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
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
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 |
DescriptionSources: http://www.drugbank.ca/drugs/DB00352Curator's Comment: Description was created based on several sources, including
http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/12429slr021_tabloid_lbl.pdf
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
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: DNA Sources: http://www.drugbank.ca/drugs/DB00352 |
|||
Target ID: CHEMBL614844 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7967706 |
20.0 µM [IC50] | ||
Target ID: CHEMBL2111369 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | TABLOID Approved UseIndications 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 Date1966 |
Cmax
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 |
T1/2
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: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Other AEs: Pain, Nausea and vomiting... Other AEs: Pain (grade 1-2, 9.6%) Sources: 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%) |
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, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Disc. AE: Pain, Nausea and vomiting... AEs leading to discontinuation/dose reduction: Pain (grade 1-3, 6.1%) Sources: 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%) |
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 Health Status: unhealthy Age Group: 22–61 years Sex: M+F Sources: |
Disc. AE: Pancreatitis, Headache... Other AEs: Headache, Nausea... AEs leading to discontinuation/dose reduction: Pancreatitis (2.7%) Other AEs:Headache (5.4%) Pneumonia (2.7%) Leucopenia (5.4%) Headache (45.9%) Sources: 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%) |
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 Health Status: unhealthy Age Group: 37-70 years Sex: M+F 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 Health Status: unhealthy Age Group: Patients < 21 years Sources: |
Other AEs: Neutropenia, Anemia... Other AEs: Neutropenia (grade 3, 16.1%) Sources: Anemia (grade 3, 16.1%) Thrombocytopenia (grade 3, 16.1%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Cardiac arrhythmias | grade 1, 0.7% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Constipation | grade 1, 0.7% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Stomatitis | grade 1, 0.7% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Blood urea nitrogen increased | grade 1, 1.4% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Hair loss | grade 1, 5.2% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Neurotoxicity | grade 1-2, 1.4% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Leukopenia | grade 1-2, 11.8% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Skin toxicity | grade 1-2, 11.8% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Nausea and vomiting | grade 1-2, 20% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Hepatotoxicity | grade 1-2, 24.4% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Headache | grade 1-2, 8.9% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Pain | grade 1-2, 9.6% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Infection | grade 1-3, 26.7% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Thrombocytopenia | grade 1-3, 3.7% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Anemia | grade 1-3, 8.9% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Gamma-glutamyltransferase increased | grade 1-4, 16.3% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Creatinine increased | grade 2, 0.7% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Diarrhea | grade 2, 1.4% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Hemorrhage | grade 3, 0.7% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Hair loss | grade 1, 0.7% 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, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Skin toxicity | grade 1, 0.7% 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, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Headache | grade 1-2, 1.7% 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, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Hepatotoxicity | grade 1-2, 2.4% 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, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Nausea and vomiting | grade 1-2, 4.4% 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, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Leukopenia | grade 1-3, 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, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Thrombocytopenia | grade 1-3, 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, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Pain | grade 1-3, 6.1% 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, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Anemia | grade 1-4, 0.7% 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, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Pericarditis | grade 2, 0.3% 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, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Gamma-glutamyltransferase increased | grade 2-3, 1% 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, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Diarrhea | grade 2-4, 1% 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, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Cardiac dysfunction | grade 3, 0.3% 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, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F 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 Health Status: unhealthy Age Group: 22–61 years Sex: M+F 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 Health Status: unhealthy Age Group: 22–61 years Sex: M+F 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 Health Status: unhealthy Age Group: 22–61 years Sex: M+F 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 Health Status: unhealthy Age Group: 22–61 years Sex: M+F 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 Health Status: unhealthy Age Group: 22–61 years Sex: M+F 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 Health Status: unhealthy Age Group: 22–61 years Sex: M+F 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 Health Status: unhealthy Age Group: 