Drug/Small Molecule:
thioguanine

last updated 01/17/2013

CPIC Dosing Guideline for thioguanine and TPMT

Summary

Start with reduced doses of thioguanine for patients with one nonfunctional TPMT allele, or drastically reduced doses for patients with malignancy and two nonfunctional alleles; adjust dose based on degree of myelosuppression and disease-specific guidelines. Consider alternative nonthiopurine immunosuppressant therapy for patients with nonmalignant conditions and two nonfunctional alleles.

Annotation

These guidelines apply to adults and pediatrics. Please see below for full details of these guidelines, with supporting evidence and disclaimers.

Guidelines regarding the use of pharmacogenomic tests in dosing for azothioprine, thioguanine and mercaptopurine were published March 2011 in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC).

Download: article and supplement

Conclusions of the CPIC guidelines update 2013, accepted for publication by Clinical Pharmacology and Therapeutics and available online Jan 2013: Literature published between June 2010-November 2012 was reviewed and there is no new evidence that would change the original guidelines. Therefore, the dosing recommendations in the original publication remain clinically current. As much of the evidence used to support the guidelines was generated in children, and the dosing recommendations are in units mg/m2 and mg/kg (see table below), they are applicable to both pediatric and adult patients.
Read the Clinical Pharmacology and Therapeutics Updated Article and supplement

Excerpt from the original thiopurine dosing guidelines:

Thiopurines are most commonly used to treat nonmalignant conditions but are also critical anticancer agents. The approach to dosing adjustments based on TPMT status may differ depending on the clinical indication and the propensity to initiate therapy at higher vs. lower starting doses. We and others advocate testing for TPMT status prior to initiating thiopurine therapy, so that starting dosages can be adjusted accordingly.

Recommended dosing of thioguanine by TPMT phenotype

Phenotype (Genotype) Examples of diplotypes Implications for pharmacologic measures after thioguanine Dosing recommendations for thioguanine Classification of recommendations
Homozygous wild-type or normal, high activity (two functional *1 alleles) *1/*1 Lower concentrations of TGN metabolites, but note that TGN after thioguanine are 5-10x higher than TGN after mercaptopurine or azathioprine Start with normal starting dose. Adjust doses of thioguanine and of other myelosuppressive therapy without any special emphasis on thioguanine . Allow 2 weeks to reach steady state after each dose adjustment. Strong
Heterozygote or intermediate activity (one functional allele - *1, plus one nonfunctional allele - *2, *3A, *3B, *3C, or *4) *1/*2, *1/*3A, *1/*3B, *1/*3C, *1/*4 Moderate to high concentrations of TGN metabolites; but note that TGN after thioguanine are 5-10x higher than TGN after mercaptopurine or azathioprine Start with reduced doses (reduce by 30-50%) and adjust doses of thioguanine based on degree of myelosuppression and disease-specific guidelines. Allow 2-4 weeks to reach steady state after each dose adjustment. In setting of myelosuppression, and depending on other therapy, emphasis should be on reducing thioguanine over other agents. Medium
Homozygous variant, mutant, low, or deficient activity (two nonfunctional alleles - *2, *3A, *3B, *3C, or *4) *3A/*3A, *2/*3A, *3C/*3A, *3C/*4, *3C/*2, *3A/*4 Extremely high concentrations of TGN metabolites; fatal toxicity possible without dose decrease Start with drastically reduced doses (reduce daily dose by 10-fold and dose thrice weekly instead of daily) and adjust doses of thioguanine based on degree of myelosuppression and disease-specific guidelines. Allow 4-6 weeks to reach steady state after each dose adjustment. In setting of myelosuppression, emphasis should be on reducing thioguanine over other agents. For nonmalignant conditions, consider alternative nonthiopurine immunosuppressant therapy. Strong

last updated 08/10/2011

Dutch Pharmacogenetics Working Group Guideline for thioguanine and TPMT

Summary

Select an alternative drug rather than thioguanine for intermediate and poor TPMT metabolizers.

Annotation

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for thioguanine based on TPMT genotype (PMID:21412232). They recommend selecting an alternative drug for patients carrying inactive alleles.

