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    
CYPXVII    
P450 17    
P450-C17    
P450c17    
Steroid 17-alpha-hydroxylase/17,20 lyase    
DiseaseBenign prostate hyperplasia
[ICD9: 600   ICD10: N40]
[1]
Prostate cancer
[ICD9: 185   ICD10: C61]
[2][3][4]
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 1.14.99.9
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.    
SequenceMWELVALLLLTLAYLFWPKRRCPGAKYPKSLLSLPLVGSLPFLPRHGHMHNNFFKLQKKY GPIYSVRMGTKTTVIVGHHQLAKEVLIKKGKDFSGRPQMATLDIASNNRKGIAFADSGAH WQLHRRLAMATFALFKDGDQKLEKIICQEISTLCDMLATHNGQSIDISFPVFVAVTNVIS LICFNTSYKNGDPELNVIQNYNEGIIDNLSKDSLVDLVPWLKIFPNKTLEKLKSHVKIRN DLLNKILENYKEKFRSDSITNMLDTLMQAKMNSDNGNAGPDQDSELLSDNHILTTIGDIF GAGVETTTSVVKWTLAFLLHNPQVKKKLYEEIDQNVGFSRTPTISDRNRLLLLEATIREV LRLRPVAPMLIPHKANVDSSIGEFAVDKGTEVIINLWALHHNEKEWHQPDQFMPERFLNP AGTQLISPSVSYLPFGAGPRSCIGEILARQELFLIMAWLLQRFDLEVPDDGQLPSLEGIP KVVFLIDSFKVKIKVRQAWREAQAEGST
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]
1-Imidazol-1-ylmethyl-4-nitro-xanthen-9-one[11]
1-Imidazol-1-ylmethylxanthen-9-one[12]
2,3,4,5-Tetrafluoro-6-pentafluorophenylazo-phenol[13]
2,3,5,6-Tetrafluoro-4-pentafluorophenylazo-phenol[13]
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-Bromo-1-imidazol-1-ylmethyl-xanthen-9-one[11]
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-Pyridin-3-yl-naphthalen-2-ol[14]
6-[4- (Pyridin-4-ylmethyl)phenyl]naphthalen-2-ol[17]
7- (1-[5]
ABIRATERONE[6]
ISOCONAZOLE[21]
N- (4'-Isonicotinoylbiphenyl-3-yl)acetamide[17]
N-3- (4-bromophenyl)propyl imidazole[8]
Pregnenolone[22][2]
Progesterone[2]
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



 

Welcome to sign our Guestbook.

If you find any error in data or bug in web service, please kindly report it to Dr. Zhu.


Dr. Chen Yuzong
Deputy Director of Center for Computational Science and Engineering
Professor in Department of Pharmacy
National University of Singapore, Singapore


All rights reserved.

   
 
 
Computer-aided Drug Design
about BIDD |  databases |  software |  teaching |  research |  links

 

Department of Computational Science | National University of Singapore | Blk S17, 3 Science Drive 2, Singapore 117543