22–61 years Sex: M+F 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 Health Status: unhealthy Age Group: 22–61 years Sex: M+F 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 Health Status: unhealthy Age Group: 22–61 years Sex: M+F 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 Health Status: unhealthy Age Group: 22–61 years Sex: M+F 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 Health Status: unhealthy Age Group: 22–61 years Sex: M+F 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 Health Status: unhealthy Age Group: 22–61 years Sex: M+F 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 Health Status: unhealthy Age Group: 22–61 years Sex: M+F 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 Health Status: unhealthy Age Group: 22–61 years Sex: M+F 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 Health Status: unhealthy Age Group: 22–61 years Sex: M+F 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 Health Status: unhealthy Age Group: 22–61 years Sex: M+F 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 Health Status: unhealthy Age Group: 22–61 years Sex: M+F 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 Health Status: unhealthy Age Group: 22–61 years Sex: M+F 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 Health Status: unhealthy Age Group: 22–61 years Sex: M+F 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 Health Status: unhealthy Age Group: 22–61 years Sex: M+F 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 Health Status: unhealthy Age Group: 22–61 years Sex: M+F 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 Health Status: unhealthy Age Group: 22–61 years Sex: M+F 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 Health Status: unhealthy Age Group: 22–61 years Sex: M+F 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 Health Status: unhealthy Age Group: 22–61 years Sex: M+F 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 Health Status: unhealthy Age Group: 37-70 years Sex: M+F 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 Health Status: unhealthy Age Group: 37-70 years Sex: M+F 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 Health Status: unhealthy Age Group: Patients < 21 years 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 Health Status: unhealthy Age Group: Patients < 21 years 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 Health Status: unhealthy Age Group: Patients < 21 years Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/11488768/ Page: 4.0 |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/11488768/ Page: 4.0 |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/11488768/ Page: 4.0 |
weak |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/12435799/ Page: 1.0 |
major | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/12435799/ Page: 1.0 |
minor | |||
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 Page: 3.0 |
PubMed
Title | Date | PubMed |
---|---|---|
Generation of single-copy transgenic mouse embryos directly from ES cells by tetraploid embryo complementation. | 2001 |
|
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 |
|
Remission induction therapy: the more intensive the better? | 2001 Aug |
|
Reversal of cytosine arabinoside (ara-C) resistance by the synergistic combination of 6-thioguanine plus ara-C plus PEG-asparaginase (TGAP) in human leukemia lines lacking or expressing p53 protein. | 2001 Aug |
|
An open-label pilot study using thioguanine as a therapeutic alternative in Crohn's disease patients resistant to 6-mercaptopurine therapy. | 2001 Aug |
|
hMSH3 overexpression and cellular response to cytotoxic anticancer agents. | 2001 Aug |
|
Renal cell carcinoma as a secondary malignancy after treatment of acute promyelocytic leukemia. | 2001 Dec |
|
Comparative pharmacokinetics of oral 6-mercaptopurine and intravenous 6-mercaptopurine riboside in children. | 2001 Dec |
|
New developments in the immunosuppressive drug monitoring of cyclosporine, tacrolimus, and azathioprine. | 2001 Feb |
|
Bilateral breast relapse in acute myelogenous leukemia. | 2001 Feb |
|
A novel protein complex distinct from mismatch repair binds thioguanylated DNA. | 2001 Feb |
|
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 |
|
6-mercaptopurine dosage and pharmacokinetics influence the degree of bone marrow toxicity following high-dose methotrexate in children with acute lymphoblastic leukemia. | 2001 Jan |
|
Therapeutic drug monitoring of azathioprine and 6-mercaptopurine metabolites in Crohn disease. | 2001 Jan |
|
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 |
|
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 |
|
Immunosuppressive and cytotoxic drugs in the treatment of rheumatic skin disorders. | 2001 Mar |
|
Analysis of mutational effects at the HPRT locus in human G(0) phase lymphocytes irradiated in vitro with gamma rays. | 2001 Mar 1 |
|
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 |
|
Substitution F569S converts UapA, a specific uric acid-xanthine transporter, into a broad specificity transporter for purine-related solutes. | 2001 Nov 2 |
|
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 |
|
Intensive timed sequential remission induction chemotherapy with high-dose cytarabine for childhood acute myeloid leukemia. | 2001 Oct |
|
Hypoxia-induced enrichment and mutagenesis of cells that have lost DNA mismatch repair. | 2001 Oct 15 |
|
Deoxythioguanosine triphosphate impairs HIV replication: a new mechanism for an old drug. | 2001 Sep |
|
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 |
|
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 |
|
Inflammatory bowel disease. | 2002 Jan |
|
Genetic toxicology studies with glutaraldehyde. | 2002 Jan-Feb |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/dosage/thioguanine.html
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/7967706
Maximum cytotoxicity against leukemic cells from patients with ALL occured at 0.5 uM
Substance Class |
Chemical
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WHO-ESSENTIAL MEDICINES LIST |
8.2
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EU-Orphan Drug |
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C1556
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NBK548502
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N0000180853
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