Phenotype (Genotype) Therapeutic Dose Recommendation Level of Evidence Clinical Relevance
IM (one inactive allele: *2, *3, *4-*18) Select alternative drug. Insufficient data to allow calculation of dose adjustment. Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. Clinical effect (S): long-standing discomfort (> 168 hr), permanent symptom or invalidating injury e.g. failure of prophylaxis of atrial fibrillation; venous thromboembolism; decreased effect of clopidogrel on inhibition of platelet aggregation; ADE resulting from increased bioavailability of phenytoin; INR > 6.0; neutropenia 0.5-1.0x109/l; leucopenia 1.0-2.0x109/l; thrombocytopenia 25-50x109/l; severe diarrhea.
PM (two inactive alleles: *2, *3, *4-*18) Select alternative drug. Insufficient data to allow calculation of dose adjustment. Published case reports, well documented, and having relevant pharmacokinetic or clinical endpoints. Well documented case series. Clinical effect (S): death; arrhythmia; unanticipated myelosuppression.
  • *See Methods or PMID: 18253145 for definition of "moderate" quality.
  • S: statistically significant difference.

PharmGKB gathers information regarding PGx on FDA drug labels from the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels", and from FDA-approved FDA and EMA-approved (European Medicines Agency) EMA labels brought to our attention. Excerpts from the label and downloadable highlighted label PDFs are manually curated by PharmGKB.

Please note that some drugs may have been removed from or added to the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels" without our knowledge. We periodically check the table for additions to this table and update PharmGKB accordingly.

There is currently no such list for European drug labels - we are working with the EMA to establish a list of European Public Assessment Reports (EPAR)s that contain PGx information. We are constructing this list by initially searching for drugs for which we have PGx-containing FDA drug labels - of these 44 EMA EPARs were identified and are being curated for pgx information.

We welcome any information regarding drug labels containing PGx information approved by the FDA, EMA or other Medicine Agencies around the world - please contact feedback.


last updated 10/25/2013

FDA Label for thioguanine and TPMT

This label is on the FDA Biomarker List
Actionable PGx

Summary

The drug label recommends substantial dosage reductions for individuals with an inherited deficiency of the enzyme thiopurine methyltransferase (TPMT) to avoid the development of life-threatening bone marrow suppression in these patients. Prescribers should be aware that some laboratories offer testing for TPMT deficiency.

Annotation

The pharmacogenomic releationship between thioguanine and TPMT is well described. See the TPMT VIP and Thiopurines Pathway for more details. Recent work by the Clinical Pharmacogenomics Implementation Consortium (CPIC) has published guidelines for dosing of thioguanine in individuals with TPMT variants.

Excerpt from the Thioguanine (Tabloid) drug label:

There are individuals with an inherited deficiency of the enzyme thiopurine methyltransferase (TPMT) who may be unusually sensitive to the myelosuppressive effects of thioguanine and prone to developing rapid bone marrow suppression following the initiation of treatment. Substantial dosage reductions may be required to avoid the development of life-threatening bone marrow suppression in these patients. Prescribers should be aware that some laboratories offer testing for TPMT deficiency. Since bone marrow suppression may be associated with factors other than TPMT deficiency, TPMT testing may not identify all patients at risk for severe toxicity. Therefore, close monitoring of clinical and hematologic parameters is important. Bone marrow suppression could be exacerbated by coadministration with drugs that inhibit TPMT, such as olsalazine, mesalazine, or sulphasalazine.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Thioguanine (Tabloid) drug label.

*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.

Full label available at DailyMed

Genes and/or phenotypes found in this label

  • Drug Toxicity
    • Precautions section
    • source: PHONT
  • Leukemia
    • Indications & usage section, Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • Neoplasms
    • Indications & usage section, Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
    • Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • TPMT
    • Dosage & administration section, Warnings section, Precautions section, metabolism/PK
    • source: FDA Label

Clinical Variants that meet the highest level of criteria, manually curated by PharmGKB, are shown below.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

? = Mouse-over for quick help

This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Gene?
DMET Plus (Affymetrix, Inc) Variant in TPMT
TPMT GenotypR rs1142345 , rs1800460 , rs1800462

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

Gene ? Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No VIP available VA TPMT *2 N/A N/A N/A
No VIP available No VIP available VA TPMT *3A N/A N/A N/A
rs1142345 18070918T>C, 18130918T>C, 29457A>G, 719A>G, TPMT*3C, Tyr240Cys
T > C
Missense
Tyr240Cys
rs1800460 18079228C>T, 18139228C>T, 21147G>A, 460G>A, Ala154Thr, TPMT*3B
C > T
Missense
Ala154Thr
rs1800462 16420G>C, 18083955C>G, 18143955C>G, 238G>C, Ala80Pro, TPMT*2, TPMT:238G>C
C > G
Missense
Ala80Pro
VIP No Clinical Annotations available No Variant Annotations available
rs1800584 18071012C>T, 18131012C>T, 29363G>A, 626-1G>A, TPMT*4
C > T
Acceptor
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • 2-Amino 6MP
  • 2-Amino-6-mercaptopurine
  • 2-Amino-6-merkaptopurin
  • 2-Amino-6-purinethiol
  • 2-Aminopurin-6-thiol
  • 2-Aminopurine-6(1H)-thione
  • 2-Aminopurine-6-thiol
  • 6-Mercapto-2-aminopurine
  • 6-Mercaptoguanine
  • 6-Thioguanine
  • TG
  • ThG
  • Tioguanin
  • Tioguanine
Trade Names
  • Lanvis
  • Tabloid
  • Wellcome U3B
Brand Mixture Names

PharmGKB Accession Id:
PA451663

Description

An antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia.

