Discovery of Potent and Practical Antiangiogenic Agents Inspired by Cortistatin A

作者：Czako Barbara; Kurti Laszlo; Mammoto Akiko; Ingber Donald E; Corey E J^*

来源：Journal of the American Chemical Society, 2009, 131(25): 9014-9019.

DOI：10.1021/ja902601e

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.

• 出版日期2009-7-1