Selective small-molecule EPAC activators

The cellular signalling enzymes, EPAC1 and EPAC2, have emerged as key intracellular sensors of the secondary messenger cyclic 3′,5′-adenosine monophosphate (cyclic adenosine monophosphate) alongside protein kinase A. Interest has been galvanised in recent years thanks to the emergence of these species as potential targets for new cardiovascular disease therapies, including vascular inflammation and insulin resistance in vascular endothelial cells. We herein summarise the current state-of-the-art in small-molecule EPAC activity modulators, including cyclic nucleotides, sulphonylureas, and N-acylsulphonamides.