Description
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 IC
50 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.
Uses
OSU 03012 is a PDK1 inhibitor and inducer of caspase and p53-independent apoptosis, also used in the development of anticancer agents by modification of novel immunosuppressant FTY720 and PDK1 inhibitor OSU-03012, compound for treating Alzheimers diseases.
Definition
ChEBI: A member of the class of pyrazoles that is N-[4-(pyrazol-1-yl)phenyl]glycinamide in which the pyrazole ring is substituted at positions 3 and 5 by trifluoromethyl and phenanthrene-2-yl groups respectively.
References
[1] zhu j1, huang jw, tseng ph, yang yt, fowble j, shiau cw, shaw yj, kulp sk, chen cs. from the cyclooxygenase-2 inhibitor celecoxib to a novel class of 3-phosphoinositide-dependent protein kinase-1 inhibitors. cancer res. 2004 jun 15;64(12):4309-18.
[2] lee tx1, packer md, huang j, akhmametyeva em, kulp sk, chen cs, giovannini m, jacob a, welling db, chang ls. growth inhibitory and anti-tumour activities of osu-03012, a novel pdk-1 inhibitor, on vestibular schwannoma and malignant schwannoma cells. eur j cancer. 2009 jun;45(9):1709-20.
