p38 is a kinase target that can act as cellular growth factors or are up-regulated in certain cancers including prostate, ovarian and multiple myeloma. Additionally, p38 may play a role in certain resistance mechanisms or metastatic progression in cancer. As a result, we believe inhibition of p38 may provide a therapeutic benefit in certain cancer patients. ARRY-797, a selective orally active p38 inhibitor, has shown good efficacy, controlled tissue distribution and a low side effect profile in preclinical models of human arthritis and certain cytokine-driven cancers. We filed an IND application with the FDA in October 2006 and initiated Phase 1 clinical trials in healthy volunteers. We also filed an IND application to initiate a Phase 1b trial in cancer patients in April 2007. We plan to initiate additional exploratory trials in both cancer and inflammation patients in 2007.
DeNovo Design
Process
We ran the docking experiment to find binding
locations with various fragments. It was
found that a benzene molecule was settled
in a hydrophobic pocket near Thr 106 and
a benzisoxazole molecule fit in the enzyme
by picking up a H-bonding interaction
with MET 109. Two molecules were sitting
in close proximity so they could be easily
connected.
Scientific Posters
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