Growth Factor Antagonism in Breast Cancer Chemotherapy
Abstract
The primary focus of this project is the first step in the aberrant cell signaling pathways that lead to uncontrolled proliferation and cancer, namely the interaction of growth factors with their receptor tyrosine kinases (RTKs). Our principal goal is to design growth factor antagonists that can inhibit ligand-induced receptor activation as a route to novel anti-cancer drugs. During the past year we have made important progress is establishing the goals of this project. We have developed efficient and direct synthetic routes to protein binding agents. We have extended our approach with the synthesis of some tetraphenylporphyrin based receptors that bind to proteins with high affinity. Most importantly, we have demonstrated that a member of our first generation of protein binding agents is able to bind to the surface of platelet derived growth factor. This binding is strong (IC50 < 250nM) under physiological conditions and is sufficient to block the activation of PDGF receptor tyrosine kinase. These results represent important steps is establishing the novel approach to breast cancer treatment that is the foundation of this project.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2000
- Accession Number
- ADA385735
Entities
People
- A. Hamilton
Organizations
- Yale University