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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:52 UTC
Update Date2017-12-07 02:50:50 UTC
HMDB IDHMDB0015392
Secondary Accession Numbers
  • HMDB15392
Metabolite Identification
Common NamePosaconazole
DescriptionPosaconazole is only found in individuals that have used or taken this drug. It is a triazole antifungal drug that is used to treat invasive infections by Candida species and Aspergillus species in severely immunocompromised patients.As a triazole antifungal agent, posaconazole exerts its antifungal activity through blockage of the cytochrome P-450 dependent enzyme, sterol 14alpha-demethylase, in fungi by binding to the heme cofactor located on the enzyme. This leads to the inhibition of the synthesis of ergosterol, a key component of the fungal cell membrane, and accumulation of methylated sterol precursors. This results in inhibition of fungal cell growth and ultimately, cell death.
Structure
Thumb
SynonymsNot Available
Chemical FormulaC37H42F2N8O4
Average Molecular Weight700.7774
Monoisotopic Molecular Weight700.329708282
IUPAC Name4-{4-[4-(4-{[(5R)-5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-1-[(2S,3S)-2-hydroxypentan-3-yl]-4,5-dihydro-1H-1,2,4-triazol-5-one
Traditional Nameposaconazole
CAS Registry Number171228-49-2
SMILES
CC[C@@H]([C@H](C)O)N1N=CN(C1=O)C1=CC=C(C=C1)N1CCN(CC1)C1=CC=C(OCC2CO[C@](CN3C=NC=N3)(C2)C2=C(F)C=C(F)C=C2)C=C1
InChI Identifier
InChI=1S/C37H42F2N8O4/c1-3-35(26(2)48)47-36(49)46(25-42-47)31-7-5-29(6-8-31)43-14-16-44(17-15-43)30-9-11-32(12-10-30)50-20-27-19-37(51-21-27,22-45-24-40-23-41-45)33-13-4-28(38)18-34(33)39/h4-13,18,23-27,35,48H,3,14-17,19-22H2,1-2H3/t26-,27?,35-,37-/m0/s1
InChI KeyRAGOYPUPXAKGKH-AGDNISCASA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as phenylpiperazines. These are compounds containing a phenylpiperazine skeleton, which consists of a piperazine bound to a phenyl group.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganoheterocyclic compounds
Sub ClassDiazinanes
Direct ParentPhenylpiperazines
Alternative Parents
Substituents
  • Phenylpiperazine
  • N-arylpiperazine
  • Phenyltriazole
  • Phenyl-1,2,4-triazole
  • Aminophenyl ether
  • Phenol ether
  • Phenoxy compound
  • Tertiary aliphatic/aromatic amine
  • Dialkylarylamine
  • Aniline or substituted anilines
  • Alkyl aryl ether
  • Fluorobenzene
  • Halobenzene
  • Benzenoid
  • Aryl fluoride
  • Aryl halide
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • 1,2,4-triazole
  • Triazole
  • Azole
  • Oxolane
  • Tertiary amine
  • Secondary alcohol
  • Ether
  • Dialkyl ether
  • Oxacycle
  • Azacycle
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Amine
  • Alcohol
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organic oxygen compound
  • Organic nitrogen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Ontology
Disposition

Biological Location:

  Subcellular:

  Biofluid and excreta:

Role

Industrial application:

  Pharmaceutical industry:

  Agriculture:

  Food and nutrition:

