The thiopurines: an update

Invest New Drugs. 2005 Dec;23(6):523-32. doi: 10.1007/s10637-005-4020-8.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / pharmacokinetics
  • Antimetabolites, Antineoplastic / therapeutic use
  • Azathioprine / therapeutic use
  • Cell Line, Tumor
  • Guanine Nucleotides / blood
  • Humans
  • Immunosuppressive Agents / pharmacokinetics
  • Immunosuppressive Agents / therapeutic use
  • Leukemia / drug therapy
  • Leukemia / enzymology*
  • Leukemia / genetics
  • Mercaptopurine / therapeutic use
  • Methyltransferases / genetics*
  • Methyltransferases / metabolism
  • Polymorphism, Genetic*
  • Thioguanine / therapeutic use
  • Thionucleotides / blood


  • Antimetabolites, Antineoplastic
  • Guanine Nucleotides
  • Immunosuppressive Agents
  • Thionucleotides
  • Mercaptopurine
  • Methyltransferases
  • thiopurine methyltransferase
  • Thioguanine
  • Azathioprine