Detail Information of Xenobiotics

General Information of Xenobiotics (ID: XEO00251)
Xenobiotics Name
Ketoconazole
Xenobiotics Type
Pharmaceutical Agent(s)
Classification
Approved/Marketed Drug
Structure
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3D MOL 2D MOL
PubChem CID
3823
DME(s) Modulated by This Xenobiotics
DME(s) Inhibited by This Xenobiotics
Steroid 11-beta-hydroxylase (CYP11B1) DME Info Homo sapiens [1]
Aldosterone synthase (CYP11B2) DME Info Homo sapiens [2]
Steroid 17-alpha-monooxygenase (CYP17A1) DME Info Homo sapiens [3]
Aromatase (CYP19A1) DME Info Homo sapiens [4]
Cytochrome P450 1A1 (CYP1A1) DME Info Homo sapiens [5]
Cytochrome P450 1A2 (CYP1A2) DME Info Homo sapiens [6]
Cytochrome P450 1B1 (CYP1B1) DME Info Homo sapiens [7]
Vitamin D(3) 24-hydroxylase (CYP24A1) DME Info Homo sapiens [8]
Retinoic acid 4-hydroxylase 26A1 (CYP26A1) DME Info Homo sapiens [9]
Retinoic acid 4-hydroxylase 26B1 (CYP26B1) DME Info Homo sapiens [10]
Cytochrome P450 2B6 (CYP2B6) DME Info Homo sapiens [7]
Mephenytoin 4-hydroxylase (CYP2C19) DME Info Homo sapiens [6]
Cytochrome P450 2C8 (CYP2C8) DME Info Homo sapiens [6]
Cytochrome P450 2C9 (CYP2C9) DME Info Homo sapiens [7], [11]
Cytochrome P450 2D6 (CYP2D6) DME Info Homo sapiens [6]
Cytochrome P450 2E1 (CYP2E1) DME Info Homo sapiens [11]
Cytochrome P450 2J2 (CYP2J2) DME Info Homo sapiens [12]
Cytochrome P450 3A4 (CYP3A4) DME Info Homo sapiens [13]
Cytochrome P450 3A5 (CYP3A5) DME Info Homo sapiens [14], [15]
Cytochrome P450 4F12 (CYP4F12) DME Info Homo sapiens [7]
Cytochrome P450 4F2 (CYP4F2) DME Info Homo sapiens [16]
Glutathione S-transferase alpha-1 (GSTA1) DME Info Homo sapiens [17]
Glutathione S-transferase alpha-2 (GSTA2) DME Info Homo sapiens [17]
HMG-CoA reductase (HMGCR) DME Info Homo sapiens [18]
Corticosteroid 11-beta-dehydrogenase 2 (HSD11B2) DME Info Homo sapiens [19]
Beta-HSD adrenal and gonadal type (HSD3B2) DME Info Homo sapiens [18]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DME Info Homo sapiens [20]
DME(s) Induced by This Xenobiotics
Asparagine synthetase (ASNS) DME Info Homo sapiens [21], [22]
Steroid 21-hydroxylase (CYP21A2) DME Info Homo sapiens [23]
Peroxisomal multifunctional enzyme 2 (HSD17B4) DME Info Homo sapiens [18]
Quinone reductase 1 (NQO1) DME Info Homo sapiens [24]
Xenobiotics-DME Activity Data
Xenobiotics-DME Activity Data Steroid 11-beta-hydroxylase (CYP11B1) DME Info IC50 = 0.116 microM [1]
Aldosterone synthase (CYP11B2) DME Info IC50 = 0.067 microM [2]
Steroid 17-alpha-monooxygenase (CYP17A1) DME Info IC50 = 0.026 microM [3]
Aromatase (CYP19A1) DME Info IC50 = 0.04 microM [4]
Cytochrome P450 1A2 (CYP1A2) DME Info IC50 = 26 microM [6]
Vitamin D(3) 24-hydroxylase (CYP24A1) DME Info IC50 = 0.126 microM [8]
Mephenytoin 4-hydroxylase (CYP2C19) DME Info IC50 = 10.1 microM [6]
Cytochrome P450 2C8 (CYP2C8) DME Info IC50 = 2.45 microM [6]
Cytochrome P450 2C9 (CYP2C9) DME Info IC50 = 40 microM [7], [11]
Cytochrome P450 2D6 (CYP2D6) DME Info IC50 = 16.3 microM [6]
Cytochrome P450 3A4 (CYP3A4) DME Info IC50 < 0.062 microM [13]
Cytochrome P450 3A5 (CYP3A5) DME Info IC50 = 0.12 microM [14], [15]
Cytochrome P450 4F2 (CYP4F2) DME Info IC50 = 1.6 microM [16]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DME Info IC50 = 13 microM [20]
References
1 Design, synthesis, and evaluation of (2S,4R)-Ketoconazole sulfonamide analogs as potential treatments for Metabolic Syndrome. Bioorg Med Chem Lett. 2016 Dec 1;26(23):5825-5829.
