Therapeutic Targets Database
BIDD Pharmainformatics Databases


TTD Target ID: TTDS00241

Target Information
Name17 alpha-hydroxylase-C17, 20-lyase    
Type of targetSuccessful target    
Synonyms17 alpha-Hydroxylase/C17-20-lyase    
CYP 17    
P450 17    
Steroid 17-alpha-hydroxylase/17,20 lyase    
DiseaseBenign prostate hyperplasia
[ICD9: 600   ICD10: N40]
Prostate cancer
[ICD9: 185   ICD10: C61]
Drug(s)ProgesteroneApprovedInfertile in women[2]
TAK-700Phase IIIMetastatic castration resistant prostate cancer (CRPC) chemo naive, Metastatic CRPC post-docetaxel
BioChemical ClassOxidoreductases acting on paired donors    
EC NumberEC
PathwayC21-Steroid hormone metabolism
Metabolic pathways
UniProt IDP05093
PDB Structure2C17; 3RUK; 3SWZ.    
FunctionConversion of pregnenolone and progesterone to their 17-alpha-hydroxylated products and subsequently to dehydroepiandrosterone (dhea) and androstenedione. Catalyzes both the 17-alpha-hydroxylation and the 17,20-lyase reaction.    
Related US Patent6,649,643
Target ValidationClick to Find Target Validation Information.    
Inhibitor1- ([5]
1- ([5]
1- (1-[5]
1- (1-[6]
1- (1-[6]
1- (1-[5]
1- (1-Biphenyl-4-yl-2-methyl-propyl)-1H-imidazole[5]
1- (1-Biphenyl-4-yl-2-phenyl-ethyl)-1H-imidazole[5]
1- (1-Biphenyl-4-yl-3-methyl-butyl)-1H-imidazole[5]
1- (1-Biphenyl-4-yl-butyl)-1H-imidazole[5]
1- (1-Biphenyl-4-yl-ethyl)-1H-imidazole[5]
1- (1-Biphenyl-4-yl-pentyl)-1H-imidazole[5]
1- (1-Biphenyl-4-yl-propyl)-1H-imidazole[5]
1- (3,4-dichlorobenzyl)-1H-imidazole[7]
1- (3,4-difluorobenzyl)-1H-imidazole[7]
1- (3,5-bis[7]
1- (3,5-dibromobenzyl)-1H-imidazole[7]
1- (3,5-dichlorobenzyl)-1H-imidazole[7]
1- (3,5-difluorobenzyl)-1H-imidazole[7]
1- (3-[8]
1- (3-[8]
1- (3-phenylpropyl)-1H-imidazole[8]
1- (4-bromobenzyl)-1H-imidazole[8]
1- (4-bromophenethyl)-1H-imidazole[8]
1- (4-chlorobenzyl)-1H-imidazole[8]
1- (4-chlorophenethyl)-1H-imidazole[8]
1- (4-fluorobenzyl)-1H-imidazole[8]
1- (4-iodobenzyl)-1H-imidazole[9]
1- (4-methyl-benzyl)-1H-imidazole[7]
1- (4-nitrobenzyl)-1H-imidazole[7]
1- (Bis-biphenyl-4-yl-methyl)-1H-imidazole[5]
1-Ethyl-5- (imidazol-1-yl-phenyl-methyl)-1H-indole[10]
2- (1-Imidazol-1-yl-ethyl)-9H-carbazole[5]
3- (1-Chloro-7-methoxy-naphthalen-2-yl)-pyridine[14]
3- (1-ethyl-3,4-dihydronaphthalen-2-yl)-pyridine[15]
3- (1-methyl-3,4-dihydronaphthalen-2-yl)-pyridine[15]
3- (6-Ethoxy-naphthalen-2-yl)-pyridine[14]
3- (6-methoxy-3,4-dihydronaphthalen-2-yl)pyridine[15]
3- (6-methoxynaphthalen-2-yl)pyridine[16]
3-Fluoro-4'- (pyridin-4-ylmethyl)biphenyl-4-ol[17]
3-[ (4'-Hydroxybiphenyl-4-yl)methyl]pyridine[17]
3-[4-Fluoro-indan- (1Z)-ylidenemethyl]-pyridine[18]
3-fluoro-4'- (1-[19]
4'- (1-[19]
4'- (2-methyl-1-[19]
4'- (Pyridin-4-ylmethyl)biphenyl-3,4-diamine[17]
4'- (Pyridin-4-ylmethyl)biphenyl-3,4-diol[17]
4'- (Pyridin-4-ylmethyl)biphenyl-3-amine[17]
4'- (Pyridin-4-ylmethyl)biphenyl-4-amine[17]
4'- (Pyridin-4-ylmethyl)biphenyl-4-carboxamide[17]
4- ([7]
4- ([9]
4- ([17]
4- (4'-Fluoro-biphenyl-4-ylmethyl)pyridine[17]
4- (4-[17]
4- (4-[17]
4-Indan- (1Z)-ylidenemethyl-pyridine[18]
4-[ (3'-Hydroxybiphenyl-4-yl)methyl]pyridine[17]
4-[ (4'-Hydroxybiphenyl-4-yl)methyl]pyridine[17]
