The long term objective of this program is to identify and develop an angiostatic compound useful in cancer treatment. The rationale is to develop a dual inhibitor of the heparin binding endothelial growth factors bFGF and VEGF. Phase I goals were to validate methods to synthesize and identify growth factor-heparin binding antagonists which block endothelial cell proliferation. Phase I work not only identified a dual bFGF and VEGF inhibitor from a pilot heparin mimetic combinatorial library, but showed the compound to be active in vitro and in vivo to block endothelial proliferation. Thus, the primary goal was achieved and methods were validated for continuing the objective of discovering optimal growth factor antagonists that have angiostatic activity. Current studies are focused on identifying additional antagonists so that medicinal chemistry (analog synthesis) can be based on multiple active structures. Current methods for combinatorial compound synthesis allow rapid iterative compound improvements and scale-up for in vivo testing in both mechanism and disease based models. The application proposes to use these validated synthesis and screening methods, together with toxicity and tumor models in vivo to complete the identification of optimal compounds suitable for development as treatments for cancer and related proliferative disorders.

Proposed Commercial Applications

Not available.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
5R44CA071255-03
Application #
2895569
Study Section
Special Emphasis Panel (ZRG2-SSS-1 (02))
Program Officer
Lees, Robert
Project Start
1996-09-16
Project End
2000-03-31
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Repligen Corporation
Department
Type
DUNS #
City
Waltham
State
MA
Country
United States
Zip Code
02453