The thiopurines: An update View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2005-10-26

AUTHORS

Sally Coulthard, Linda Hogarth

ABSTRACT

The thiopurine drugs, 6-mercaptopurine (6-MP), 6-thioguanine (6-TG) are commonly used cytotoxic agents. A derivative of 6-MP, azathioprine, is commonly used as an immunosuppressant. A prominent route for the metabolism of these agents is mediated by the enzyme thiopurine methyltransferase (TPMT). This enzyme exhibits considerable inter-individual variation in activity, partly due to the presence of common genetic polymorphisms, which influence cytotoxicity of the thiopurine drugs. Variations in the number of tandem repeats in the 5′ promoter region have also been shown to influence TPMT expression in vitro. In this article, we review the impact of variations in TPMT activity on sensitivity to the thiopurine drugs in vitro and also in vivo in terms of their clinical efficacy and toxicity. A possible relationship between TPMT and secondary malignancies is also reviewed. More... »

PAGES

523-532

References to SciGraph publications

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  • 1981-07. Clinical pharmacology of oral thioguanine in acute myelogenous leukemia in CANCER CHEMOTHERAPY AND PHARMACOLOGY
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  • 2003-06-19. Real-time RT-PCR methodology for quantification of thiopurine methyltransferase gene expression in EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
  • 2000-12-01. Co-operative study group for childhood acute lymphoblastic leukemia (COALL): long-term follow-up of trials 82, 85, 89 and 92 in LEUKEMIA
  • 1992-10. The clinical pharmacology of 6-mercaptopurine in EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
  • 1998-06. Thiopurine S-methyltransferase activity in human erythrocytes: a new HPLC method using 6-thioguanine as substrate in EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
  • 2001-04. Recent advances in the pharmacogenomics of thiopurine methyltransferase in THE PHARMACOGENOMICS JOURNAL
  • 1997-10-09. Olsalazine and 6‐mercaptopurine‐related bone marrow suppression: A possible drug‐drug interaction in CLINICAL PHARMACOLOGY & THERAPEUTICS
  • 1993-07. Is 6-thioguanine more appropriate than 6-mercaptopurine for children with acute lymphoblastic leukaemia? in BRITISH JOURNAL OF CANCER
  • 2000-09-01. Genomic structure and multiple single-nucleotide polymorphisms (SNPs) of the thiopurine S-methyltransferase (TPMT) gene in JOURNAL OF HUMAN GENETICS
  • 2000-04-01. Genetic polymorphism of thiopurine methyltransferase and its clinical relevance for childhood acute lymphoblastic leukemia in LEUKEMIA
  • 1999-03. Pharmacogenetics as a Molecular Basis for Individualized Drug Therapy: The Thiopurine S-methyltransferase Paradigm in PHARMACEUTICAL RESEARCH
  • 1998-03-01. Etoposide and antimetabolite pharmacology in patients who develop secondary acute myeloid leukemia in LEUKEMIA
  • 2003-06-20. A novel TPMT missense mutation associated with TPMT deficiency in a 5-year-old boy with ALL in LEUKEMIA
  • 1989-08-26. Pharmacogenetics of acute azathioprine toxicity: Relationship to thiopurine methyltransferase genetic polymorphism in CLINICAL PHARMACOLOGY & THERAPEUTICS
  • 2000-08. Thiopurine methyltransferase polymorphic tandem repeat: Genotype‐phenotype correlation analysis in CLINICAL PHARMACOLOGY & THERAPEUTICS
  • 1998-08. Pharmacokinetics and metabolism of thiopurines in children with acute lymphoblastic leukemia receiving 6-thioguanine versus 6-mercaptopurine in CANCER CHEMOTHERAPY AND PHARMACOLOGY
  • 2001-08. Influence of the variable number of tandem repeats located in the promoter region of the thiopurine methyltransferase gene on enzymatic activity in CLINICAL PHARMACOLOGY & THERAPEUTICS
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s10637-005-4020-8

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    http://dx.doi.org/10.1007/s10637-005-4020-8

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/16267626


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