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Details

Stereochemistry ACHIRAL
Molecular Formula C5H5N5S
Molecular Weight 167.193
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of THIOGUANINE ANHYDROUS

SMILES

c1nc2c([nH]1)[nH]c(=N)nc2S

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
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.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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

-1.24847997E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
313 nM
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

AUC

ValueDoseCo-administeredAnalytePopulation
586 pM × h
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
4.4 h
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

Doses

DosePopulationAdverse events​
20 mg 1 times / day multiple, oral (median)
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 135
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 135
Sources:
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:
40 mg 1 times / day multiple, oral (median)
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 296
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 296
Sources:
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:
40 mg 1 times / day multiple, oral
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 22–61 years
n = 37
Health Status: unhealthy
Condition: Crohn's disease
Age Group: 22–61 years
Sex: M+F
Population Size: 37
Sources:
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:
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:
unhealthy, 37-70 years
n = 4
Health Status: unhealthy
Condition: colorectal carcinoma
Age Group: 37-70 years
Sex: M+F
Population Size: 4
Sources:
Disc. AE: Creatinine increased...
Other AEs: Leukopenia...
AEs leading to
discontinuation/dose reduction:
Creatinine increased (25%)
Other AEs:
Leukopenia (25%)
Sources:
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:
unhealthy, Patients < 21 years
n = 31
Health Status: unhealthy
Condition: advanced malignancies
Age Group: Patients < 21 years
Population Size: 31
Sources:
Other AEs: Neutropenia, Anemia...
Other AEs:
Neutropenia (grade 3, 16.1%)
Anemia (grade 3, 16.1%)
Thrombocytopenia (grade 3, 16.1%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Cardiac arrhythmias grade 1, 0.7%
20 mg 1 times / day multiple, oral (median)
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 135
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 135
Sources:
Constipation grade 1, 0.7%
20 mg 1 times / day multiple, oral (median)
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 135
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 135
Sources:
Stomatitis grade 1, 0.7%
20 mg 1 times / day multiple, oral (median)
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 135
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 135
Sources:
Blood urea nitrogen increased grade 1, 1.4%
20 mg 1 times / day multiple, oral (median)
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 135
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 135
Sources:
Hair loss grade 1, 5.2%
20 mg 1 times / day multiple, oral (median)
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 135
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 135
Sources:
Neurotoxicity grade 1-2, 1.4%
20 mg 1 times / day multiple, oral (median)
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 135
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 135
Sources:
Leukopenia grade 1-2, 11.8%
20 mg 1 times / day multiple, oral (median)
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 135
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 135
Sources:
Skin toxicity grade 1-2, 11.8%
20 mg 1 times / day multiple, oral (median)
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 135
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 135
Sources:
Nausea and vomiting grade 1-2, 20%
20 mg 1 times / day multiple, oral (median)
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 135
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 135
Sources:
Hepatotoxicity grade 1-2, 24.4%
20 mg 1 times / day multiple, oral (median)
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 135
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 135
Sources:
Headache grade 1-2, 8.9%
20 mg 1 times / day multiple, oral (median)
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 135
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 135
Sources:
Pain grade 1-2, 9.6%
20 mg 1 times / day multiple, oral (median)
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 135
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 135
Sources:
Infection grade 1-3, 26.7%
20 mg 1 times / day multiple, oral (median)
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 135
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 135
Sources:
Thrombocytopenia grade 1-3, 3.7%
20 mg 1 times / day multiple, oral (median)
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 135
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 135
Sources:
Anemia grade 1-3, 8.9%
20 mg 1 times / day multiple, oral (median)
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 135
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 135
Sources:
