text: Herein, we report the identification and characterization of << 3-(5-tert-butyl-isoxazol-3-yl)-2-[(3-chloro-phenyl)-hydrazono]-3-oxo-propionitrile >> (ESI-09), a novel noncyclic 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 β cells.