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 language | English (US) |
|---|---|
| Pages (from-to) | 203-214 |
| Number of pages | 12 |
| Journal | Trends in Pharmacological Sciences |
| Volume | 36 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 1 2015 |
Funding
Work in S.J.Y. and T.M.P.\u2019s laboratories was funded by project grants from the British Heart Foundation (BHF) (PG/05/026, PG/08/125/26415, PG/10/026/28303) and the Biotechnology and Biological Sciences Research Council (BBSRC) (BB/D015324/1). E.P. was supported by a doctoral training studentship from the BBSRC Doctoral Training Programme in Biochemistry and Molecular Biology at the University of Glasgow (BB/F016735/1).
Keywords
- EPAC
- agonism
- antagonism
- cAMP
- diabetes
- inflammation
ASJC Scopus subject areas
- Toxicology
- Pharmacology
