Information on EC 1.14.14.32 - 17alpha-hydroxyprogesterone deacetylase

androgen and estrogen metabolism

-

17alpha-hydroxylation

695150

BRENDA

KEGG

Steroid hormone biosynthesis

MetaCyc

11-oxyandrogens biosynthesis, androgen biosynthesis, backdoor pathway of androgen biosynthesis

17alpha-hydroxyprogesterone,NADPH-hemoprotein reductase:oxygen oxidoreductase (17alpha-hydroxylating, acetate-releasing)

A microsomal cytochrome P-450 (heme-thiolate) protein that catalyses two independent reactions at the same active site - the 17-hydroxylation of pregnenolone and progesterone, which is part of glucocorticoid hormones biosynthesis (EC 1.14.14.19), and the conversion of the 17-hydroxylated products via a 17,20-lyase reaction to form androstenedione and 3beta-hydroxyandrost-5-en-17-one, leading to sex hormone biosynthesis. The activity of this reaction is dependent on the allosteric interaction of the enzyme with cytochrome b5 without any transfer of electrons from the cytochrome [2,4]. The enzymes from different organisms differ in their substrate specificity. While the enzymes from pig, hamster, and rat accept both 17alpha-hydroxyprogesterone and 17alpha-hydroxypregnenolone, the enzymes from human, bovine, sheep, goat, and bison do not accept the former, and the enzyme from guinea pig does not accept the latter [1].

62213-24-5

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17-hydroxy-5alpha-pregnan-3alpha-ol-20-one + [reduced NADPH-hemoprotein reductase] + O2

androsterone + [oxidized NADPH-hemoprotein reductase] + H2O

Substrates: -
Products: -

?

17-hydroxyprogesterone + [reduced NADPH-hemoprotein reductase] + O2

androstenedione + acetate + [oxidized NADPH-hemoprotein reductase] + H2O

-

695147, 706775

Substrates: -
Products: -

?

17alpha-hydroxy-5alpha-dihydroprogesterone + [reduced NADPH-hemoprotein reductase] + O2

5alpha-androstanedione + acetate + [oxidized NADPH-hemoprotein reductase] + H2O

Substrates: -
Products: -

?

17alpha-Hydroxypregnenolone

Dehydroepiandrosterone + acetaldehyde

9 entries

17alpha-hydroxypregnenolone + ? + cytochrome b5

dehydroepiandrosterone + ?

-

Substrates: -
Products: -

?

17alpha-hydroxypregnenolone + AH2 + O2

?

-

Substrates: -
Products: -

?

17alpha-hydroxypregnenolone + AH2 + O2

dehydroepiandrosterone + acetate + A + H2O

8 entries

17alpha-hydroxypregnenolone + [reduced NADPH-hemoprotein reductase] + O2

3beta-hydroxyandrost-5-en-17-one + acetate + [oxidized NADPH-hemoprotein reductase] + H2O

6 entries

17alpha-hydroxypregnenolone + [reduced NADPH-hemoprotein reductase] + O2

dehydroepiandrosterone + [oxidized NADPH-hemoprotein reductase] + acetate + H2O

Substrates: -
Products: -

?

17alpha-hydroxyprogesterone + ?

androstenedione + ?

Cavia porcellus

Q64410

658149

Substrates: -
Products: -

?

17alpha-hydroxyprogesterone + AH2 + O2

dehydroepiandrosterone + androstenedione + A + H2O

-

Substrates: -
Products: -

?

17alpha-hydroxyprogesterone + [reduced NADPH-hemoprotein reductase] + O2

androstenedione + acetate + [oxidized NADPH-hemoprotein reductase] + H2O

20 entries

17alpha-picolyl-androst-4-en-3beta,17beta-diol + [reduced NADPH-hemoprotein reductase] + O2

? + acetate + [oxidized NADPH-hemoprotein reductase] + H2O

-

Substrates: -
Products: 66% conversion in 17,20-lyase reaction

?

17beta-hydroxy-17alpha-picolyl-androst-4-en-3-one + [reduced NADPH-hemoprotein reductase] + O2

? + acetate + [oxidized NADPH-hemoprotein reductase] + H2O

-

Substrates: -
Products: 73% conversion in 17,20-lyase reaction

?

5alpha-dihydroprogesterone + [reduced NADPH-hemoprotein reductase] + O2

17alpha-hydroxy-5alpha-dihydroprogesterone + [oxidized NADPH-hemoprotein reductase] + H2O

Substrates: -
Products: -

?

5alpha-pregnan-17alpha-ol-3,20-dione + ?

androstanedione

-

Substrates: -
Products: very little product formation

?

5alpha-pregnan-3alpha,11beta,17alpha-triol-20-one + [reduced NADPH-hemoprotein reductase] + O2

11beta-hydroxyandrosterone + [oxidized NADPH-hemoprotein reductase] + H2O

767360

Substrates: -
Products: -

?

5alpha-pregnan-3alpha,17alpha-diol-11,20-dione + [reduced NADPH-hemoprotein reductase] + O2

11-ketoandrosterone + [oxidized NADPH-hemoprotein reductase] + H2O

767360

Substrates: -
Products: -

?

5alpha-pregnan-3alpha,17alpha-diol-20-one + ? + cytochrome b5

androsterone + ?

-

Substrates: better substrate than 17alpha-hydroxypregenolone
Products: rapid reaction

?

5alpha-pregnan-3alpha-ol-20-one + [reduced NADPH-hemoprotein reductase] + O2

17-hydroxy-5alpha-pregnan-3alpha-ol-20-one + [oxidized NADPH-hemoprotein reductase] + H2O

Substrates: -
Products: -

?

7,12-dimethylbenz[a]anthracene + AH2 + O2

?

