|
Activation of human and zebrafish PXRs by androstane and estrane steroids |
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| Cmp. # |
Compound |
hPXR Activity |
hPXR Efficacy |
zfPXR Activity |
zfPXR Efficacy |
Toxicity |
|
|
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| ANDROSTANES |
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| AN1 |
5α-Androstan-3α,17β-diol |
5.38 |
0.68 |
5.19 |
0.84 |
None |
| AN2 |
5α-Androstan-3,17-dione (androstanedione) |
4.90 |
0.87 |
5.50 |
0.86 |
None |
| AN3 |
5α-Androstan-3α-ol (androstanol) |
5.20 |
0.5 |
5.34 |
1.00 |
None |
| AN4 |
5α-Androstan-3α-ol-17-one (androsterone) |
4.73 |
0.93 |
5.60 |
0.87 |
None |
| AN5 |
5α-Androstan-17β-ol-3-one (dihydrotestosterone) |
4.94 |
0.39 |
5.21 |
0.59 |
None |
| AN6 |
5β-Androstan-3α-ol-17-one (etiocholanolone) |
5.24 |
0.54 |
5.47 |
0.88 |
200 |
| AN7 |
4-Androsten-3,17-dione (androstenedione) |
4.69 |
0.59 |
5.44 |
0.14 |
None |
| AN8 |
4-Androsten-17β-ol-3-one (testosterone) |
4.14 |
0.22 |
5.61 |
0.12 |
None |
| AN9 |
5-Androsten-3β-ol-17-one (DHEA) |
4.49 |
0.52 |
4.89 |
0.35 |
None |
| AN10 |
5α-Androst-16-en-3α-ol (androstenol) |
5.26 |
0.7 |
5.44 |
1.02 |
None |
| AN11 |
5β-Androstan-3α,11β-diol-17-one |
4.72 |
0.51 |
4.52 |
1.04 |
None |
| AN12 |
5-Androsten-3β-sulfate-17-one (DHEA sulfate) |
4.32 |
0.22 |
None |
None |
|
| AN13 |
5β-Androstan-3α-ol-17-one (epiandrosterone) |
5.31 |
0.7 |
5.02 |
0.43 |
None |
| AN14 |
5β-Androstan-3α-ol-11,17-dione |
4.39 |
0.15 |
5.01 |
0.49 |
None |
| AN15 |
4-Androsten-17α-ol-3-one (epitestosterone) |
4.17 |
0.9 |
None |
None |
|
| AN16 |
4-Androsten-17α-glucosiduronate-3-one (epitestosterone glucuronide) |
4.86 |
0.69 |
None |
None |
|
| AN17 |
4-Androsten-17α-sulfate-3-one (epitestosterone sulfate) |
5.47 |
0.67 |
None |
None |
|
| AN18 |
5β-Androstan-3α-glucosiduronate-17-one (etiocholanolone glucuronide) |
None |
None |
None |
||
| AN19 |
5α-Androstane |
None |
None |
100 |
||
| AN20 |
5α-Androstan-3β-ol |
6.10 |
0.43 |
5.57 |
1.66 |
50 |
| AN21 |
5α-Androst-16-en-3β-ol |
5.32 |
1.01 |
5.48 |
2.11 |
50 |
| AN22 |
5α-Androst-16-en-3-one |
5.52 |
0.96 |
5.58 |
0.68 |
100 |
| AN23 |
5β-Androstan-3α-ol |
5.85 |
1.12 |
5.59 |
0.33 |
None |
| AN24 |
Androst-4,16-dien-3-one |
5.15 |
0.64 |
5.96 |
0.17 |
100 |
| AN25 |
Androst-5,16-dien-3β-ol |
None |
5.60 |
1.50 |
100 |
|
| ESTRANES |
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| ES1 |
1,3,5(10)-Estratrien-3,17β-diol (estradiol) |
4.80 |
0.34 |
None |
200 |
|
| ES2 |
1,3,5(10)-Estratrien-3-ol-17-one (estrone) |
4.42 |
0.47 |
None |
200 |
|
| ES3 |
1,3,5(10)-Estratrien-3,16α,17β-triol (estriol) |
None |
None |
200 |
||
| ES4 |
1,3,5(10)-Estratrien-3,16α-diol-17-one (16α-hydroxyestrone) |
5.60 |
0.42 |
5.70 |
0.17 |
None |
| ES5 |
1,3,5(10)-Estratrien-3-ol-4-methoxy-17-one (4-methoxyestrone) |
5.40 |
0.93 |
5.62 |
0.19 |
None |
| ES6 |
1,3,5(10)-Estratrien-3,15α,16α,17β-tetrol (estetrol) |
5.67 |
0.29 |
None |
200 |
|
| ES7 |
1,3,5(10)-Estratrien-2,3-diol-17-one (2-hydroxyestrone) |
5.44 |
0.93 |
5.74 |
0.19 |
None |
| ES8 |
1,3,5(10)-Estratrien-17-one-3-sulfate (estrone sulfate) |
5.47 |
0.43 |
None |
None |
|
| ES9 |
1,3,5(10)-Estratrien-17β-ol-3-glucosiduronate (estradiol glucuronide) |
None |
None |
None |
||
| ES10 |
1,3,5(10)-Estratrien-17β-ol-3-sulfate (estradiol sulfate) |
6.05 |
0.6 |
None |
200 |
|
| ES11 |
1,3,5(10)-Estratrien-17α-ethinyl-3,17β-diol (ethinyl estradiol) |
5.72 |
0.68 |
None |
200 |
|
|
Activities are in -log(EC50), with EC50 in molar units for the activation of human or zebrafish PXR. Efficacy is relative to 10 μM rifampicin (human PXR) or 20 μM 5α-androstan-3α-ol (zebrafish PXR) which are assigned an efficacy of 1.0. Toxicity is the lowest concentration in micromolar that produced significant toxicity in the HepG2 cells. | ||||||
Ekins et al. BMC Evolutionary Biology 2008 8:103 doi:10.1186/1471-2148-8-103 |
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