Source: Drug Bank

Indication

For remission induction and remission consolidation treatment of acute nonlymphocytic leukemias.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

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.

Source: Drug Bank

Pharmacology

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).

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic. First converted to 6-thioguanilyic acid (TGMP). TGMP is further converted to the di- and tri-phosphates, thioguanosine diphosphate (TGDP) and thioguanosine triphosphate (TGTP) by the same enzymes that metabolize guanine nucleotides.

Source: Drug Bank

Absorption

Absorption of an oral dose is incomplete and variable, averaging approximately 30% of the administered dose (range: 14% to 46%)

Source: Drug Bank

Half-Life

80 minutes (range 25-240 minutes)

Source: Drug Bank

Toxicity

Oral, mouse: LD 50 = 160 mg/kg. Symptoms of overdose include nausea, vomiting, malaise, hypotension, and diaphoresis.

Source: Drug Bank

Chemical Properties

Chemical Formula

C5H5N5S

Source: Drug Bank

Isomeric SMILES

c1[nH]c2c(=S)[nH]c(nc2n1)N

Source: OpenEye

Canonical SMILES

NC1=NC(=S)C2=C(N1)N=CN2

Source: Drug Bank

Average Molecular Weight

167.192

Source: Drug Bank

Monoisotopic Molecular Weight

167.026565875

Source: Drug Bank

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

External Pathways

Links to non-PharmGKB pathways.

PharmGKB contains no links to external pathways for this drug. To report a pathway, click here.

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

EvidenceGene
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
NHLRC1
TPMT

Drug Targets

Gene Description
HPRT1 (source: Drug Bank)
IMPDH1 (source: Drug Bank)
PPAT (source: Drug Bank)

Drug Interactions

Drug Description
thioguanine The 5-ASA derivative increases the toxicity of thiopurine (source: Drug Bank)
thioguanine The 5-ASA derivative increases the toxicity of thiopurine (source: Drug Bank)
thioguanine The 5-ASA derivative increases the toxicity of thiopurine (source: Drug Bank)
thioguanine The 5-ASA derivative increases the toxicity of thiopurine (source: Drug Bank)
busulfan Busulfan increases the hepatoxicity of Thioguanine during long-term concomitant therapy. (source: Drug Bank)
mercaptopurine Complete cross resistance may occur. (source: Drug Bank)
mesalazine The 5-ASA derivative increases the toxicity of thiopurine (source: Drug Bank)
mesalazine The 5-ASA derivative increases the toxicity of thiopurine (source: Drug Bank)
natalizumab The immunosuppressant, Thioguanine, may increase the adverse effects of Natalizumab. Increased risk of Progressive Multifocal Leukoencephalopathy (PML) and other infections. Concurrent therapy should be avoided. (source: Drug Bank)
olsalazine The 5-ASA derivative increases the toxicity of thiopurine (source: Drug Bank)
olsalazine The 5-ASA derivative increases the toxicity of thiopurine (source: Drug Bank)
sulfasalazine The 5-ASA derivative increases the toxicity of thiopurine (source: Drug Bank)
sulfasalazine The 5-ASA derivative increases the toxicity of thiopurine (source: Drug Bank)
thioguanine Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events. (source: Drug Bank)

Curated Information ?

