Discovery of potent and practical antiangiogenic agents inspired by cortistatin A. J Am Chem Soc 2009 Jul 01;131(25):9014-9
Date
05/28/2009Pubmed ID
19469509DOI
10.1021/ja902601eScopus ID
2-s2.0-67649576730 (requires institutional sign-in at Scopus site) 56 CitationsAbstract
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.
Author List
Czakó B, Kürti L, Mammoto A, Ingber DE, Corey EJAuthor
Akiko Mammoto MD, PhD Associate Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Angiogenesis InhibitorsAnimals
Cell Movement
Cell Proliferation
Cells, Cultured
Endothelial Cells
Humans
Isoquinolines
Mice
Mice, Inbred C57BL
Microtubules
Models, Molecular
Molecular Structure
Neovascularization, Physiologic
Polycyclic Compounds
Retina
Umbilical Veins
