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Therapeutic Potentials of Small‐Molecule Inhibitors Targeting Exchange Protein Activated by cAMP (EPAC)
Author(s) -
Cheng Xiaodong,
Zhu Yingmin,
Mei Fang
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1272.5
Subject(s) - second messenger system , microbiology and biotechnology , protein kinase a , receptor , small molecule , signal transduction , knockout mouse , intracellular , g protein coupled receptor , biology , chemistry , kinase , biochemistry
The pleotropic second messenger cAMP is an important stress signal that regulates a multitude of physiological functions under normal and diseased conditions. The major cellular effects of cAMP are transduced by two ubiquitously expressed intracellular cAMP receptors, protein kinase A (PKA) and exchange protein directly activated by cAMP (EPAC) in human. Using genetically engineered EPAC knockout mouse models, we have demonstrated that EPAC proteins play important roles in the development of major human diseases, including obesity, cancer and chronic pain etc. Furthermore, we have developed first‐in‐class EPAC specific inhibitors with favorable in vivo pharmacological and toxicological profiles. Applications of EPAC inhibitors in various animal disease models recapitulate the genetic phenotypes of EPAC knockout mice. These Studies validate the therapeutic potentials of small molecule EPAC specific inhibitors. Support or Funding Information Research is supported by grants from the National Institute Health (GM061770, GM106218 and AI111464).