D-19575--a sugar-linked isophosphoramide mustard derivative exploiting transmembrane glucose transport.

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.

• Authors: J Pohl, B Bertram, P Hilgard, M R Nowrousian, J Stüben, M Wiessler
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 35 Issue 5 Pg. 364-70 ( 1995) ISSN: 0344-5704 [Print] Germany
• PMID: 7850916 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antineoplastic Agents
• Monosaccharide Transport Proteins
• Phosphoramide Mustards
• beta-D-glucosylisophosphoramide mustard
• isophosphamide mustard
• Phlorhizin
• Glucose
• Ifosfamide

Topics

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