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When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
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Updated: Jan 4, 2026

Drug-induced Sensitization of Adenylyl Cyclase: Assay Streamlining and Miniaturization for Small Molecule and siRNA Screening Applications
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Selective small-molecule EPAC activators.

Urszula Luchowska-Stańska1, David Morgan2, Stephen J Yarwood1

  • 1Institute of Biological Chemistry, Biophysics, and Bioengineering, Heriot-Watt University, Edinburgh EH14 4AS, U.K.

Biochemical Society Transactions
|November 1, 2019
PubMed
Summary
This summary is machine-generated.

Epac1 and Epac2 are key cyclic adenosine monophosphate sensors involved in cardiovascular health. Small molecules targeting these enzymes show promise for treating vascular inflammation and insulin resistance.

Keywords:
cAMPexchange proteinssignalling

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Area of Science:

  • Biochemistry and Molecular Biology
  • Pharmacology
  • Cardiovascular Research

Background:

  • Epac1 and Epac2 are intracellular sensors of cyclic adenosine monophosphate (cAMP).
  • They function alongside protein kinase A in cellular signaling pathways.
  • Emerging evidence highlights their role in vascular inflammation and insulin resistance.

Purpose of the Study:

  • To review the current landscape of small-molecule modulators targeting Epac1 and Epac2.
  • To highlight the therapeutic potential of targeting Epac enzymes in cardiovascular diseases.

Main Methods:

  • Literature review of small-molecule EPAC activity modulators.
  • Summary of existing research on EPAC1 and EPAC2 function and therapeutic targeting.

Main Results:

  • Identification and categorization of EPAC modulators, including cyclic nucleotides, sulfonylureas, and N-acylsulfonamides.
  • Overview of the therapeutic potential for cardiovascular conditions.

Conclusions:

  • Small-molecule modulators of Epac1 and Epac2 represent a promising area for cardiovascular disease therapy.
  • Further research into these modulators could lead to novel treatments for vascular inflammation and insulin resistance.