Substrates: substrate for CYP17A1
Products: -

?

7-dehydro-17alpha-hydroxypregnenolone + AH2 + O2

7-dehydro-dehydroepiandrosterone + acetate + A + H2O

7-dehydro-pregnenolone + AH2 + O2

7-dehydro-17alpha-hydroxy-pregnenolone + A + H2O

Substrates: -
Products: -

?

7-dehydro-pregnenolone + AH2 + O2

7-dehydro-17alpha-hydroxypregnenolone + A + H2O

7alpha-hydroxypregnenolone + [reduced NADPH-hemoprotein reductase] + O2

3beta-hydroxyandrost-5-en-17-one + acetate + [oxidized NADPH-hemoprotein reductase] + H2O

-

Substrates: 17,20-lyase activity
Products: -

?

aflatoxin B1 + AH2 + O2

aflatoxin B1epoxide + A + H2O

Substrates: substrate for CYP17A1
Products: -

?

allopregnanolone + [reduced NADPH-hemoprotein reductase] + O2

androstenedione + acetate + [oxidized NADPH-hemoprotein reductase] + H2O

737726

Substrates: -
Products: -

?

pregnenolone + AH2 + O2

17alpha-hydroxypregnenolone + A + H2O

Substrates: -
Products: -

?

pregnenolone + reduced acceptor + O2

17alpha-hydroxypregnenolone + oxidized acceptor + H2O

-

Substrates: i.e. pregn-5-en-3beta-ol-20-one
Products: -

?

pregnenolone + [reduced NADPH-hemoprotein reductase] + 2 O2

3beta-hydroxyandrost-5-en-17-one + acetate + [oxidized NADPH-hemoprotein reductase] + 2 H2O

Substrates: -
Products: -

?

pregnenolone + [reduced NADPH-hemoprotein reductase] + O2

17alpha-hydroxypregnenolone + [oxidized NADPH-hemoprotein reductase] + H2O

progesterone + AH2 + O2

17alpha-hydroxyprogesterone + A + H2O

14 entries

progesterone + reduced acceptor + O2

17alpha-hydroxyprogesterone + acceptor + H2O

Substrates: -
Products: -

?

progesterone + [reduced NADPH-hemoprotein reductase] + O2

16alpha-hydroxyprogesterone + [oxidized NADPH-hemoprotein reductase] + H2O

Substrates: minor product
Products: -

?

progesterone + [reduced NADPH-hemoprotein reductase] + O2

17alpha-hydroxyprogesterone + [oxidized NADPH-hemoprotein reductase] + H2O

additional information

?

-

26 entries

17-hydroxy-5alpha-pregnan-3alpha-ol-20-one + [reduced NADPH-hemoprotein reductase] + O2

androsterone + [oxidized NADPH-hemoprotein reductase] + H2O

Substrates: -
Products: -

?

17alpha-hydroxy-5alpha-dihydroprogesterone + [reduced NADPH-hemoprotein reductase] + O2

5alpha-androstanedione + acetate + [oxidized NADPH-hemoprotein reductase] + H2O

Substrates: -
Products: -

?

17alpha-Hydroxypregnenolone

Dehydroepiandrosterone + acetaldehyde

17alpha-hydroxypregnenolone + AH2 + O2

dehydroepiandrosterone + acetate + A + H2O

7 entries

17alpha-hydroxypregnenolone + [reduced NADPH-hemoprotein reductase] + O2

3beta-hydroxyandrost-5-en-17-one + acetate + [oxidized NADPH-hemoprotein reductase] + H2O

17alpha-hydroxyprogesterone + [reduced NADPH-hemoprotein reductase] + O2

androstenedione + acetate + [oxidized NADPH-hemoprotein reductase] + H2O

6 entries

5alpha-dihydroprogesterone + [reduced NADPH-hemoprotein reductase] + O2

17alpha-hydroxy-5alpha-dihydroprogesterone + [oxidized NADPH-hemoprotein reductase] + H2O

Substrates: -
Products: -

?

5alpha-pregnan-3alpha-ol-20-one + [reduced NADPH-hemoprotein reductase] + O2

17-hydroxy-5alpha-pregnan-3alpha-ol-20-one + [oxidized NADPH-hemoprotein reductase] + H2O

Substrates: -
Products: -

?

7-dehydro-17alpha-hydroxypregnenolone + AH2 + O2

7-dehydro-dehydroepiandrosterone + acetate + A + H2O

7-dehydro-pregnenolone + AH2 + O2

7-dehydro-17alpha-hydroxy-pregnenolone + A + H2O

Substrates: -
Products: -

?

7-dehydro-pregnenolone + AH2 + O2

7-dehydro-17alpha-hydroxypregnenolone + A + H2O

7alpha-hydroxypregnenolone + [reduced NADPH-hemoprotein reductase] + O2

3beta-hydroxyandrost-5-en-17-one + acetate + [oxidized NADPH-hemoprotein reductase] + H2O

-

Substrates: 17,20-lyase activity
Products: -

?

pregnenolone + reduced acceptor + O2

17alpha-hydroxypregnenolone + oxidized acceptor + H2O

-

Substrates: i.e. pregn-5-en-3beta-ol-20-one
Products: -

?

pregnenolone + [reduced NADPH-hemoprotein reductase] + O2

17alpha-hydroxypregnenolone + [oxidized NADPH-hemoprotein reductase] + H2O

progesterone + AH2 + O2

17alpha-hydroxyprogesterone + A + H2O

14 entries

progesterone + [reduced NADPH-hemoprotein reductase] + O2

17alpha-hydroxyprogesterone + [oxidized NADPH-hemoprotein reductase] + H2O

additional information

?

