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The Rediscovery of DON (6-Diazo-5-oxo-L-norleucine)

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Cancer Chemo- and Immunopharmacology

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 74))

Summary

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.

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References

  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 19:317

    Google Scholar 

  2. Cooney DA, Jayaram HN, Milman HA, Homan ER, Pittillo R, Geran RI, Ryan J, Rosenbluth RJ (1976) DON, CONV and DONV-III, pharmacologic and toxicologic studies. Biochem Pharmacol 25:1859–1870

    Article  PubMed  CAS  Google Scholar 

  3. Hill GJ, Larsen RR, Sas EM (1973) Cancer chemotherapy II. Results of 603 courses of therapy in 400 consecutive patients followed for 18-52 months. Oncology 27:137–152

    Article  PubMed  Google Scholar 

  4. Li MC (1961) Management of chariocarcinoma and related tumors of the uterus and testis. Med Clin North Am 45:661–676

    PubMed  CAS  Google Scholar 

  5. Livingston RB, Vendetti JM, Cooney DA, Carter SK (1970) Glutamine antagonists in chemotherapy, vol 8. Academic, New York, pp 62–83

    Google Scholar 

  6. Magill GB, Myers WPL, Reilly HC, Putnam RC, Magill JW, Sykes MP, Escher GC, Karnofsky GC, Burchenal JH (1957) Pharmacological and initial therapeutic observations on 6-diazo-5-oxo-L-norleucine (DON) in human neoplastic disease. Cancer 10:1138–1150

    Article  PubMed  CAS  Google Scholar 

  7. Moore E, Hulbert R (1961) Biosynthesis of RNA cytosine and RNA purines; differential inhibition by 6-diazo-5-oxo-L-norleucine. Cancer Res 21:257–261

    PubMed  CAS  Google Scholar 

  8. Moore EC, LePage GA (1957) In vivo sensitivity of normal and neoplastic mouse tissues to azaserine. Cancer Res 17:804–808

    PubMed  CAS  Google 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 2:1144–1146

    Google Scholar 

  10. Pittillo RF, Wooley C, Brockman RW, Ho DH (1971) Azotomycin (NSC-1566454): Biologic fate in mice and man. Cancer Chemother Rep 55:47–52

    PubMed  CAS  Google Scholar 

  11. Prusiner S, Stadtman ER (eds) (1973) The enzymes of glutamine metabolism. Academic, New York

    Google Scholar 

  12. Rosenbluth RJ, Cooney DA, Jayaram HN, Milman HA, Homan ER (1976) DON, CONV, and DONV.-II, inhibition of L-asparaginase synthetase in vivo. Biochem Pharmacol 25:1851–1858

    Article  PubMed  CAS  Google 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 22:433–439

    Google Scholar 

  14. Weiss AJ, Mastrangelo MJ (1970) Phase I study of a combination of azotomycin + 5-FU in malignant disease. Cancer Chemother Rep 54:109–111

    PubMed  CAS  Google Scholar 

  15. Weiss AJ, Ramirez G, Grage T, Strawitz J, Goldman L, Downing V (1968) Phase II study of azotomycin. Cancer Chemother Rep 52:611–614

    PubMed  CAS  Google Scholar 

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© 1980 Springer-Verlag Berlin Heidelberg

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Kisner, D.L., Catane, R., Muggia, F.M. (1980). The Rediscovery of DON (6-Diazo-5-oxo-L-norleucine). In: Mathé, G., Muggia, F.M. (eds) Cancer Chemo- and Immunopharmacology. Recent Results in Cancer Research, vol 74. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-81488-4_30

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  • DOI: https://doi.org/10.1007/978-3-642-81488-4_30

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-81490-7

  • Online ISBN: 978-3-642-81488-4

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