THIOGUANINE

US Previously Marketed

First approved in 1966

Details

Stereochemistry	ACHIRAL
Molecular Formula	2C5H5N5S.H2O
Molecular Weight	352.399
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.NC1=NC2=C(N=CN2)C(=S)N1.NC3=NC4=C(N=CN4)C(=S)N3

InChI

InChIKey=VOXBZHOHGGBLCQ-UHFFFAOYSA-N

InChI=1S/2C5H5N5S.H2O/c2*6-5-9-3-2(4(11)10-5)7-1-8-3;/h2*1H,(H4,6,7,8,9,10,11);1H2

HIDE SMILES / InChI

Molecular Formula	C5H5N5S
Molecular Weight	167.192
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	H2O
Molecular Weight	18.0153
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.drugbank.ca/drugs/DB00352
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/12429slr021_tabloid_lbl.pdf

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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
DNA 282 Target ID: DNA Sources: http://www.drugbank.ca/drugs/DB00352	Interacts 323
Leukemia cells 2 Target ID: CHEMBL614844 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7967706	Inhibitor 8504	20.0 µM [IC50]
Inosine-5'-monophosphate dehydrogenase (IMPDH) 11 Target ID: CHEMBL2111369 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2004/12429s022lbl.pdf	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Acute non-lymphocytic leukemia 10 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/12429slr021_tabloid_lbl.pdf	Primary		Approved 8583	TABLOID Approved Use Indications and Usage for Thioguanine a) Acute Nonlymphocytic Leukemias TABLOID brand Thioguanine is indicated for remission induction and remission consolidation treatment of acute nonlymphocytic leukemias. However, it is not recommended for use during maintenance therapy or similar long-term continuous treatments due to the high risk of liver toxicity. The response to this agent depends upon the age of the patient (younger patients faring better than older) and whether Thioguanine is used in previously treated or previously untreated patients. Reliance upon Thioguanine alone is seldom justified for initial remission induction of acute nonlymphocytic leukemias because combination chemotherapy including Thioguanine results in more frequent remission induction and longer duration of remission than Thioguanine alone. b) Other Neoplasms TABLOID brand Thioguanine is not effective in chronic lymphocytic leukemia, Hodgkin’s lymphoma, multiple myeloma, or solid tumors. Although Thioguanine is one of several agents with activity in the treatment of the chronic phase of chronic myelogenous leukemia, more objective responses are observed with MYLERAN® (busulfan), and therefore busulfan is usually regarded as the preferred drug. Launch Date 1966

C_max

Value	Dose	Co-administered	Analyte	Population
313 nM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/11422012	40 mg/m² 1 times / day multiple, oral dose: 40 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered:		THIOGUANINE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
586 pmol × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/11422012	40 mg/m² 1 times / day multiple, oral dose: 40 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered:		THIOGUANINE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
4.4 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/27463047	40 mg 1 times / day multiple, oral dose: 40 mg route of administration: Oral experiment type: MULTIPLE co-administered:		THIOGUANINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED

