Details of Drug-Metabolizing Enzyme (DME)
General Information of Drug-Metabolizing Enzyme (DME) (ID: DEX2KIA)
DME Name | Steroid 17-alpha-monooxygenase (CYP17A1) | ||||
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Synonyms | Steroid 17-alpha-hydroxylase/17,20 lyase; Cytochrome P450 17A1; 17-alpha-hydroxyprogesterone aldolase; Cytochrome P450-C17; Cytochrome P450c17; CYP17; CYP17A1; CYPXVII; S17AH | ||||
Gene Name | CYP17A1 | ||||
UniProt ID | |||||
INTEDE ID | |||||
3D Structure | |||||
Gene ID | |||||
EC Number | EC: 1.14.99.9 | ||||
Lineage | Species: Homo sapiens | ||||
Sequence |
MWELVALLLLTLAYLFWPKRRCPGAKYPKSLLSLPLVGSLPFLPRHGHMHNNFFKLQKKY
GPIYSVRMGTKTTVIVGHHQLAKEVLIKKGKDFSGRPQMATLDIASNNRKGIAFADSGAH WQLHRRLAMATFALFKDGDQKLEKIICQEISTLCDMLATHNGQSIDISFPVFVAVTNVIS LICFNTSYKNGDPELNVIQNYNEGIIDNLSKDSLVDLVPWLKIFPNKTLEKLKSHVKIRN DLLNKILENYKEKFRSDSITNMLDTLMQAKMNSDNGNAGPDQDSELLSDNHILTTIGDIF GAGVETTTSVVKWTLAFLLHNPQVKKKLYEEIDQNVGFSRTPTISDRNRLLLLEATIREV LRLRPVAPMLIPHKANVDSSIGEFAVDKGTEVIINLWALHHNEKEWHQPDQFMPERFLNP AGTQLISPSVSYLPFGAGPRSCIGEILARQELFLIMAWLLQRFDLEVPDDGQLPSLEGIP KVVFLIDSFKVKIKVRQAWREAQAEGST |
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Function |
This enzyme is involved in corticoid and androgen biosynthesis. It catalyzes 17-alpha hydroxylation of C21 steroids, which is common for both pathways. A second oxidative step, required only for androgen synthesis, involves an acyl-carbon cleavage. The 17-alpha hydroxy intermediates, as part of adrenal glucocorticoids biosynthesis pathway, are precursors of cortisol. Hydroxylates steroid hormones, pregnenolone and progesterone to form 17-alpha hydroxy metabolites, followed by the cleavage of the C17-C20 bond to form C19 steroids, dehydroepiandrosterone (DHEA) and androstenedione. It has 16-alpha hydroxylase activity. It catalyzes 16-alpha hydroxylation of 17-alpha hydroxy pregnenolone, followed by the cleavage of the C17-C20 bond to form 16-alpha-hydroxy DHEA and also 16-alpha hydroxylates androgens, relevant for estriol synthesis.
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KEGG Pathway | |||||
Reactome Pathway | |||||
Molecular Interaction Atlas (MIA) of This DME
Molecular Interaction Atlas (MIA) | ||||||||||||||||||||||||||||||||||
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2 Approved Drug(s) Metabolized by This DME
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1 Discontinued Drug(s) Metabolized by This DME
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1 Investigative Drug(s) Metabolized by This DME
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Molecular Expression Atlas (MEA) of This DME
The Drug Therapeutic Target (DTT) Role of This DME
DME DTT Name | Steroid 17-alpha-monooxygenase (S17AH) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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DME DTT Type | Successful | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
2 Approved Drug(s) Targeting This DTT
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5 Clinical Trial Drug(s) Targeting This DTT
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89 Investigative Drug(s) Targeting This DTT
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References
1 | 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4. | ||||
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2 | CYP17A1 inhibitors in castration-resistant prostate cancer.Steroids.2015 Mar;95:80-7. | ||||
3 | Orteronel (TAK-700), a novel non-steroidal 17,20-lyase inhibitor: effects on steroid synthesis in human and monkey adrenal cells and serum steroid levels in cynomolgus monkeys. J Steroid Biochem Mol Biol. 2012 Apr;129(3-5):115-28. | ||||
4 | Clinical pipeline report, company report or official report of Tavanta Therapeutics | ||||
5 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | ||||
6 | Recent progress in pharmaceutical therapies for castration-resistant prostate cancer. Int J Mol Sci. 2013 Jul 4;14(7):13958-78. | ||||
7 | Clinical pipeline report, company report or official report of DisperSol Technologies. | ||||