-

17 entries

cytochrome b5

-

heme

-

NADPH

-

(17beta)-17-[(5R)-2-(2-chlorophenyl)-4,5-dihydro-1,3-oxazol-5-yl]androst-4-en-3-one

-

(17beta)-17-[(5R)-2-(3-chlorophenyl)-4,5-dihydro-1,3-oxazol-5-yl]androst-4-en-3-one

-

(17beta)-17-[(5R)-2-(4-bromophenyl)-4,5-dihydro-1,3-oxazol-5-yl]androst-4-en-3-one

-

(17beta)-17-[(5R)-2-(4-chlorophenyl)-4,5-dihydro-1,3-oxazol-5-yl]androst-4-en-3-one

-

(17beta)-17-[(5R)-2-(4-nitrophenyl)-4,5-dihydro-1,3-oxazol-5-yl]androst-4-en-3-one

-

(17beta)-17-[(5R)-2-phenyl-4,5-dihydro-1,3-oxazol-5-yl]androst-4-en-3-one

-

(2S,4aR,4bS,6aS,6bR,7S,9aS,10aS,10bS)-4a,6a,7-trimethyl-2,3,4,4a,4b,5,6,6a,6b,7,9,9a,10,10a,10b,11-hexadecahydro-1H-naphtho[2',1':4,5]indeno[2,1-c][1,2]oxazol-2-ol

-

(2S,4aR,4bS,6aS,6bS,7S,10aS,10bS)-4a,6a,7-trimethyl-8-(4-methylphenyl)-1,2,3,4,4a,4b,5,6,6a,6b,7,8,10,10a,10b,11-hexadecahydronaphtho[2',1':4,5]indeno[2,1-c]pyrazol-2-ol

-

(3beta,17beta)-17-[(5R)-2-(3-chlorophenyl)-4,5-dihydro-1,3-oxazol-5-yl]androst-5-en-3-ol

-

(3beta,17beta)-17-[(5R)-2-(4-nitrophenyl)-4,5-dihydro-1,3-oxazol-5-yl]androst-5-en-3-ol

-

(3beta,17beta)-17-[2-(4-chlorophenyl)-5,6-dihydro-4H-1,3-oxazin-4-yl]androst-5-en-3-ol

-

decreases enzyme activity by 70% at 50 µM

713518

(5'R)-17beta-[2-(2-chlorophenyl)-4,5-dihydrooxazol-5-yl]androst-5-en-3-one

-

(5'R)-17beta-[2-(2-chlorophenyl)-4,5-dihydrooxazol-5-yl]androst-5-en-3beta-ol

-

(5'R)-17beta-[2-(3-chlorophenyl)-4,5-dihydrooxazol-5-yl]androst-5-en-3-one

-

(5'R)-17beta-[2-(3-chlorophenyl)-4,5-dihydrooxazol-5-yl]androst-5-en-3beta-ol

-

(5'R)-17beta-[2-(4-bromophenyl)-4,5-dihydrooxazol-5-yl]androst-5-en-3-one

-

(5'R)-17beta-[2-(4-bromophenyl)-4,5-dihydrooxazol-5-yl]androst-5-en-3beta-ol

-

(5'R)-17beta-[2-(4-chlorophenyl)-4,5-dihydrooxazol-5-yl]androst-5-en-3-one

-

(5'R)-17beta-[2-(4-chlorophenyl)-4,5-dihydrooxazol-5-yl]androst-5-en-3beta-ol

-

(5'R)-17beta-[2-(4-fluorophenyl)-4,5-dihydrooxazol-5-yl]androst-5-en-3-one

-

(5'R)-17beta-[2-(4-nitrophenyl)-4,5-dihydrooxazol-5-yl]androst-5-en-3-one

-

(5'R)-17beta-[2-(4-nitrophenyl)-4,5-dihydrooxazol-5-yl]androst-5-en-3beta-ol

-

(5'R)-17beta-[2-phenyl-4,5-dihydrooxazol-5-yl]androst-5-en-3-one

-

(S)-orteronel

three times more inhibitory toward the conversion of 17alpha-hydroxypregnenolone to dehydroepiandrosterone than toward the 17alpha-hydroxylation of pregnenolone. The (S)-enantiomer of orteronel is more inhibitory than the (R) enantiomer

