Heparin (or structurally related gycosaminoglycans such as heparan) are obligatory cofactors for pro-angiogenic growth factors such as basic fibroblast growth factor (b-FGF) and vascular endothelial growth factor (VEGF). Compounds that bind heparin/heparan are hypothesized to sequester glycosaminoglycans, thereby inhibiting the binding of angiogenic growth factors to their cognate receptors.

We have now developed and validated a high-throughput screen that enables the rapid identification of heparin-binding compounds, and quantitative measurements of their binding affinity to heparin (heparin is used in these assays as a model glycosaminoglycans). We have identified a class of compounds that bind heparin strongly, and have demonstrated in preliminary in vitro assays that the relative affinity of binding to heparin is strongly correlated to inhibition of angiogenic growth factor-driven proliferation of endothelial cells.

Assays to confirm that the mechanism of inhibition of endothelial proliferation is indeed mediated via the sequestration of heparin/heparan, and consequent abrogation of growth factor-receptor engagement is now underway. Pilot experiments to test whether these compounds inhibit tumor growth and metastases in vivo is being performed using a well-established murine model.The primary discovery/invention is the identification of a class of anti-angiogenic agents. Also of potential IP value is the assay that enables the rapid and quantitative evaluation of such compounds.

File Number: 2005 FY 20 

Web site: http://www.medchem.ku.edu

Other Information: *State of Development* Ongoing