Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth


NEOVASCULARIZATION is critical for the growth of tumours1–3 and is a dominant feature in a variety of angiogenic diseases4 such as diabetic retinopathy, haemangiomas, arthritis and psoriasis. Recognition of the potential therapeutic benefit of controlling unabated capillary growth5 has led to a search for safe and effective angiogenesis inhibitors. We report here the synthesis of a family of novel inhibitors that are analogues of fumagillin, a naturally secreted antibiotic6 of Aspergillus fumigatus fresenius. We first isolated this fungus from a contaminated culture of capillary endothelial cells. Purified fumagillin inhibited endothelial cell proliferation in vitro and tumour-induced angiogenesis in vivo; it also inhibited tumour growth in mice, but prolonged administration was limited because it caused severe weight loss. Synthesis of fumagillin analogues yielded potent angiogenesis inhibitors ('angioinhibins') which suppress the growth of a wide variety of tumours with relatively few side-effects.

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  1. 1

    Folkman, J. Ann. Int. Med. 82, 96–100 (1975).

    CAS  Article  Google Scholar 

  2. 2

    Folkman, J., Watson, K., Ingber, D. & Hanahan, D. Nature 339, 58–61 (1989).

    ADS  CAS  Article  Google Scholar 

  3. 3

    Folkman, J. J. natn. Canc. Inst. 82, 4–6 (1990).

    CAS  Article  Google Scholar 

  4. 4

    Folkman, J. & Ingber, D. E. Ann. Surg. 206, 374–383 (1987).

    CAS  Article  Google Scholar 

  5. 5

    Folkman, J. New Engl. J. Med. 285, 1182–1186 (1972).

    Google Scholar 

  6. 6

    McCowen, M. C., Callender, M. E. & Lawlis, Jr J. F. Science 113, 202–203 (1951).

    ADS  CAS  Article  Google Scholar 

  7. 7

    Folkman, J. & Moscona, A. Nature 273, 345–350 (1978).

    ADS  CAS  Article  Google Scholar 

  8. 8

    Ingber, D. Proc. natn. Acad. Sci. U.S.A. 87, 3579–3583 (1990).

    ADS  CAS  Article  Google Scholar 

  9. 9

    Ingber, D., Madri, J. A. & Folkman, J. Endocrinology 119, 1768–1773 (1986).

    CAS  Article  Google Scholar 

  10. 10

    Killough, J. H., Magill, G. B. & Smith, R. C. Science 115, 71–72 (1952).

    ADS  CAS  Article  Google Scholar 

  11. 11

    DiPaolo, J. A., Tarbell, D. S. & Moore, G. E. Antibiotics Annual 541–546 (1958–1959).

  12. 12

    Crum, R., Szabo, S. & Folkman, J. Science 230, 1375–1377 (1985).

    ADS  CAS  Article  Google Scholar 

  13. 13

    Folkman, J., Langer, R., Lindhart, R., Haudenschild, C. & Taylor, S. Science 221, 719–725 (1983).

    ADS  CAS  Article  Google Scholar 

  14. 14

    Folkman, J., Weisz, P. B., Joullie, M. M., Li, W. W. & Ewing, W. R. Science 243, 1490–1493 (1989).

    ADS  CAS  Article  Google Scholar 

  15. 15

    Ingber, D. E. & Folkman, J. Lab. Invest. 59, 44–50 (1988).

    CAS  PubMed  Google Scholar 

  16. 16

    Maione, T. E. et al. Science 247, 77–79 (1990).

    ADS  CAS  Article  Google Scholar 

  17. 17

    Moses, M. A., Sudhalter, J. & Langer, R. Science 248, 1408–1410 (1990).

    ADS  CAS  Article  Google Scholar 

  18. 18

    Tanaka, N. G. et al. Canc. Res. 49, 6727–6730 (1989).

    CAS  Google Scholar 

  19. 19

    Oikawa, T., Hirotani, K., Shimamura, M., Ashino-Fuse, H. & Iwaguchi, T. J. Antibiotics 42, 1202–1204 (1989).

    CAS  Article  Google Scholar 

  20. 20

    White, C. W., Sondheimer, H. M., Crouch, E. C., Wilson, H. & Fanll, L. L. New Engl. J. Med. 320, 1197–1200 (1989).

    CAS  Article  Google Scholar 

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Ingber, D., Fujita, T., Kishimoto, S. et al. Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth. Nature 348, 555–557 (1990).

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