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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

PubMed

PubMed

TitleDatePubMed
Role of glutathione S-transferase mu (GSTM1) in styrene-7,8-oxide toxicity and mutagenicity.
2001
Gene- and tissue-specificity of mutation in Big Blue rats treated with the hepatocarcinogen N-hydroxy-2-acetylaminofluorene.
2001
hMSH3 overexpression and cellular response to cytotoxic anticancer agents.
2001 Aug
The histone deacetylase inhibitor trichostatin A reduces nickel-induced gene silencing in yeast and mammalian cells.
2001 Aug 8
Toxoplasma gondii: mechanism of the parasitostatic action of 6-thioxanthine.
2001 Dec
Pharmacotherapeutic options in inflammatory bowel disease: an update.
2001 Feb
6-mercaptopurine dosage and pharmacokinetics influence the degree of bone marrow toxicity following high-dose methotrexate in children with acute lymphoblastic leukemia.
2001 Jan
Therapeutic drug monitoring of azathioprine and 6-mercaptopurine metabolites in Crohn disease.
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
Hamster and rat fetal cells have low spontaneous mutation frequencies and rates.
2001 Jul 1
[Primary pulmonary manifestation of extramedullary acute myelocytic leukemia].
2001 Jun
Amplification of ERBB2, RARA, and TOP2A genes in a myelodysplastic syndrome transforming to acute myeloid leukemia.
2001 Jun
6-Thioguanine in children with acute lymphoblastic leukaemia: influence of food on parent drug pharmacokinetics and 6-thioguanine nucleotide concentrations.
2001 Jun
Improved methods for determining the concentration of 6-thioguanine nucleotides and 6-methylmercaptopurine nucleotides in blood.
2001 Jun 5
Acute myeloid leukaemia (AML): treatment of the older patient.
2001 Mar
Pretreatment leukaemia cell drug resistance is correlated to clinical outcome in acute myeloid leukaemia.
2001 Mar
Immunosuppressive and cytotoxic drugs in the treatment of rheumatic skin disorders.
2001 Mar
Analysis of mutational effects at the HPRT locus in human G(0) phase lymphocytes irradiated in vitro with gamma rays.
2001 Mar 1
Human thiopurine S-methyltransferase activity in uremia and after renal transplantation.
2001 May
Utilisation of erythrocyte 6-thioguanine metabolite levels to optimise azathioprine therapy in patients with inflammatory bowel disease.
2001 May
In vivo mutant frequency of thioguanine-resistant T-cells in the peripheral blood and lymph nodes of melanoma patients.
2001 May 9
High 6-thioguanine nucleotide levels and low thiopurine methyltransferase activity in patients with lupus erythematosus treated with azathioprine.
2001 May-Jun
The mouse guanylate kinase double mutant E72Q/D103N is a functional adenylate kinase.
2001 Nov
Possible implication of thiopurine S-methyltransferase in occurrence of infectious episodes during maintenance therapy for childhood lymphoblastic leukemia with mercaptopurine.
2001 Nov
Treatment of psoriasis. Part 2. Systemic therapies.
2001 Nov
Loss of DNA mismatch repair imparts defective cdc2 signaling and G(2) arrest responses without altering survival after ionizing radiation.
2001 Nov 15
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
Acute arterial occlusion as the presenting feature in acute promyelocytic leukaemia.
2001 Oct
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
Targeting DNA mismatch repair for radiosensitization.
2001 Oct
Hypoxia-induced enrichment and mutagenesis of cells that have lost DNA mismatch repair.
2001 Oct 15
Transport of cyclic nucleotides and estradiol 17-beta-D-glucuronide by multidrug resistance protein 4. Resistance to 6-mercaptopurine and 6-thioguanine.
2001 Sep 7
Role of glutathione in the multidrug resistance protein 4 (MRP4/ABCC4)-mediated efflux of cAMP and resistance to purine analogues.
2002 Feb 1
Flow cytometric determination of HPRT-variants in human peripheral blood lymphocytes.
2002 Jan 29
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
Implication of protein kinase C in the regulation of DNA mismatch repair protein expression and function.
2002 May 17
Patents

