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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

Molecular Formula C5H5N5S
Molecular Weight 167.193
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
Pharmacogenetics: the therapeutic drug monitoring of the future?
2001
Gene- and tissue-specificity of mutation in Big Blue rats treated with the hepatocarcinogen N-hydroxy-2-acetylaminofluorene.
2001
Determinants of outcome after intensified therapy of childhood lymphoblastic leukaemia: results from Medical Research Council United Kingdom acute lymphoblastic leukaemia XI protocol.
2001 Apr
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
Continuing therapy for childhood acute lymphoblastic leukaemia: clinical and cellular pharmacology of methotrexate, 6-mercaptopurine and 6-thioguanine.
2001 Dec
Bilateral breast relapse in acute myelogenous leukemia.
2001 Feb
A novel protein complex distinct from mismatch repair binds thioguanylated DNA.
2001 Feb
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
The use of denaturing high-pressure liquid chromatography for the detection of mutations in thiopurine methyltransferase.
2001 Jan 30
[Thioguanine, pancreatotoxicity?].
2001 Jan-Feb
Hamster and rat fetal cells have low spontaneous mutation frequencies and rates.
2001 Jul 1
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
Heterozygosity for the thiopurine methyltransferase *3A allele in an acute non-lymphoblastic leukaemia patient with delayed marrow regeneration following H-DAT chemotherapy.
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
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
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
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
Review article: the treatment of inflammatory bowel disease with 6-mercaptopurine or azathioprine.
2001 Nov
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
6-mercaptopurine metabolite levels in children with inflammatory bowel disease.
2001 Oct
Determination of thiopurine methyltransferase activity in human erythrocytes by high-performance liquid chromatography: comparison with the radiochemical method.
2001 Oct
Desmutagenic and bio-antimutagenic activity of docosahexaenoic acid and eicosapentaenoic acid in cultured Chinese hamster V79 cells.
2001 Oct 18
Deoxythioguanosine triphosphate impairs HIV replication: a new mechanism for an old drug.
2001 Sep
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
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
Novel glutathione-dependent thiopurine prodrugs: evidence for enhanced cytotoxicity in tumor cells and for decreased bone marrow toxicity in mice.
2002 Apr
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
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
Substance Class Chemical
Created
by admin
on Sat Jun 26 00:26:05 UTC 2021
Edited
by admin
on Sat Jun 26 00:26:05 UTC 2021
Record UNII
WIX31ZPX66
Record Status Validated (UNII)
Record Version
  • Download
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
Related Record Type Details
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
TARGET -> INHIBITOR
Related Record Type Details
PRODRUG -> METABOLITE ACTIVE
METABOLITE INACTIVE -> PARENT
PRODRUG -> METABOLITE ACTIVE
METABOLITE ACTIVE -> PRODRUG
METABOLITE ACTIVE -> PRODRUG
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ACTIVE MOIETY