8 | Synthesis, biological evaluation, and molecular modeling studies of methylene imidazole substituted biaryls as inhibitors of human 17alpha-hydroxyl... Bioorg Med Chem. 2008 Aug 15;16(16):7715-27. | ||||
9 | Synthesis, biological evaluation and molecular modelling studies of methyleneimidazole substituted biaryls as inhibitors of human 17alpha-hydroxyla... Bioorg Med Chem. 2008 Feb 15;16(4):1992-2010. | ||||
10 | Synthesis and biochemical evaluation of a range of potent benzyl imidazole-based compounds as potential inhibitors of the enzyme complex 17alpha-hy... Bioorg Med Chem Lett. 2006 Aug 1;16(15):4011-5. | ||||
11 | Synthesis, biochemical evaluation and rationalisation of the inhibitory activity of a range of 4-substituted phenyl alkyl imidazole-based inhibitor... Bioorg Med Chem Lett. 2006 Sep 15;16(18):4752-6. | ||||
12 | Synthesis and biochemical evaluation of a range of (4-substituted phenyl)sulfonate derivatives of 4-hydroxybenzyl imidazole-based compounds as pote... Bioorg Med Chem Lett. 2010 Sep 1;20(17):5345-8. | ||||
13 | New selective nonsteroidal aromatase inhibitors: synthesis and inhibitory activity of 2,3 or 5-(alpha-azolylbenzyl)-1H-indoles. Bioorg Med Chem Lett. 1999 Feb 8;9(3):333-6. | ||||
14 | 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. J Med Chem. 2001 Mar 1;44(5):672-80. | ||||
15 | Novel highly potent and selective nonsteroidal aromatase inhibitors: synthesis, biological evaluation and structure-activity relationships investigation. J Med Chem. 2010 Jul 22;53(14):5347-51. | ||||
16 | Hydroxyperfluoroazobenzenes: novel inhibitors of enzymes of androgen biosynthesis. J Med Chem. 1990 Sep;33(9):2452-5. | ||||
17 | Heteroaryl-substituted naphthalenes and structurally modified derivatives: selective inhibitors of CYP11B2 for the treatment of congestive heart fa... J Med Chem. 2005 Oct 20;48(21):6632-42. | ||||
18 | Synthesis and evaluation of heteroaryl-substituted dihydronaphthalenes and indenes: potent and selective inhibitors of aldosterone synthase (CYP11B... J Med Chem. 2006 Apr 6;49(7):2222-31. | ||||
19 | In vivo active aldosterone synthase inhibitors with improved selectivity: lead optimization providing a series of pyridine substituted 3,4-dihydro-... J Med Chem. 2008 Dec 25;51(24):8077-87. | ||||
20 | Isopropylidene substitution increases activity and selectivity of biphenylmethylene 4-pyridine type CYP17 inhibitors. J Med Chem. 2010 Jul 8;53(13):5049-53. | ||||
21 | Replacement of imidazolyl by pyridyl in biphenylmethylenes results in selective CYP17 and dual CYP17/CYP11B1 inhibitors for the treatment of prosta... J Med Chem. 2010 Aug 12;53(15):5749-58. | ||||
22 | Synthesis and evaluation of (pyridylmethylene)tetrahydronaphthalenes/-indanes and structurally modified derivatives: potent and selective inhibitor... J Med Chem. 2005 Mar 10;48(5):1563-75. | ||||
23 | Synthesis, biological evaluation and molecular modelling studies of novel ACD- and ABD-ring steroidomimetics as inhibitors of CYP17. Bioorg Med Chem Lett. 2008 Jan 1;18(1):267-73. | ||||
24 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1361). | ||||
25 | Three dimensional pharmacophore modeling of human CYP17 inhibitors. Potential agents for prostate cancer therapy. J Med Chem. 2003 Jun 5;46(12):2345-51. | ||||
26 | Novel CYP17 inhibitors: synthesis, biological evaluation, structure-activity relationships and modelling of methoxy- and hydroxy-substituted methyl... Eur J Med Chem. 2009 Jul;44(7):2765-75. | ||||
27 | Contribution of human hepatic cytochrome P450s and steroidogenic CYP17 to the N-demethylation of aminopyrine. Xenobiotica. 1999 Feb;29(2):187-93. | ||||
28 | Identifying susceptibility genes for prostate cancer--a family-based association study of polymorphisms in CYP17, CYP19, CYP11A1, and LH-beta. Cancer Epidemiol Biomarkers Prev. 2005 Aug;14(8):2035-9. | ||||
29 | In vitro metabolism of dexamethasone (DEX) in human liver and kidney: the involvement of CYP3A4 and CYP17 (17,20 LYASE) and molecular modelling studies. Biochem Pharmacol. 1997 Sep 1;54(5):605-11. | ||||
30 | Transcriptional complexes at the CYP17 CRS. Endocr Res. 2002 Nov;28(4):551-8. | ||||