EP4 Receptor Antagonist 1

EP₄ receptor antagonist 1 is an antagonist of the prostaglandin E₂ (PGE₂) receptor EP₄ that has an IC₅₀ value of 6.1 nM in a calcium flux assay using CHO cells co-expressing the human receptor and Gα₁₆.¹ It is selective for EP₄ over EP₁, EP₂, and EP₃ receptors (IC₅₀s = >10,000 nM for all). EP₄ receptor antagonist 1 inhibits PGE₂-induced β-arrestin recruitment in HEK293 cells expressing EP₄. It reverses ERK phosphorylation induced by PGE₂ in CHO cells expressing EP₄ and decreases GM-CSF-induced expression of Il1b, Il4ra, Il6, Arg1, Cox2, and Il10 in RAW 264.7 cells when used at a concentration of 10 µM. EP₄ receptor antagonist 1 (50 and 150 mg/kg once per day) reduces tumor volume and increases infiltration of CD8⁺ T cells into tumors in a murine colon carcinoma model.

1.Yang, J.-J., Yu, W.-W., Hu, L.-L., et al.Discovery and characterization of 1 H-1,2,3-triazole derivatives as novel prostanoid EP4 receptor antagonists for cancer immunotherapyJ. Med. Chem.63(2)569-590(2020)