esi-09

ESI-09 is a **small molecule inhibitor** that acts as a selective, competitive antagonist of exchange proteins directly activated by cAMP (EPAC), specifically targeting both EPAC1 and EPAC2. It competes with cAMP for the EPAC binding site and inhibits EPAC-mediated guanine nucleotide exchange factor (GEF) activity, suppressing downstream signaling. ESI-09 exhibits much higher selectivity for EPAC over protein kinase A (PKA) and has been shown to inhibit EPAC-mediated cellular functions such as insulin secretion, cancer cell migration/invasion, and pain signaling in both cellular and animal models. Its highest affinity and selectivity are attributed to the structural features of its 3-chlorophenyl moiety. In preclinical studies, ESI-09 has demonstrated efficacy in models of **chemotherapy-induced peripheral neuropathy (CIPN)** and pancreatic cancer, among other indications. The compound shows good bioavailability and specifically recapitulates EPAC1 knockout phenotypes in vivo. ESI-09 has also been used to probe the role of EPAC in a variety of preclinical systems[1][2][3][4][5].