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Table 1 Activation of human and zebrafish PXRs by androstane and estrane steroids

From: Evolution of pharmacologic specificity in the pregnane X receptor

Cmp. #

Compound

hPXR Activity

hPXR Efficacy

zfPXR Activity

zfPXR Efficacy

Toxicity

 

ANDROSTANES

     

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

     

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

  1. 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.