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EntreMed Presents Preclinical Data for MKC-1 in Hematological,Cancers

ROCKVILLE, Md., April 19, 2007 /PRNewswire-FirstCall/-- EntreMed, Inc. , a clinical-stage pharmaceutical company developing therapeutics for the treatment of cancer and inflammatory diseases, today announced the presentation of preclinical results for MKC-1, its novel cell cycle inhibitor. The data were presented by EntreMed scientists at the American Association for Cancer Research (AACR) Annual Meeting being held this week in Los Angeles, California.

MKC-1 is a novel, orally-active cell cycle inhibitor with in vitro and in vivo efficacy against a broad range of human solid tumor cell lines, including multi-drug resistant cell lines. In previous studies, MKC-1 demonstrated broad-acting antitumor effects, showing tumor growth inhibition or regression in multiple preclinical models, including paclitaxel-resistant models. MKC-1 has been shown to inhibit mitotic spindle formation, prevent chromosome segregation in the M-phase (mitosis) of the cell cycle, and induce apoptosis. These effects are consistent with mechanisms resulting from MKC-1 binding to multiple intracellular targets, including tubulin and the importin-beta proteins. The importin-beta family of proteins plays a critical role in nuclear transport and cell division.

In these studies, MKC-1 showed potent, dose-dependent activity against a variety of cell lines derived from cancers of human blood cells, and inhibited growth of primary cells derived from acute and chronic myelogenous leukemia (AML and CML) patients in vitro. MKC-1 was also shown to inhibit PI3-Kinase and mTOR pathways by inducing a dose-dependent reduction in the levels of the activated forms of the oncogenic kinases Akt and p70S6K. These signaling pathways are strongly linked to cancer proliferation and survival.

Additionally, MKC-1 showed enhanced activity with cytosine arabinoside (Ara-C) in combination studies in vitro when added either simultaneously or sequenti
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