( e monosphospate dehydrogenase (IMPDH) ...)Avalon Pharmaceuticals to Present at the American Association for,Cancer Research 2007 Annual Meeting,Health

e monosphospate dehydrogenase (IMPDH), an enzyme that is critical for cells to be able to synthesize guanosine triphosphate (GTP), a molecule required for DNA synthesis and cellular signaling. IMPDH is over expressed in some cancer cells, especially in the case of hematological malignancies. In laboratory experiments, AVN944 has been shown to inhibit IMPDH activity in cells, and suppress pools of GTP. Anticancer activities of IMPDH inhibitors correlate with sustained depletion of GTP pools both in cellular models and in human subjects. AVN944 appears to have a selective effect on cancer cells in that deprivation of GTP in normal cells results in a temporary slowing of cell growth, while GTP deprivation in cancer cells induces cell death, or apoptosis. Results from preclinical studies of AVN944 indicate that AVN944 inhibited the proliferation of lymphoid and myeloid cells, the principal cells involved in the most common types of human leukemias. In a single-dose, dose- escalation phase I clinical trial of AVN944 conducted in the United Kingdom in healthy volunteers, AVN944: (1) was well tolerated at all tested doses with no notable side effects; (2) demonstrated good pharmacokinetic properties; and (3) had a significant inhibitory effect on IMPDH enzyme activity. Avalon filed an IND with the FDA in August 2005 and initiated U.S. phase I clinical trials in January 2006 for the treatment of hematological cancers.

Avalon Pharmaceuticals is a biopharmaceutical company using its proprietary technology, AvalonRx(R), to discover and develop cancer therapeutics. Avalon has a lead product in Phase I clinical development (AVN944 - IMPDH inhibitor), as well as preclinical programs to discover inhibitors for the beta-catenin and aurora pathways now in late stage lead candidate optimization. Avalon also has discovery programs on modulators of survivin function and a drug discovery program targeting the MYC oncoprotein, one of the most important and previously intractable c
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