We have developed a cyclic peptide (Angstroms 36) that potently inhibits the binding of urokinase plasminogen activator (uPA) to its receptor (uPAR). The binding of uPA to uPAR initiates several pathways (matrix remodeling, signal transduction) that lead to rumor cell invasion, angiogenesis and metastasis. We propose to evaluate Angstroms 36 in studies designed to assess its pharmacokinetic and toxicological properties. Further, we will evaluate Angstroms 36 for anti-tumor activity in several orthotopic models of spontaneous metastasis. These studies will be used to determine the suitability of Angstroms 36 as a clinical candidate for further pre-clinical development and eventual clinical testing. Based on this approach, we propose to confirm Angstroms 36 as a clinical candidate by the completion of the Phase I period of this grant and have it completing Phase I clinical trials by the end of the Phase II period of this SBIR.
The urokinase plasminogen activator system is a validated target for anti-tumor therapy. We have developed a potent cyclic peptide, Angstroms 36, that inhibits the uPA-uPAR interaction with an IC50 =2 nM. This peptide will be developed as a clinical candidate for the treatment of carcinoma metastasis and angiogenesis. This compound represents a new class of non-cytotoxic anti-tumor agents that may have activity against a broad spectrum of cancer.
