Discovery of potent and practical antiangiogenic agents inspired by cortistatin A

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Angiogenesis Inhibitors / chemical synthesis*
  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Humans
  • Isoquinolines / chemical synthesis*
  • Isoquinolines / chemistry
  • Isoquinolines / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Microtubules / drug effects
  • Microtubules / metabolism
  • Models, Molecular
  • Molecular Structure
  • Neovascularization, Physiologic / drug effects*
  • Polycyclic Compounds / chemical synthesis*
  • Polycyclic Compounds / chemistry
  • Polycyclic Compounds / pharmacology*
  • Retina / drug effects
  • Umbilical Veins / cytology


  • Angiogenesis Inhibitors
  • Isoquinolines
  • Polycyclic Compounds
  • cortistatin A