Indirect biological role:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.012 g/LNot Available
LogP5.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.012 g/LALOGPS
logP4.71ALOGPS
logP5.41ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)14.83ChemAxon
pKa (Strongest Basic)3.93ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area111.79 ŲChemAxon
Rotatable Bond Count12ChemAxon
Refractivity200.71 m³·mol⁻¹ChemAxon
Polarizability74.25 ųChemAxon
Number of Rings7ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-0040039200-08b07b2fdb6037d69badView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0006-0720039000-7e147a828156c564ac33View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00fr-9371110000-e757e7e4205eb5a2addaView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-9000142000-912e0dd76ed50c57ab1cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-014i-9010023000-d36da0a08d20809373faView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-014i-9021020000-0edf495d49e1ace75ed5View in MoNA
Biological Properties
Cellular Locations
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
NameSMPDB/PathwhizKEGG
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01263 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01263 details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiofluidValueOriginal ageOriginal sexOriginal conditionComments
Blood0-1 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0-1 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01263
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID130409
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkPosaconazole
METLIN IDNot Available
PubChem Compound147912
PDB IDNot Available
ChEBI IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Kwon DS, Mylonakis E: Posaconazole: a new broad-spectrum antifungal agent. Expert Opin Pharmacother. 2007 Jun;8(8):1167-78. [PubMed:17516880 ]
  2. Groll AH, Walsh TJ: Posaconazole: clinical pharmacology and potential for management of fungal infections. Expert Rev Anti Infect Ther. 2005 Aug;3(4):467-87. [PubMed:16107193 ]
  3. Ullmann AJ, Lipton JH, Vesole DH, Chandrasekar P, Langston A, Tarantolo SR, Greinix H, Morais de Azevedo W, Reddy V, Boparai N, Pedicone L, Patino H, Durrant S: Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med. 2007 Jan 25;356(4):335-47. [PubMed:17251530 ]
  4. Cornely OA, Maertens J, Winston DJ, Perfect J, Ullmann AJ, Walsh TJ, Helfgott D, Holowiecki J, Stockelberg D, Goh YT, Petrini M, Hardalo C, Suresh R, Angulo-Gonzalez D: Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med. 2007 Jan 25;356(4):348-59. [PubMed:17251531 ]
  5. Schiller DS, Fung HB: Posaconazole: an extended-spectrum triazole antifungal agent. Clin Ther. 2007 Sep;29(9):1862-86. [PubMed:18035188 ]
  6. Frampton JE, Scott LJ: Posaconazole : a review of its use in the prophylaxis of invasive fungal infections. Drugs. 2008;68(7):993-1016. [PubMed:18457464 ]
  7. Rachwalski EJ, Wieczorkiewicz JT, Scheetz MH: Posaconazole: an oral triazole with an extended spectrum of activity. Ann Pharmacother. 2008 Oct;42(10):1429-38. doi: 10.1345/aph.1L005. Epub 2008 Aug 19. [PubMed:18713852 ]
  8. Li Y, Theuretzbacher U, Clancy CJ, Nguyen MH, Derendorf H: Pharmacokinetic/pharmacodynamic profile of posaconazole. Clin Pharmacokinet. 2010 Jun;49(6):379-96. doi: 10.2165/11319340-000000000-00000. [PubMed:20481649 ]
  9. Bhattacharya M, Rajeshwari K, Dhingra B: Posaconazole. J Postgrad Med. 2010 Apr-Jun;56(2):163-7. doi: 10.4103/0022-3859.65281. [PubMed:20622401 ]

Enzymes

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
  1. Nagappan V, Deresinski S: Reviews of anti-infective agents: posaconazole: a broad-spectrum triazole antifungal agent. Clin Infect Dis. 2007 Dec 15;45(12):1610-7. doi: 10.1086/523576. [PubMed:18190324 ]
  2. Kharuzhyk SA, Matskevich SA, Filjustin AE, Bogushevich EV, Ugolkova SA: Survey of computed tomography doses and establishment of national diagnostic reference levels in the Republic of Belarus. Radiat Prot Dosimetry. 2010 Apr-May;139(1-3):367-70. doi: 10.1093/rpd/ncq070. Epub 2010 Feb 24. [PubMed:20181649 ]
  3. Kwon DS, Mylonakis E: Posaconazole: a new broad-spectrum antifungal agent. Expert Opin Pharmacother. 2007 Jun;8(8):1167-78. [PubMed:17516880 ]

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
  1. Nagappan V, Deresinski S: Reviews of anti-infective agents: posaconazole: a broad-spectrum triazole antifungal agent. Clin Infect Dis. 2007 Dec 15;45(12):1610-7. doi: 10.1086/523576. [PubMed:18190324 ]