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Semafore Achieves a Preclinical Milestone with SF2626, a PI3K-MEK Dual Pathway Kinase Inhibitor
Date:3/17/2009

INDIANAPOLIS, March 17 /PRNewswire/ -- Semafore Pharmaceuticals, Inc. announced today that it has achieved proof of concept in its CRIMP (Control Resulting from Inhibiting Multiple Pathways) kinase platform by designing a small molecule that was demonstrated to inhibit members of both the PI3K (Phosphoinositide-3-kinase) pathway and the Ras-MAPK (Ras-mitogen activated protein kinase) pathway. Specifically, SF2626 has demonstrated the ability to inhibit both PI3K and MEK, the key component of the RAS/RAF/MEK/ERK pathway. Both PI3K and MEK are frequently activated in human tumors and are thus considered high value targets in treating cancer. SF2626 is the first combination PI3K and MEK kinase inhibitor that, in preclinical studies, blocks both pathways simultaneously.

There is clear rationale for inhibiting both pathways in treating cancer. Both the PI3K pathway and the Ras-MAPK pathways have emerged as central conduits of cell signaling networks that regulate cell growth and survival. Recent scientific studies demonstrate that the Ras-MAPK pathway has the ability to cross-talk to the PI3K pathway thereby activating it and that in some cancers both pathways require inhibition to induce programmed cell death.

Additionally, clinical studies in cancer patients with KRAS mutations show that EGFR inhibitors alone are not sufficient to block the downstream activation of the Ras-MAPK pathway. In these patients, it may also be necessary to block both pathways to inhibit cancer cell growth.

With the evolving knowledge of cancer biology and further understanding of the mechanisms of drug resistance Semafore's CRIMP platform technology offers a distinctive approach to rational drug design for combination pathway kinase inhibitors.

Semafore's dual PI3K-MEK kinase inhibitor, SF2626, is a promising lead for targeting cancer. The Company is actively seeking a partner for the continued development
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SOURCE Semafore Pharmaceuticals, Inc.
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