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.
Subscribe to Journal
Get full journal access for 1 year
only $3.83 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Folkman, J. Ann. Int. Med. 82, 96–100 (1975).
Folkman, J., Watson, K., Ingber, D. & Hanahan, D. Nature 339, 58–61 (1989).
Folkman, J. J. natn. Canc. Inst. 82, 4–6 (1990).
Folkman, J. & Ingber, D. E. Ann. Surg. 206, 374–383 (1987).
Folkman, J. New Engl. J. Med. 285, 1182–1186 (1972).
McCowen, M. C., Callender, M. E. & Lawlis, Jr J. F. Science 113, 202–203 (1951).
Folkman, J. & Moscona, A. Nature 273, 345–350 (1978).
Ingber, D. Proc. natn. Acad. Sci. U.S.A. 87, 3579–3583 (1990).
Ingber, D., Madri, J. A. & Folkman, J. Endocrinology 119, 1768–1773 (1986).
Killough, J. H., Magill, G. B. & Smith, R. C. Science 115, 71–72 (1952).
DiPaolo, J. A., Tarbell, D. S. & Moore, G. E. Antibiotics Annual 541–546 (1958–1959).
Crum, R., Szabo, S. & Folkman, J. Science 230, 1375–1377 (1985).
Folkman, J., Langer, R., Lindhart, R., Haudenschild, C. & Taylor, S. Science 221, 719–725 (1983).
Folkman, J., Weisz, P. B., Joullie, M. M., Li, W. W. & Ewing, W. R. Science 243, 1490–1493 (1989).
Ingber, D. E. & Folkman, J. Lab. Invest. 59, 44–50 (1988).
Maione, T. E. et al. Science 247, 77–79 (1990).
Moses, M. A., Sudhalter, J. & Langer, R. Science 248, 1408–1410 (1990).
Tanaka, N. G. et al. Canc. Res. 49, 6727–6730 (1989).
Oikawa, T., Hirotani, K., Shimamura, M., Ashino-Fuse, H. & Iwaguchi, T. J. Antibiotics 42, 1202–1204 (1989).
White, C. W., Sondheimer, H. M., Crouch, E. C., Wilson, H. & Fanll, L. L. New Engl. J. Med. 320, 1197–1200 (1989).
About this article
Cite this article
Ingber, D., Fujita, T., Kishimoto, S. et al. Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth. Nature 348, 555–557 (1990). https://doi.org/10.1038/348555a0
Antitumor activity and mechanism of costunolide and dehydrocostus lactone: Two natural sesquiterpene lactones from the Asteraceae family
Biomedicine & Pharmacotherapy (2020)
Antimicrobial Agents and Chemotherapy (2020)
Efficacy and safety of recombinant human endostatin combined with radiotherapy or chemoradiotherapy in patients with locally advanced non-small cell lung cancer: a pooled analysis
Radiation Oncology (2020)
Bengamide Analogues Show A Potent Antitumor Activity against Colon Cancer Cells: A Preliminary Study
Marine Drugs (2020)
European Journal of Medicinal Chemistry (2020)