(S)-seviteronel

17alpha-hydroxylation and lyase activity are inhibited

-

1-(3-phenylpropyl)-1H-imidazole

-

1-(4-bromobenzyl)-1H-imidazole

-

1-(4-iodo-benzyl)-1H-imidazole

-

1-(4-phenylbutyl)-1H-imidazole

-

1-(5-phenylpentyl)-1H-imidazole

-

1-(7-phenyl-heptyl)-1H-imidazole

-

1-[3-(4-bromo-phenyl)-propyl]-1H-imidazole

-

1-[3-(4-chlorophenyl)-propyl]-1H-imidazole

-

1-[3-(4-fluorophenyl)-propyl]-1H-imidazole

-

1-[5-(4-bromo-phenyl)-pentyl]-1H-imidazole

-

1-[5-(4-chlorophenyl)-pentyl]-1H-imidazole

-

1-[5-(4-fluorophenyl)-pentyl]-1H-imidazole

-

1-[7-(4-fluorophenyl)-heptyl]-1H-imidazole

-

17(E)-picolinyliden-androst-4-en-3beta-ol

-

17(E)-picolinyliden-androst-5-en-3beta-ol

-

17-(1H-1,2,3-triazol-1-yl)androsta-4,16-dien-3-one

-

VN/85-1

17-(1H-imidazole-1-yl)androsta-4,16-dien-3-one

-

VN/108-1

17beta-(1-p-chlorophenyl-3-pyrazolyl)androst-4-en-3-one

-

91% relative conversion at 0.05 mM

17beta-(1-p-chlorophenyl-3-pyrazolyl)androst-5-en-3beta-ol

-

74% relative conversion at 0.05 mM

17beta-(1-p-chlorophenyl-5-pyrazolyl)androst-4-en-3-one

-

78% relative conversion at 0.05 mM

17beta-(1-p-chlorophenyl-5-pyrazolyl)androst-5-en-3beta-ol

-

17beta-(1-p-cyanophenyl-3-pyrazolyl)androst-4-en-3-one

-

34% relative conversion at 0.05 mM

17beta-(1-p-cyanophenyl-3-pyrazolyl)androst-5-en-3beta-ol

-

17beta-(1-p-cyanophenyl-5-pyrazolyl)androst-4-en-3-one

-

69% relative conversio at 0.05 mMn

17beta-(1-p-cyanophenyl-5-pyrazolyl)androst-5-en-3beta-ol

-

17beta-(1-p-methoxyphenyl-3-pyrazolyl)androst-4-en-3-one

-

54% relative conversion at 0.05 mM

17beta-(1-p-methoxyphenyl-3-pyrazolyl)androst-5-en-3beta-ol

-

95% relative conversion at 0.05 mM

17beta-(1-p-methoxyphenyl-5-pyrazolyl)androst-4-en-3-one

-

91% relative conversion at 0.05 mM

17beta-(1-p-methoxyphenyl-5-pyrazolyl)androst-5-en-3beta-ol

-

17beta-(1-p-tolyl-3-pyrazolyl)androst-4-en-3-one

-

92% relative conversion at 0.05 mM

17beta-(1-p-tolyl-5-pyrazolyl)androst-4-en-3-one

-

86% relative conversion at 0.05 mM

17beta-(1-p-tolyl-5-pyrazolyl)androst-5-en-3beta-ol

-

89% relative conversion at 0.05 mM

17beta-(1-p-tolylphenyl-3-pyrazolyl)androst-5-en-3beta-

-

17beta-(1-p-tolylphenyl-3-pyrazolyl)androst-5-en-3beta-ol

-

93% relative conversion at 0.05 mM

17beta-(1-p-tolylphenyl-5-pyrazolyl)androst-5-en-3beta-

-

17beta-(1-phenyl-3-pyrazolyl)androst-4-en-3-one

-

86% relative conversion at 0.05 mM

17beta-(1-phenyl-3-pyrazolyl)androst-5-en-3beta-ol

-

65% relative conversion at 0.05 mM

17beta-(1-phenyl-5-pyrazolyl)androst-4-en-3-one

-

87% relative conversion at 0.05 mM

17beta-(1-phenyl-5-pyrazolyl)androst-5-en-3beta-ol

-

92% relative conversion at 0.05 mM

17beta-(2-oxazolidon-5-yl)-androst-4-en-3-one

-

17beta-(2-oxazolidon-5-yl)androst-5-en-3beta-ol

-

17beta-[3-(N-3,5-dimethylphenyl)-2-oxazolidon-5-yl]androst-4-en-3-one

-

17beta-[3-(N-3,5-dimethylphenyl)-2-oxazolidon-5-yl]androst-5-en-3beta-ol

-

17beta-[3-(N-4-bromophenyl)-2-oxazolidon-5-yl]androst-4-en-3-one

-

17beta-[3-(N-4-bromophenyl)-2-oxazolidon-5-yl]androst-5-en-3beta-ol

-

17beta-[3-(N-4-chlorophenyl)-2-oxazolidon-5-yl]androst-4-en-3-one

-

17beta-[3-(N-4-chlorophenyl)-2-oxazolidon-5-yl]androst-5-en-3beta-ol

-

17beta-[3-(N-4-fluorophenyl)-2-oxazolidon-5-yl]androst-4-en-3-one

-

17beta-[3-(N-4-fluorophenyl)-2-oxazolidon-5-yl]androst-5-en-3beta-ol

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17beta-[3-(N-4-methoxyphenyl)-2-oxazolidon-5-yl]androst-4-en-3-one

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17beta-[3-(N-4-methoxyphenyl)-2-oxazolidon-5-yl]androst-5-en-3beta-ol

-

17beta-[3-(N-phenyl)-2-oxazolidon-5-yl]androst-4-en-3-one

-

17beta-[3-(N-phenyl)-2-oxazolidon-5-yl]androst-5-en-3beta-ol

-

2'-[[(E)-3beta-hydroxyandrost-5-en-17-ylidene]methyl]-4',4'-dimethyl-4',5'-dihydro-1',3'-oxazole

-

2'-[[(E)-3beta-hydroxyandrost-5-en-17-ylidene]methyl]-4',5'-dihydro-1',3'-oxazole

-

2-fluoro-4-[5-(pyridin-4-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]phenol

