Fluorescence-based screening of potential Epac1-selective agonists

Exchange protein activated by cAMP 1 (Epac1), a sensor for the ubiquitous second messenger cAMP, plays an important role in all major organ systems. Moreover, it is also implied in a vast array of pathophysiological processes and diseases, which makes Epac1 an interesting and potentially promising therapeutic target. Unfortunately, the pharmacological tools currently available to study Epac1 function are limited. Recently, a partial Epac1-selective agonist, I942, has been described. I942 is the first non-cyclic-nucleotide compound that has been shown to be able to act as an agonist towards Epac1. However, compared to cAMP and other (non-selective) agonists, its effects are relatively weak. Further development of the I942 compound towards more potent Epac1-selective agonists is therefore needed. I will present an approach to screening such compounds, using several fluorescence-based assays, and its practical application to a series of novel I942 analogues.