ESI-09 is a novel noncyclic nucleotide EPAC antagonist, showcasing selective inhibitory properties with IC50 values of 3.2 μM for EPAC1 and 1.4 μM for EPAC2, underscoring its potential in targeting these exchange proteins directly activated by cAMP[1].
体内研究
Moreover, ESI-09 treatment in wild-type (WT) mice infected with R. australis resulted in notably milder disease manifestations and significantly improved survival rates[2].
体外研究
This antagonist demonstrates enhanced efficacy in comparison to cAMP, displacing 8-NBD-cAMP binding with an apparent IC50 of 10 μM, and effectively inhibiting cAMP-mediated GEF activity of both EPAC2 and EPAC1. Additionally, ESI-09 dose-dependently suppresses 007-AM-stimulated Akt phosphorylation at T308 and S473, indicating its role in modulating key signaling pathways[1].
Beyond its anticancer potential, ESI-09 has been shown to significantly reduce both intracellular and total bacterial counts in human umbilical vein endothelial cells (HUVECs) post-infection with R. australis at a multiplicity of infection (MOI) of 10, compared to controls. This demonstrates its utility in infectious disease models, particularly in reducing bacterial burden[2].
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