2287259-07-6

EP4 receptor antagonist 1 is a highly potent and selective competitive prostanoid EP4 receptor antagonist for cancer immunotherapy. EP4 receptor antagonist 1 inhibits human and mouse EP4 receptor with IC50s of 6.1 nM and 16.2 nM, respectively. IC50s >10 μM for human EP1, EP2,and EP3 receptors[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)