The future of EPAC-targeted therapies: agonism versus antagonism

Euan Parnell, Timothy M. Palmer, Stephen J Yarwood

    Research output: Contribution to journalArticlepeer-review

    54 Citations (Scopus)

    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
    Pages (from-to)203-214
    Number of pages12
    JournalTrends in Pharmacological Sciences
    Volume36
    Issue number4
    DOIs
    Publication statusPublished - Apr 2015

    Keywords

    • Animals
    • Cyclic AMP
    • Drug Delivery Systems
    • Forecasting
    • Guanine Nucleotide Exchange Factors
    • Humans
    • Protein Structure, Secondary
    • Protein Structure, Tertiary

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