Design, Synthesis, and Testing of Breast Cancer Angiogenesis Inhibitors
Abstract
Tumor angiogenesis is the process by which a growing tumor mass recruits the new blood vessels required for its continued growth, and through which the tumor can spread to distant sites. This proposal focuses on the development of inhibitors of a particular angiogenic factor, thymidine phosphorylase, by targeting the enzymatic activity of TP, since it has been found to be required for angiogenesis. In the past year, several compounds were synthesized as potential TP inhibitors, including one having high potency as an enzyme inhibitor (IC50 = 180 nM). TP was found to induce human endothelial cell migration in vitro, a process found to require both a TP gradient and the presence of thymidine. The TP-mediated endothelial cell migration was blocked by TP inhibitors, and this was found to be specific in that the actions of a different angiogenic factor, VEGF (vascular endothelial cell growth factor), were not blocked.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1999
- Accession Number
- ADB257696
Entities
People
- Edward L. Schwartz