TY - JOUR
T1 - Recent advances in the discovery of small molecules targeting exchange proteins directly activated by cAMP (EPAC)
AU - Chen, Haijun
AU - Wild, Christopher
AU - Zhou, Xiaobin
AU - Ye, Na
AU - Cheng, Xiaodong
AU - Zhou, Jia
N1 - Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2014/5/8
Y1 - 2014/5/8
N2 - 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.
AB - 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.
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U2 - 10.1021/jm401425e
DO - 10.1021/jm401425e
M3 - Review article
C2 - 24256330
AN - SCOPUS:84900319333
SN - 0022-2623
VL - 57
SP - 3651
EP - 3665
JO - Journal of medicinal chemistry
JF - Journal of medicinal chemistry
IS - 9
ER -