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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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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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