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Mercaptopurine

July 24, 2017
Common Name

Mercaptopurine Description

Mercaptopurine 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 intracellliar 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

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source 1,7-dihydro-6H-Purine-6-thioneChEBI 3H-Purine-6-thiolChEBI 6-MPChEBI 6-ThiohypoxanthineChEBI 6 MPHMDB 6-MercaptopurineHMDB Mercaptopurine monohydrateHMDB MercapurinHMDB MPHMDB 6 Mercaptopurine monohydrateMeSH 6-Mercaptopurine monohydrateMeSH Puri-netholMeSH 6 MercaptopurineMeSH GlaxoSmithKline brand OF 6 mercaptopurineMeSH LeupurinMeSH Wellcome brand OF 6-mercaptopurineMeSH 6 ThiohypoxanthineMeSH 6 ThiopurineMeSH glaxo Wellcome brand OF 6 mercaptopurineMeSH GlaxoSmithKline brand OF 6-mercaptopurineMeSH Puri netholMeSH Wellcome brand OF 6 mercaptopurineMeSH 6-ThiopurineMeSH glaxo Wellcome brand OF 6-mercaptopurineMeSH Mercaptopurina wellcomeMeSH PurimetholMeSH PurinetholMeSH

Chemical Formlia

C5H4N4S Average Molecliar Weight

152.177 Monoisotopic Molecliar Weight

152.015666838 IUPAC Name

6,7-dihydro-3H-purine-6-thione Traditional Name

mercaptopurine CAS Registry Number

50-44-2 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 Key

GLVAUDGFNGKCSF-UHFFFAOYSA-N Chemical Taxonomy Description

This compound belongs to the class of organic compounds known as purinethiones. These are purines in which the purine moiety bears a thioketone. Kingdom

Organic compounds Super Class

Organoheterocyclic compounds Class

Imidazopyrimidines Sub Class

Purines and purine derivatives Direct Parent

Purinethiones Alternative Parents

  • Pyrimidinethiones
  • Imidazoles
  • Heteroaromatic compounds
  • Azacyclic compounds
  • Organoslifur compounds
  • Organopnictogen compounds
  • Organonitrogen compounds
  • Hydrocarbon derivatives

    • Substituents

  • Purinethione
  • Pyrimidinethione
  • Pyrimidine
  • Heteroaromatic compound
  • Imidazole
  • Azole
  • Azacycle
  • Organic nitrogen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organoslifur compound
  • Organonitrogen compound
  • Aromatic heteropolycyclic compound

    • Molecliar Framework

    Aromatic heteropolycyclic compounds External Descriptors

  • aryl thiol (CHEBI:2208 )

    • Ontology Status

    Expected 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

    • Cellliar locations

  • Cytoplasm
  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting Point313 °CNot Available Boiling PointNot AvailableNot Available Water Solubility7.35e-01 g/LNot Available LogP-0.4Not Available

    Predicted Properties

    Property Value Source 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 Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QQ , negativesplash10-0udi-1900000000-80fade3542b1b7a4f542View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QQ , negativesplash10-0udi-4900000000-ae3cab845511e09fd7d8View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QQ , negativesplash10-052f-9400000000-eb3a9e5b93f0954dda1fView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QQ , negativesplash10-066u-9300000000-e920208db376745577aeView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QQ , negativesplash10-014r-9100000000-9452425dda09b342a804View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QQ , positivesplash10-000i-0900000000-fb1e1ed0d15536d940b5View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QQ , positivesplash10-00di-9300000000-ae82c485895af50f18e0View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QQ , positivesplash10-01ba-9700000000-70542617d846459d1edbView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QQ , positivesplash10-00kb-9400000000-34922db319d482f338c7View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QQ , positivesplash10-0006-9000000000-7de65dacfd12ff92f5e4View in MoNA Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available

    Biological Properties Cellliar Locations

  • Cytoplasm
  • Membrane

    • Biofluid Locations

  • Blood
  • Urine

    • Tissue Location

  • Kidney
  • Liver

    • Pathways

    Name SMPDB Link KEGG Link Azathioprine Metabolism PathwaySMP00645Not Available Azathioprine PathwaySMP00427Not Available Mercaptopurine Metabolism PathwaySMP00609Not Available Mercaptopurine PathwaySMP00428Not Available Thioguanine PathwaySMP00430Not Available

    Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01033

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01033

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB01033 DrugBank Metabolite ID

    DBMET00630 Phenol Explorer Compound ID

    Not Available Phenol Explorer Metabolite ID

    Not Available FoodDB ID

    Not Available KNApSAcK ID

    Not Available Chemspider ID

    580869 KEGG Compound ID

    Not Available BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Mercaptopurine NuGOwiki Link

    HMDB15167 Metagene Link

    HMDB15167 METLIN ID

    Not Available PubChem Compound

    667490 PDB ID

    PM6 ChEBI ID

    2208

    Product: Sevelamer

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References Not 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 peroxide details
    References
    1. Dubinsky MC: Azathioprine, 6-mercaptopurine in inflammatory bowel disease: pharmacology, efficacy, and safety. Clin Gastroenterol Hepatol. 2004 Sep;2(9):731-43. [PubMed: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-Adenosylhomocysteine details
    References
    1. Dubinsky MC: Azathioprine, 6-mercaptopurine in inflammatory bowel disease: pharmacology, efficacy, and safety. Clin Gastroenterol Hepatol. 2004 Sep;2(9):731-43. [PubMed: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 + Pyrophosphate details
    References
    1. Dubinsky MC: Azathioprine, 6-mercaptopurine in inflammatory bowel disease: pharmacology, efficacy, and safety. Clin Gastroenterol Hepatol. 2004 Sep;2(9):731-43. [PubMed: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. [PubMed: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. [PubMed:10840050 ]

    PMID: 9327720

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