title: Recent advances in the discovery of small molecules targeting exchange proteins directly activated by cAMP (EPAC).
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.
authors.affiliation: Department of Pharmacology and Toxicology, University of Texas Medical Branch , Galveston, Texas 77555, United States.
authors.forename: Haijun
authors.initials: H
authors.lastname: Chen
authors.forename: Christopher
authors.initials: C
authors.lastname: Wild
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Zhou
authors.forename: Na
authors.initials: N
authors.lastname: Ye
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Cheng
authors.forename: Jia
authors.initials: J
authors.lastname: Zhou
mesh_terms: D018360:Crystallography, X-Ray; D055808:Drug Discovery; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D008958:Models, Molecular; D015398:Signal Transduction; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C116122:RAPGEF3 protein, human; D054852:Small Molecule Libraries