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Nucleotidases and Nucleoside Analog Cytotoxicity

  • Sally Anne Hunsucker
  • Beverly S. Mitchell
  • Jozef Spychala
Part of the Cancer Drug Discovery and Development book series (CDD&D)

Abstract

Nucleoside analogs are an important part of therapeutic strategies in a broad range of diseases, especially cancer and viral infections. Most nucleoside analogs need to be phosphorylated to attain full clinical potency; thus, knowledge of the metabolism of this class of drugs is required to improve their clinical use. The 5′-nucleotidases are a family of enzymes that catalyze the final dephosphorylation step of nucleotides in the cell and, by opposing the activation step catalyzed by nucleoside kinases, initiate subsequent purine and pyrimidine catabolism. They also catalyze a critical step in nucleotide analog degradation; therefore, their expression and regulation in various tissues will likely have an impact on a nucleoside drug’s half-life in the human body. Numerous studies in vitro and in vivo indicate that increased expression of 5′_nucleotidase may decrease nucleoside analog activation and thereby contribute to drug resistance. Because cloned 5′_nucleotidases have been described in human tissues, it is not always possible to assess which particular 5′-nucleotidase is important in nucleoside drug catabolism. In this chapter, we review the properties of all cloned 5′-nucleotidases and the important role of these enzymes in nucleoside analog metabolism and clinical resistance.

Key Words

Drug metabolism drug resistance nucleoside analogs 5′-nucleotidase 

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Copyright information

© Humana Press Inc., Totowa, NJ 2006

Authors and Affiliations

  • Sally Anne Hunsucker
    • 1
  • Beverly S. Mitchell
    • 2
  • Jozef Spychala
    • 3
    • 4
  1. 1.Lineberger Comprehensive Cancer Center, Department of PharmacologyUniversity of North Carolina at Chapel HillChapel Hill
  2. 2.George E. Becker Professor of Medicine, Comprehensive Cancer CenterStanford UniversityStanford
  3. 3.VisiScience CorporationChapel Hill
  4. 4.Department of Pharmacology, Lineberger Comprehensive Cancer CenterUniversity of North Carolina at Chapel HillChapel Hill

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