-

2-fluoro-4-[5-(pyridin-4-yl)-7,8-dihydronaphthalen-2-yl]phenol

-

3-[5-(4-fluorophenyl)-2,3-dihydro-1H-inden-1-yl]pyridine

-

3-[6-(4-fluorophenyl)-1H-inden-3-yl]pyridine

-

3beta-acetoxy-21-chloropregn-5-ene-20beta-N-phenylurethane

-

3beta-acetoxy-5alpha,6beta,17alpha,21-tetrabromo-pregnane-20-one

-

3beta-hydroxy-17-(1H-1,2,3-triazol-1-yl)androsta-5,16-diene

-

VN/87-1

3beta-hydroxy-17-(1H-benzimidazol-1-yl)androsta-5,16-diene

-

VN/124-1

694117

3beta-hydroxy-17-(1H-benzimidazole-1-yl)androsta-5,16-diene

-

VN/124-1

3beta-hydroxy-17-(50-[30-methyl]-10,20,40-oxadiazolyl)androst-5,16-diene

4-(1H-imidazol-1-ylmethyl)-7-[(3-methylbenzyl)oxy]-2H-chromen-2-one

-

4-(1H-imidazol-1-ylmethyl)-7-[[3-(trifluoromethyl)benzyl]oxy]-2Hchromen-2-one

-

4-(1H-imidazol-1-ylmethyl)phenyl 4-(trifluoromethyl)benzenesulfonate

-

4-(1H-imidazol-1-ylmethyl)phenyl 4-bromobenzenesulfonate

-

4-(1H-imidazol-1-ylmethyl)phenyl 4-chlorobenzenesulfonate

-

4-(1H-imidazol-1-ylmethyl)phenyl 4-fluorobenzenesulfonate

-

4-(1H-imidazol-1-ylmethyl)phenyl 4-iodobenzenesulfonate

-

4-(1H-imidazol-1-ylmethyl)phenyl 4-methoxybenzenesulfonate

-

4-(1H-imidazol-1-ylmethyl)phenyl 4-nitrobenzenesulfonate

-

4-(1H-imidazol-1-ylmethylphenyl)-4-toluenesulfonate

-

4-iodobenzyl imidazole

-

4-nonylphenol

Dicentrarchus labrax

-

strong inhibitory effect at 0.1 mM

677795

4-[5-(4-fluorophenyl)-2,3-dihydro-1H-inden-1-yl]pyridine

-

4-[5-(pyridin-4-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]benzene-1,2-diol

-

4-[5-(pyridin-4-yl)-7,8-dihydronaphthalen-2-yl]benzene-1,2-diol

-

4-[6-(3,4-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl]pyridine

-

4-[6-(3,4-difluorophenyl)-3,4-dihydronaphthalen-1-yl]pyridine

-

4-[6-(4-fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl]pyridine

-

4-[6-(4-fluorophenyl)-1H-inden-3-yl]pyridine

-

4-[6-(4-fluorophenyl)-3,4-dihydronaphthalen-1-yl]pyridine

-

4-[6-(4-methoxyphenyl)-1H-inden-3-yl]pyridine

-

5-(4-fluorophenyl)-1-(pyridin-3-yl)-2,3-dihydro-1H-inden-1-ol

-

6-(3,4-difluorophenyl)-1-(pyridin-3-yl)-1,2,3,4-tetrahydronaphthalen-1-ol

-

6-(3-fluoro-4-methoxyphenyl)-1-(pyridin-3-yl)-1,2,3,4-tetrahydronaphthalen-1-ol

-

7-[(3-chlorobenzyl)oxy]-4-(1H-imidazol-1-ylmethyl)-2H-chromen-2-one

-

7-[(3-fluorobenzyl)oxy]-4-(1H-imidazol-1-ylmethyl)-2H-chromen-2-one

-

abiraterone

abiraterone acetate

-

bitertanol

-

clotrimazole

17alpha-hydroxylation and lyase activity are inhibited

cyclopregnenolone

-

i.e. 3alpha5-cyclo-6beta-methoxy-5alpha-pregnane-20-one

diethylstilbestrol

-

dioctyltin chloride

-

estradiol-17beta

-

concentration of 0.3 mM both, testicular and male duodenal enzyme with exogenous 17alpha-hydroxyprogesterone as substrate are inhibited by 30-40%

fluconazole

-

flusilazole

Insulin

-

acute and selective

5126

-

ketoconazole

9 entries

methylmercury

Sus scrofa

-

O-3beta-acetoxyandrost-5,16-diene-17-acyl-p-methoxybenzamidoxime

-

compound displays in vitro cytotoxic activity against HeLa cells, MCF-7 cells, A-2780 cells and A-431 cells which are higher than or comparable to that of the reference cisplatin

727424

O-3beta-acetoxyandrost-5,16-diene-17-acylacetamidoxime

-

compound displays in vitro cytotoxic activity against HeLa cells, MCF-7 cells, A-2780 cells and A-431 cells which are higher than or comparable to that of the reference cisplatin

727424

orteronel

17alpha-hydroxylation and lyase activity are inhibited

Promegestone

-

competitive

Propiconazole

-

SU10603

tebuconazole

tetrabromobisphenol A

-

TOK-001

-

triadimenol

-

VT-464

-

selective suppression of androgen synthesis through CYP17 lyase inhibition

745754

additional information

10 entries

-

cytochrome b5

18 entries

-

P450 oxidoreductase

-

-

PD98059

-

inhibitor of the MEK/ERK pathway. Treatment of cells with PD98059 (10 mM) at 24 and 48 h results in significant increases in the protein levels of CYP17. Production of androstenedione and estradiol significantly increases after treatment with PD98059

738346

additional information

-

serine phosphorylation of P450c17

-

0.00027 - 0.00091

17alpha-hydroxypregnenolone

0.000015 - 0.0071

17alpha-hydroxyprogesterone

8 entries

0.0006

5alpha-pregnan-3alpha,17alpha-diol-20-one

-

pH 7.4

0.00049 - 0.0011

pregnenolone

0.0011 - 0.0097

progesterone

0.002 - 128

17alpha-hydroxypregnenolone

6 entries

0.00031 - 0.0082

17alpha-hydroxyprogesterone

0.0037 - 0.11

pregnenolone

0.0064 - 0.17

progesterone

7.8 - 10

17alpha-hydroxypregnenolone

0.11 - 2.7

17alpha-hydroxyprogesterone

7.4 - 100

pregnenolone

4.7 - 40

progesterone

0.0000553 - 0.000207

1-(7-phenyl-heptyl)-1H-imidazole

0.00004 - 0.000208

1-[5-(4-chlorophenyl)-pentyl]-1H-imidazole

0.000052 - 0.000265

1-[5-(4-fluorophenyl)-pentyl]-1H-imidazole

0.0000215 - 0.0000775

1-[7-(4-fluorophenyl)-heptyl]-1H-imidazole

0.000665 - 0.00124

ketoconazole

0.014

(17beta)-17-[(5R)-2-(2-chlorophenyl)-4,5-dihydro-1,3-oxazol-5-yl]androst-4-en-3-one

