Troxacitabine prodrugs for pancreatic cancer.

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Adema AD, Radi M, Daft J, Narayanasamy J, Hoebe EK, Alexander LE, Chu CK, Peters GJ

Troxacitabine prodrugs for pancreatic cancer.

Nucleosides Nucleotides Nucleic Acids. 2007;26(8-9):1073-7.

PubMed ID

18058539 [ View in PubMed

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Abstract

Troxacitabine is a cytotoxic deoxycytidine analogue with an unnatural L-configuration, which is activated by deoxycytidine kinase (dCK). The configuration is responsible for differences in the uptake and metabolism of troxacitabine compared to other deoxynucleoside analogues. The main drawback in the use of most nucleoside anticancer agents originates from their hydrophilic nature, which property requires a high and frequent dosage for an intravenous administration. To overcome this problem several troxacitabine prodrugs modified in the aminogroup with a linear aliphatic chain with a higher lipophilicity were developed. To determine whether these prodrugs have an advantage over Troxacitabine pancreatic cancer cell lines were exposed to Troxacitabine and the lipophilic prodrugs. The addition of linear aliphatic chains to troxacitabine increased sensitivity of pancreatic cancer cell lines to the drug > 100-fold, possibly due to a better uptake and retention of the drug.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Troxacitabine	Deoxycytidine kinase	Protein	Humans	Unknown	Activator	Details