Reductive activation of the prodrug 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-[[1-(4-nitrophenyl)ethoxy]carbonyl]hydrazine (KS119) selectively occurs in oxygen-deficient cells and overcomes O6-alkylguanine-DNA alkyltransferase mediated KS119 tumor cell resistance
Baumann RP, Penketh PG, Ishiguro K, Shyam K, Zhu YL, Sartorelli AC. Reductive activation of the prodrug 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-[[1-(4-nitrophenyl)ethoxy]carbonyl]hydrazine (KS119) selectively occurs in oxygen-deficient cells and overcomes O6-alkylguanine-DNA alkyltransferase mediated KS119 tumor cell resistance. Biochemical Pharmacology 2009, 79: 1553-1561. PMID: 20005211, PMCID: PMC2885764, DOI: 10.1016/j.bcp.2009.12.004.Peer-Reviewed Original ResearchConceptsAlkylguanine-DNA alkyltransferaseDNA GO6-alkylguanine-DNA alkyltransferaseCell linesBase-catalyzed activationCellular protectionReductive activationCross-link lesionsTumor cell resistanceCultured cellsCell lethalityReductase enzymePosition of guanineDifferent tumor typesIntracellular activationAlkyltransferaseCell resistanceActivationEnzymeCytotoxic effectsCellsOxygen-deficient cellsHypoxic cellsOxygen-deficient conditions