Gamma-glutamyltransferase increased grade 1-4, 16.3%
20 mg 1 times / day multiple, oral (median)
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 135
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 135
Sources:
Creatinine increased grade 2, 0.7%
20 mg 1 times / day multiple, oral (median)
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 135
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 135
Sources:
Diarrhea grade 2, 1.4%
20 mg 1 times / day multiple, oral (median)
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 135
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 135
Sources:
Hemorrhage grade 3, 0.7%
20 mg 1 times / day multiple, oral (median)
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 135
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 135
Sources:
Hair loss grade 1, 0.7%
Disc. AE
40 mg 1 times / day multiple, oral (median)
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 296
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 296
Sources:
Skin toxicity grade 1, 0.7%
Disc. AE
40 mg 1 times / day multiple, oral (median)
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 296
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 296
Sources:
Headache grade 1-2, 1.7%
Disc. AE
40 mg 1 times / day multiple, oral (median)
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 296
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 296
Sources:
Hepatotoxicity grade 1-2, 2.4%
Disc. AE
40 mg 1 times / day multiple, oral (median)
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 296
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 296
Sources:
Nausea and vomiting grade 1-2, 4.4%
Disc. AE
40 mg 1 times / day multiple, oral (median)
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 296
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 296
Sources:
Leukopenia grade 1-3, 2.7%
Disc. AE
40 mg 1 times / day multiple, oral (median)
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 296
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 296
Sources:
Thrombocytopenia grade 1-3, 2.7%
Disc. AE
40 mg 1 times / day multiple, oral (median)
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 296
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 296
Sources:
Pain grade 1-3, 6.1%
Disc. AE
40 mg 1 times / day multiple, oral (median)
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 296
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 296
Sources:
Anemia grade 1-4, 0.7%
Disc. AE
40 mg 1 times / day multiple, oral (median)
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 296
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 296
Sources:
Pericarditis grade 2, 0.3%
Disc. AE
40 mg 1 times / day multiple, oral (median)
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 296
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 296
Sources:
Gamma-glutamyltransferase increased grade 2-3, 1%
Disc. AE
40 mg 1 times / day multiple, oral (median)
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 296
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 296
Sources:
Diarrhea grade 2-4, 1%
Disc. AE
40 mg 1 times / day multiple, oral (median)
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 296
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 296
Sources:
Cardiac dysfunction grade 3, 0.3%
Disc. AE
40 mg 1 times / day multiple, oral (median)
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 16–82 years
n = 296
Health Status: unhealthy
Condition: inflammatory bowel disease
Age Group: 16–82 years
Sex: M+F
Population Size: 296
Sources:
Eczema 10.8%
40 mg 1 times / day multiple, oral
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 22–61 years
n = 37
Health Status: unhealthy
Condition: Crohn's disease
Age Group: 22–61 years
Sex: M+F
Population Size: 37
Sources:
Urinary tract infections 10.8%
40 mg 1 times / day multiple, oral
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 22–61 years
n = 37
Health Status: unhealthy
Condition: Crohn's disease
Age Group: 22–61 years
Sex: M+F
Population Size: 37
Sources:
Anaemia 2.7%
40 mg 1 times / day multiple, oral
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 22–61 years
n = 37
Health Status: unhealthy
Condition: Crohn's disease
Age Group: 22–61 years
Sex: M+F
Population Size: 37
Sources:
Dysaesthesia 2.7%
40 mg 1 times / day multiple, oral
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 22–61 years
n = 37
Health Status: unhealthy
Condition: Crohn's disease
Age Group: 22–61 years
Sex: M+F
Population Size: 37
Sources:
Erythema nodosum 2.7%
40 mg 1 times / day multiple, oral
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 22–61 years
n = 37
Health Status: unhealthy
Condition: Crohn's disease
Age Group: 22–61 years
Sex: M+F
Population Size: 37
Sources:
Herpes labialis 2.7%
40 mg 1 times / day multiple, oral
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 22–61 years
n = 37
Health Status: unhealthy
Condition: Crohn's disease
Age Group: 22–61 years
Sex: M+F
Population Size: 37
Sources:
Rotavirus infection 2.7%
40 mg 1 times / day multiple, oral
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 22–61 years
n = 37
Health Status: unhealthy
Condition: Crohn's disease
Age Group: 22–61 years
Sex: M+F
Population Size: 37
Sources:
Thrombopenia 2.7%
40 mg 1 times / day multiple, oral