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
Contraindicated With

Publications related to thioguanine: 55

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Nomenclature for alleles of the thiopurine methyltransferase gene. Pharmacogenetics and genomics. 2013. Appell Malin L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Clinical Pharmacogenetics Implementation Consortium Guidelines for Thiopurine Methyltransferase Genotype and Thiopurine Dosing: 2013 Update. Clinical pharmacology and therapeutics. 2013. Relling M V, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
PACSIN2 polymorphism influences TPMT activity and mercaptopurine-related gastrointestinal toxicity. Human molecular genetics. 2012. Stocco Gabriele, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Thiopurine S-methyltransferase polymorphism in Iranian kidney transplant recipients. Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation. 2011. Aghdaie Mahdokht Hossein, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Clinical pharmacogenetics implementation consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing. Clinical pharmacology and therapeutics. 2011. Relling M V, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics: From Bench to Byte- An Update of Guidelines. Clinical pharmacology and therapeutics. 2011. Swen J J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Ancestry and pharmacogenomics of relapse in acute lymphoblastic leukemia. Nature genetics. 2011. Yang Jun J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Ecto-5'-nucleotidase and thiopurine cellular circulation: association with cytotoxicity. Drug metabolism and disposition: the biological fate of chemicals. 2010. Li Fang, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Identifying genomic and developmental causes of adverse drug reactions in children. Pharmacogenomics. 2010. Becker Mara L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics. 2010. Beaulieu Mathieu, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Multivariate models to detect genomic signatures for a class of drugs: application to thiopurines pharmacogenomics. The pharmacogenomics journal. 2010. Fridley B L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Very important pharmacogene summary: thiopurine S-methyltransferase. Pharmacogenetics and genomics. 2010. Wang Liewei, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Drug transporter pharmacogenetics in nucleoside-based therapies. Pharmacogenomics. 2010. Errasti-Murugarren Ekaitz, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenomics in the treatment of inflammatory bowel disease. Pharmacogenomics. 2010. Smith Melissa A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ADME pharmacogenetics: current practices and future outlook. Expert opinion on drug metabolism & toxicology. 2009. Grossman Iris. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Azathioprine-associated acute myeloid leukemia in a patient with Crohn's disease and thiopurine S-methyltransferase deficiency. American journal of hematology. 2008. Yenson Paul R, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Differential effects of targeted disruption of thiopurine methyltransferase on mercaptopurine and thioguanine pharmacodynamics. Cancer research. 2007. Hartford Christine, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The thiopurine methyltransferase genetic polymorphism is associated with thioguanine-related veno-occlusive disease of the liver in children with acute lymphoblastic leukemia. Clinical pharmacology and therapeutics. 2006. Lennard Lynne, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Three novel thiopurine S-methyltransferase allelic variants (TPMT*20, *21, *22) - association with decreased enzyme function. Human mutation. 2006. Schaeffeler Elke, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Involvement of the concentrative nucleoside transporter 3 and equilibrative nucleoside transporter 2 in the resistance of T-lymphoblastic cell lines to thiopurines. Biochemical and biophysical research communications. 2006. Fotoohi Alan Kambiz, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Thiopurine S-methyltransferase pharmacogenetics: variant allele functional and comparative genomics. Pharmacogenetics and genomics. 2005. Salavaggione Oreste E, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Development of a large-scale chemogenomics database to improve drug candidate selection and to understand mechanisms of chemical toxicity and action. Journal of biotechnology. 2005. Ganter Brigitte, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Structural and functional analysis of mutations at the human hypoxanthine phosphoribosyl transferase (HPRT1) locus. Human mutation. 2004. Duan Jianxin, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Methylated metabolites of 6-mercaptopurine are associated with hepatotoxicity. Clinical pharmacology and therapeutics. 2004. Nygaard Ulrikka, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Pharmacogenetics of thiopurine S-methyltransferase and thiopurine therapy. Therapeutic drug monitoring. 2004. Evans William E. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Drug methylation in cancer therapy: lessons from the TPMT polymorphism. Oncogene. 2003. Krynetski Eugene, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Thiopurine metabolism and identification of the thiopurine metabolites transported by MRP4 and MRP5 overexpressed in human embryonic kidney cells. Molecular pharmacology. 2002. Wielinga P R, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The thiopurine S-methyltransferase gene locus -- implications for clinical pharmacogenomics. Pharmacogenomics. 2002. McLeod Howard L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Differing contribution of thiopurine methyltransferase to mercaptopurine versus thioguanine effects in human leukemic cells. Cancer research. 2001. Dervieux T, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Preponderance of thiopurine S-methyltransferase deficiency and heterozygosity among patients intolerant to mercaptopurine or azathioprine. