Skip to main content
SpringerLink
Log in

m-AMSA and PALA: Two new agents in cancer chemotherapy

  • General Review
  • m-AMSA and PALA
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Summary

4′-(9-Acridinylamino)methanesulfon-m-anisidide (m-AMSA) and N-(phosphonacetyl)-l-aspartate (PALA) are two new anticancer agents that have been recently introduced into clinical investigation. This review summarizes the preclinical information that has accumulated with these compounds as well as the very preliminary data presently available from early clinical trials. This information indicates the promising potential of m-AMSA and PALA in the treatment of cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Baguley, B. C., Falkenhaug, E. M., Rastrick, J. M., Marbrook, J.: An assessment of the immunosuppressive activity of the antitumour compound 4′-[9-acridinyl)amino]methanesulfon-m-anisidide (m-AMSA). Eur. J. Cancer 10, 169 (1974)

    Google Scholar 

  2. Byrd, D. M.: Antiviral activities of 4′-(9-acridinylamino)-methanesulfon-m-aniside (SN11841). Ann. NY Acad. Sci. 284, 463 (1977)

    Google Scholar 

  3. Cain, B. F., Atwell, G. J.: The experimental antitumour properties of three congeners of the acridylmethanesulphonailide (AMSA) series. Eur. J Cancer 10, 539 (1974)

    Google Scholar 

  4. Carter, S. K.: Clinical trials in cancer chemotherapy. Cancer 40, 544 (1977)

    Google Scholar 

  5. Carter, S. K.: The clinical evaluation of analogues: I. The overall problem. Cancer Chemother. Pharmacol. 1, 69 (1978)

    Google Scholar 

  6. Chadwick, M., Silveira, D. M., MacGregor, J. A., Branfman, A. R., Liss, R. H., Yesair, D. W.: Physiological disposition of PALA in several species. Proc. Am. Assoc. Cancer Res. 19, 182 (1978)

    Google Scholar 

  7. Collins, K. D., Stark, G. R.: Aspartate transcarbamylase. Interaction with the transition state analog N-(phosphonacetyl)-l-aspartate. J. Biol. Chem. 246, 6599 (1971)

    Google Scholar 

  8. Cooney, D. A., Karlowicz, M. G., Cubillan, J., Roettger, M., Jayaram, H. N.: An enzymatic technique for measuring N-phosphonacetyl-l-aspartic acid in tissues. Cancer Treat. Rep. 62, 1503 (1978)

    Google Scholar 

  9. Corbett, T. H., Griswold, D. P., Jr., Roberts, B. J., Peckham, J. C., Schabel, F. M., Jr.: Evaluation of single agents and combinations of chemotherapeutic agents in mouse colon carcinomas. Cancer 40, 2660 (1977)

    Google Scholar 

  10. Cysyk, R. L., Shoemaker, D., Adamson, R. H.: The pharmacologic disposition of 4′-(9-acridinylamino)methanesulfon-m-anisidide in mice and rats. Drug Metab. Dispos. 5, 579 (1977)

    Google Scholar 

  11. Cysyk, R. L., Shoemaker, D., Ayers, O. C., Adamson, R. H.: Oral absorption and selective tissue localization of 4′-(9-acridinylamino)-methanesulfon-m-anisidide. Pharmacology 16, 206 (1978)

    Google Scholar 

  12. Deaven, L. L., Oka, M. S., Tobey, R. A.: Cell-cycle-specific chromosome damage following treatment of cultured Chinese hamster cells with 4′[(9-acridinyl)-amino]methanesulfon-m-anisidide-HCl. J. Natl. Cancer Inst. 60, 1155 (1978)

    Google Scholar 

  13. DeVita, V. T., Jr., Schein, P. S.: The use of drugs in combination for the therapy of cancer. N. Engl. J. Med. 288, 988 (1973)

    Google Scholar 

  14. DeVita, V. T., Jr., Lewis, B. J., Rozencweig, M., Muggia, F. M.: The chemotherapy of Hodgkin's disease: Past experiences and future directions. Cancer 42, 979 (1978)

    Google Scholar 

  15. Furlong, N. B., Sato, J., Brown, T., Chavez, F., Hurlbert, R. B.: Induction of limited DNA damage by the antitumor agent Cain's acridine. Cancer Res. 38, 1329 (1978)

