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.

Proposed Commercial Applications

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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
5R43CA086150-02
Application #
6350445
Study Section
Special Emphasis Panel (ZCA1-SRRB-Y (J4))
Program Officer
Lees, Robert G
Project Start
2000-08-18
Project End
2004-07-31
Budget Start
2001-09-14
Budget End
2004-07-31
Support Year
2
Fiscal Year
2001
Total Cost
$252,156
Indirect Cost
Name
Angstrom Pharmaceuticals, Inc.
Department
Type
DUNS #
City
Solana Beach
State
CA
Country
United States
Zip Code
92075