Abstract

Nucleoside analogs serve as important chemotherapeutic agents in a number of severe diseases such as cancer and viral infections. These agents are pro-drugs that have to be taken up and phosphorylated in several steps to be trapped in the cells and transformed to active metabolites that inhibit essential steps in the replication of viruses or malignant cells. The anabolic deoxynucleoside kinases (dNKs) and catabolic 5'- nucleotidases(5'-NTs) are involved in maintaining substrate cycles, and act as regulators for the intracellular pools of active nucleotide metabolites. In this chapter the expression patterns of the four dNKs i.e. cytosolic deoxycytidine kinase (dCK) and thymidine kinase 1 (TK1) and the mitochondrial thymidine kinase 2 (TK2) and deoxyguanosine kinase (dGK) as well as the six intracellular 5'-NTs: cN-IA, cN-IB, cN-II, cN-III, cdN, mdN, present in animal cells and tissues will be described. Their role as primary controllers of the accumulation and activation of important anti viral and anti cancer nucleoside analogs in different tissues involved in the pathophysiology of these diseases will be evaluated. The predictability of using the ratios between the activities of the dNKs and 5'-NTs for estimating efficacy and side effects of nucleoside drug candidates will be discussed as well as recommendations on how to use this information to improve future therapies with nucleoside drugs.

Keywords

Nucleoside analogs; deoxynucleoside kinases; 5 '-nucleotidases; cell culture models; tissues extracts; efficacy; toxicity

Published in

Current Medicinal Chemistry
2013, Volume: 20, number: 34, pages: 4241-4248
Publisher: BENTHAM SCIENCE PUBL LTD

SLU Authors

• Eriksson, Staffan

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    

Sustainable Development Goals

SDG3 Ensure healthy lives and promote well-being for all at all ages


UKÄ Subject classification

Pharmaceutical Chemistry
Biochemistry and Molecular Biology


Publication identifier

DOI: https://doi.org/10.2174/0929867311320340004

Permanent link to this page (URI)

https://res.slu.se/id/publ/54897