The Rediscovery of DON (6-Diazo-5-oxo-L-norleucine)
DON (6-diazo-5-oxo-l-norleucine) and azotomycin are glutamine antagonists that were tested in human malignancies in the 1950s. Azotomycin demonstrated significant activity in colorectal cancer. DON is probably the active form of azotomycin. Recent impressive results for both of these agents in human tumor xenografts (especially the CX-2 colon tumor) have stimulated renewed clinical interest in DON, the more readily available agent. DON mechanism of action, clinical pharmacology, previous clinical data, and current phase I studies are discussed.
KeywordsLymphoma Leukemia Oncol Sarcoma Glutamine
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- 1.Catane R, Ovejera AA, Houchens DP, Von Hoff DD, Davis HL Jr, Wolpert MK, Rozencweig M, Muggia FM (1978) Rationale for further clinical trials with 6-dia- zo-5-oxo-L-norleucine (DON) (abstr). Proc Am Assoc Cancer Res and Am Soc Clin Oncol 19:317Google Scholar
- 5.Livingston RB, Vendetti JM, Cooney DA, Carter SK (1970) Glutamine antagonists in chemotherapy, vol 8. Academic, New York, pp 62–83Google Scholar
- 9.Ovejera AA, Houchens DP, Barker AD (1977) Chemotherapeutic sensitivity to anticancer agents of human tumor xenografts in athymic mice. Current Chemotherapy: Proc. 10th International Congress on Chemotherapy 2:1144–1146Google Scholar
- 11.Prusiner S, Stadtman ER (eds) (1973) The enzymes of glutamine metabolism. Academic, New YorkGoogle Scholar
- 13.Veterans Administration Cancer Chemotherapy Study Group (1959) A clinical study of the comparative effect of nitrogen mustard and DON in patients with bronchogenic carcinoma, Hodgkin’s disease, lymphosarcoma and melanoma. J Natl Cancer Inst 22:433–439Google Scholar