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Record Information
Version3.6
Creation Date2012-09-06 15:16:51 UTC
Update Date2016-02-11 01:31:43 UTC
HMDB IDHMDB15167
Secondary Accession NumbersNone
Metabolite Identification
Common NameMercaptopurine
DescriptionMercaptopurine is only found in individuals that have used or taken this drug. It is an antimetabolite antineoplastic agent with immunosuppressant properties. It interferes with nucleic acid synthesis by inhibiting purine metabolism and is used, usually in combination with other drugs, in the treatment of or in remission maintenance programs for leukemia. [PubChem]Mercaptopurine competes with hypoxanthine and guanine for the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) and is itself converted to thioinosinic acid (TIMP). This intracellular nucleotide inhibits several reactions involving inosinic acid (IMP), including the conversion of IMP to xanthylic acid (XMP) and the conversion of IMP to adenylic acid (AMP) via adenylosuccinate (SAMP). In addition, 6-methylthioinosinate (MTIMP) is formed by the methylation of TIMP. Both TIMP and MTIMP have been reported to inhibit glutamine-5-phosphoribosylpyrophosphate amidotransferase, the first enzyme unique to the de novo pathway for purine ribonucleotide synthesis. Experiments indicate that radiolabeled mercaptopurine may be recovered from the DNA in the form of deoxythioguanosine. Some mercaptopurine is converted to nucleotide derivatives of 6-thioguanine (6-TG) by the sequential actions of inosinate (IMP) dehydrogenase and xanthylate (XMP) aminase, converting TIMP to thioguanylic acid (TGMP).
Structure
Thumb
Synonyms
ValueSource
1,7-dihydro-6H-Purine-6-thioneChEBI
3H-Purine-6-thiolChEBI
6-MPChEBI
6-ThiohypoxanthineChEBI
6 MPHMDB
6-MercaptopurineHMDB
Mercaptopurine monohydrateHMDB
MercapurinHMDB
MPHMDB
Chemical FormulaC5H4N4S
Average Molecular Weight152.177
Monoisotopic Molecular Weight152.015666838
IUPAC Name6,7-dihydro-3H-purine-6-thione
Traditional Namemercaptopurine
CAS Registry Number50-44-2
SMILES
S=C1N=CNC2=C1NC=N2
InChI Identifier
InChI=1S/C5H4N4S/c10-5-3-4(7-1-6-3)8-2-9-5/h1-2H,(H2,6,7,8,9,10)
InChI KeyInChIKey=GLVAUDGFNGKCSF-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
  • Heteroaromatic compound
  • Imidazole
  • Azole
  • Azacycle
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organonitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Drug
  • Drug metabolite
Biofunction
  • Antimetabolites
  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • Immunosuppressive Agents
  • Nucleic Acid Synthesis Inhibitors
  • Purine analogues
  • Waste products
Application
  • Pharmaceutical
Cellular locations
  • Cytoplasm
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point313 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility7.35e-01 g/LNot Available
LogP-0.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.73 mg/mLALOGPS
logP-0.13ALOGPS
logP-0.12ChemAxon
logS-2.3ALOGPS
pKa (Strongest Acidic)9.5ChemAxon
pKa (Strongest Basic)2.99ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area53.07 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity43.6 m3·mol-1ChemAxon
Polarizability14.04 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
Azathioprine Metabolism PathwaySMP00645Not Available
Azathioprine PathwaySMP00427Not Available
Mercaptopurine Metabolism PathwaySMP00609Not Available
Mercaptopurine PathwaySMP00428Not Available
Thioguanine PathwaySMP00430Not Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01033
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01033
  • Not Applicable
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01033
DrugBank Metabolite IDDBMET00630
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID580869
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkMercaptopurine
NuGOwiki LinkHMDB15167
Metagene LinkHMDB15167
METLIN IDNot Available
PubChem Compound667490
PDB IDPM6
ChEBI ID2208
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General ReferencesNot Available

Enzymes

General function:
Involved in oxidoreductase 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
Reactions
Mercaptopurine + Water + Oxygen → 6-Thiourate + Hydrogen peroxidedetails
References
  1. Dubinsky MC: Azathioprine, 6-mercaptopurine in inflammatory bowel disease: pharmacology, efficacy, and safety. Clin Gastroenterol Hepatol. 2004 Sep;2(9):731-43. [15354273 ]
General function:
Involved in thiopurine S-methyltransferase activity
Specific function:
Catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine.
Gene Name:
TPMT
Uniprot ID:
P51580
Molecular weight:
28180.09
Reactions
Mercaptopurine + S-Adenosylmethionine → 6-Methylmercaptopurine + S-Adenosylhomocysteinedetails
References
  1. Dubinsky MC: Azathioprine, 6-mercaptopurine in inflammatory bowel disease: pharmacology, efficacy, and safety. Clin Gastroenterol Hepatol. 2004 Sep;2(9):731-43. [15354273 ]
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
Mercaptopurine + Phosphoribosyl pyrophosphate → 6-Thioinosine-5'-monophosphate + Pyrophosphatedetails
References
  1. Dubinsky MC: Azathioprine, 6-mercaptopurine in inflammatory bowel disease: pharmacology, efficacy, and safety. Clin Gastroenterol Hepatol. 2004 Sep;2(9):731-43. [15354273 ]

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. Chen ZS, Lee K, Kruh GD: Transport of cyclic nucleotides and estradiol 17-beta-D-glucuronide by multidrug resistance protein 4. Resistance to 6-mercaptopurine and 6-thioguanine. J Biol Chem. 2001 Sep 7;276(36):33747-54. Epub 2001 Jul 10. [11447229 ]
General function:
Involved in ATP binding
Specific function:
Acts as a multispecific organic anion pump which can transport nucleotide analogs
Gene Name:
ABCC5
Uniprot ID:
O15440
Molecular weight:
160658.8
References
  1. Wijnholds J, Mol CA, van Deemter L, de Haas M, Scheffer GL, Baas F, Beijnen JH, Scheper RJ, Hatse S, De Clercq E, Balzarini J, Borst P: Multidrug-resistance protein 5 is a multispecific organic anion transporter able to transport nucleotide analogs. Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7476-81. [10840050 ]