Exchange proteins directly activated by cAMP (EPACs): Emerging therapeutic targets

Bioorg Med Chem Lett. 2017 Apr 15;27(8):1633-1639. doi: 10.1016/j.bmcl.2017.02.065. Epub 2017 Feb 27.

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.

Keywords: Agonist; Antagonist; EPAC; Modulator; cAMP.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclic AMP / metabolism
  • Drug Discovery / methods*
  • Guanine Nucleotide Exchange Factors / agonists
  • Guanine Nucleotide Exchange Factors / antagonists & inhibitors
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Humans
  • Models, Molecular
  • Molecular Targeted Therapy / methods
  • Signal Transduction / drug effects
  • Small Molecule Libraries / chemistry*
  • Small Molecule Libraries / pharmacokinetics
  • Small Molecule Libraries / pharmacology*

Substances

  • Guanine Nucleotide Exchange Factors
  • RAPGEF3 protein, human
  • RAPGEF4 protein, human
  • Small Molecule Libraries
  • Cyclic AMP