Rattus norvegicus

-

37°C

0.0048

(17beta)-17-[(5R)-2-(3-chlorophenyl)-4,5-dihydro-1,3-oxazol-5-yl]androst-4-en-3-one

Rattus norvegicus

-

37°C

0.005

(17beta)-17-[(5R)-2-(4-bromophenyl)-4,5-dihydro-1,3-oxazol-5-yl]androst-4-en-3-one

Rattus norvegicus

-

37°C

0.052

(17beta)-17-[(5R)-2-(4-chlorophenyl)-4,5-dihydro-1,3-oxazol-5-yl]androst-4-en-3-one

Rattus norvegicus

-

37°C

0.0077

(17beta)-17-[(5R)-2-(4-nitrophenyl)-4,5-dihydro-1,3-oxazol-5-yl]androst-4-en-3-one

Rattus norvegicus

-

37°C

0.03

(17beta)-17-[(5R)-2-phenyl-4,5-dihydro-1,3-oxazol-5-yl]androst-4-en-3-one

Rattus norvegicus

-

37°C

0.026

(2S,4aR,4bS,6aS,6bR,7S,9aS,10aS,10bS)-4a,6a,7-trimethyl-2,3,4,4a,4b,5,6,6a,6b,7,9,9a,10,10a,10b,11-hexadecahydro-1H-naphtho[2',1':4,5]indeno[2,1-c][1,2]oxazol-2-ol

Rattus norvegicus

-

37°C

0.0058

(2S,4aR,4bS,6aS,6bS,7S,10aS,10bS)-4a,6a,7-trimethyl-8-(4-methylphenyl)-1,2,3,4,4a,4b,5,6,6a,6b,7,8,10,10a,10b,11-hexadecahydronaphtho[2',1':4,5]indeno[2,1-c]pyrazol-2-ol

Rattus norvegicus

-

37°C

0.011

(3beta,17beta)-17-[(5R)-2-(3-chlorophenyl)-4,5-dihydro-1,3-oxazol-5-yl]androst-5-en-3-ol

Rattus norvegicus

-

37°C

0.0079

(3beta,17beta)-17-[(5R)-2-(4-nitrophenyl)-4,5-dihydro-1,3-oxazol-5-yl]androst-5-en-3-ol

