Table 2

Activation of human and zebrafish PXRs by pregnane steroids and related compounds
Cmp. #
 Compound
 hPXR Activity
 hPXR Efficacy
 zfPXR Activity
 zfPXR Efficacy
 Toxicity
PR1
 5β-Pregnan-3α,20α-diol (5β-pregnanediol)
 5.29
 0.34
 None
100
PR2
 5β-Pregnan-3,20-dione (5β-pregnanedione)
 5.59
 0.97
 6.08
 0.85
 None
PR3
 4-Pregnen-11β,21-diol-3,20-dione (corticosterone)
 5.00
 0.54
 None
None
PR4
 4-Pregnen-17,21-diol-3,20-dione (cortexolone)
 4.64
 0.49
 None
None
PR5
 4-Pregnen-11β,21-diol-3,18,20-trione (aldosterone)
 4.26
 0.21
 None
None
PR6
 4-Pregnen-17,21-diol-3,11,20-trione (cortisone)
 4.16
 0.28
 None
200
PR7
 4-Pregnen-3,20-dione (progesterone)
 4.83
 0.57
 None
200
PR8
 4-Pregnen-17-ol-3,20-dione
 4.75
 0.7
 None
None
PR9
 4-Pregnen-21-ol-3,20-dione (cortexone)
 5.61
 0.3
 None
200
PR10
 4-Pregnen-3β,17,21-triol-3,20-dione (cortisol)
 4.32
 0.66
 None
None
PR11
 5-Pregnen-3β,17-diol-20-one
 4.47
 0.36
 None
None
PR12
 5-Pregnen-3β-diol-20-one (pregnenolone)
 5.64
 1.26
 6.32
 2.05
 None
PR13
 5-Pregnen-16α-cyano-3β-ol-20-one
 None
None
None
PR14
 5α-Pregnan-3α-ol-20-one (allopregnanolone)
 5.38
 0.46
 5.40
 0.30
 None
PR15
 5α-Pregnan-3α,20α-diol (allopregnanediol)
 4.28
 0.16
 4.58
 0.29
 None
PR16
 5β-Pregnan-3α,20α-diol-3-glucosiduronate (pregnanediol glucuconide)
 4.26
 0.17
 4.78
 1.42
 None
PR17
 5β-Pregnan-3α,11β,17,20α-21-pentol (cortol)
 4.33
 0.83
 3.95
 0.98
 200
PR18
 5β-Pregnan-3α,17,20α-21-tetrol-11-one (cortolone)
 4.35
 0.72
 4.34
 0.25
 200
PR19
 5β-Pregnan-3α,17,21-triol-11,20-dione
 4.28
 0.8
 4.43
 0.33
 None
PR20
 5α-Pregnan-3α,11β,21-triol-20-one
 4.90
 0.26
 None
None
PR21
 4-Pregnen-17α,20β-diol-3,20-dione
 None
None
200
PR22
 4-Pregnen-20β-ol-3,20-dione-17α-sulfate
 5.73
 0.66
 None
None
PR23
 5β-Pregnan-3α,20β-diol
 5.42
 0.49
 5.95
 0.25
 None
PR24
 5β-Pregnan-3α,11β,17,21-tetrol-20-one
 4.33
 0.73
 3.94
 0.11
 None
PR25
 5β-Pregnan-3α-ol-20-one
 4.98
 0.55
 6.64
 1.22
 100
PR26
 5-Pregnen-20-one-3β-sulfate
 None
4.95
 0.23
 None
PR27
 4-Estren-17α-ethynyl-18-homo-17β-ol-3-one (levonorgestrel)
 5.37
 0.35
 6.00
 0.86
 None
PR28
 4-Estren-17α-ethynyl-17β-ol-3-one (norethindrone)
 4.59
 0.32
 5.85
 0.40
 None
PR29
 1,4-Pregnadien-9α-fluoro-16α-methyl-11β,17,21-triol-3,20-dione (dexamethasone)
 4.39
 0.83
 None
None

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