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The future of EPAC-targeted therapies: agonism versus antagonism

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 appr...

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Autores principales: Parnell, Euan, Palmer, Timothy M., Yarwood, Stephen J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Published By Elsevier In Association With The International Union Of Pharmacology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392396/
https://www.ncbi.nlm.nih.gov/pubmed/25744542
http://dx.doi.org/10.1016/j.tips.2015.02.003
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author Parnell, Euan
Palmer, Timothy M.
Yarwood, Stephen J.
author_facet Parnell, Euan
Palmer, Timothy M.
Yarwood, Stephen J.
author_sort Parnell, Euan
collection PubMed
description 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.
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spelling pubmed-43923962015-04-13 The future of EPAC-targeted therapies: agonism versus antagonism Parnell, Euan Palmer, Timothy M. Yarwood, Stephen J. Trends Pharmacol Sci Review 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. Published By Elsevier In Association With The International Union Of Pharmacology 2015-04 /pmc/articles/PMC4392396/ /pubmed/25744542 http://dx.doi.org/10.1016/j.tips.2015.02.003 Text en © 2015 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Parnell, Euan
Palmer, Timothy M.
Yarwood, Stephen J.
The future of EPAC-targeted therapies: agonism versus antagonism
title The future of EPAC-targeted therapies: agonism versus antagonism
title_full The future of EPAC-targeted therapies: agonism versus antagonism
title_fullStr The future of EPAC-targeted therapies: agonism versus antagonism
title_full_unstemmed The future of EPAC-targeted therapies: agonism versus antagonism
title_short The future of EPAC-targeted therapies: agonism versus antagonism
title_sort future of epac-targeted therapies: agonism versus antagonism
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392396/
https://www.ncbi.nlm.nih.gov/pubmed/25744542
http://dx.doi.org/10.1016/j.tips.2015.02.003
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