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Showing metabocard for Itraconazole (HMDB0015298)
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Version | 4.0 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Status | Expected but not Quantified | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Creation Date | 2012-09-06 15:16:51 UTC | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Update Date | 2020-02-26 21:41:20 UTC | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
HMDB ID | HMDB0015298 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Secondary Accession Numbers |
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Metabolite Identification | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Common Name | Itraconazole | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Description | Itraconazole is only found in individuals that have used or taken this drug. It is one of the triazole antifungal agents that inhibits cytochrome P-450-dependent enzymes resulting in impairment of ergosterol synthesis. It has been used against histoplasmosis, blastomycosis, cryptococcal meningitis & aspergillosis. [PubChem]Itraconazole interacts with 14-alpha demethylase, a cytochrome P-450 enzyme necessary to convert lanosterol to ergosterol. As ergosterol is an essential component of the fungal cell membrane, inhibition of its synthesis results in increased cellular permeability causing leakage of cellular contents. Itraconazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms, inhibit purine uptake, and impair triglyceride and/or phospholipid biosynthesis. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Structure | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Synonyms |
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Chemical Formula | C35H38Cl2N8O4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Average Molecular Weight | 705.633 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Monoisotopic Molecular Weight | 704.239307158 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
IUPAC Name | 1-(butan-2-yl)-4-{4-[4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-4,5-dihydro-1H-1,2,4-triazol-5-one | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Traditional Name | itraconazole | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CAS Registry Number | 84625-61-6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
SMILES | CCC(C)N1N=CN(C1=O)C1=CC=C(C=C1)N1CCN(CC1)C1=CC=C(OC[C@H]2CO[C@@](CN3C=NC=N3)(O2)C2=C(Cl)C=C(Cl)C=C2)C=C1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
InChI Identifier | InChI=1S/C35H38Cl2N8O4/c1-3-25(2)45-34(46)44(24-40-45)29-7-5-27(6-8-29)41-14-16-42(17-15-41)28-9-11-30(12-10-28)47-19-31-20-48-35(49-31,21-43-23-38-22-39-43)32-13-4-26(36)18-33(32)37/h4-13,18,22-25,31H,3,14-17,19-21H2,1-2H3/t25?,31-,35-/m0/s1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
InChI Key | VHVPQPYKVGDNFY-ZPGVKDDISA-N | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Chemical Taxonomy | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Description | belongs to the class of organic compounds known as phenylpiperazines. Phenylpiperazines are compounds containing a phenylpiperazine skeleton, which consists of a piperazine bound to a phenyl group. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Kingdom | Organic compounds | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Super Class | Organoheterocyclic compounds | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Class | Diazinanes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sub Class | Piperazines | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Direct Parent | Phenylpiperazines | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Alternative Parents |
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Substituents |
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Molecular Framework | Aromatic heteromonocyclic compounds | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
External Descriptors |
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Ontology | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Disposition | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Role | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Physical Properties | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
State | Solid | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Experimental Properties |
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Predicted Properties |
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Spectra | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Biological Properties | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Cellular Locations |
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Biospecimen Locations |
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Tissue Locations | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Pathways |
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Normal Concentrations | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Abnormal Concentrations | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Predicted Concentrations | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Associated Disorders and Diseases | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Disease References | None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Associated OMIM IDs | None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
External Links | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
DrugBank ID | DB01167 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Phenol Explorer Compound ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
FooDB ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
KNApSAcK ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Chemspider ID | 49927 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
KEGG Compound ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
BioCyc ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
BiGG ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Wikipedia Link | Itraconazole | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
METLIN ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
PubChem Compound | 55283 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
PDB ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ChEBI ID | 6076 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Food Biomarker Ontology | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
VMH ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
MarkerDB ID | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
References | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Synthesis Reference | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Material Safety Data Sheet (MSDS) | Download (PDF) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
General References | Not Available |
Enzymes
- General function:
- Involved in monooxygenase activity
- Specific function:
- Catalyzes C14-demethylation of lanosterol; it transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol.
