Tmic
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Record Information
Version2.0
Creation Date2009-07-21 20:26:16 UTC
Update Date2014-12-24 20:25:50 UTC
Accession NumberT3D2711
Identification
Common NameFluconazole
ClassSmall Molecule
DescriptionFluconazole is only found in individuals that have used or taken this drug. It is a triazole antifungal agent that is used to treat oropharyngeal candidiasis and cryptococcal meningitis in AIDS. Fluconazole interacts with 14-α 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. Fluconazole 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.
Compound Type
  • Amine
  • Antifungal Agent
  • Drug
  • Metabolite
  • Organic Compound
  • Organofluoride
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
2,4-Difluoro-alpha,alpha-bis(1H-1,2,4-triazol-1-ylmethyl)benzyl alcohol
2-(2,4-DIFLUOROPHENYL)-1,3-di(1H-1,2,4-triazol-1-yl)propan-2-ol
Biozole
Diflucan
Elazor
Flucazol
Fluconazol
Fluconazolum
Flucostat
Flunizol
Monicure
Pritenzol
Trican
Triflucan
Chemical FormulaC13H12F2N6O
Average Molecular Mass306.271 g/mol
Monoisotopic Mass306.104 g/mol
CAS Registry Number86386-73-4
IUPAC Name2-(2,4-difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)propan-2-ol
Traditional Namefluconazole
SMILESOC(CN1C=NC=N1)(CN1C=NC=N1)C1=C(F)C=C(F)C=C1
InChI IdentifierInChI=1S/C13H12F2N6O/c14-10-1-2-11(12(15)3-10)13(22,4-20-8-16-6-18-20)5-21-9-17-7-19-21/h1-3,6-9,22H,4-5H2
InChI KeyInChIKey=RFHAOTPXVQNOHP-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as fluorobenzenes. Fluorobenzenes are compounds containing one or more fluorine atoms attached to a benzene ring.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassHalobenzenes
Direct ParentFluorobenzenes
Alternative Parents
Substituents
  • Fluorobenzene
  • Aryl fluoride
  • Aryl halide
  • Azole
  • Tertiary alcohol
  • 1,2,4-triazole
  • Heteroaromatic compound
  • Organoheterocyclic compound
  • Azacycle
  • Aromatic alcohol
  • Organic nitrogen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Organopnictogen compound
  • Alcohol
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point138-140°C
Boiling PointNot Available
Solubility1 mg/L
LogP0.4
Predicted Properties
PropertyValueSource
Water Solubility1.39 g/LALOGPS
logP0.58ALOGPS
logP0.56ChemAxon
logS-2.3ALOGPS
pKa (Strongest Acidic)12.71ChemAxon
pKa (Strongest Basic)2.56ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area81.65 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity97.2 m³·mol⁻¹ChemAxon
Polarizability26.52 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-05bf-7950000000-e40a22ece3de9aec6341View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-003s-7190000000-b0fd755fce78f1747bddView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0g70-2920000000-a8a6188f5a32495c6efaView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0006-0900000000-339ec0708a6a6299e4d1View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0006-0900000000-ea278fc262275613a1feView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0006-0900000000-bbdadb624a7360b26fa3View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-00kf-6900000000-0316b801589bae74a3f9View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-014i-9100000000-d7b76913f55978a00d10View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-014i-9000000000-45cd8f87d45358745d5bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-014i-9000000000-2f3230e2968762340fb0View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0006-0900000000-ea0bdd0dd4905f7ca2a7View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0006-0900000000-643df112c60eecdd6f26View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-00kf-6900000000-636d53fe2393f25b4cc4View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-014i-9100000000-2d05579f16a7ce194afbView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-014i-9000000000-bb834fc848ba7398b278View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-014i-9000000000-e3f46745a82b72dc28b0View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0006-0900000000-565636d9f9e684b11429View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0006-0900000000-224c620bb2943c3558aaView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-000i-0090000000-d00a2d66aa1d04145279View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a4i-0019000000-9ddd55ba2decdc6d3007View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0079-0091000000-5501d6ab39e3fb2e3676View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-0019000000-476f05b29d87ff403349View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0r09-0093000000-61a1882c6efca9aa9bdbView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00di-7690000000-8c3dcc7b7469b99a5ee8View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-052f-0905000000-e49e8ab1264fe8c94232View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-2469000000-a1df61d9dd20cf349f79View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-014i-9340000000-a2819b76c4147ab6396dView in MoNA
Toxicity Profile
Route of ExposureIntravenous, Oral
Mechanism of ToxicityFluconazole interacts with 14-α 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. Fluconazole 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.
