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Cyclooxygenase-2 (COX-2) appears to play a significant role in the development and progression of cancer and COX-2 inhibitors such as celecoxib exhibit anti-cancer activity. OSU03012 is an analog of celecoxib that exhibits anti-cancer activity in a COX-2-independent manner via inhibition of the phosphatidyl inositol-3-kinase/Akt pathway.,, It has an IC50 value of 5 µM for inhibition of 3-phosphoinositide-dependent kinase-1, and therefore Akt activation, with no measurable COX-2 inhibition up to 50 µM. OSU03012 is a potent inhibitor of tumor cell growth with an average inhibitory concentration of 1.1 µM across a panel of 60 cancer cell lines. It does not inhibit signal transduction through the mitogen-activated protein kinase (MAPK) pathway. OSU03012 induces apoptosis of chronic lymphocytic leukemia cells independent of bcl-2 overexpression using both caspase-dependent and independent pathways.
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