Abstract
D-19575 is a glucose derivative of ifosfamide mustard with a broad spectrum of antitumor activity in animal models. In comparison with ifosfamide, D-19575 is less toxic and is better tolerated by tumor-bearing animals, achieving a better therapeutic efficacy. D-19575 is directly cytotoxic in vitro—in contrast to ifosfamide— and it is possible to modulate this cytotoxicity by inhibition of transmembrane glucose transporters. Correspondingly, renal reabsorption of filtered D-19575 could be blocked by pre- and cotreatment with phlorizin, resulting in a higher urinary excretion of the unchanged drug. The toxicity to white blood cells, colony-forming units (CFU-C), and spleen-cell colony-forming units (CFU-S) is considerably lower for D-19575 as compared with ifosfamide. In conclusion, D-19575 is a new alkylating cytotoxic agent with increased antitumor selectivity, probably caused by an active transmembrane transport mechanism.
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Pohl, J., Bertram, B., Hilgard, P. et al. D-19575—a sugar-linked isophosphoramide mustard derivative exploiting transmembrane glucose transport. Cancer Chemother. Pharmacol. 35, 364–370 (1995). https://doi.org/10.1007/s002800050248
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DOI: https://doi.org/10.1007/s002800050248