4-[1- (4'-Methoxybiphenyl-4-yl)propyl]pyridine[17]
4-[4- (6-methoxynaphthalen-2-yl)benzyl]pyridine[17]
4-[5-Bromo-indan- (1E)-ylidenemethyl]-pyridine[18]
4-[5-Bromo-indan- (1Z)-ylidenemethyl]-pyridine[18]
4-[5-Chloro-indan- (1E)-ylidenemethyl]-pyridine[18]
4-[5-Chloro-indan- (1Z)-ylidenemethyl]-pyridine[18]
4-[5-Fluoro-indan- (1E)-ylidenemethyl]-pyridine[18]
4-[5-Fluoro-indan- (1Z)-ylidenemethyl]-pyridine[18]
5-[4- (Pyridin-4-ylmethyl)phenyl]-1H-indole[17]
5-[5-Fluoro-indan- (1E)-ylidenemethyl]-pyrimidine[18]
6- (3-[20]
6- (pyridin-3-yl)-2-naphthonitrile[16]
6-Pyridin-3-yl-3,4-dihydroquinoline-2 (1H)-thione[16]
6-[4- (Pyridin-4-ylmethyl)phenyl]naphthalen-2-ol[17]
7- (1-[5]
N- (4'-Isonicotinoylbiphenyl-3-yl)acetamide[17]
N-3- (4-bromophenyl)propyl imidazole[8]
rac-4'- (1-Imidazol-1-yl-propyl)-biphenyl-3,4-diol[23]
rac-4'- (1-Imidazol-1-yl-propyl)-biphenyl-3,5-diol[23]
rac-4'- (1-Imidazol-1-yl-propyl)-biphenyl-3-ol[23]
rac-4'- (1-Imidazol-1-yl-propyl)-biphenyl-4-ol[23]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1Synthesis and evaluation of novel steroidal oxime inhibitors of P450 17 (17 alpha-hydroxylase/C17-20-lyase) and 5 alpha-reductase types 1 and 2. J Med Chem. 2000 Nov 2;43(22):4266-77. To Reference
Ref 2C16 and C17 substituted derivatives of pregnenolone and progesterone as inhibitors of 17alpha-hydroxylase-C17, 20-lyase: synthesis and biological evaluation. Arch Pharm (Weinheim). 2002;335(11-12):526-34. To Reference
Ref 3Inhibition of CYP 17, a new strategy for the treatment of prostate cancer. Arch Pharm (Weinheim). 2002 Apr;335(4):119-28. To Reference
Ref 4A molecular model for the enzyme cytochrome P450(17 alpha), a major target for the chemotherapy of prostatic cancer. Biochem Biophys Res Commun. 1990 Sep 28;171(3):1160-7. To Reference
Ref 5Bioorg Med Chem. 2008 Aug 15;16(16):7715-27. Epub 2008 Jul 9.Synthesis, biological evaluation, and molecular modeling studies of methylene imidazole substituted biaryls as inhibitors of human 17alpha-hydroxylase-17,20-lyase (CYP17)--part II: Core rigidification and influence of substituents at the methylene bridge. To Reference
Ref 6Bioorg Med Chem. 2008 Feb 15;16(4):1992-2010. Epub 2007 Nov 4.Synthesis, biological evaluation and molecular modelling studies of methyleneimidazole substituted biaryls as inhibitors of human 17alpha-hydroxylase-17,20-lyase (CYP17). Part I: Heterocyclic modifications of the core structure. To Reference
Ref 7Bioorg Med Chem Lett. 2006 Aug 1;16(15):4011-5. Epub 2006 Jun 5.Synthesis and biochemical evaluation of a range of potent benzyl imidazole-based compounds as potential inhibitors of the enzyme complex 17alpha-hydroxylase/17,20-lyase (P450(17alpha)). To Reference
Ref 8Bioorg Med Chem Lett. 2006 Sep 15;16(18):4752-6. Epub 2006 Jul 25.Synthesis, biochemical evaluation and rationalisation of the inhibitory activity of a range of 4-substituted phenyl alkyl imidazole-based inhibitors of the enzyme complex 17alpha-hydroxylase/17,20-lyase (P450(17alpha)). To Reference
