OSU-03012

OSU-03012 is a novel and potent inhibitor of PDK-1. OSU-03012 exhibits anti-cancer activity in a COX-2-independent manner via inhibition of the phosphatidyl inositol-3-kinase (PI3K)/Akt pathway. It has an IC50 of 5 µM for inhibition of 3-phosphoinositide-dependent kinase-1 (PDK-1), and therefore Akt activation, with no measurable COX-2 inhibition up to 50 µM. OSU-03012 induces apoptosis of chronic lymphocytic leukemia (CLL) cells independent of bcl-2 overexpression using both caspase-dependent and independent pathways. A recent study shows that OSU-03012 could enhance the susceptibility of (Bcr)-Abl mutant cell lines to imatinib-induced apoptosis. OSU-03012 may lead to cell swelling and shortening of AP via reduced ATP production in mouse ventricular cells.