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.
MeSH terms
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Absorption / drug effects
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Administration, Oral
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Animals
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Antineoplastic Agents / adverse effects
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Antineoplastic Agents / therapeutic use
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Bone Marrow / drug effects
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Bone Marrow Cells
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Cells, Cultured
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Colony-Forming Units Assay
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Disease Models, Animal
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Drug Evaluation
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Drug Tolerance
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Female
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Glucose / administration & dosage
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Glucose / analogs & derivatives*
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Glucose / chemical synthesis
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Glucose / metabolism
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Glucose / pharmacology
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Glucose / therapeutic use
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Ifosfamide / administration & dosage
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Ifosfamide / analogs & derivatives*
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Ifosfamide / chemical synthesis
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Ifosfamide / chemistry
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Ifosfamide / metabolism
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Ifosfamide / pharmacology
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Ifosfamide / therapeutic use
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Kidney / drug effects
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Leukocytes / drug effects
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Mice
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Monosaccharide Transport Proteins / drug effects*
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Neoplasm Transplantation
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Neoplasms, Experimental / drug therapy
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Phlorhizin / pharmacology
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Phosphoramide Mustards*
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Rats
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Rats, Sprague-Dawley
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Specific Pathogen-Free Organisms
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Spleen / cytology
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Spleen / drug effects
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Tumor Cells, Cultured
Substances
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Antineoplastic Agents
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Monosaccharide Transport Proteins
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Phosphoramide Mustards
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beta-D-glucosylisophosphoramide mustard
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isophosphamide mustard
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Phlorhizin
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Glucose
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Ifosfamide