ESI-09, a novel non-cyclic nucleotide EPAC antagonist, that is capable of specifically blocking intracellular EPAC-mediated Rap1 activation and Akt phosphorylation, as well as EPAC-mediated insulin secretion in pancreatic β cells. On the other hand, ESI-09 fails to suppress epidermal growth factor (EGF)-induced phosphorylation of Akt in AsPC1 cells. In pancreatic cancer cells, ESI-09 inhibits cells migration and invasion through decreasing 007-AM-induced cell adhesion dose-dependently. ESI-09 significantly reduces intracellular and total bacterial counts in human umbilical vein endothelial cells. ESI-09 effectively antagonizes Schwann cells (SC) differentiation induced by CPT-cAMP as well as the formation of myelin. In SC-neuron cultures, ESI-09 dramatically reduces the number of O1 positive and MBP positive SCs without compromising the health of the neurons or the SCs themselves.
In vivo
ESI-09 (10 mg/kg/d, i.p.), via pharmacological inhibition of EPAC1, protects WT C57BL/6 mice from fatal SFG rickettsiosis.
