title: Exchange proteins directly activated by cAMP (EPACs): Emerging therapeutic targets.
abstract: Exchange proteins directly activated by cAMP (EPACs) are critical cAMP-dependent signaling pathway mediators. The discovery of EPAC proteins has significantly facilitated understanding on cAMP-dependent signaling pathway and efforts along this line open new avenues for developing novel therapeutics for cancer, diabetes, heart failure, inflammation, infections, neurological disorders and other human diseases. Over the past decade, important progress has been made in the identification of EPAC agonists, antagonists and their biological and pharmacological applications. In this review, we briefly summarize recently reported novel functions of EPACs and the discovery of their small molecule modulators. The challenges and future perspectives are also discussed.
authors.affiliation: Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555, United States.
authors.forename: Pingyuan
authors.initials: P
authors.lastname: Wang
authors.affiliation: Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555, United States.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555, United States.
authors.forename: Haiying
authors.initials: H
authors.lastname: Chen
authors.affiliation: Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555, United States.
authors.forename: Na
authors.initials: N
authors.lastname: Ye
authors.affiliation: Department of Integrative Biology and Pharmacology, Texas Therapeutics Institute, University of Texas Health Science Center, Houston, TX 77030, United States.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555, United States. Electronic address: jizhou@utmb.edu.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D055808:Drug Discovery / Q000379:methods*; D020662:Guanine Nucleotide Exchange Factors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D058990:Molecular Targeted Therapy / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C116122:RAPGEF3 protein, human; C442864:RAPGEF4 protein, human; D054852:Small Molecule Libraries; D000242:Cyclic AMP
keywords: Agonist; Antagonist; EPAC; Modulator; cAMP