Background:

HJC0197 is a cell-permeable inhibitor of Epac1 and Epac2.

Exchange proteins directly activated by cAMP (Epac) are Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP implicated in regulating a wide variety of intracellular processes in response to second messenger cAMP [1].

In vitro: HJC0197 showed an inhibitory effect against Epac2 with an IC50 value of 5.9 μM. In the presence of equal concentration of cAMP, HJC0197 inhibited Epac2 GEF activity to basal levels at 25 μM. HJC0197 also inhibited Epac1-mediated Rap1-GDP exchange activity at 25 μM in the presence of equal concentration of cAMP. HJC0197 was Epac-specific inhibitors that selectively blocked cAMP-induced Epac activation, but didn’t inhibit cAMP-mediated PKA activation. In HEK293/Epac1 and HEK293/Epac2 cells, pretreatment of with 10 μM HJC0197 for 5 min before the administration of 007-AM, a membrane permeable Epac selective agonist, completely blocked Epac1 and Epac2-mediated Akt phosphorylation [2]. In chicken micromass cultures, inhibition of the PKA-independent cAMP-mediators Epac1 and Epac2 with HJC0197 enhanced cartilage formation [3].

参考文献:
[1].  De Rooij J, Zwartkruis F J T, Verheijen M H G, et al. Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP[J]. Nature, 1998, 396(6710): 474-477.
[2].  Chen H, Tsalkova T, Mei F C, et al. 5-Cyano-6-oxo-1, 6-dihydro-pyrimidines as potent antagonists targeting exchange proteins directly activated by cAMP[J]. Bioorganic & medicinal chemistry letters, 2012, 22(12): 4038-4043.
[3].  Juhász T, Matta C, Somogyi C, et al. Mechanical loading stimulates chondrogenesis via the PKA/CREB-Sox9 and PP2A pathways in chicken micromass cultures [J]. Cellular signaling, 2014, 26(3): 468-482.