MetabolismHepatic Route of Elimination: In normal volunteers, fluconazole is cleared primarily by renal excretion, with approximately 80% of the administered dose appearing in the urine as unchanged drug. Half Life: 30 hours (range 20-50 hours)
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of fungal infections.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSymptoms of overdose include hallucinations and paranoid behavior.
TreatmentIn the event of overdose, symptomatic treatment (with supportive measures and gastric lavage if clinically indicated) should be instituted. (2)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00196
HMDB IDHMDB14342
PubChem Compound ID3365
ChEMBL IDCHEMBL106
ChemSpider ID3248
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI ID46081
BioCyc IDNot Available
CTD IDNot Available
Stitch IDFluconazole
PDB IDTPF
ACToR IDNot Available
Wikipedia LinkFluconazole
References
Synthesis Reference

DrugSyn.org

MSDSLink
General References
  1. Drugs.com [Link]
  2. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Sterol 14-demethylase 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:
56805.26 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>200 uMNot AvailableBindingDB 25817
Dissociation40 uMNot AvailableBindingDB 25817
Dissociation70 uMNot AvailableBindingDB 25817
Dissociation120 uMNot AvailableBindingDB 25817
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Fukuoka T, Johnston DA, Winslow CA, de Groot MJ, Burt C, Hitchcock CA, Filler SG: Genetic basis for differential activities of fluconazole and voriconazole against Candida krusei. Antimicrob Agents Chemother. 2003 Apr;47(4):1213-9. [12654649 ]
  3. Bellamine A, Lepesheva GI, Waterman MR: Fluconazole binding and sterol demethylation in three CYP51 isoforms indicate differences in active site topology. J Lipid Res. 2004 Nov;45(11):2000-7. Epub 2004 Aug 16. [15314102 ]
  4. Guinea J, Sanchez-Somolinos M, Cuevas O, Pelaez T, Bouza E: Fluconazole resistance mechanisms in Candida krusei: the contribution of efflux-pumps. Med Mycol. 2006 Sep;44(6):575-8. [16966178 ]
  5. Chau AS, Chen G, McNicholas PM, Mann PA: Molecular basis for enhanced activity of posaconazole against Absidia corymbifera and Rhizopus oryzae. Antimicrob Agents Chemother. 2006 Nov;50(11):3917-9. Epub 2006 Sep 11. [16966400 ]
  6. Korosec T, Acimovic J, Seliskar M, Kocjan D, Tacer KF, Rozman D, Urleb U: Novel cholesterol biosynthesis inhibitors targeting human lanosterol 14alpha-demethylase (CYP51). Bioorg Med Chem. 2008 Jan 1;16(1):209-21. Epub 2007 Oct 4. [17964172 ]
  7. Warrilow AG, Jackson CJ, Parker JE, Marczylo TH, Kelly DE, Lamb DC, Kelly SL: Identification, characterization, and azole-binding properties of Mycobacterium smegmatis CYP164A2, a homolog of ML2088, the sole cytochrome P450 gene of Mycobacterium leprae. Antimicrob Agents Chemother. 2009 Mar;53(3):1157-64. doi: 10.1128/AAC.01237-08. Epub 2008 Dec 15. [19075057 ]
  8. Ekins S, Mankowski DC, Hoover DJ, Lawton MP, Treadway JL, Harwood HJ Jr: Three-dimensional quantitative structure-activity relationship analysis of human CYP51 inhibitors. Drug Metab Dispos. 2007 Mar;35(3):493-500. Epub 2006 Dec 28. [17194716 ]
General Function:
Vitamin d3 25-hydroxylase 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 (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599).
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5025 uMNot AvailableBindingDB 25817
References
  1. Roy K, Pratim Roy P: Comparative chemometric modeling of cytochrome 3A4 inhibitory activity of structurally diverse compounds using stepwise MLR, FA-MLR, PLS, GFA, G/PLS and ANN techniques. Eur J Med Chem. 2009 Jul;44(7):2913-22. doi: 10.1016/j.ejmech.2008.12.004. Epub 2008 Dec 16. [19128860 ]
General Function:
Nad binding
Specific Function:
Not Available
Gene Name:
MDH1
Uniprot ID:
P40925
Molecular Weight:
36425.795 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>400 uMNot AvailableBindingDB 25817
References
  1. Seidler J, McGovern SL, Doman TN, Shoichet BK: Identification and prediction of promiscuous aggregating inhibitors among known drugs. J Med Chem. 2003 Oct 9;46(21):4477-86. [14521410 ]
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.56 uMNVS_ADME_hCYP2C19Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]