Rattus norvegicus

-

37°C

0.0048

(5'R)-17beta-[2-(2-chlorophenyl)-4,5-dihydrooxazol-5-yl]androst-5-en-3-one

Rattus norvegicus

-

pH 7.3, 37°C

0.014

(5'R)-17beta-[2-(3-chlorophenyl)-4,5-dihydrooxazol-5-yl]androst-5-en-3-one

Rattus norvegicus

-

pH 7.3, 37°C

0.005

(5'R)-17beta-[2-(4-bromophenyl)-4,5-dihydrooxazol-5-yl]androst-5-en-3-one

Rattus norvegicus

-

pH 7.3, 37°C

0.052

(5'R)-17beta-[2-(4-chlorophenyl)-4,5-dihydrooxazol-5-yl]androst-5-en-3-one

Rattus norvegicus

-

pH 7.3, 37°C

0.0077

(5'R)-17beta-[2-(4-nitrophenyl)-4,5-dihydrooxazol-5-yl]androst-5-en-3-one

Rattus norvegicus

-

pH 7.3, 37°C

0.0079

(5'R)-17beta-[2-(4-nitrophenyl)-4,5-dihydrooxazol-5-yl]androst-5-en-3beta-ol

Rattus norvegicus

-

pH 7.3, 37°C

0.03

(5'R)-17beta-[2-phenyl-4,5-dihydrooxazol-5-yl]androst-5-en-3-one

Rattus norvegicus

-

pH 7.3, 37°C

0.00343

(S)-seviteronel

Homo sapiens

pH 7.4, 37°C, 17alpha-OH pregnenolone lyase activity

-

0.00614 - 0.03095

1-(3-phenylpropyl)-1H-imidazole

0.00285 - 0.01655

1-(4-bromobenzyl)-1H-imidazole

0.00158 - 0.01006

1-(4-iodo-benzyl)-1H-imidazole

0.00223 - 0.00865

1-(4-phenylbutyl)-1H-imidazole

0.00131 - 0.0022

1-(5-phenylpentyl)-1H-imidazole

0.0001 - 0.00032

1-(7-phenyl-heptyl)-1H-imidazole

0.00033 - 0.00295

1-[3-(4-bromo-phenyl)-propyl]-1H-imidazole

0.00055 - 0.00585

1-[3-(4-chlorophenyl)-propyl]-1H-imidazole

0.00196 - 0.02781

1-[3-(4-fluorophenyl)-propyl]-1H-imidazole

0.000058 - 0.0005

1-[5-(4-bromo-phenyl)-pentyl]-1H-imidazole

0.000086 - 0.00057

1-[5-(4-chlorophenyl)-pentyl]-1H-imidazole

0.0001 - 0.00075

1-[5-(4-fluorophenyl)-pentyl]-1H-imidazole

0.000057 - 0.00017

1-[7-(4-fluorophenyl)-heptyl]-1H-imidazole

0.014

17(E)-picolinyliden-androst-4-en-3beta-ol

Rattus norvegicus

-

C17,20-lyase activity, pH 7.3, 37°C

0.0082

17(E)-picolinyliden-androst-5-en-3beta-ol

Rattus norvegicus

-

C17,20-lyase activity, pH 7.3, 37°C

0.022

17beta-(1-p-cyanophenyl-3-pyrazolyl)androst-4-en-3-one

0.059

17beta-(1-p-methoxyphenyl-3-pyrazolyl)androst-4-en-3-one

Rattus norvegicus

-

0.059

17beta-(1-phenyl-5-pyrazolyl)androst-4-en-3-one

Rattus norvegicus

-

pH and temperature not specified in the publication

0.003

17beta-(2-oxazolidon-5-yl)-androst-4-en-3-one

Rattus norvegicus

-

0.013

2'-[[(E)-3beta-hydroxyandrost-5-en-17-ylidene]methyl]-4',4'-dimethyl-4',5'-dihydro-1',3'-oxazole

Homo sapiens

-

at pH 7.4 and 37°C

0.0009

2'-[[(E)-3beta-hydroxyandrost-5-en-17-ylidene]methyl]-4',5'-dihydro-1',3'-oxazole

Homo sapiens

-

at pH 7.4 and 37°C

0.00006

3beta-hydroxy-17-(50-[30-methyl]-10,20,40-oxadiazolyl)androst-5,16-diene

Rattus norvegicus

-

pH 7.3, 37°C

727424

0.0002908

4-(1H-imidazol-1-ylmethyl)phenyl 4-(trifluoromethyl)benzenesulfonate

Rattus norvegicus

-

at 37°C

0.0000704

4-(1H-imidazol-1-ylmethyl)phenyl 4-bromobenzenesulfonate

Rattus norvegicus

-

at 37°C

0.0000987

4-(1H-imidazol-1-ylmethyl)phenyl 4-chlorobenzenesulfonate

Rattus norvegicus

-

at 37°C

0.00021

4-(1H-imidazol-1-ylmethyl)phenyl 4-fluorobenzenesulfonate

Rattus norvegicus

-

at 37°C

0.0000651

4-(1H-imidazol-1-ylmethyl)phenyl 4-iodobenzenesulfonate

Rattus norvegicus

-

at 37°C

0.0001009

4-(1H-imidazol-1-ylmethyl)phenyl 4-methoxybenzenesulfonate

Rattus norvegicus

-

at 37°C

0.000085

4-(1H-imidazol-1-ylmethyl)phenyl 4-nitrobenzenesulfonate

Rattus norvegicus

-

at 37°C

0.00023

4-(1H-imidazol-1-ylmethylphenyl)-4-toluenesulfonate

Rattus norvegicus

-

at 37°C

0.00158

4-iodobenzyl imidazole

Rattus norvegicus

-

at 37°C

0.0000012 - 0.0013

abiraterone

0.000099

clotrimazole

Homo sapiens

pH 7.4, 37°C, 17alpha-OH pregnenolone lyase activity

0.014

diethylstilbestrol

Sus scrofa

-

adrenal cortex microsomes, pH and temperature not specified in the publication

0.000084

dioctyltin chloride

Homo sapiens

H295R cell assay, pH and temperature not specified in the publication

0.00013 - 0.016

flusilazole

0.000032 - 0.00376

ketoconazole

10 entries

0.02 - 2

methylmercury

Sus scrofa

-

adrenal cortex microsomes, pH and temperature not specified in the publication

0.00106

orteronel

Homo sapiens

pH 7.4, 37°C, 17alpha-OH pregnenolone lyase activity

0.000039 - 0.000061

SU10603

0.00014

tebuconazole

Sus scrofa

-

adrenal cortex microsomes, pH and temperature not specified in the publication

0.093

tetrabromobisphenol A

Sus scrofa

-

adrenal cortex microsomes, pH and temperature not specified in the publication

0.0000073

Sus scrofa

-

adrenal cortex microsomes, pH and temperature not specified in the publication

0.0000375

H295R cell assay, pH and temperature not specified in the publication

additional information

13 entries

7.3

-

assay at

7.4

-

activity assay

37

-

-

-

-

-

UniProt

sea bass

-

-

-

-

-

-

-

cynomolgus monkey

-

-

-

Golden Syrian hamster

-

C57BL/6 mice

-

rainbow trout

-

Oryctolagus cuniculus

New Zealand rabbit

-

-

-

-

-

-

-

Spermophilus dauricus

-

-

-

-

-

-

-

-

weakly present

-

human adrenocorticocarcinoma cell line

-

-

-

is most consistent in the testicular interstitial cells surrounding existing or developing cysts

706819

intestine

B2D2I4

weakly present

703775

kidney

ovarian theca-interstitial cell

weakly present

-

-

peripheral blood leukocyte

-

-

-

ovarian

5127

-

ovary cancer cell line

-

ovarian granulosa-like tumor cell line, most of the cells are strongly positive for CYP17 and CYP19, especially in the perinuclear region

-

-

peripheral blood leukocyte

Spermophilus dauricus

-

intensely present during the breeding season

705389

spleen

endoplasmic reticulum membrane

weakly present

-

-

-

additional information

16 entries

-

-

perinucleus

5634

738346

Highest Expressing Human Cell Lines

Filter by:

Cell Line Links

Gene Links

drug target

the multifunctional enzyme, cytochrome P450 (CYP17A1), plays a crucial role in the production of androgens, whose involvement in the proliferation of prostate cancer has generated intense interest in developing inhibitors of CYP17A1

