tcsc3420 ESI-09

ESI-09 is a novel noncyclic nucleotide EPAC antagonist with IC₅₀ values of 3.2 and 1.4 μM for EPAC1 and EPAC2, respectively.

IC50 & Target: IC50: 3.2 μM (EPAC1), 1.4 μM (EPAC2)^[1]

In Vitro: While cAMP competes with 8-NBD-cAMP binding with an IC₅₀ of 39 µM, ESI-09 shows an increased potency with an apparent IC₅₀ of 10 µM. ESI-09 inhibis cAMP-mediated EPAC2 and EPAC1 GEF activity with an IC₅₀ of 1.4 and 3.2µM, respectively. ESI-09 could fit well into the functional cAMP-binding pocket of EPAC1, establishing favorable hydrophobic and hydrogen bonding interactions with the protein’s active-site residues. ESI-09 inhibits 007-AM-stimulated Akt phosphorylation at T308 and S473 in a dose-dependent manner. ESI-09 inhibits pancreatic cancer cells AsPC-1 and PANC-1 migration. ESI-09 inhibits EPAC1-mediated adhesion of PDA cells on collagen I^[1]. Exposure to ESI-09 significantly reduces intracellular and total bacterial counts in HUVECs at 30 min postinfection with 10 multiplicities of infection (MOI) of R. australis compared with similarly infected controls^[2].

In Vivo: Treatment with ESI-09 dramatically protects WT mice against R. australis infection with much milder disease manifestations and significantly improves survival^[2].