ep4-in-1

EP4-IN-1 is a potent prostaglandin EP4 receptor inhibitor with potential anti-tumor, anti-inflammatory, and analgesic activities for studying immune and tumor diseases.

EP4 receptor antagonist 7 (Compound 14) is an antagonist of the prostaglandin E2 (PGE2) receptor subtype EP4, with an IC50 of 1.1 nM. This compound inhibits PGE2-induced β-arrestin recruitment in HEK293 cells with an IC50 of 0.9 nM. In RAW 264.7 macrophages, it reduces the expression of PGE2-induced IL-4, macrophage mannose receptor 1 (Mrc1), chitinase-like protein 3 (Chil3), chemokine (C-X-C motif) ligand 1 (Cxcl1), triggering receptor expressed on myeloid cells 2 (Trem2), and arginase 1 (Arg1) mRNA. In the CT26 mouse colon cancer model, EP4 receptor antagonist 7, combined with an anti-PD-1 antibody, inhibits tumor growth and enhances CD8+ T cell infiltration into the tumor.

Butaprost is a selective agonist of the prostaglandin E receptor EP2 that exhibits an EC50 of 33 nM and a Ki of 2.4 μM toward the murine EP2 receptor, while showing markedly lower activity against murine EP1, EP3, and EP4 receptors. Butaprost effectively attenuates fibrotic responses by inhibiting the TGF-β/Smad2 signaling pathway, supporting its utility in fibrosis, inflammation, and prostaglandin receptor signaling research.

Rivenprost is a selective agonist of the prostaglandin E receptor (EP4), exhibiting extremely high selectivity for the EP4 receptor with a Ki value of 0.7 nM. Rivenprost can be used in research on bone metabolism regulation, as well as anti-inflammatory and tissue protection studies.

17-phenyl trinor PGE2 ethyl amide is derived from 17-phenyl trinor PGE2, a synthetic analog of PGE2 that acts as an agonist of EP1 and EP3 receptors in mice (Ki = 14 and 3.7 nM, respectively) and EP1, EP3, and EP4 in rats (Ki = 25, 4.3, and 54 nM, respectively). 17-phenyl trinor PGE2 causes contraction of guinea pig ileum at a concentration of 11 μM and is 4.4 times more potent than PGE2 as an antifertility agent in hamsters. Modification of the C-1 carboxyl group to an ethyl amide serves to increase lipid solubility, thereby improving uptake into tissues and further lowering the effective concentration. Ethyl amide groups are then removed by amidases, regenerating the active free acid.

15-keto-Prostaglandin E2 is an endogenous bioactive metabolite that inhibits STAT3 activation through covalent interaction with the Cys259 residue, while also binding to and stabilizing EP2 and EP4 receptors, thereby exerting inhibitory effects on breast cancer cell growth and tumor progression, activating PPAR-γ signaling, and promoting fungal growth, collectively positioning this lipid mediator as a multifunctional regulator in cancer biology, immunometabolism, and host–pathogen interaction research.

EP4 antagonist 14 is a prostaglandin E2 receptor subtype EP4 antagonist, demonstrating an IC50 of 1.1 nM in a HEK293 human receptor reporter assay and blocking β-arrestin recruitment due to PGE2 with an IC50 of 0.9 nM. At 10 µM, it reduces PGE2-stimulated mRNA levels of Il-4, macrophage mannose receptor 1 (Mrc1), chitinase-like protein 3 (Chil3), chemokine (C-X-C) motif ligand 1 (Cxcl1), triggering receptor expressed on myeloid cells 2 (Trem2), and arginase-1 (Arg1) in RAW 264.7 macrophages. When used at 30 mg/kg per day alongside anti-PD-1 antibodies, it curbs tumor growth and enhances CD8+ T cell infiltration in tumors using a CT26 murine colon cancer model.

MF-766 is a highly potent, selective, and orally active EP4 antagonist with a Ki of 0.23 nM, acting as a full antagonist with an IC50 of 1.4 nM (shifted to 1.8 nM in the presence of 10% HS) in the functional assay. It is useful for cancer and inflammation diseases research [1][2].