EP4 receptor antagonist 1 is a potent and selective antagonist of the prostaglandin E2 receptor EP4 subtype. EP4 receptor antagonist 1 exhibits half-maximal inhibitory concentration (IC₅₀) values of 6.1nM and 16.2nM for human and mouse EP4 receptors. EP4 receptor antagonist 1 shows inhibitory activity greater than 10μM against EP1, EP2, and EP3 receptors, demonstrating excellent selectivity. EP4 receptor antagonist 1 is primarily used in cancer-related research[1-2].
In vitro, EP4 receptor antagonist 1 (0.1-10μM) was used to pretreat Raw 264.7 macrophages for 24 hours, followed by stimulation with GM-CSF/IL-4 combined with PGE₂ (10nM). EP4 receptor antagonist 1 significantly suppressed the expression of multiple immunosuppression-related genes, including IL-1β, IL-4R, IL-6, ARG1, iNOS, COX2, IL-10, and CXCL1, while reducing inflammation associated with the tumor immunosuppressive microenvironment[1]. EP4 receptor antagonist 1 (600nM) was used to pretreat fetal T cells for 1 hour, followed by co-treatment with PGE2 (10μM) and PMA stimulation. This pretreatment significantly reversed the inhibitory effect of PGE2 on TNF-α+ and IFN-γ+ T cells, indicating that EP4 receptor antagonist 1 can block the PTGES3-PTGER4 signaling pathway-mediated immunosuppression[2].
In vivo, EP4 receptor antagonist 1 (16, 50, 150mg/kg) was orally administered once daily for 14 days to BALB/c mice bearing CT26 colon tumors. EP4 receptor antagonist 1 significantly inhibited tumor growth and enhanced the infiltration of CD8+ T cells in the tumor microenvironment[1].
References:
[1] Yang JJ, Yu WW, Hu LL, et al. Discovery and Characterization of 1H-1,2,3-Triazole Derivatives as Novel Prostanoid EP4 Receptor Antagonists for Cancer Immunotherapy. J Med Chem. 2020 Jan 23;63(2):569-590.
[2] He S, Luo CL, Luo T, et al. Systemic immune activity occurs during human immune system maturation. Cell. 2025 Dec 11;188(25):7291-7308.e23.
EP4 receptor antagonist 1前列腺素E2受体EP4亚型的高效选择性拮抗剂，对人和小鼠EP4受体的半抑制浓度（IC₅₀）分别为6.1nM和16.2nM。EP4 receptor antagonist 1对EP1、EP2和EP3受体的抑制活性均大于10μM，显示出良好的选择性。EP4 receptor antagonist 1主要被用于癌症相关的研究[1-2]。
在体外，EP4 receptor antagonist 1（0.1-10μM）预处理Raw 264.7巨噬细胞24小时，随后以GM-CSF/IL-4联合PGE₂（10nM）刺激，EP4 receptor antagonist 1显著抑制多种免疫抑制相关基因（包括IL-1β、IL-4R、IL-6、ARG1、iNOS、COX2、IL-10、CXCL1）的表达，同时降低肿瘤免疫抑制微环境相关炎症反应[1]。EP4 receptor antagonist 1（600nM）预处理胎儿T细胞1小时，随后与PGE2（10μM）共处理并进行PMA刺激，显著逆转了PGE2对TNF-α+和IFN-γ+ T细胞的抑制效应，EP4 receptor antagonist 1可阻断PTGES3-PTGER4信号通路介导的免疫抑制作用[2]。
在体内，EP4 receptor antagonist 1（16，50，150mg/kg）口服给药，每日一次，用于处理荷CT26结肠癌的BALB/c小鼠，持续14天。EP4 receptor antagonist 1显著抑制了肿瘤生长，并增强了肿瘤微环境中CD8+ T细胞的浸润[1]。