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SF1126, Semafore's PI3 Kinase Inhibitor, Found to Block Angiogenic Signaling From Both VEGF and Bv8 in Multiple Cell Lines
Date:8/26/2008

INDIANAPOLIS, Aug. 26 /PRNewswire/ -- Semafore Pharmaceuticals Inc. announced data presented at the Seventh International Congress on Targeted Therapies in Cancer in Washington, D.C., showing additional antiangiogenic activity of vascular-targeted PI3 kinase (PI3K) inhibitor SF1126, by blocking both VEGF and Bv8 signaling.

PI3K is part of a very powerful pathway, the PI3/AKT /mTOR pathway that has been shown to play a major role in cancer. Studies have shown that by inhibiting this pathway, tumor growth can be suppressed.

SF1126, a vascular targeted pan-PI3K inhibitor conjugate currently in Phase I clinical trials, was shown to block the pAKT pathway through which the angiogenic factors VEGF and Bv8 are involved. Bv8 is a recently identified protein that, like VEGF, plays a role in the angiogenic process and can significantly upregulate pAKT levels thereby supporting tumor growth.

In vitro inhibition of the PI3K/AKT/mTOR pathway by SF1126 was demonstrated to impede the ability of angiogenic stimulants VEGF and Bv8 to activate AKT in a dose dependant manner in two cancer cell lines (786-0 -- renal cell and PC3 prostate) and one endothelial cell line (HBEC -- human brain endothelial cells). Inhibiting Bv8 with antibodies has also been shown by others to have antitumor effects in mouse xenograft models.

"SF1126 could have additional impact in treating cancer where Bv8 is an important component of angiogenesis," said Dr. Dennis McKeever, Semafore's Chief Executive Officer. "In addition to targeting angiogenesis, SF1126 blocks key targets involved in tumor growth including mTOR, DNA-PK, PIM-1 and PLK-1. This adds another layer of versatility to what SF1126 can do as an antitumor agent."

About Semafore

Semafore is a clinical stage drug discovery and development company focused on small molecule modulators of the PI3 kinase and PTEN cell signaling pathway, a promising target pathway for multiple disorders, including the comp
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SOURCE Semafore Pharmaceuticals Inc.
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