Recent advances in the discovery of small molecules targeting exchange proteins directly activated by cAMP (EPAC)

Haijun Chen, Christopher Wild, Xiaobin Zhou, Na Ye, Xiaodong Cheng, Jia Zhou

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

3′,5′-Cyclic adenosine monophosphate (cAMP) is a pivotal second messenger that regulates numerous biological processes under physiological and pathological conditions, including cancer, diabetes, heart failure, inflammation, and neurological disorders. In the past, all effects of cAMP were initially believed to be mediated by protein kinase A (PKA) and cyclic nucleotide-regulated ion channels. Since the discovery of exchange proteins directly activated by cyclic adenosine 5′-monophosphate (EPACs) in 1998, accumulating evidence has demonstrated that the net cellular effects of cAMP are also regulated by EPAC. The pursuit of the biological functions of EPAC has benefited from the development and applications of a growing number of pharmacological probes targeting EPACs. In this review, we seek to provide a concise update on recent advances in the development of chemical entities including various membrane-permeable analogues of cAMP and newly discovered EPAC-specific ligands from high throughput assays and hit-to-lead optimizations.

Original languageEnglish (US)
Pages (from-to)3651-3665
Number of pages15
JournalJournal of Medicinal Chemistry
Volume57
Issue number9
DOIs
StatePublished - May 8 2014

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Protein Transport
Cyclic AMP
Proteins
Biological Phenomena
Cyclic Nucleotides
Second Messenger Systems
Cyclic AMP-Dependent Protein Kinases
Nervous System Diseases
Ion Channels
Heart Failure
Pharmacology
Ligands
Inflammation
Membranes
Neoplasms
erythromycin propionate-N-acetylcysteinate

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Recent advances in the discovery of small molecules targeting exchange proteins directly activated by cAMP (EPAC). / Chen, Haijun; Wild, Christopher; Zhou, Xiaobin; Ye, Na; Cheng, Xiaodong; Zhou, Jia.

In: Journal of Medicinal Chemistry, Vol. 57, No. 9, 08.05.2014, p. 3651-3665.

Research output: Contribution to journalArticle

Chen, Haijun ; Wild, Christopher ; Zhou, Xiaobin ; Ye, Na ; Cheng, Xiaodong ; Zhou, Jia. / Recent advances in the discovery of small molecules targeting exchange proteins directly activated by cAMP (EPAC). In: Journal of Medicinal Chemistry. 2014 ; Vol. 57, No. 9. pp. 3651-3665.
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