TY - JOUR T1 - A Novel EPAC Specific Inhibitor Suppresses Pancreatic Cancer Cell Migration and Invasion JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.112.080689 SP - mol.112.080689 AU - Muayad Almahariq AU - Tamara Tsalkova AU - Mei C. Fang AU - Haijun Chen AU - Jia Zhou AU - Sarita Sastry AU - Frank Schwede AU - Xiaodong Cheng Y1 - 2012/10/11 UR - http://molpharm.aspetjournals.org/content/early/2012/10/11/mol.112.080689.abstract N2 - Exchange protein directly activated by cAMP (EPAC) and cAMP-dependent protein kinase (PKA) are two intracellular receptors that mediate the effects of the prototypic second messenger cAMP. Identifying pharmacological probes for selectively modulating EPAC activity represents a significant unmet need within the research field. Herein, we report the identification and characterization of ESI-09, a novel non-cyclic nucleotide EPAC antagonist that is capable of specifically blocking intracellular EPAC-mediated Rap1 activation and Akt phosphorylation, as well as EPAC-mediated insulin secretion in pancreatic beta cells. Using this novel EPAC-specific inhibitor, we have probed the functional roles of over-expression of EPAC1 in pancreatic cancer cells. Our studies show that EPAC1 plays an important role in pancreatic cancer cell migration and invasion, and thus represents a potential target for developing novel therapeutic strategies for pancreatic cancer. ER -