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Details

Stereochemistry ACHIRAL
Molecular Formula C5H5N5S
Molecular Weight 167.192
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of THIOGUANINE ANHYDROUS

SMILES

NC1=NC2=C(N=CN2)C(=S)N1

InChI

InChIKey=WYWHKKSPHMUBEB-UHFFFAOYSA-N
InChI=1S/C5H5N5S/c6-5-9-3-2(4(11)10-5)7-1-8-3/h1H,(H4,6,7,8,9,10,11)

HIDE SMILES / InChI

Description

Thioguanine is an antineoplastic anti-metabolite used in the treatment of several forms of leukemia including acute nonlymphocytic leukemia. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. Thioguanine was first synthesized and entered into clinical trial more than 30 years ago. It is a 6-thiopurine analogue of the naturally occurring purine bases hypoxanthine and guanine. Intracellular activation results in incorporation into DNA as a false purine base. An additional cytotoxic effect is related to its incorporation into RNA. Thioguanine is cross-resistant with mercaptopurine. Cytotoxicity is cell cycle phase-specific (S-phase). 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. Thioguanine is used for remission induction and remission consolidation treatment of acute nonlymphocytic leukemias. It is marketed under the trade name Lanvis and Tabloid among others.

CNS Activity

Approval Year

PMID

PMID

TitleDatePMID
Clinical evaluation of thioguanosine.
1961 Sep
Veno-occlusive disease of the liver associated with thiopurines in a child with acute lymphoblastic leukemia.
2000 Jul-Aug
Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias.
2000 May
Role of glutathione S-transferase mu (GSTM1) in styrene-7,8-oxide toxicity and mutagenicity.
2001
Favorable outcome for children and adolescents with T-cell lymphoblastic lymphoma with an intensive ALL-type therapy without local radiotherapy.
2001
Pharmacokinetic considerations in the treatment of inflammatory bowel disease.
2001
Gene- and tissue-specificity of mutation in Big Blue rats treated with the hepatocarcinogen N-hydroxy-2-acetylaminofluorene.
2001
Remission induction therapy: the more intensive the better?
2001 Aug
Reversal of cytosine arabinoside (ara-C) resistance by the synergistic combination of 6-thioguanine plus ara-C plus PEG-asparaginase (TGAP) in human leukemia lines lacking or expressing p53 protein.
2001 Aug
Differing contribution of thiopurine methyltransferase to mercaptopurine versus thioguanine effects in human leukemic cells.
2001 Aug 1
The histone deacetylase inhibitor trichostatin A reduces nickel-induced gene silencing in yeast and mammalian cells.
2001 Aug 8
Bilateral breast relapse in acute myelogenous leukemia.
2001 Feb
New developments in the immunosuppressive drug monitoring of cyclosporine, tacrolimus, and azathioprine.
2001 Feb
Pharmacotherapeutic options in inflammatory bowel disease: an update.
2001 Feb
A novel protein complex distinct from mismatch repair binds thioguanylated DNA.
2001 Feb
Molecular dynamics of DNA quadruplex molecules containing inosine, 6-thioguanine and 6-thiopurine.
2001 Jan
Antimetabolites and cytotoxic drugs.
2001 Jan
Thioguanine for refractory psoriasis: a 4-year experience.
2001 Jan
Antimutagenic activity of fluphenazine in short-term tests.
2001 Jan
Patients with de novo acute myeloid leukaemia and complex karyotype aberrations show a poor prognosis despite intensive treatment: a study of 90 patients.
2001 Jan
Topoisomerase I-mediated cytotoxicity of N-methyl-N'-nitro-N-nitrosoguanidine: trapping of topoisomerase I by the O6-methylguanine.
2001 Jan 1