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2001. Evans W E, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Thioguanine substitution alters DNA cleavage mediated by topoisomerase II. The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2000. Krynetskaia N F, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Multidrug-resistance protein 5 is a multispecific organic anion transporter able to transport nucleotide analogs. Proceedings of the National Academy of Sciences of the United States of America. 2000. Wijnholds J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Genetic polymorphism of thiopurine methyltransferase and its clinical relevance for childhood acute lymphoblastic leukemia. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2000. McLeod H L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Severe 6-thioguanine-induced marrow aplasia in a child with acute lymphoblastic leukemia and inherited thiopurine methyltransferase deficiency. Journal of pediatric hematology/oncology. 2000. McBride K L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Thioguanine administered as a continuous intravenous infusion to pediatric patients is metabolized to the novel metabolite 8-hydroxy-thioguanine. The Journal of pharmacology and experimental therapeutics. 1999. Kitchen B J, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Enhanced proteasomal degradation of mutant human thiopurine S-methyltransferase (TPMT) in mammalian cells: mechanism for TPMT protein deficiency inherited by TPMT*2, TPMT*3A, TPMT*3B or TPMT*3C. Pharmacogenetics. 1999. Tai H L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Possible carcinogenic effect of 6-mercaptopurine on bone marrow stem cells: relation to thiopurine metabolism. Cancer. 1999. Bo J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The frequency and distribution of thiopurine methyltransferase alleles in Caucasian and Asian populations. Pharmacogenetics. 1999. Collie-Duguid E S, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Genotypic and phenotypic analysis of the polymorphic thiopurine S-methyltransferase gene (TPMT) in a European population. British journal of pharmacology. 1998. Spire-Vayron de la Moureyre C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Clinical implications of thiopurine methyltransferase--optimization of drug dosage and potential drug interactions. Therapeutic drug monitoring. 1998. Lennard L. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacokinetics, dose adjustments, and 6-mercaptopurine/methotrexate drug interactions in two patients with thiopurine methyltransferase deficiency. Acta paediatrica (Oslo, Norway : 1992). 1998. Andersen J B, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Human thiopurine methyltransferase pharmacogenetics: gene sequence polymorphisms. Clinical pharmacology and therapeutics. 1997. Otterness D, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Enhanced proteolysis of thiopurine S-methyltransferase (TPMT) encoded by mutant alleles in humans (TPMT*3A, TPMT*2): mechanisms for the genetic polymorphism of TPMT activity. Proceedings of the National Academy of Sciences of the United States of America. 1997. Tai H L, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Molecular diagnosis of thiopurine S-methyltransferase deficiency: genetic basis for azathioprine and mercaptopurine intolerance. Annals of internal medicine. 1997. Yates C R, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Individualizing therapy with 6-mercaptopurine and 6-thioguanine related to the thiopurine methyltransferase genetic polymorphism. Therapeutic drug monitoring. 1996. Lennard L, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Thiopurine S-methyltransferase deficiency: two nucleotide transitions define the most prevalent mutant allele associated with loss of catalytic activity in Caucasians. American journal of human genetics. 1996. Tai H L, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Thiopurine methyltransferase pharmacogenetics: human gene cloning and characterization of a common polymorphism. DNA and cell biology. 1996. Szumlanski C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Methylation of mercaptopurine, thioguanine, and their nucleotide metabolites by heterologously expressed human thiopurine S-methyltransferase. Molecular pharmacology. 1995. Krynetski E Y, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
A single point mutation leading to loss of catalytic activity in human thiopurine S-methyltransferase. Proceedings of the National Academy of Sciences of the United States of America. 1995. Krynetski E Y, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Purine substrates for human thiopurine methyltransferase. Biochemical pharmacology. 1994. Deininger M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Reversal of 6-mercaptopurine and 6-methylmercaptopurine ribonucleoside cytotoxicity by amidoimidazole carboxamide ribonucleoside in Molt F4 human malignant T-lymphoblasts. Biochemical pharmacology. 1993. Stet E H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
The clinical pharmacology of 6-mercaptopurine. European journal of clinical pharmacology. 1992. Lennard L. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Altered mercaptopurine metabolism, toxic effects, and dosage requirement in a thiopurine methyltransferase-deficient child with acute lymphocytic leukemia. The Journal of pediatrics. 1991. Evans W E, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Genetic variation in response to 6-mercaptopurine for childhood acute lymphoblastic leukaemia. Lancet. 1990. Lennard L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Biochemical mechanism of resistance of cultured sarcoma 180 cells to 6-thioguanine. Biochemical pharmacology. 1981. Lee S H, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0173-0880-25
DrugBank:
DB00352
KEGG Compound:
C07648
PubChem Compound:
2723601
PubChem Substance:
152248
46508170
Drugs Product Database (DPD):
282081
BindingDB:
50200099
ChemSpider:
2005804
Therapeutic Targets Database:
DAP000194
FDA Drug Label at DailyMed:
dfda4177-3c9d-44ab-3ca6-e4db8e9fc603

Clinical Trials

These are trials that mention thioguanine and are related to either pharmacogenetics or pharmacogenomics.

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Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.