    Google Scholar 

  16. Goldin, A., Venditti, J. M., Muggia, F. M., Rozencweig, M., DeVita, V. T.: New animal models. In: Proceedings of the XII International Cancer Congress. Buenos Aires, Pergamon (in press, 1979)

  17. Gormley, P. E., Sethi, V. S., Cysyk, R. L.: Interaction of 4′-(9-acridinylamino)methansulfon-m-anisidide with DNA and inhibition of oncornavirus reverse transcriptase and cellular nucleic acid polymerases. Cancer Res. 38, 1300 (1978)

    Google Scholar 

  18. Jacobs, E. M., Muggia, F. M., Rozencweig, M.: Chemotherapy of testicular cancer: From palliation to curative adjuvant therapy. Semin. Oncol. 6, 3 (1979)

    Google Scholar 

  19. Jayaram, H. N., Cooney, D. A., Vistica, D. T., Kariya, S., Johnson, R. K.: Mechanisms of sensitivity or resistance of murine tumors to N-(phosphonacetyl)-l-aspartate. Cancer Treat. Rep. (in press, 1979)

  20. Johnson, R. K.: Reversal of toxicity and antitumor activity of N-(phosphonacetyl)-l-aspartate by uridine or carbamyl-dl-aspartate in vivo. Biochem. Pharmacol. 26, 81 (1977)

    Google Scholar 

  21. Johnson, R. K., Chitnis, M. P., Goldin, A.: Characteristics of resistance and cross-resistance in vivo of a subline of P388 leukemia resistant to adriamycin. Pharmacologist 18, 173 (1976)

    Google Scholar 

  22. Johnson, R. K., Swyryd, E. A., Stark, G. R.: Effects of N-(phosphanacetyl)-l-aspartate on murine tumors and normal tissues in vivo and in vitro and the relationship of sensitivity to rate of proliferation and level of asparate transcarbamylase. Cancer Res 38, 371 (1978)

    Google Scholar 

  23. Kempe, T. D., Swyryd, E. A., Bruist, M., Stark, G. R.: Stable mutants of mamalian cells that overproduce the first three enzymes of pyrimidine nucleotide biosynthesis. Cell 9, 541 (1976)

    Google Scholar 

  24. Legha, S. S., Gutterman, J. U., Hall, S. W., Benjamin, R. S., Burgess, M. A., Valdivieso, M., Bodey, G. P.: Phase I clinical investigation of 4′-(9-acridinylamino)methanesulfon-m-anisidide (NSC-249992), a new acridine derivative. Cancer Res. 38, 3712 (1978)

    Google Scholar 

  25. Mellanby, E.: Report on work carried out in the pharmacological laboratory, Sheffield University. British Empire Cancer Campaign 10th Annual Report, p. 102, 1933

  26. Muggia, F. M., Rozencweig, M., Von Hoff, D. D.: Evaluation of anticancer drugs: Analysis of recent results by disease. In: Recent Advances in Cancer Treatment. Tagnon, H. J., Staquet, M. J. (eds.), p. 187. New York: Raven Press 1977

    Google Scholar 

  27. Muggia, F. M., McGuire, W. P., Rozencweig, M.: Rationale, design and methodology of Phase II clinical trials. In: Methods in Cancer Research. Bush, H., DeVita, V. T., Jr. (eds.) 17, 199 (1979)

  28. Muggia, F. M., Rozencweig, M., Bono, V. H., Jacobs, E. M., Jr.: Platinum: The trail from an inert electrode to a therapeutic solution. Cancer Treat. Rep. (in press, 1979)

  29. Nayak, R., Martin, D., Stolfi, R., Furth, J., Spiegelman, S.: Pyrimidine nucleosides enhance the anti-cancer activity of FU and augment its incorporation into nuclear RNA. Proc. Am. Assoc. Cancer Res. 19, 63 (1978)

    Google Scholar 

  30. Osieka, R., Houchens, D. P., Goldin, A., Johnson, R. K.: Chemotherapy of human colon cancer xenografts in athymic nude mice. Cancer 40, 2640 (1977)

    Google Scholar 

  31. Rozencweig, M., Von Hoff, D. D., Venditti, J. M., Muggia, F. M.: Correlation between experimental activity of anticancer agents and their hematologic toxicity in man. Blood 48, 984 (1976)

    Google Scholar 

  32. Rozencweig, M., Von Hoff, D. D., Henney, J. E., Muggia, F. M.: VM 26 and VP 16-213: A comparative analysis. Cancer 40, 334 (1977)