2 First selective CYP11B1 inhibitors for the treatment of cortisol-dependent diseases. ACS Med Chem Lett. 2010 Oct 22;2(1):2-6.
3 Novel steroidal inhibitors of human cytochrome P45017 alpha (17 alpha-hydroxylase-C17,20-lyase): potential agents for the treatment of prostatic cancer. J Med Chem. 1995 Jun 23;38(13):2463-71.
4 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. J Med Chem. 2006 Apr 6;49(7):2222-31.
5 Ketoconazole stereoisomers differentially induce cytochrome P450 1A1 between human hepatoma HepG2 and mouse hepatoma Hepa1c1c7 cells. J Pharm Sci. 2016 Mar;105(3):1318-26.
6 Identifying a selective substrate and inhibitor pair for the evaluation of CYP2J2 activity. Drug Metab Dispos. 2012 May;40(5):943-51.
7 Highly selective inhibition of human CYP3Aa in vitro by azamulin and evidence that inhibition is irreversible. Drug Metab Dispos. 2004 Jan;32(1):105-12.
8 Synthesis and CYP24A1 inhibitory activity of N-(2-(1H-imidazol-1-yl)-2-phenylethyl)arylamides. Bioorg Med Chem. 2010 Jul 15;18(14):4939-46.
9 Induction of CYP26A1 by metabolites of retinoic acid: evidence that CYP26A1 is an important enzyme in the elimination of active retinoids. Mol Pharmacol. 2015;87(3):430-41.
10 A novel human cytochrome P450, CYP26C1, involved in metabolism of 9-cis and all-trans isomers of retinoic acid. J Biol Chem. 2004 Jan 2;279(1):77-85.
11 In vitro inhibitory effect of 1-aminobenzotriazole on drug oxidations catalyzed by human cytochrome P450 enzymes: a comparison with SKF-525A and ketoconazole. Drug Metab Pharmacokinet. 2003;18(5):287-95.
12 In vitro inhibition of human small intestinal and liver microsomal astemizole O-demethylation: different contribution of CYP2J2 in the small intestine and liver. Xenobiotica. 2003 Jun;33(6):615-23.
13 Discovery of novel pyrimidine and malonamide derivatives as TGR5 agonists. Bioorg Med Chem Lett. 2014 Sep 1;24(17):4271-5.
14 Metabolism of alfentanil by cytochrome p4503a (cyp3a) enzymes. Drug Metab Dispos. 2005 Mar;33(3):303-11.
15 CYP3A5 mediates bioactivation and cytotoxicity of tetrandrine. Arch Toxicol. 2016 Jul;90(7):1737-48.
16 CYP4F enzymes are responsible for the elimination of fingolimod (FTY720), a novel treatment of relapsing multiple sclerosis. Drug Metab Dispos. 2011 Feb;39(2):191-8.
17 Ketoconazole and miconazole are antagonists of the human glucocorticoid receptor: consequences on the expression and function of the constitutive androstane receptor and the pregnane X receptor. Mol Pharmacol. 2006 Jul;70(1):329-39.
18 The H295R system for evaluation of endocrine-disrupting effects. Ecotoxicol Environ Saf. 2006 Nov;65(3):293-305.
19 In the search for specific inhibitors of human 11beta-hydroxysteroid-dehydrogenases (11beta-HSDs): chenodeoxycholic acid selectively inhibits 11beta-HSD-I. Eur J Endocrinol. 2000 Feb;142(2):200-7.
20 Correlation between bilirubin glucuronidation and estradiol-3-gluronidation in the presence of model UDP-glucuronosyltransferase 1A1 substrates/inhibitors. Drug Metab Dispos. 2011 Feb;39(2):322-9.
21 A toxicogenomic approach to drug-induced phospholipidosis: analysis of its induction mechanism and establishment of a novel in vitro screening system. Toxicol Sci. 2005 Feb;83(2):282-92.
22 Determination of phospholipidosis potential based on gene expression analysis in HepG2 cells. Toxicol Sci. 2007 Mar;96(1):101-14.
23 A fission yeast-based test system for the determination of IC50 values of anti-prostate tumor drugs acting on CYP21. J Enzyme Inhib Med Chem. 2006 Oct;21(5):547-56.
24 Identification of ketoconazole as an AhR-Nrf2 activator in cultured human keratinocytes: the basis of its anti-inflammatory effect. J Invest Dermatol. 2012 Jan;132(1):59-68.

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