Second-Generation Anti-Tumor Compound Precinical Trial Is Successful
Progen Pharmaceuticals Limited announced preclinical study results evaluating the anti-angiogenic and anti-tumor activity of new family of heparan sulfate mimetic compounds, known as the PG500 series.
Dr. Keith Dredge, Progen's Preclinical Development Manager, is presenting the data in a poster entitled, "Heparan Sulfate Mimetics-Potent Angiogenesis Inhibitors for Cancer Therapeutics" at the 2007 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, in San Francisco.
These studies evaluated the compounds' ability to inhibit new blood vessel formation in several in vitro models of angiogenesis. The investigators reported that multiple PG500 compounds, decreased or prevented human endothelial cell (HUVEC) proliferative responses to growth factors including fibroblast growth factors 1 and 2 (FGF-1, FGF-2) and to vascular endothelial cell growth factor (VEGF). Blocking these interactions inhibits the angiogenesis and metastasis processes critical in tumor growth and progression.
These compounds also prevented new blood vessel formation as determined in the rat aortic assay. In animal models of melanoma (B16F1 syngeneic mouse model) and human colorectal cancer (HT29 xenograft model), the heparan sulfate mimetic (HSM) compounds inhibited tumor progression. Progen has recently filed a second provisional patent application to cover these newer, more potent compounds presented at this conference.
Mr. Justus Homburg, Progen's CEO, commented: "Clinical progress with our lead clinical candidate, PI-88, validates the principle of using HSMs as potent anti-cancer drugs. As we move forward in the clinic with this drug candidate, we continue to develop novel HSMs with properties that may extend and enhance their therapeutic applications.
"The data presented today support the continued development of selected PG500 compounds and the program is on track to file an investigational new drug (IND) application by end 2008."
Progen's Drug Discovery Group is comprised of a multi-disciplinary team with expertise in medicinal chemistry, molecular and cell biology, analytical biochemistry, and molecular modeling. At the core of their research is an understanding of the role of carbohydrate/protein interactions that are implicated in the initiation and development of cancer.