The future of EPAC-targeted therapies: Agonism versus antagonism

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

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.

Citation

Parnell, E., Palmer, T. M., & Yarwood, S. J. (2015). The future of EPAC-targeted therapies: Agonism versus antagonism. Trends in Pharmacological Sciences, 36(4), 203-214. https://doi.org/10.1016/j.tips.2015.02.003

• Journal Article Type: Review
• Acceptance Date: Mar 2, 2015
• Online Publication Date: Mar 3, 2018
• Publication Date: Apr 1, 2015
• Deposit Date: Oct 30, 2018
• Publicly Available Date: Oct 31, 2018
• Journal: Trends in Pharmacological Sciences
• Print ISSN: 0165-6147
• Electronic ISSN: 1873-3735
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 36
• Issue: 4
• Pages: 203-214
• DOI: https://doi.org/10.1016/j.tips.2015.02.003
• Keywords: Toxicology; Pharmacology; EPAC; cAMP; Inflammation; Diabetes; Agonism; Antagonism
• Public URL: https://hull-repository.worktribe.com/output/1137533
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S016561471500022X?via%3Dihub
• Additional Information: This article is maintained by: Elsevier; Article Title: The future of EPAC-targeted therapies: agonism versus antagonism; Journal Title: Trends in Pharmacological Sciences; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.tips.2015.02.003; Content Type: article; Copyright: Copyright © 2015 The Authors. Published by Elsevier Ltd.