Exchange protein activated by cAMP (Epac) proteins mediate cAMP signaling independent of protein kinase A (PKA). HJC0197 is a cell-permeable inhibitor of Epac1 and Epac2 (IC50 = 5.9 μM for Epac2). It inhibits Epac1-mediated Rap1-GDP exchange activity at 25 μM, but has no effect on cAMP-induced type I and II PKA activity at this concentration. Pretreatment of HEK293 cells expressing either Epac1 or Epac2 with 10 μM HJC0197 completely blocks Epac-mediated phosphorylation of Akt. HJC0197 has been used to study the role of Epac signaling in chondrogenesis in chicken micromass cultures.
