Bad is capable of creating a functional hetero dimer with antiapoptotic proteins Bcl XL and antagonizes their anti apoptotic activity. Similarly, overexpression of catalytically active GSK 3h may induce apoptosis. GSK 3h is previously defined as a goal of AKT, which can be inhibited by phosphorylation. In our research, we demonstrated that API 59 OME inhibited AKT kinase activity as substrates when using GSK 3a/h and Bad, and inhibited AKT phosphorylation at Ser473 and GSK 3a/h phosphorylation at Ser21/9 in A2780, MDAH 2774 and OVCAR 8 ovarian cancer cell lines. API 59 OME also induced apoptosis and the cleavage of PARP in these natural product libraries three cancer cell lines. Among a large number of substrates which are separated during apoptosis, PARP is regarded as an extremely reliable sign of apoptosis. And the specific proteolysis of PARP is really a crucial apoptotic event that occurs early in the process of programmed cell death. PARP has been indicated to-be a helpful goal for enhancing the cytotoxity of several drugs. These results suggested that API 5-9 OME blocks the phosphorylation of AKT downstream goals by inhibiting AKT kinase, consequently resulting in apoptosis of these ovarian cancer cells. Additionally, AKT might influence expansion through signals to the cell cycle machinery. GSK 3h, as one of the principal physiological substrates of AKT, is really a ubiquitously expressed protein serine/threonine kinase and is demonstrated to play a significant part in the Wnt pathway by managing destruction of cyclin D1 and h catenin. AKT may be involved in stopping cyclin D1 destruction by controlling the exercise of GSK 3h. AKT can directly phosphorylate GSK 3h and stop its kinase activity, therefore allowing cyclin D1 to accumulate and to promote cell cycle progression. GSK 3h continues to be shown to phosphorylate cyclin D1 specifically about the same threonine residue, therefore targeting cyclin D1 for proteosomal degradation. At present, inhibitors that target AKT upstream specialists PI3 E and PDK1 have been described. Inhibitors that potentially target the pleckstrin homology domain of AKT are also described recently. Via a screening approach, we’ve identified a non peptide tiny molecule inhibitor that targets the AKT pathway. Our data demonstrated that pifithrin �� API 59 OME restricted AKT kinase activity, but didn’t prevent JNK and ERK kinase activities. Also, our results showed that API 59 OME seemed to increase ERK kinase actions and the activation of ERK was associated with an in phosphorylation of its substrate Elk 1 at Ser383 in A2780, MDAH2774, and OVCAR 8 cell lines. The transcription factor Elk 1 is really a component of the ternary complex that binds the serum response factor and mediates gene activity in response to serum and growth factors.