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: Oral
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 Oct 22 00:36:32 UTC 2019 , Edited by admin on Tue Oct 22 00:36:32 UTC 2019
NCI_THESAURUS C1556
Created by admin on Tue Oct 22 00:36:32 UTC 2019 , Edited by admin on Tue Oct 22 00:36:32 UTC 2019
NCI_THESAURUS C2254
Created by admin on Tue Oct 22 00:36:32 UTC 2019 , Edited by admin on Tue Oct 22 00:36:32 UTC 2019
WHO-ATC L01BB03
Created by admin on Tue Oct 22 00:36:32 UTC 2019 , Edited by admin on Tue Oct 22 00:36:32 UTC 2019
WHO-VATC QL01BB03
Created by admin on Tue Oct 22 00:36:32 UTC 2019 , Edited by admin on Tue Oct 22 00:36:32 UTC 2019
Code System Code Type Description
NCI_THESAURUS
C61970
Created by admin on Tue Oct 22 00:36:32 UTC 2019 , Edited by admin on Tue Oct 22 00:36:32 UTC 2019
PRIMARY
LactMed
154-42-7
Created by admin on Tue Oct 22 00:36:32 UTC 2019 , Edited by admin on Tue Oct 22 00:36:32 UTC 2019
PRIMARY
ECHA (EC/EINECS)
205-827-2
Created by admin on Tue Oct 22 00:36:32 UTC 2019 , Edited by admin on Tue Oct 22 00:36:32 UTC 2019
PRIMARY
ChEMBL
CHEMBL727
Created by admin on Tue Oct 22 00:36:32 UTC 2019 , Edited by admin on Tue Oct 22 00:36:32 UTC 2019
PRIMARY
HSDB
154-42-7
Created by admin on Tue Oct 22 00:36:32 UTC 2019 , Edited by admin on Tue Oct 22 00:36:32 UTC 2019
PRIMARY
DRUG BANK
DB00352
Created by admin on Tue Oct 22 00:36:32 UTC 2019 , Edited by admin on Tue Oct 22 00:36:32 UTC 2019
PRIMARY
EVMPD
SUB11084MIG
Created by admin on Tue Oct 22 00:36:32 UTC 2019 , Edited by admin on Tue Oct 22 00:36:32 UTC 2019
PRIMARY
CAS
154-42-7
Created by admin on Tue Oct 22 00:36:32 UTC 2019 , Edited by admin on Tue Oct 22 00:36:32 UTC 2019
PRIMARY
PUBCHEM
2723601
Created by admin on Tue Oct 22 00:36:32 UTC 2019 , Edited by admin on Tue Oct 22 00:36:32 UTC 2019
PRIMARY
WIKIPEDIA
TIOGUANINE
Created by admin on Tue Oct 22 00:36:32 UTC 2019 , Edited by admin on Tue Oct 22 00:36:32 UTC 2019
PRIMARY
INN
1998
Created by admin on Tue Oct 22 00:36:32 UTC 2019 , Edited by admin on Tue Oct 22 00:36:32 UTC 2019
PRIMARY
RXCUI
1546005
Created by admin on Tue Oct 22 00:36:32 UTC 2019 , Edited by admin on Tue Oct 22 00:36:32 UTC 2019
PRIMARY RxNorm
EPA CompTox
154-42-7
Created by admin on Tue Oct 22 00:36:32 UTC 2019 , Edited by admin on Tue Oct 22 00:36:32 UTC 2019
PRIMARY
MERCK INDEX
M10760
Created by admin on Tue Oct 22 00:36:32 UTC 2019 , Edited by admin on Tue Oct 22 00:36:32 UTC 2019
PRIMARY Merck Index