D-19575 - A SUGAR-LINKED ISOPHOSPHORAMIDE MUSTARD DERIVATIVE EXPLOITING TRANSMEMBRANE GLUCOSE-TRANSPORT

D-19575 is a glucose derivative of ifosfamide mustard with a broad spe ctrum of antitumor activity in animal models. In comparison with ifosf amide, 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 mod ulate this cytotoxicity by inhibition of transmembrane glucose transpo rters. Correspondingly, renal reabsorption of filtered D-19575 could b e blocked by pre- and cotreatment with phlorizin, resulting in a highe r urinary excretion of the unchanged drug. The toxicity to white blood cells, colony-forming units (CFU-C), and spleen-cell colony-forming u nits (CFU-S) is considerably lower for D-19575 as compared with ifosfa mide. In conclusion, D-19575 is a new alkylating cytotoxic agent with increased antitumor selectivity, probably caused by an active transmem brane transport mechanism.