Tmic
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Record Information
Version2.0
Creation Date2009-07-30 17:58:37 UTC
Update Date2014-12-24 20:26:06 UTC
Accession NumberT3D3477
Identification
Common NameAllopurinol
ClassSmall Molecule
DescriptionAllopurinol is only found in individuals that have used or taken this drug. It is a xanthine oxidase inhibitor that decreases uric acid production. It also acts as an antimetabolite on some simpler organisms. [PubChem] Allopurinol and its active metabolite, oxypurinol, inhibits the enzyme xanthine oxidase, blocking the conversion of the oxypurines hypoxanthine and xanthine to uric acid. Elevated concentrations of oxypurine and oxypurine inhibition of xanthine oxidase through negative feedback results in a decrease in the concentrations of uric acid in the serum and urine. Allopurinol also facilitates the incorporation of hypoxanthine and xanthine into DNA and RNA, leading to a feedback inhibition of de novo purin synthesis and a decrease in serum uric acid concentrations as a result of an increase in nucleotide concentration.
Compound Type
  • Amide
  • Antimetabolite
  • Drug
  • Enzyme Inhibitor
  • Free Radical Scavenger
  • Gout Suppressant
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
1,5-Dihydro-4H-pyrazolo(3,4-D)pyrimidin-4-one
1,5-Dihydro-4H-pyrazolo(3,4-D)pyrimidine-4-one
1H-Pyrazolo(3,4-D)pyrimidin-4-ol
4'-Hydroxypyrazolol(3,4-D)pyrimidine
4-HPP
4-Hydroxy-1H-pyrazolo(3,4-D)pyrimidine
4-Hydroxy-3,4-pyrazolopyrimidine
4-Hydroxypyrazolo(3,4-D)pyrimidine
4-Hydroxypyrazolopyrimidine
4-Hydroxypyrazolyl(3,4-D)pyrimidine
4H-Pyrazolo(3,4-D)pyrimidin-4-one
Adenock
AL-100
Allohexal
Allopurinolum
Alloril
Aloprim
Alopurinol
Aluron
Milurit
Progout
Zyloprim
Zyloric
Zyrik
Chemical FormulaC5H4N4O
Average Molecular Mass136.112 g/mol
Monoisotopic Mass136.039 g/mol
CAS Registry Number315-30-0
IUPAC Name1H,2H,4H-pyrazolo[3,4-d]pyrimidin-4-one
Traditional NameALLO
SMILESOC1=NC=NC2=NNC=C12
InChI IdentifierInChI=1S/C5H4N4O/c10-5-3-1-8-9-4(3)6-2-7-5/h1-2H,(H2,6,7,8,9,10)
InChI KeyInChIKey=OFCNXPDARWKPPY-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as pyrazolo[3,4-d]pyrimidines. These are aromatic heterocyclic compounds containing a pyrazolo[3,4-d]pyrimidine ring system, which consists of a pyrazole ring fused to but and not sharing a nitrogen atom with a pyrimidine ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPyrazolopyrimidines
Sub ClassPyrazolo[3,4-d]pyrimidines
Direct ParentPyrazolo[3,4-d]pyrimidines
Alternative Parents
Substituents
  • Pyrazolo[3,4-d]pyrimidine
  • Pyrimidone
  • Pyrimidine
  • Azole
  • Pyrazole
  • Vinylogous amide
  • Heteroaromatic compound
  • Azacycle
  • Organonitrogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Organooxygen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic 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 Point350°C
Boiling PointNot Available
Solubility569 mg/L (at 25°C)
LogP-0.55
Predicted Properties
PropertyValueSource
Water Solubility5.88 g/LALOGPS
logP-1.7ALOGPS
logP-1.8ChemAxon
logS-1.4ALOGPS
pKa (Strongest Acidic)7.83ChemAxon
pKa (Strongest Basic)2.57ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area65.85 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity54.24 m³·mol⁻¹ChemAxon
Polarizability11.67 ųChemAxon
Number of Rings2ChemAxon
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, Positivesplash10-0550-8900000000-225d53e43d6b82e006bfView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-000i-4900000000-5d6d365d7525c7325e01View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-000i-4900000000-ea448e075f973faea5ecView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-000l-8900000000-98d308813f954ccc66e0View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0006-9300000000-a0c962d1b7e8e76fd526View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0006-9100000000-d692c85314f5809e4758View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-01ox-9000000000-2662f35a8efe21c51958View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-000i-0900000000-4f38b316b66733e5ca8bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-000i-0900000000-547b3dac7e9b0d01ef66View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-000i-0900000000-43ea9e7d5a0f94da482fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-000i-1900000000-fee6f9103fdd4cb1b6edView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-01p9-1900000000-eb9ece2b9b724a6af483View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-03dr-2900000000-85aef327ef1281780d05View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0900000000-1eb7584dbb0630e49004View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-000i-1900000000-4e5cd23deb565d2f87e0View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-07wc-9200000000-214c548ad4d15f5bfbf4View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0900000000-b7681f9e17751c711d37View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000i-2900000000-a7c487c6207a07bf2903View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9100000000-af7211d0cc75dda0b005View in MoNA
MSMass Spectrum (Electron Ionization)splash10-000i-7900000000-f5a7601a354a9d25428fView in MoNA
Toxicity Profile
Route of ExposureApproximately 80-90% absorbed from the gastrointestinal tract.
Mechanism of ToxicityAllopurinol inhibits the enzyme xanthine oxidase, blocking the conversion of the oxypurines hypoxanthine and xanthine to uric acid. Elevated concentrations of oxypurine and oxypurine inhibition of xanthine oxidase through negative feedback results in a decrease in the concentrations of uric acid in the blood and urine. Allopurinol also facilitates the incorporation of hypoxanthine and xanthine into DNA and RNA, resulting in further reductions of serum uric acid concentrations.
MetabolismHepatic Route of Elimination: Approximately 20% of the ingested allopurinol is excreted in the feces. Half Life: 1-3 hours
Toxicity ValuesLD50=214 mg/kg (in mice)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of hyperuricemia associated with primary or secondary gout. Also indicated for the treatment of primary or secondary uric acid nephropathy, with or without the symptoms of gout, as well as chemotherapy-induced hyperuricemia and recurrent renal calculi.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsLD50=214 mg/kg (in mice)
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00437
HMDB IDHMDB14581
PubChem Compound ID2094
ChEMBL IDCHEMBL1467
ChemSpider ID2010
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI ID40279
BioCyc IDCPD-9024
CTD IDNot Available
Stitch IDAllopurinol
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkAllopurinol
References
Synthesis Reference