The use of denaturing high-pressure liquid chromatography for the detection of mutations in thiopurine methyltransferase.
2001 Jan 30
[Primary pulmonary manifestation of extramedullary acute myelocytic leukemia].
2001 Jun
Isodicentric 7p, idic(7)(q11.2), in acute myeloid leukemia associated with older age and favorable response to induction chemotherapy: a new clinical entity?
2001 Mar
Plasma pharmacokinetics and cerebrospinal fluid penetration of thioguanine in children with acute lymphoblastic leukemia: a collaborative Pediatric Oncology Branch, NCI, and Children's Cancer Group study.
2001 Mar
Acute myeloid leukaemia (AML): treatment of the older patient.
2001 Mar
Heterozygosity for the thiopurine methyltransferase *3A allele in an acute non-lymphoblastic leukaemia patient with delayed marrow regeneration following H-DAT chemotherapy.
2001 Mar
Cell killing and mutation induction by heavy ion beams.
2001 May
Molecular characterisation of camptothecin-induced mutations at the hprt locus in Chinese hamster cells.
2001 May 9
Possible implication of thiopurine S-methyltransferase in occurrence of infectious episodes during maintenance therapy for childhood lymphoblastic leukemia with mercaptopurine.
2001 Nov
Substitution F569S converts UapA, a specific uric acid-xanthine transporter, into a broad specificity transporter for purine-related solutes.
2001 Nov 2
Co-amplification of dhfr and a homologue of hmsh3 in a Chinese hamster methotrexate-resistant cell line correlates with resistance to a range of chemotherapeutic drugs.
2001 Oct
Determination of thiopurine methyltransferase activity in human erythrocytes by high-performance liquid chromatography: comparison with the radiochemical method.
2001 Oct
Managing the glucocorticoid dependent inflammatory bowel disease patient.
2001 Oct
Targeting DNA mismatch repair for radiosensitization.
2001 Oct
FAB M4 and high CD14 surface expression is associated with high cellular resistance to Ara-C and daunorubicin: implications for clinical outcome in acute myeloid leukaemia.
2001 Oct
Hypoxia-induced enrichment and mutagenesis of cells that have lost DNA mismatch repair.
2001 Oct 15
Desmutagenic and bio-antimutagenic activity of docosahexaenoic acid and eicosapentaenoic acid in cultured Chinese hamster V79 cells.
2001 Oct 18
The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial.
2001 Sep 1
Attempts to improve treatment outcomes in acute myeloid leukemia (AML) in older patients: the results of the United Kingdom Medical Research Council AML11 trial.
2001 Sep 1
Photodynamic therapy of DNA mismatch repair-deficient and -proficient tumour cells.
2002 Apr 8
Effect of methotrexate polyglutamates on thioguanine nucleotide concentrations during continuation therapy of acute lymphoblastic leukemia with mercaptopurine.
2002 Feb
Diversity of the apoptotic response to chemotherapy in childhood leukemia.
2002 Feb
Inflammatory bowel disease.
2002 Jan
Frequent detection of T cells with mutations of the hypoxanthine-guanine phosphoribosyl transferase gene in patients with paroxysmal nocturnal hemoglobinuria.
2002 Jan 1
Flow cytometric determination of HPRT-variants in human peripheral blood lymphocytes.
2002 Jan 29
[Hypomethylation and multiple sclerosis, the susceptibility factor?].
2002 Mar
Pharmacological characterization of the ATP-dependent low K(m) guanosine 3',5'-cyclic monophosphate (cGMP) transporter in human erythrocytes.
2002 Mar 1
Childhood hyperuricemia and acute renal failure resulting from a missense mutation in the HPRT gene.
2002 Mar 15
X-ray induced mutation in Syrian hamster fetal cells.
2002 Mar 20
Patent

