EP4 Receptor Antagonist 1 is a highly potent and selective competitive prostanoid EP4 receptor antagonist, effective for cancer immunotherapy. It inhibits both human and mouse EP4 receptors with IC50 values of 6.1 nM and 16.2 nM, respectively, while displaying minimal activity (IC50s >10 μM) against human EP1, EP2, and EP3 receptors.

EP4 receptor (mouse):16.2 nM , EP4 receptor (human):6.1 nM

EP4 receptor antagonist 1 inhibits the activity of the CRE reporter in HEK293 cells with an IC50 of 5.2±0.4 nM in a dose-dependent manner. EP4 receptor antagonist 1 dose-dependently inhibits PGE2-stimulated β-arrestin recruitment in HEK293-EP4 cells with an IC50 of 0.4±0.1 nM. EP4 receptor antagonist 1 inhibits PGE2-stimulated cAMP accumulation in HEK293-EP4 cells with an IC50 of 18.7±0.6 nM in a dose-dependent manner. EP4 receptor antagonist 1 (1 nM-10 μM) reverses PGE2-induced ERK phosphorylation in a concentration-dependent manner. The IC50s are >10 μM for human EP1, EP2, and EP3 receptors[1].

EP4 receptor antagonist 1 (1 mg/kg; i.v.) demonstrates moderate clearance of 1.7 L/h/kg in mice with a corresponding favorable half-life of 4.1 h. EP4 receptor antagonist 1 (5 mg/kg; orally) exhibits good bioavailability of 48.0% in mice with a corresponding favorable half-life of 4.7 h. EP4 receptor antagonist 1 (16, 50, and 150 mg/kg; oral) causes significant inhibition of tumor growth in BALB/c female mice. No significant body weight loss is found in any mouse cohorts. EP4 receptor antagonist 1 is well tolerated in mice at the tested dosage[1].