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 22–61 years
n = 37
Health Status: unhealthy
Condition: Crohn's disease
Age Group: 22–61 years
Sex: M+F
Population Size: 37
Sources:
Pancreatitis 2.7%
Disc. AE
40 mg 1 times / day multiple, oral
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 22–61 years
n = 37
Health Status: unhealthy
Condition: Crohn's disease
Age Group: 22–61 years
Sex: M+F
Population Size: 37
Sources:
Pneumonia 2.7%
Disc. AE
40 mg 1 times / day multiple, oral
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 22–61 years
n = 37
Health Status: unhealthy
Condition: Crohn's disease
Age Group: 22–61 years
Sex: M+F
Population Size: 37
Sources:
Nausea 27%
40 mg 1 times / day multiple, oral
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 22–61 years
n = 37
Health Status: unhealthy
Condition: Crohn's disease
Age Group: 22–61 years
Sex: M+F
Population Size: 37
Sources:
Respiratory tract infections 29.7%
40 mg 1 times / day multiple, oral
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 22–61 years
n = 37
Health Status: unhealthy
Condition: Crohn's disease
Age Group: 22–61 years
Sex: M+F
Population Size: 37
Sources:
Headache 45.9%
40 mg 1 times / day multiple, oral
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 22–61 years
n = 37
Health Status: unhealthy
Condition: Crohn's disease
Age Group: 22–61 years
Sex: M+F
Population Size: 37
Sources:
Exanthema 5.4%
40 mg 1 times / day multiple, oral
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 22–61 years
n = 37
Health Status: unhealthy
Condition: Crohn's disease
Age Group: 22–61 years
Sex: M+F
Population Size: 37
Sources:
Genital candidiasis 5.4%
40 mg 1 times / day multiple, oral
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 22–61 years
n = 37
Health Status: unhealthy
Condition: Crohn's disease
Age Group: 22–61 years
Sex: M+F
Population Size: 37
Sources:
Photosensitivity allergic reac 5.4%
40 mg 1 times / day multiple, oral
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 22–61 years
n = 37
Health Status: unhealthy
Condition: Crohn's disease
Age Group: 22–61 years
Sex: M+F
Population Size: 37
Sources:
Transaminases increased 5.4%
40 mg 1 times / day multiple, oral
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 22–61 years
n = 37
Health Status: unhealthy
Condition: Crohn's disease
Age Group: 22–61 years
Sex: M+F
Population Size: 37
Sources:
Vomiting 5.4%
40 mg 1 times / day multiple, oral
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 22–61 years
n = 37
Health Status: unhealthy
Condition: Crohn's disease
Age Group: 22–61 years
Sex: M+F
Population Size: 37
Sources:
Headache 5.4%
Disc. AE
40 mg 1 times / day multiple, oral
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 22–61 years
n = 37
Health Status: unhealthy
Condition: Crohn's disease
Age Group: 22–61 years
Sex: M+F
Population Size: 37
Sources:
Leucopenia 5.4%
Disc. AE
40 mg 1 times / day multiple, oral
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 22–61 years
n = 37
Health Status: unhealthy
Condition: Crohn's disease
Age Group: 22–61 years
Sex: M+F
Population Size: 37
Sources:
Alopecia 8.1%
40 mg 1 times / day multiple, oral
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 22–61 years
n = 37
Health Status: unhealthy
Condition: Crohn's disease
Age Group: 22–61 years
Sex: M+F
Population Size: 37
Sources:
Arthralgia 8.1%
40 mg 1 times / day multiple, oral
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 22–61 years
n = 37
Health Status: unhealthy
Condition: Crohn's disease
Age Group: 22–61 years
Sex: M+F
Population Size: 37
Sources:
Leucopenia 8.1%
40 mg 1 times / day multiple, oral
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 22–61 years
n = 37
Health Status: unhealthy
Condition: Crohn's disease
Age Group: 22–61 years
Sex: M+F
Population Size: 37
Sources:
Pruritus 8.1%
40 mg 1 times / day multiple, oral
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 22–61 years
n = 37
Health Status: unhealthy
Condition: Crohn's disease
Age Group: 22–61 years
Sex: M+F
Population Size: 37
Sources:
Leukopenia 25%
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:
unhealthy, 37-70 years
n = 4
Health Status: unhealthy
Condition: colorectal carcinoma
Age Group: 37-70 years
Sex: M+F
Population Size: 4
Sources:
Creatinine increased 25%
Disc. AE
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:
unhealthy, 37-70 years
n = 4
Health Status: unhealthy
Condition: colorectal carcinoma
Age Group: 37-70 years
Sex: M+F
Population Size: 4
Sources:
Anemia grade 3, 16.1%
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:
unhealthy, Patients < 21 years
n = 31
Health Status: unhealthy
Condition: advanced malignancies
Age Group: Patients < 21 years
Population Size: 31
Sources:
Neutropenia grade 3, 16.1%
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:
unhealthy, Patients < 21 years
n = 31
Health Status: unhealthy
Condition: advanced malignancies
Age Group: Patients < 21 years
Population Size: 31
Sources:
Thrombocytopenia grade 3, 16.1%
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:
unhealthy, Patients < 21 years
n = 31
Health Status: unhealthy
Condition: advanced malignancies
Age Group: Patients < 21 years
Population Size: 31
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer






Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
weak
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
minor
yes
yes (pharmacogenomic study)
Comment: patients with reduced TPMT receiving usual doses of mercaptopurine, accumulate excessive cellular concentrations of active 6-TGNs
Page: 3.0
PubMed

PubMed

TitleDatePubMed
Recent advances in the pharmacogenomics of thiopurine methyltransferase.
2001
Generation of single-copy transgenic mouse embryos directly from ES cells by tetraploid embryo complementation.
2001
Favorable outcome for children and adolescents with T-cell lymphoblastic lymphoma with an intensive ALL-type therapy without local radiotherapy.
2001
Pharmacogenetics: the therapeutic drug monitoring of the future?
2001
Pharmacokinetic considerations in the treatment of inflammatory bowel disease.
2001
Remission induction therapy: the more intensive the better?
2001 Aug
6-Thioguanine: a naked bullet? (Or how pharmacogenomics can make old drugs brand new).
2001 Aug
Erythroleukaemia in the north of England: a population based study.
2001 Aug
hMSH3 overexpression and cellular response to cytotoxic anticancer agents.
2001 Aug
Differing contribution of thiopurine methyltransferase to mercaptopurine versus thioguanine effects in human leukemic cells.
2001 Aug 1
Continuing therapy for childhood acute lymphoblastic leukaemia: clinical and cellular pharmacology of methotrexate, 6-mercaptopurine and 6-thioguanine.
2001 Dec
Renal cell carcinoma as a secondary malignancy after treatment of acute promyelocytic leukemia.
2001 Dec
Toxoplasma gondii: mechanism of the parasitostatic action of 6-thioxanthine.
2001 Dec
Why measure thiopurine methyltransferase activity? Direct administration of 6-thioguanine might be the alternative for 6-mercaptopurine or azathioprine.
2001 Dec
Mechanisms of tolerance to DNA damaging therapeutic drugs.
2001 Dec
Photoactivation of DNA thiobases as a potential novel therapeutic option.
2001 Jul 24
The mouse guanylate kinase double mutant E72Q/D103N is a functional adenylate kinase.
2001 Nov
Review article: the treatment of inflammatory bowel disease with 6-mercaptopurine or azathioprine.
2001 Nov
Possible implication of thiopurine S-methyltransferase in occurrence of infectious episodes during maintenance therapy for childhood lymphoblastic leukemia with mercaptopurine.
2001 Nov
Leucopenia resulting from a drug interaction between azathioprine or 6-mercaptopurine and mesalamine, sulphasalazine, or balsalazide.
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
Substitution F569S converts UapA, a specific uric acid-xanthine transporter, into a broad specificity transporter for purine-related solutes.
2001 Nov 2
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
Managing the glucocorticoid dependent inflammatory bowel disease patient.
2001 Oct
Acute arterial occlusion as the presenting feature in acute promyelocytic leukaemia.
2001 Oct
6-mercaptopurine metabolite levels in children with inflammatory bowel disease.
2001 Oct
Targeting DNA mismatch repair for radiosensitization.
2001 Oct
Suppression of spontaneous and hydrogen peroxide-induced mutagenesis by the antioxidant ascorbate in mismatch repair-deficient human colon cancer cells.
2001 Oct
Hypoxia-induced enrichment and mutagenesis of cells that have lost DNA mismatch repair.
2001 Oct 15
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
Enhanced expression and activity of DNA polymerase beta in human ovarian tumor cells: impact on sensitivity towards antitumor agents.
2001 Sep 27
Novel glutathione-dependent thiopurine prodrugs: evidence for enhanced cytotoxicity in tumor cells and for decreased bone marrow toxicity in mice.
2002 Apr
Photodynamic therapy of DNA mismatch repair-deficient and -proficient tumour cells.
2002 Apr 8
Specific [(3)H]-guanosine binding sites in rat brain membranes.
2002 Feb
Diversity of the apoptotic response to chemotherapy in childhood leukemia.
2002 Feb
Effect of methotrexate polyglutamates on thioguanine nucleotide concentrations during continuation therapy of acute lymphoblastic leukemia with mercaptopurine.
2002 Feb
Role of glutathione in the multidrug resistance protein 4 (MRP4/ABCC4)-mediated efflux of cAMP and resistance to purine analogues.
2002 Feb 1
Aphidicolin induces 6-thioguanine resistant mutants in human diploid fibroblasts.
2002 Feb 20
The thiopurine S-methyltransferase gene locus -- implications for clinical pharmacogenomics.
2002 Jan
Inflammatory bowel disease.
2002 Jan
HPLC determination of thiopurine nucleosides and nucleotides in vivo in lymphoblasts following mercaptopurine therapy.
2002 Jan
Different drug sensitivity profiles of acute myeloid and lymphoblastic leukemia and normal peripheral blood mononuclear cells in children with and without Down syndrome.
2002 Jan 1
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
Genetic toxicology studies with glutaraldehyde.
2002 Jan-Feb
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
Implication of protein kinase C in the regulation of DNA mismatch repair protein expression and function.
2002 May 17
Patents