Druey, J. and Schmidt, P.; US. Patent 2868,803; January 13,1959; assigned to Ciba Pharmaceutical Products Inc.
Hitchings, G.H. and Falco, EA.; U.S. Patent 3,474,098; October 21,1969; assigned to Bur-
roughs Wellcome & Co.
Cresswell, R.M.and Mentha, J.W.; US.Patent4,146,713; March27,1979; assigned to Bur-
roughs Wellcome & Co.

MSDSLink
General References
  1. Pacher P, Nivorozhkin A, Szabo C: Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. Pharmacol Rev. 2006 Mar;58(1):87-114. [16507884 ]
  2. Schlesinger N: Diagnosing and treating gout: a review to aid primary care physicians. Postgrad Med. 2010 Mar;122(2):157-61. doi: 10.3810/pgm.2010.03.2133. [20203467 ]
  3. Suzuki I, Yamauchi T, Onuma M, Nozaki S: Allopurinol, an inhibitor of uric acid synthesis--can it be used for the treatment of metabolic syndrome and related disorders? Drugs Today (Barc). 2009 May;45(5):363-78. doi: 10.1358/dot.2009.45.5.1370460. [19584965 ]
  4. Terkeltaub R: Update on gout: new therapeutic strategies and options. Nat Rev Rheumatol. 2010 Jan;6(1):30-8. doi: 10.1038/nrrheum.2009.236. [20046204 ]
  5. George J, Struthers AD: Role of urate, xanthine oxidase and the effects of allopurinol in vascular oxidative stress. Vasc Health Risk Manag. 2009;5(1):265-72. Epub 2009 Apr 8. [19436671 ]
  6. Drugs.com [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated GenesNot Available

Targets

General Function:
Xanthine oxidase activity
Specific Function:
Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Has also low oxidase activity towards aldehydes (in vitro).
Gene Name:
XDH
Uniprot ID:
P47989
Molecular Weight:
146422.99 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]