8-pCPT-2'-O-Me-cAMP-AM: an improved Epac-selective cAMP analogue.

Epac1 and Epac2 are guanine nucleotide exchange factors for the small G-proteins Rap1 and Rap2. Epac is activated by direct binding of cAMP. The cAMP analogue 8-pCPT-2’-O-Me-cAMP (alias: 007) can activate Epac, but not protein kinase A and is widely used as a selective activator of Epac. To increase membrane permeability and thus to improve bioavailability we have synthesised the AMester of 8-pCPT-2’-O-Me-cAMP. The resultant 8-pCPT-2’-O-Me-cAMP-AM (007-AM) activates Epac much more rapidly and at much lower extracellular concentrations than 007, as demonstrated in vivo by the use of an Epac1-based FRET sensor. In line with this, we observed efficient activation of Rap1 and efficient induction of Rap1-mediated biological effects under cell culture conditions upon application of 007-AM.