Sample Use Guides

In Vivo Use Guide
Single Agent Chemotherapy: Usual Initial dose: 2 mg/kg/day orally. If, after 4 weeks on this dosage, there is no clinical improvement and no leukocyte or platelet depression, the dosage may be cautiously increased to 3 mg/kg per day. The total daily dose may be given at one time. As a part of combination therapy for induction of remission in patients with acute nonlymphocytic leukemia: 75 to 200 mg/m2/day in 1 to 2 divided doses for 5 to 7 days or until remission is attained.
Route of Administration:
In Vitro Use Guide
Maximum cytotoxicity against leukemic cells from patients with ALL occured at 0.5 uM
Name Type Language
THIOGUANINE ANHYDROUS
Common Name English
THIOGUANINE, ANHYDROUS
Common Name English
NSC-752
Code English
TIOGUANINE [WHO-DD]
Common Name English
6-THIOGUANINE
Systematic Name English
2-AMINOPURINE-6(1H)-THIONE
Systematic Name English
TIOGUANINE [INN]
Common Name English
TIOGUANINE
INN   WHO-DD  
INN  
Official Name English
6H-PURINE-6-THIONE, 2-AMINO-1,7-DIHYDRO-
Systematic Name English
THIOGUANINE [HSDB]
Common Name English
THIOGUANINE [MI]
Common Name English
NSC-76504
Code English
Classification Tree Code System Code
NDF-RT N0000180853
Created by admin on Tue Mar 06 11:20:34 UTC 2018 , Edited by admin on Tue Mar 06 11:20:34 UTC 2018
WHO-ATC L01BB03
Created by admin on Tue Mar 06 11:20:34 UTC 2018 , Edited by admin on Tue Mar 06 11:20:34 UTC 2018
WHO-VATC QL01BB03
Created by admin on Tue Mar 06 11:20:34 UTC 2018 , Edited by admin on Tue Mar 06 11:20:34 UTC 2018
Code System Code Type Description
NCI_THESAURUS
C61970
Created by admin on Tue Mar 06 11:20:34 UTC 2018 , Edited by admin on Tue Mar 06 11:20:34 UTC 2018
PRIMARY
LactMed
154-42-7
Created by admin on Tue Mar 06 11:20:34 UTC 2018 , Edited by admin on Tue Mar 06 11:20:34 UTC 2018
PRIMARY
ECHA (EC/EINECS)
205-827-2
Created by admin on Tue Mar 06 11:20:34 UTC 2018 , Edited by admin on Tue Mar 06 11:20:34 UTC 2018
PRIMARY
ChEMBL
CHEMBL727
Created by admin on Tue Mar 06 11:20:34 UTC 2018 , Edited by admin on Tue Mar 06 11:20:34 UTC 2018
PRIMARY
HSDB
154-42-7
Created by admin on Tue Mar 06 11:20:34 UTC 2018 , Edited by admin on Tue Mar 06 11:20:34 UTC 2018
PRIMARY
DRUG BANK
DB00352
Created by admin on Tue Mar 06 11:20:34 UTC 2018 , Edited by admin on Tue Mar 06 11:20:34 UTC 2018
PRIMARY
EVMPD
SUB11084MIG
Created by admin on Tue Mar 06 11:20:34 UTC 2018 , Edited by admin on Tue Mar 06 11:20:34 UTC 2018
PRIMARY
CAS
154-42-7
Created by admin on Tue Mar 06 11:20:34 UTC 2018 , Edited by admin on Tue Mar 06 11:20:34 UTC 2018
PRIMARY
PUBCHEM
2723601
Created by admin on Tue Mar 06 11:20:34 UTC 2018 , Edited by admin on Tue Mar 06 11:20:34 UTC 2018
PRIMARY SWITZERF
WIKIPEDIA
TIOGUANINE
Created by admin on Tue Mar 06 11:20:34 UTC 2018 , Edited by admin on Tue Mar 06 11:20:34 UTC 2018
PRIMARY
INN
1998
Created by admin on Tue Mar 06 11:20:34 UTC 2018 , Edited by admin on Tue Mar 06 11:20:34 UTC 2018
PRIMARY
RXCUI
1546005
Created by admin on Tue Mar 06 11:20:34 UTC 2018 , Edited by admin on Tue Mar 06 11:20:34 UTC 2018
PRIMARY RxNorm
EPA CompTox
154-42-7
Created by admin on Tue Mar 06 11:20:34 UTC 2018 , Edited by admin on Tue Mar 06 11:20:34 UTC 2018
PRIMARY
MERCK INDEX
M10760
Created by admin on Tue Mar 06 11:20:34 UTC 2018 , Edited by admin on Tue Mar 06 11:20:34 UTC 2018
PRIMARY Merck Index