 | 110 ± 20 | 52 ± 4 | 7.4 ± 0.1 | − | − | − |
| abiraterone | ≪100b | 92 ± 4 | 36 ± 2 | 9.4 ± 0.3 | 1.7 ± 0.1 | + | + | + |
aBinding measurements with UV-VIS. Mean value over 2 measurements ± standard error.
bThe measurement suffers of intrinsic inaccuracy because of the Kd value smaller than the lowest protein concentration at which the titration can be performed with acceptable signal: noise (100 nM).
cInhibition measurements in recombinant CYP17A1. Mean value over 3 measurements ± standard error. Assays based on the conversion of PRO to 17-OH-PRO and 17-OH-PRE into DHEA for hydroxylase and lyase, respectively.
dInhibition in H295R cells. Mean value over 6 to 15 measurements ± standard error.
eBased on the conversion of PRE into 17-OH-PRE.
fBased on the conversion of 17-OH-PRE into DHEA. Abbreviations are defined in Fig. 1.