Abstract The American Cancer Society estimates that over 43,000 new cases of pancreatic cancer are diagnosed each year in the United States, with a five-year survival rate below 6%. Conventional therapies are often of limited use because of the resistance development and cancer relapse. Therefore, identification of novel strategies to control and treat pancreatic cancer is of great importance. GS-19 is a novel compound designated as a GSK inhibitor and shown good activity in neural protective assay using MC65 cells. In this study, we determined the cytotoxic effects of GS-19 in pancreatic cancer cells. GS-19 treatment inhibited the growth of Panc-1 and BxPC-3 cells in a concentration-dependent manner. Both the cell lines treated with GS-19 exhibited G-1 cell cycle arrest as well as apoptosis. Western blot analysis of both BxPC-3 and Panc-1 cells treated with GS-19 inhibited the activation (phosphorylation) and expression of key survival signaling proteins such as EGFR, STAT3 and AKT. The apoptosis induced by GS-19 was associated with cleavage of caspase-3 and PARP. Taken together, our results suggest that GS-19 suppress pancreatic cancer cell growth by inhibiting EGFR/AKT/STAT-3 signaling. However, further mechanistic studies are in progress to establish the role of EGFR/AKT/STAT-3 signaling in pancreatic cancer cells and correlate it with G1 cell cycle arrest and apoptosis induced by GS-19. The studies in part were supported by R01 grant CA129038 awarded by NIH to S.K.S Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C58. Citation Format: Alok Ranjan, Sanjay K. Srivastava, Parul Gupta, Ashlee Birkenfeld, Duy Hua, Jianyu Lu. GS-19, a novel GSK inhibitor suppresses the growth of pancreatic cancer cells by inhibiting EGFR/AKT/STAT-3 signaling. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C58.