In vitro activity: 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.

Cell Assay: In the pancreatic cancer cell line AsPC-1, ESI-09 inhibited Akt phosphorylation at T308 and S473 stimulated by 007-AM in a dose dependent way. In pancreatic endocrine β cells, ESI-09 inhibited the increase of insulin secretion stimulated by 007-AM in a dose dependent way. In pancreatic cancer cell lines AsPC-1 and PANC-1, ESI-09 significantly reduced cell migration through the inhibition of EPAC1.

Mol Pharmacol. 2013 Jan;83(1):122-8; Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19615-20; PLoS One. 2013 Dec 11;8(12):e82354.