767016

malfunction

physiological function

54000

-

immunoblot analysis

705402

57000

Spermophilus dauricus

-

Western blotting, SDS-PAGE

705389

58000

-

x * 58000, SDS-PAGE

715984

?

phosphoprotein

resonance Raman spectroscopy of ferric form reveals that binding of substrate causes variable degrees of conversion from the low spin to high spin state, with the nonhydroxylated progesterone and pregnenolone yielding almost complete high spin form, while the two hydroxylated substrates (17-hydroxyprogesterone and 17-hydroxypregnenolone) give only about a 60% conversion to high spin. The heme structure and its interactions with the active site protein residues remain constant for all four substrates

D298A

mutation has no influence on the overall activity

E305A

the variant shows no activity towards progesterone

F114A

mutant enzyme with decreased activity

G297A

the enzyme variant shows lower product formation than the wild type enzyme

G301A

mutant enzyme with decreased activity

I205A

the variant shows no activity towards progesterone

I371A

the variant shows no activity towards progesterone

L105A

the wild-type enzyme shows, with 1.3%, very little but measurable 16alpha-hydroxyprogesterone formation, whereas the L105A mutant does not produce this side product. Mutant enzyme with decreased activity

L206A

the enzyme variant shows lower product formation than the wild type enzyme

L482A

mutation has no influence on the overall activity

N202A

the variant shows no activity towards progesterone

R239A

the enzyme variant shows lower product formation than the wild type enzyme

T306A

the variant shows negligible activity towards progesterone

V201A

mutation has no influence on the overall activity

V366A

mutation has no influence on the overall activity

V483A

the ratio between 17alpha-hydroxyprogesterone and 16alpha-hydroxyprogesterone is 1:0.67

A355T

-

shows a complete loss of enzymatic activity. Is expressed in transfected COS-1 cells in a fashion comparable to the wild-type protein. Less severely affected patient with ambiguous genitalia

D298V

mutant without heme-binding properties

DELTAF54

-

partially reduces enzymatic activities

705509

E305G

naturally occurring P450 17A1 mutation, impairs 17,20-lyase activity. Cytochrome b5 fails to rescue the poor coupling with 17-hydroxypregnenolone

737726

G111D

mutant without heme-binding properties

G111S

-

shows a complete loss of enzymatic activity. Is expressed in transfected COS-1 cells in a fashion comparable to the wild-type protein. Leads to complete lack of masculinization in the patient

G301I

mutant without heme-binding properties

G90D

the mutation results in loss of the 17alpha-hydroxylase and 17,20-lyase activities

H373N

-

mutation almost completely eliminates enzymatic activities

705509

I332T

-

retains some residual 17,20-lyase activity (10%). Is expressed in transfected COS-1 cells in a fashion comparable to the wild-type protein. Less severely affected patient with ambiguous genitalia

N202S

the mutation causes active site structural changes that alter the H-bonding interactions with the key Fe-O-O fragment and the degree of protonation of the reactive ferric peroxo intermediate, thereby impacting lyase efficiency

766216

P342T

the mutant shows 20% of wild type activity

Q461stop

naturally occuring mutation, inactive mutant

R347H

R358Q

R358X

-

mutant, CGA to TGA, alteration introduces premature stop codon, inactive protein

693809

R440H

-

shows a complete loss of enzymatic activity. Leads to complete lack of masculinization in the patient

R449A

R496C

naturally occuring mutation, the mutant has low 17alpha-hydroxylase and 17,20-lyase activities

R96W

the mutation results in loss of the 17alpha-hydroxylase and 17,20-lyase activities

S106P

the mutation results in loss of the 17alpha-hydroxylase and 17,20-lyase activities

T306A

T64S

the mutant shows 15% of wild type activity

Y329DEL-SUB

-

mutant, TAC to AA, alteration introduces premature stop codon, inactive protein

693809

additional information

dimethyl sulfoxide

-

5% v/v, no significant reduction of activity

propylene glycol

-

3% v/v, no significant reduction of activity

-

-

expressed in Pichia pastoris

-

680978

full length cDNA clone encoding cytochrome P-450c17 (17alpha-hydrolase/17,20 lyase), expression in mammalian COS-1 cells

Oncorhynchus mykiss

-

5127

full length cDNA clone encoding cytochrome P450C17 expressed in COS 1 cells

Mesocricetus auratus

-

390127

gene CYP17A1, DNA and amino acid sequence determination and analysis, sequence comparisons and phylogenetic analysis, expression of wild-type and mutant enzymes in COS-1 cells

gene encoding cytochrome P450 17alpha-hydrolase/C17-20-lyase (P450 17alpha)

Mus musculus

-

5128

recombinant expression in Escherichia coli

-

sequence comparisons and phylogenetic analysis

12 entries

the wild-type and mutant CYP17A1 complementary DNAs (cDNAs) are amplified and cloned into a pcDNA3.1(+) vector. These plasmids are transfected transiently into HEK-293T cells

766751

wild-type or mutant CYP17A1 cDNA, after addition of an N-terminal myc-tag, inserted into a pcDNA3.1 vector, transiently transfected into confluent COS-1 cells

-

CYP17 mRNA levels are reduced by 50% in CYP17 chimeric compared to wild-type mouse brain, whereas the levels of brain dehydroepiandrosterone levels are comparable

CYP17A1 gene expression continuously rises throughout the ovarian development, except for a slight drop during the primary yolk stage. During the atretic follicles stage, the expression of CYP17A1 is remarkably upregulated and reaches the highest level. During the tertiary yolk stage, brain CYP17AI expression is 3.1fold higher than the primary yolk stage, and 4.4fold higher than that at atretic follicles stage

B2D2I4

703775

in the brain, during the atretic follicles stage, the gene expression drops sharply to the lowest level