Growth Factor Antagonism in Breast Cancer Chemotherapy.

摘要

The primary focus of this work is the identification of molecules that block the interaction of growth factors with their receptor tyrosine kinases (RTKs) . We have designed, synthesized and evaluated a novel series of synthetic agents that bind to the surface of growth factors and block their interaction with their RTKs. We have now prepared two classes of protein binding agents. The first involves the attachment of four peptide loops to a central scaffold based on the calix4arene unit. The second is based around a tetraphenylporphyrin unit in which different recognition groups are attached. We have identified one molecule that binds to the surface of platelet derived growth factor and shows potent antitumor activity in a mouse xenograft model of a human cancer that is activated by PDGF. From a different family of agents we have identified a molecule that binds tightly to epidermal growth factor.