Ref 9Bioorg Med Chem Lett. 2010 Sep 1;20(17):5345-8. Epub 2010 Mar 3.Synthesis and biochemical evaluation of a range of (4-substituted phenyl)sulfonate derivatives of 4-hydroxybenzyl imidazole-based compounds as potent inhibitors of 17alpha-hydroxylase/17,20-lyase (P45017alpha) derived from rat testicular microsomes. To Reference
Ref 10Bioorg Med Chem Lett. 1999 Feb 8;9(3):333-6.New selective nonsteroidal aromatase inhibitors: synthesis and inhibitory activity of 2,3 or 5-(alpha-azolylbenzyl)-1H-indoles. To Reference
Ref 11J Med Chem. 2001 Mar 1;44(5):672-80.A new class of nonsteroidal aromatase inhibitors: design and synthesis of chromone and xanthone derivatives and inhibition of the P450 enzymes aromatase and 17 alpha-hydroxylase/C17,20-lyase. To Reference
Ref 12J. Med. Chem. 53(14):5347-5351 (2010) To Reference
Ref 13J Med Chem. 1990 Sep;33(9):2452-5.Hydroxyperfluoroazobenzenes: novel inhibitors of enzymes of androgen biosynthesis. To Reference
Ref 14J Med Chem. 2005 Oct 20;48(21):6632-42.Heteroaryl-substituted naphthalenes and structurally modified derivatives: selective inhibitors of CYP11B2 for the treatment of congestive heart failure and myocardial fibrosis. To Reference
Ref 15J Med Chem. 2006 Apr 6;49(7):2222-31.Synthesis and evaluation of heteroaryl-substituted dihydronaphthalenes and indenes: potent and selective inhibitors of aldosterone synthase (CYP11B2) for the treatment of congestive heart failure and myocardial fibrosis. To Reference
Ref 16J Med Chem. 2008 Dec 25;51(24):8077-87.In vivo active aldosterone synthase inhibitors with improved selectivity: lead optimization providing a series of pyridine substituted 3,4-dihydro-1H-quinolin-2-one derivatives. To Reference
Ref 17J Med Chem. 2010 Aug 12;53(15):5749-58.Replacement of imidazolyl by pyridyl in biphenylmethylenes results in selective CYP17 and dual CYP17/CYP11B1 inhibitors for the treatment of prostate cancer. To Reference
Ref 18J Med Chem. 2005 Mar 10;48(5):1563-75.Synthesis and evaluation of (pyridylmethylene)tetrahydronaphthalenes/-indanes and structurally modified derivatives: potent and selective inhibitors of aldosterone synthase. To Reference
Ref 19J Med Chem. 2010 Jul 8;53(13):5049-53.Isopropylidene substitution increases activity and selectivity of biphenylmethylene 4-pyridine type CYP17 inhibitors. To Reference
Ref 20Bioorg Med Chem Lett. 2008 Jan 1;18(1):267-73. Epub 2007 Oct 30.Synthesis, biological evaluation and molecular modelling studies of novel ACD- and ABD-ring steroidomimetics as inhibitors of CYP17. To Reference
Ref 21J Med Chem. 2003 Jun 5;46(12):2345-51.Three dimensional pharmacophore modeling of human CYP17 inhibitors. Potential agents for prostate cancer therapy. To Reference
Ref 22Comparison of the 17 alpha-hydroxylase/C17,20-lyase activities of porcine, guinea pig and bovine P450c17 using purified recombinant fusion proteins containing P450c17 linked to NADPH-P450 reductase. Drug Metab Rev. 2007;39(2-3):289-307. To Reference
Ref 23Eur J Med Chem. 2009 Jul;44(7):2765-75. Epub 2009 Jan 19.Novel CYP17 inhibitors: synthesis, biological evaluation, structure-activity relationships and modelling of methoxy- and hydroxy-substituted methyleneimidazolyl biphenyls. To Reference


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