Progenics Pharmaceuticals to present preclinical data of multiplex PI3K inhibitors

Feb 4 2010

Progenics Pharmaceuticals, Inc. (Nasdaq: PGNX) today announced the presentation of preclinical data on a series of novel compounds that simultaneously blocked two critical pathways involved in the growth and survival of cancer cells. The compounds were identified as part of the Company’s ongoing oncology drug discovery efforts. The data are being presented in both oral and poster sessions at the American Association for Cancer Research (AACR) conference on Protein Translation and Cancer in Coronado, CA.

“Progenics’ identification of these small-molecule compounds as part of our discovery program underscores our long-standing commitment to oncology drug development”

“Progenics’ identification of these small-molecule compounds as part of our discovery program underscores our long-standing commitment to oncology drug development,” stated Paul J. Maddon, M.D., Ph.D., Founder, Chief Executive Officer and Chief Science Officer of Progenics. “In laboratory studies, the synthetic, small-molecule compounds blocked both phosphoinositide 3-kinase (PI3K), which is a key regulator of one molecular signaling pathway, and MNK, an oncogenic kinase in the Ras pathway. We look forward to exploring the therapeutic potential of this series of compounds which are being optimized for clinical development.”

“Our findings add to a growing body of scientific evidence that demonstrates the importance of blocking both the PI3K and Ras pathways at once,” said William C. Olson, Ph.D., Senior Vice President, Research and Development at Progenics. “These interlinked cellular pathways are directly involved in a variety of difficult-to-treat cancers. The cancer cells become dependent on each of these pathways, such that when one pathway is blocked, the cells often adjust to use the other pathway. Blocking both pathways simultaneously can switch off oncogenic signaling altogether and therefore holds great promise as a strategy to combat some of our most aggressive forms of cancer.”

Multiplex PI3K inhibitors: Summary of results

The multiplex PI3K inhibitors discovered by Progenics constitute a novel series of synthetic, drug-like compounds that, in vitro, demonstrated potent activity against diverse tumor cells, including those derived from lung, colon, liver, breast, prostate and pancreatic cancers. Activity was demonstrated against both PI3K and MNK, an oncogenic kinase in the Ras pathway. Kinases are enzymes that modify other molecules by chemically adding phosphate groups to them (phosphorylation). Phosphorylation frequently results in a change in the biological activity of molecules. In in vitro assays, the multiplex PI3K inhibitor compounds exhibited potent cell-eradicating activity against cancer cells containing activating mutations in either or both the PI3K and Ras pathways. In addition to blocking PI3K- and Ras-dependent signaling in cells, the compounds selectively blocked expression of critical growth and survival proteins that are associated with cancer, without altering the expression of “housekeeping” proteins that are associated with normal cellular functions.

The presentation, entitled, “Novel Multiplex PI3-Kinase Inhibitors Potently Inhibit Ras-mutated Tumors via Suppression of eIF-4E-mediated Protein Translation” is scheduled for presentation in a plenary session at the AACR Conference on Protein Translation and Cancer on Saturday, February 6th by Mark Hamilton, Ph.D., Investigator, Drug Discovery at Progenics. These data are also being presented at the Conference in a poster session today. A copy of the poster can be accessed via the following link: