Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth

@article{Ingber1990SyntheticAO,
  title={Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth},
  author={Donald E. Ingber and Takeshi Fujita and Shoji Kishimoto and Katsuichi Sudo and Tsuneo Kanamaru and Henry Brem and Judah Folkman},
  journal={Nature},
  year={1990},
  volume={348},
  pages={555-557}
}
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… Expand
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References

SHOWING 1-10 OF 18 REFERENCES
Inhibition of angiogenesis by recombinant human platelet factor-4 and related peptides.
TLDR
Recombinant human platelet factor-4 (rhPF4), purified from Escherichia coli, inhibited blood vessel proliferation in the chicken chorioallantoic membrane in a dose-dependent manner and suggested that the angiostatic effect was due to specific inhibition of growth factor-stimulated endothelial cell proliferation. Expand
Control of angiogenesis with synthetic heparin substitutes.
TLDR
Cyclodextrin tetradecasulfate administered with a steroid inhibits angiogenesis at 100 to 1000 times the effectiveness of heparin in the chick embryo bioassay and augments the anti-angiogenic effect of angiostatic steroids against corneal neovascularization in rabbits. Expand
Inhibition of angiogenesis through modulation of collagen metabolism.
  • D. Ingber, J. Folkman
  • Chemistry, Medicine
  • Laboratory investigation; a journal of technical methods and pathology
  • 1988
TLDR
Findings suggest that growing capillaries may be "switched" into a regressive mode through alterations of collagen metabolism that result in loss of ECM structural integrity. Expand
Angiostatic steroids. Method of discovery and mechanism of action.
TLDR
A new class of steroids has been found that inhibits angiogenesis in the presence of nonanticoagulant heparin, and may find potential therapeutic use as adjuncts to anticancer therapy, and in diseases dominated by abnormal neovascularization, i.e., angiogenic-dependent diseases. Expand
Induction of angiogenesis during the transition from hyperplasia to neoplasia
TLDR
It is reported here that angiogenic activity first appears in a subset of hyperplastic islets before the onset of tumour formation, suggesting that induction of angiogenesis is an important step in carcinogenesis. Expand
A possible mechanism for inhibition of angiogenesis by angiostatic steroids: induction of capillary basement membrane dissolution.
TLDR
Capillary BM dissolution is the first biochemical action identified for this new class of antiangiogenic steroids, which acts independently of previously identified steroid functions to inhibit angiogenesis when administered with heparin. Expand
Identification of an inhibitor of neovascularization from cartilage.
TLDR
A protein derived from cartilage was purified that inhibits angiogenesis in vivo and capillary endothelial cell proliferation and migration in vitro in three separate bioassays, and may help elucidate the mechanisms by which neovascularization is controlled in both normal and pathological states. Expand
Angiogenesis inhibition and tumor regression caused by heparin or a heparin fragment in the presence of cortisone.
TLDR
Of all the heparin fragments tested, the most potent inhibition of angiogenesis in the presence of cortisone was provided by a hexasaccharide with a molecular weight of about 1600. Expand
A new class of steroids inhibits angiogenesis in the presence of heparin or a heparin fragment.
TLDR
This newly discovered steroid function appears to be governed by distinct structural configurations of the pregnane nucleus that inhibit angiogenesis in the presence of heparin or specific Heparin fragments. Expand
Fibronectin controls capillary endothelial cell growth by modulating cell shape.
  • D. Ingber
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1990
TLDR
The results suggest that FN controls capillary endothelial cell proliferation based on its ability to support tension-dependent alterations of cell shape--i.e., both by binding to cell-surface integrins and by resisting mechanical loads that are applied to these receptors. Expand
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