EP₄receptor antagonist 1 is an antagonist of the prostaglandin E₂(PGE₂) receptor EP₄that has an IC₅₀value of 6.1 nM in a calcium flux assay using CHO cells co-expressing the human receptor and Gα₁₆.¹It is selective for EP₄over EP₁, EP₂, and EP₃receptors (IC₅₀s = >10,000 nM for all). EP₄receptor antagonist 1 inhibits PGE₂-induced β-arrestin recruitment in HEK293 cells expressing EP₄. It reverses ERK phosphorylation induced by PGE₂in CHO cells expressing EP₄and decreases GM-CSF-induced expression ofIl1b,Il4ra,Il6,Arg1,Cox2, andIl10in RAW 264.7 cells when used at a concentration of 10 µM. EP₄receptor 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)