Doses

Dose	Population	Adverse events
20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17943403/	unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/17943403/	Other AEs: Pain, Nausea and vomiting... Other AEs: Pain (grade 1-2, 9.6%) Nausea and vomiting (grade 1-2, 20%) Leukopenia (grade 1-2, 11.8%) Thrombocytopenia (grade 1-3, 3.7%) Hepatotoxicity (grade 1-2, 24.4%) Headache (grade 1-2, 8.9%) Anemia (grade 1-3, 8.9%) Gamma-glutamyltransferase increased (grade 1-4, 16.3%) Diarrhea (grade 2, 1.4%) Skin toxicity (grade 1-2, 11.8%) Hair loss (grade 1, 5.2%) Infection (grade 1-3, 26.7%) Blood urea nitrogen increased (grade 1, 1.4%) Neurotoxicity (grade 1-2, 1.4%) Hemorrhage (grade 3, 0.7%) Stomatitis (grade 1, 0.7%) Creatinine increased (grade 2, 0.7%) Cardiac arrhythmias (grade 1, 0.7%) Constipation (grade 1, 0.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/17943403/
40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17943403/	unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/17943403/	Disc. AE: Pain, Nausea and vomiting... AEs leading to discontinuation/dose reduction: Pain (grade 1-3, 6.1%) Nausea and vomiting (grade 1-2, 4.4%) Leukopenia (grade 1-3, 2.7%) Thrombocytopenia (grade 1-3, 2.7%) Hepatotoxicity (grade 1-2, 2.4%) Headache (grade 1-2, 1.7%) Anemia (grade 1-4, 0.7%) Gamma-glutamyltransferase increased (grade 2-3, 1%) Diarrhea (grade 2-4, 1%) Skin toxicity (grade 1, 0.7%) Hair loss (grade 1, 0.7%) Cardiac dysfunction (grade 3, 0.3%) Pericarditis (grade 2, 0.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/17943403/
40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12622758/	unhealthy, 22–61 years Health Status: unhealthy Age Group: 22–61 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/12622758/	Disc. AE: Pancreatitis, Headache... Other AEs: Headache, Nausea... AEs leading to discontinuation/dose reduction: Pancreatitis (2.7%) Headache (5.4%) Pneumonia (2.7%) Leucopenia (5.4%) Other AEs: Headache (45.9%) Nausea (27%) Vomiting (5.4%) Pruritus (8.1%) Arthralgia (8.1%) Alopecia (8.1%) Dysaesthesia (2.7%) Eczema (10.8%) Exanthema (5.4%) Photosensitivity allergic reac (5.4%) Erythema nodosum (2.7%) Rotavirus infection (2.7%) Respiratory tract infections (29.7%) Urinary tract infections (10.8%) Genital candidiasis (5.4%) Herpes labialis (2.7%) Transaminases increased (5.4%) Leucopenia (8.1%) Anaemia (2.7%) Thrombopenia (2.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/12622758/
1200 mg/m2 1 times / 3 weeks multiple, intravenous Highest studied dose Dose: 1200 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 1200 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/7105383/	unhealthy, 37-70 years Health Status: unhealthy Age Group: 37-70 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/7105383/	Disc. AE: Creatinine increased... Other AEs: Leukopenia... AEs leading to discontinuation/dose reduction: Creatinine increased (25%) Other AEs: Leukopenia (25%) Sources: https://pubmed.ncbi.nlm.nih.gov/7105383/
300 mg/m2 1 times / week multiple, intravenous MTD Dose: 300 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 300 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/7521908/	unhealthy, Patients < 21 years Health Status: unhealthy Age Group: Patients < 21 years Sources: https://pubmed.ncbi.nlm.nih.gov/7521908/	Other AEs: Neutropenia, Anemia... Other AEs: Neutropenia (grade 3, 16.1%) Anemia (grade 3, 16.1%) Thrombocytopenia (grade 3, 16.1%) Sources: https://pubmed.ncbi.nlm.nih.gov/7521908/

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 UGT1A9 148 UGT2B7 197	TPMT 5 MRP4 91 MRP5 41

Drug as perpetrator

Target	Modality	Activity
UGT1A9 155	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/11488768/ Page: 4.0	no
UGT2B7 210	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/11488768/ Page: 4.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/11488768/ Page: 4.0	weak

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
MRP4 91	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12435799/ Page: 1.0	major	tGMP 2
MRP5 41	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12435799/ Page: 1.0	minor	tGMP 2
TPMT 5	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/012429s028lbl.pdf#page=3 Page: 3.0	yes		yes (pharmacogenomic study) Comment: patients with reduced TPMT receiving usual doses of mercaptopurine, accumulate excessive cellular concentrations of active 6-TGNs Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/012429s028lbl.pdf#page=3 Page: 3.0