Sample Use Guides

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 Sat Jun 26 00:26:06 UTC 2021 , Edited by admin on Sat Jun 26 00:26:06 UTC 2021
NCI_THESAURUS C1556
Created by admin on Sat Jun 26 00:26:06 UTC 2021 , Edited by admin on Sat Jun 26 00:26:06 UTC 2021
NCI_THESAURUS C2254
Created by admin on Sat Jun 26 00:26:06 UTC 2021 , Edited by admin on Sat Jun 26 00:26:06 UTC 2021
WHO-ATC L01BB03
Created by admin on Sat Jun 26 00:26:06 UTC 2021 , Edited by admin on Sat Jun 26 00:26:06 UTC 2021
WHO-VATC QL01BB03
Created by admin on Sat Jun 26 00:26:06 UTC 2021 , Edited by admin on Sat Jun 26 00:26:06 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C61970
Created by admin on Sat Jun 26 00:26:06 UTC 2021 , Edited by admin on Sat Jun 26 00:26:06 UTC 2021
PRIMARY
ECHA (EC/EINECS)
205-827-2
Created by admin on Sat Jun 26 00:26:06 UTC 2021 , Edited by admin on Sat Jun 26 00:26:06 UTC 2021
PRIMARY
ChEMBL
CHEMBL727
Created by admin on Sat Jun 26 00:26:06 UTC 2021 , Edited by admin on Sat Jun 26 00:26:06 UTC 2021
PRIMARY
HSDB
2504
Created by admin on Sat Jun 26 00:26:06 UTC 2021 , Edited by admin on Sat Jun 26 00:26:06 UTC 2021
PRIMARY
DRUG BANK
DB00352
Created by admin on Sat Jun 26 00:26:06 UTC 2021 , Edited by admin on Sat Jun 26 00:26:06 UTC 2021
PRIMARY
EVMPD
SUB11084MIG
Created by admin on Sat Jun 26 00:26:06 UTC 2021 , Edited by admin on Sat Jun 26 00:26:06 UTC 2021
PRIMARY
CAS
154-42-7
Created by admin on Sat Jun 26 00:26:06 UTC 2021 , Edited by admin on Sat Jun 26 00:26:06 UTC 2021
PRIMARY
PUBCHEM
2723601
Created by admin on Sat Jun 26 00:26:06 UTC 2021 , Edited by admin on Sat Jun 26 00:26:06 UTC 2021
PRIMARY
WIKIPEDIA
TIOGUANINE
Created by admin on Sat Jun 26 00:26:06 UTC 2021 , Edited by admin on Sat Jun 26 00:26:06 UTC 2021
PRIMARY
FDA UNII
WIX31ZPX66
Created by admin on Sat Jun 26 00:26:06 UTC 2021 , Edited by admin on Sat Jun 26 00:26:06 UTC 2021
PRIMARY
INN
1998
Created by admin on Sat Jun 26 00:26:06 UTC 2021 , Edited by admin on Sat Jun 26 00:26:06 UTC 2021
PRIMARY
RXCUI
1546005
Created by admin on Sat Jun 26 00:26:06 UTC 2021 , Edited by admin on Sat Jun 26 00:26:06 UTC 2021
PRIMARY RxNorm
EPA CompTox
154-42-7
Created by admin on Sat Jun 26 00:26:06 UTC 2021 , Edited by admin on Sat Jun 26 00:26:06 UTC 2021
PRIMARY
MERCK INDEX
M10760
Created by admin on Sat Jun 26 00:26:06 UTC 2021 , Edited by admin on Sat Jun 26 00:26:06 UTC 2021
PRIMARY Merck Index