The future of EPAC-targeted therapies: Agonism versus antagonism

Euan Parnell, Timothy M. Palmer, Stephen J. Yarwood*

*Corresponding author for this work

Research output: Contribution to journalReview article

45 Scopus citations

Abstract

Pharmaceutical manipulation of cAMP levels exerts beneficial effects through the regulation of the exchange protein activated by cAMP (EPAC) and protein kinase A (PKA) signalling routes. Recent attention has turned to the specific regulation of EPAC isoforms (EPAC1 and EPAC2) as a more targeted approach to cAMP-based therapies. For example, EPAC2-selective agonists could promote insulin secretion from pancreatic β cells, whereas EPAC1-selective agonists may be useful in the treatment of vascular inflammation. By contrast, EPAC1 and EPAC2 antagonists could both be useful in the treatment of heart failure. Here we discuss whether the best way forward is to design EPAC-selective agonists or antagonists and the current strategies being used to develop isoform-selective, small-molecule regulators of EPAC1 and EPAC2 activity.

Original languageEnglish (US)
Pages (from-to)203-214
Number of pages12
JournalTrends in Pharmacological Sciences
Volume36
Issue number4
DOIs
StatePublished - Apr 1 2015

Keywords

  • EPAC
  • agonism
  • antagonism
  • cAMP
  • diabetes
  • inflammation

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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