    Google Scholar 

  33. Rozencweig, M., Von Hoff, D. D., Slavik, M., Muggia, F. M.: cis-Diamminedichloroplatinum (II): A new anticancer drug. Ann. Intern. Med. 86, 803 (1977)

    Google Scholar 

  34. Rozencweig, M., De Sloover, C., Von Hoff, D. D., Tagnon, H. J., Muggia, F. M.: Anthracycline derivatives in new drug development programs. Cancer Treat. Rep. (in press, 1979)

  35. Schabel, F. M., Jr., Laster, W. R., Jr., Rose, W. C.: The role of experimental tumor systems. In: Lung Cancer: Progress in Therapeutic Research. Muggia, F. M., Rozencweig, M. (eds.), p. 15. New York: Raven Press 1979

    Google Scholar 

  36. Shoemaker, D. D., Legha, S. S., Cysyk, R. L.: Selective localization of 4′(9-acridinylamino)methanesulfon-m-anisidide in B16 melanoma. Pharmacology 16, 221 (1978)

    Google Scholar 

  37. Strong, J. M., Kinney, Y. E., Branfman, A. R., Cysyk, R. L.: Determination of N-(phosphonacetyl)-l-aspartic acid (PALA) in biological fluids by gas chromatography and by selected ion monitoring. Cancer Treat. Rep. (in press, 1979)

  38. Sweeney, M. J., Hoffman, D. H., Poore, G. A.: Enzymes in pyrimidine biosynthesis. Adv. Enzyme Regul. 9, 51 (1970)

    Google Scholar 

  39. Tobey, R. A., Deaven, L. L., Oka, M. S.: Kinetic response of cultured Chinese hamster cells to treatment with 4′-[(9-acridinyl)-amino]methanesulfon-m-anisidide-HCl. J. Natl. Cancer Inst. 60, 1147 (1978)

    Google Scholar 

  40. Von Hoff, D. D., Rozencweig, M., Soper, W. T., Helman, L. J., Penta, J. S., Davis, H. L., Muggia, F. M.: Whatever happened to NSC? — An analysis of clinical results of discontinued anticancer agents. Cancer Treat. Rep. 61, 759 (1977)

    Google Scholar 

  41. Von Hoff, D. D., Howser, D., Gormley, P., Bender, R. A., Glaubiger, D., Levine, A. S., Young, R. C.: Phase I study of methanesulfonamide, N-[4-(9-acridinylamino)-3-methoxyphenyl]-(m-AMSA) using a single-dose schedule. Cancer Treat. Rep. 62, 1421 (1978)

    Google Scholar 

  42. Waring, M. J.: DNA-binding characteristics of acridinylmethanesulphonanilide drugs: Comparison with antitumour properties. Eur. J. Cancer 12, 995 (1976)

    Google Scholar 

  43. Wilson, W. R.: Studies on mechanism of action of an experimental antitumor drug. Chem. N.Z. 37, 148 (1973)

    Google Scholar 

  44. Yoshida, T., Stark, G. R., Hoogenraad, N. J.: Inhibition by N-(Phosphonacetyl)-l-aspartate of aspartate transcarbamylase activity and drug-induced cell proliferation in mice. J. Biol. Chem. 249, 6951 (1974)

    Google Scholar 

  45. Young, J. E., Prager, M. D., Atkins, I. C.: Comparative activities of aspartate transcarbamylase in various tissues of the rat (32224). Proc. Soc. Exp. Biol. Med. 125, 860 (1967)

    Google Scholar 

Download references

Author information

Author notes

  1. M. Rozencweig

    Present address: Investigational Drug Section, Institut Jules Bordet, 1, rue Héger-Bordet, B-1000, Brussels, Belgium

Authors and Affiliations

  1. Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland, USA

    M. Rozencweig, D. D. Von Hoff, R. L. Cysyk & F. M. Muggia

Authors
  1. M. Rozencweig
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. D. Von Hoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. L. Cysyk
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. F. M. Muggia
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rozencweig, M., Von Hoff, D.D., Cysyk, R.L. et al. m-AMSA and PALA: Two new agents in cancer chemotherapy. Cancer Chemother. Pharmacol. 3, 135–141 (1979). https://doi.org/10.1007/BF00262414

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00262414

Keywords

Search

Navigation