A novel EPAC-specific inhibitor suppresses pancreatic cancer cell migration and invasion

Muayad Almahariq, Tamara Tsalkova, Fang C. Mei, Haijun Chen, Jia Zhou, Sarita K. Sastry, Frank Schwede, Xiaodong Cheng

Research output: Contribution to journalArticle

129 Scopus citations


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 3-(5-tert-butyl-isoxazol-3-yl)-2-[(3-chlorophenyl)-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. Using this novel EPAC-specific inhibitor, we have probed the functional roles of overexpression 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.

Original languageEnglish (US)
Pages (from-to)122-128
Number of pages7
JournalMolecular pharmacology
Issue number1
StatePublished - Jan 1 2013


ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Almahariq, M., Tsalkova, T., Mei, F. C., Chen, H., Zhou, J., Sastry, S. K., Schwede, F., & Cheng, X. (2013). A novel EPAC-specific inhibitor suppresses pancreatic cancer cell migration and invasion. Molecular pharmacology, 83(1), 122-128. https://doi.org/10.1124/mol.112.080689