PubMed

Title	Date	PubMed
Generation of single-copy transgenic mouse embryos directly from ES cells by tetraploid embryo complementation.	2001	11782291
Pharmacogenetics: the therapeutic drug monitoring of the future?	2001	11735602
Gene- and tissue-specificity of mutation in Big Blue rats treated with the hepatocarcinogen N-hydroxy-2-acetylaminofluorene.	2001	11317338
Remission induction therapy: the more intensive the better?	2001 Aug	11587366
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	11561778
An open-label pilot study using thioguanine as a therapeutic alternative in Crohn's disease patients resistant to 6-mercaptopurine therapy.	2001 Aug	11515842
hMSH3 overexpression and cellular response to cytotoxic anticancer agents.	2001 Aug	11470740
Renal cell carcinoma as a secondary malignancy after treatment of acute promyelocytic leukemia.	2001 Dec	11902306
Comparative pharmacokinetics of oral 6-mercaptopurine and intravenous 6-mercaptopurine riboside in children.	2001 Dec	11737747
New developments in the immunosuppressive drug monitoring of cyclosporine, tacrolimus, and azathioprine.	2001 Feb	11239509
Bilateral breast relapse in acute myelogenous leukemia.	2001 Feb	11216705
A novel protein complex distinct from mismatch repair binds thioguanylated DNA.	2001 Feb	11160874
P53 modulates the effect of loss of DNA mismatch repair on the sensitivity of human colon cancer cells to the cytotoxic and mutagenic effects of cisplatin.	2001 Feb 15	11245458
6-mercaptopurine dosage and pharmacokinetics influence the degree of bone marrow toxicity following high-dose methotrexate in children with acute lymphoblastic leukemia.	2001 Jan	11243403
Therapeutic drug monitoring of azathioprine and 6-mercaptopurine metabolites in Crohn disease.	2001 Jan	11218242
Topoisomerase I-mediated cytotoxicity of N-methyl-N'-nitro-N-nitrosoguanidine: trapping of topoisomerase I by the O6-methylguanine.	2001 Jan 1	11196197
The use of denaturing high-pressure liquid chromatography for the detection of mutations in thiopurine methyltransferase.	2001 Jan 30	11179762
[Thioguanine, pancreatotoxicity?].	2001 Jan-Feb	11322024
Hamster and rat fetal cells have low spontaneous mutation frequencies and rates.	2001 Jul 1	11406169
Heterozygosity for the thiopurine methyltransferase *3A allele in an acute non-lymphoblastic leukaemia patient with delayed marrow regeneration following H-DAT chemotherapy.	2001 Mar	11324641
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	11320662
Immunosuppressive and cytotoxic drugs in the treatment of rheumatic skin disorders.	2001 Mar	11308138
Analysis of mutational effects at the HPRT locus in human G(0) phase lymphocytes irradiated in vitro with gamma rays.	2001 Mar 1	11239972
Utilisation of erythrocyte 6-thioguanine metabolite levels to optimise azathioprine therapy in patients with inflammatory bowel disease.	2001 May	11302961
Cell killing and mutation induction by heavy ion beams.	2001 May	11295113
Substitution F569S converts UapA, a specific uric acid-xanthine transporter, into a broad specificity transporter for purine-related solutes.	2001 Nov 2	11697902
Targeting DNA mismatch repair for radiosensitization.	2001 Oct	11677655
Suppression of spontaneous and hydrogen peroxide-induced mutagenesis by the antioxidant ascorbate in mismatch repair-deficient human colon cancer cells.	2001 Oct	11577013
Intensive timed sequential remission induction chemotherapy with high-dose cytarabine for childhood acute myeloid leukemia.	2001 Oct	11568900
Hypoxia-induced enrichment and mutagenesis of cells that have lost DNA mismatch repair.	2001 Oct 15	11606400
Deoxythioguanosine triphosphate impairs HIV replication: a new mechanism for an old drug.	2001 Sep	11532970
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	11447229
Effect of methotrexate polyglutamates on thioguanine nucleotide concentrations during continuation therapy of acute lymphoblastic leukemia with mercaptopurine.	2002 Feb	11840287
Role of glutathione in the multidrug resistance protein 4 (MRP4/ABCC4)-mediated efflux of cAMP and resistance to purine analogues.	2002 Feb 1	11802779
Aphidicolin induces 6-thioguanine resistant mutants in human diploid fibroblasts.	2002 Feb 20	11827715
Inflammatory bowel disease.	2002 Jan	11778131
Genetic toxicology studies with glutaraldehyde.	2002 Jan-Feb	11807929

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

Substance Class	Chemical Created by `admin` on `Mon Mar 31 21:23:42 GMT 2025` Edited by `admin` on `Mon Mar 31 21:23:42 GMT 2025`
Record UNII	FTK8U1GZNX
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

THIOGUANINE

Official Name

English

TIOGUANINE HEMIHYDRATE

Preferred Name

English

LANVIS

Brand Name

English

Tioguanine hemihydrate [WHO-DD]

Common Name

English

THIOGUANINE [VANDF]

Common Name

English

TIOGUANINE [MART.]

Common Name

English

THIOGUANINE [USP MONOGRAPH]

Common Name

English

TABLOID

Brand Name

English

THIOGUANINE HEMIHYDRATE

Common Name

English

THIOGUANINE [USP-RS]

Common Name

English

THIOGUANINE [USAN]

Common Name

English

THIOGUANINE [ORANGE BOOK]

Common Name

English

6H-PURINE-6-THIONE, 2-AMINO-1,9-DIHYDRO-, HYDRATE (2:1)

Systematic Name

English

THIOGUANINE [USP IMPURITY]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2254