 Another ESI, CE3F4, with modest selectivity for EPAC1 over EPAC2, has also been reported.The discovery of EPAC specific antagonists represents a research milestone that allows the pharmacological manipulation of EPAC activity.In particular, one EPAC antagonist, ESI-09, with excellent activity and minimal toxicity in vivo, has been shown to be a useful pharmacological tool for probing physiological functions of EPAC proteins and for testing therapeutic potential of targeting EPAC in animal disease models.