CE3F4

CE3F4 is a selective antagonist of exchange protein directly activated by cAMP (Epac1), with IC₅₀s of 10.7 μM and 66 μM for Epac1 and Epac2(B), respectively. IC50 & Target: IC50: 10.7 μM (Epac1), 66 μM (Epac2(B))^[1] In Vitro: CE3F4 is a selective antagonist of Epac1, with IC₅₀s of 10.7 μM and 66 μM for Epac1 and Epac2(B), respectively. CE3F4 is more active on Epac1 than (S)-stereoisomer ((S)-CE3F4, IC₅₀, 56 μM), but less active than (R)-CE3F4 (IC₅₀, 5.8 μM). CE3F4 (50 μM) shows more inhibitory activities against GEF activity of Epac1, than that of Epac2(AB) or Epac2(B)^[1]. CE3F4 reduces the exchange activity of Epac1 induced by 007, with IC₅₀ of 23 ± 3 μM. CE3F4 (40 μM) specifically inhibits Epac1 guanine nucleotide exchange activity without interference with Rap1 activity or Epac1-Rap1 interaction. CE3F4 has no influence on PKA activity. CE3F4 (20 μM) inhibits Epac-induced Rap1 activation in living cultured HEK293 cells^[2]. CE3F4 (20 μM) significantly inhibits the late phase of ERK activation stimulated by glucose in INS-1 cells^[3]. In Vivo: CE3F4 (1-3 mg/kg; through a catheter in the internal jugular vein) inhibits atrial fibrillation (AF) and CE3F4 (3 mg/kg; i.v.) inhibits ventricular arrhythmias^[4].
CE3F4 (10 mg/kg; i.v.) improves cardiac function after myocardial infarction in mice^[5].