- Gene Name:
- CYP51A1
- Uniprot ID:
- Q16850
- Molecular weight:
- 57277.81
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
- Cotrim PC, Garrity LK, Beverley SM: Isolation of genes mediating resistance to inhibitors of nucleoside and ergosterol metabolism in Leishmania by overexpression/selection. J Biol Chem. 1999 Dec 31;274(53):37723-30. [PubMed:10608831 ]
- Carrillo-Munoz AJ, Giusiano G, Ezkurra PA, Quindos G: Antifungal agents: mode of action in yeast cells. Rev Esp Quimioter. 2006 Jun;19(2):130-9. [PubMed:16964330 ]
- General function:
- Involved in monooxygenase activity
- Specific function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
- Gene Name:
- CYP3A4
- Uniprot ID:
- P08684
- Molecular weight:
- 57255.585
References
- Niwa T, Shiraga T, Takagi A: Effect of antifungal drugs on cytochrome P450 (CYP) 2C9, CYP2C19, and CYP3A4 activities in human liver microsomes. Biol Pharm Bull. 2005 Sep;28(9):1805-8. [PubMed:16141567 ]
- Sakaeda T, Iwaki K, Kakumoto M, Nishikawa M, Niwa T, Jin JS, Nakamura T, Nishiguchi K, Okamura N, Okumura K: Effect of micafungin on cytochrome P450 3A4 and multidrug resistance protein 1 activities, and its comparison with azole antifungal drugs. J Pharm Pharmacol. 2005 Jun;57(6):759-64. [PubMed:15969931 ]
- Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
- General function:
- Involved in monooxygenase activity
- Specific function:
- Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms.
- Gene Name:
- CYP2E1
- Uniprot ID:
- P05181
- Molecular weight:
- 56848.42
References
- Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
- General function:
- Involved in monooxygenase activity
- Specific function:
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
- Gene Name:
- CYP2D6
- Uniprot ID:
- P10635
- Molecular weight:
- 55768.94
References
- Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
- General function:
- Involved in monooxygenase activity
- Specific function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
- Gene Name:
- CYP2B6
- Uniprot ID:
- P20813
- Molecular weight:
- 56277.81
References
- Walsky RL, Astuccio AV, Obach RS: Evaluation of 227 drugs for in vitro inhibition of cytochrome P450 2B6. J Clin Pharmacol. 2006 Dec;46(12):1426-38. [PubMed:17101742 ]
- General function:
- Involved in monooxygenase activity
- Specific function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
- Gene Name:
- CYP3A5
- Uniprot ID:
- P20815
- Molecular weight:
- 57108.065
- General function:
- Involved in monooxygenase activity
- Specific function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
- Gene Name:
- CYP1A1
- Uniprot ID:
- P04798
- Molecular weight:
- 58164.815
References
- Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
- General function:
- Involved in monooxygenase activity
- Specific function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
- Gene Name:
- CYP3A7
- Uniprot ID:
- P24462
- Molecular weight:
- 57525.03
Transporters
- General function:
- Involved in ATP binding
- Specific function:
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
- Gene Name:
- ABCB1
- Uniprot ID:
- P08183
- Molecular weight:
- 141477.3
References
- Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. [PubMed:11716514 ]
- Wang EJ, Lew K, Casciano CN, Clement RP, Johnson WW: Interaction of common azole antifungals with P glycoprotein. Antimicrob Agents Chemother. 2002 Jan;46(1):160-5. [PubMed:11751127 ]
- Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. [PubMed:12699389 ]
- Takara K, Tanigawara Y, Komada F, Nishiguchi K, Sakaeda T, Okumura K: Cellular pharmacokinetic aspects of reversal effect of itraconazole on P-glycoprotein-mediated resistance of anticancer drugs. Biol Pharm Bull. 1999 Dec;22(12):1355-9. [PubMed:10746169 ]
- Masuda S, Inui K: [Molecular mechanisms on drug transporters in the drug absorption and disposition]. Nihon Rinsho. 2002 Jan;60(1):65-73. [PubMed:11808341 ]
- Lilja JJ, Backman JT, Laitila J, Luurila H, Neuvonen PJ: Itraconazole increases but grapefruit juice greatly decreases plasma concentrations of celiprolol. Clin Pharmacol Ther. 2003 Mar;73(3):192-8. [PubMed:12621384 ]
- Sakaeda T, Iwaki K, Kakumoto M, Nishikawa M, Niwa T, Jin JS, Nakamura T, Nishiguchi K, Okamura N, Okumura K: Effect of micafungin on cytochrome P450 3A4 and multidrug resistance protein 1 activities, and its comparison with azole antifungal drugs. J Pharm Pharmacol. 2005 Jun;57(6):759-64. [PubMed:15969931 ]
- Saito M, Hirata-Koizumi M, Miyake S, Hasegawa R: Comparison of information on the pharmacokinetic interactions of Ca antagonists in the package inserts from three countries (Japan, USA and UK). Eur J Clin Pharmacol. 2005 Aug;61(7):531-6. Epub 2005 Jul 23. [PubMed:16041596 ]
- Shon JH, Yoon YR, Hong WS, Nguyen PM, Lee SS, Choi YG, Cha IJ, Shin JG: Effect of itraconazole on the pharmacokinetics and pharmacodynamics of fexofenadine in relation to the MDR1 genetic polymorphism. Clin Pharmacol Ther. 2005 Aug;78(2):191-201. [PubMed:16084853 ]