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Record Information
Version3.6
Creation Date2012-09-06 15:16:49 UTC
Update Date2016-02-11 01:28:44 UTC
HMDB IDHMDB14496
Secondary Accession NumbersNone
Metabolite Identification
Common NameThioguanine
DescriptionThioguanine is only found in individuals that have used or taken this drug. It is an antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia. [PubChem]Thioguanine competes with hypoxanthine and guanine for the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) and is itself converted to 6-thioguanilyic acid (TGMP), which reaches high intracellular concentrations at therapeutic doses. TGMP interferes with the synthesis of guanine nucleotides by its inhibition of purine biosynthesis by pseudofeedback inhibition of glutamine-5-phosphoribosylpyrophosphate amidotransferase, the first enzyme unique to the de novo pathway of purine ribonucleotide synthesis. TGMP also inhibits the conversion of inosinic acid (IMP) to xanthylic acid (XMP) by competition for the enzyme IMP dehydrogenase. Thioguanine nucleotides are incorporated into both the DNA and the RNA by phosphodiester linkages, and some studies have shown that incorporation of such false bases contributes to the cytotoxicity of thioguanine. Its tumor inhibitory properties may be due to one or more of its effects on feedback inhibition of de novo purine synthesis; inhibition of purine nucleotide interconversions; or incorporation into the DNA and RNA. The overall result of its action is a sequential blockade of the utilization and synthesis of the purine nucleotides.
Structure
Thumb
Synonyms
ValueSource
2-amino 6MPChEBI
2-amino-1,7-dihydro-6H-Purine-6-thioneChEBI
2-amino-1,9-Dihydropurine-6-thioneChEBI
2-amino-6-MercaptopurineChEBI
2-amino-6-MerkaptopurinChEBI
2-amino-6-PurinethiolChEBI
2-Aminopurin-6-thiolChEBI
2-Aminopurine-6(1H)-thioneChEBI
2-Aminopurine-6-thiolChEBI
6-mercapto-2-AminopurineChEBI
6-MercaptoguanineChEBI
6-TGChEBI
6-ThioguanineChEBI
TGChEBI
ThGChEBI
ThioguanineChEBI
TioguaninChEBI
TioguaninaChEBI
TioguaninumChEBI
Chemical FormulaC5H5N5S
Average Molecular Weight167.192
Monoisotopic Molecular Weight167.026565875
IUPAC Name2-amino-6,7-dihydro-3H-purine-6-thione
Traditional Namethioguanine
CAS Registry Number154-42-7
SMILES
NC1=NC(=S)C2=C(N1)N=CN2
InChI Identifier
InChI=1S/C5H5N5S/c6-5-9-3-2(4(11)10-5)7-1-8-3/h1H,(H4,6,7,8,9,10,11)
InChI KeyInChIKey=WYWHKKSPHMUBEB-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as purinethiones. These are purines in which the purine moiety bears a thioketone.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassImidazopyrimidines
Sub ClassPurines and purine derivatives
Direct ParentPurinethiones
Alternative Parents
Substituents
  • Purinethione
  • Pyrimidinethione
  • Pyrimidine
  • Primary aromatic amine
  • Heteroaromatic compound
  • Imidazole
  • Azole
  • Azacycle
  • Hydrocarbon derivative
  • Primary amine
  • Organosulfur compound
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Drug metabolite
Biofunction
  • Antimetabolites
  • Antineoplastic
  • Waste products
Application
  • Pharmaceutical
Cellular locations
  • Cytoplasm
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point> 360 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility8.34e-01 g/LNot Available
LogP-0.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.83 mg/mLALOGPS
logP-0.36ALOGPS
logP-0.35ChemAxon
logS-2.3ALOGPS
pKa (Strongest Acidic)10.53ChemAxon
pKa (Strongest Basic)3.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area79.09 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity46.89 m3·mol-1ChemAxon
Polarizability15.65 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
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, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue Location
  • Kidney
  • Liver
Pathways
NameSMPDB LinkKEGG Link
Thioguanine Metabolism PathwaySMP00647Not Available
Thioguanine PathwaySMP00430Not Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00352
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00352
  • Not Applicable
details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiofluidValueOriginal ageOriginal sexOriginal conditionComments
Blood0-6 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0-3 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00352
DrugBank Metabolite IDDBMET00623
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID2005804
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkThioguanine
NuGOwiki LinkHMDB14496
Metagene LinkHMDB14496
METLIN IDNot Available
PubChem Compound2723601
PDB IDDX4
ChEBI ID136864
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. FDA label

Enzymes

General function:
Involved in hypoxanthine phosphoribosyltransferase activity
Specific function:
Converts guanine to guanosine monophosphate, and hypoxanthine to inosine monophosphate. Transfers the 5-phosphoribosyl group from 5-phosphoribosylpyrophosphate onto the purine. Plays a central role in the generation of purine nucleotides through the purine salvage pathway.
Gene Name:
HPRT1
Uniprot ID:
P00492
Molecular weight:
24579.155
Reactions
Thioguanine + Phosphoribosyl pyrophosphate → 6-Thioguanosine monophosphate + Pyrophosphatedetails
References
  1. Shivashankar K, Subbayya IN, Balaram H: Development of a bacterial screen for novel hypoxanthine-guanine phosphoribosyltransferase substrates. J Mol Microbiol Biotechnol. 2001 Oct;3(4):557-62. [11545274 ]
  2. Horikawa K, Kawaguchi T, Ishihara S, Nagakura S, Hidaka M, Kagimoto T, Mitsuya H, Nakakuma H: Frequent detection of T cells with mutations of the hypoxanthine-guanine phosphoribosyl transferase gene in patients with paroxysmal nocturnal hemoglobinuria. Blood. 2002 Jan 1;99(1):24-9. [11756148 ]
  3. Fuscoe JC, Zimmerman LJ, Fekete A, Setzer RW, Rossiter BJ: Analysis of X-ray-induced HPRT mutations in CHO cells: insertion and deletions. Mutat Res. 1992 Oct;269(2):171-83. [1383700 ]
  4. Elgemeie GH: Thioguanine, mercaptopurine: their analogs and nucleosides as antimetabolites. Curr Pharm Des. 2003;9(31):2627-42. [14529546 ]
  5. Suzuki M, Tsuruoka C, Kanai T, Kato T, Yatagai F, Watanabe M: Qualitative and quantitative difference in mutation induction between carbon- and neon-ion beams in normal human cells. Biol Sci Space. 2003 Dec;17(4):302-6. [15136753 ]

Transporters

General function:
Involved in ATP binding
Specific function:
May be an organic anion pump relevant to cellular detoxification
Gene Name:
ABCC4
Uniprot ID:
O15439
Molecular weight:
149525.3
References
  1. Bai J, Lai L, Yeo HC, Goh BC, Tan TM: Multidrug resistance protein 4 (MRP4/ABCC4) mediates efflux of bimane-glutathione. Int J Biochem Cell Biol. 2004 Feb;36(2):247-57. [14643890 ]