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J Am Chem Soc. 2009 Jul 1;131(25):9014-9. doi: 10.1021/ja902601e.

Discovery of potent and practical antiangiogenic agents inspired by cortistatin A.

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  • 1Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA.


The discovery that cortistatins A and J show noteworthy antiangiogenic activity prompted an investigation of the possibility that simpler and much more easily made compounds based on a steroid core might have useful bioactivity. These studies have led to the development of several potent, water-soluble compounds that may be suitable for local application to treat ocular wet macular degeneration, an important cause of blindness, as well as for treatment of various other angiogenesis-dependent diseases. One of these substances was tested in a mouse retinal angiogenesis model and found to inhibit angiogenesis at a locally administered dose of 500 pmol. Comparison of cell migration data for this and two other synthetic compounds with published data on cortistatin A indicate that they inhibit vascular endothelial growth factor-induced cell migration of human umbilical vein endothelial cells more strongly than cortistatin A.

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