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。
Cas No.:2287259-07-6
Sample solution is provided at 25 µL, 10mM.
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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]。
| Cell experiment [1]: | |
Cell lines | CHO-human EP4-Gα16 cells, HEK293-EP4 cells, Raw 264.7 macrophage cells |
Preparation Method | CHO-human EP4-Gα16 cells were pretreated with EP4 receptor antagonist 1 (0.1-100nM) for 15 minutes, then stimulated with PGE2 (10nM) for calcium flux measurement. HEK293-EP4 cells were co-transfected with EP4 and pGloSensor-22F cAMP plasmids, pretreated with EP4 receptor antagonist 1 (1-100nM) for 15 minutes, then stimulated with PGE2 (10nM) for cAMP detection. Raw 264.7 cells were treated with GM-CSF/IL-4/PGE2 in the presence or absence of EP4 receptor antagonist 1 (0.1-10μM) for 24 hours. |
Reaction Conditions | 0.1-100nM; 15 minutes pretreatment (calcium flux and cAMP assays); 0.1-10μM; 24 hours (gene expression analysis). |
Applications | EP4 receptor antagonist 1 dose-dependently inhibited PGE2-induced calcium flux in CHO-human EP4-Gα16 cells (IC₅₀=6.1nM) and suppressed PGE2-stimulated cAMP accumulation in HEK293-EP4 cells (IC₅₀=18.7nM). In Raw 264.7 cells, EP4 receptor antagonist 1 significantly reduced the expression of immunosuppression-related genes (IL-1β, IL-4R, IL-6, ARG1, iNOS, COX2, IL-10, and CXCL1) induced by GM-CSF/IL-4/PGE2 stimulation. |
| Animal experiment [1]: | |
Animal models | BALB/c mice bearing CT26 colon carcinoma tumors |
Preparation Method | Mice were orally administered EP4 receptor antagonist 1 once daily for 14 days. Tumor sizes and body weights were measured every other day, and tumor tissues were collected for analysis on day 14. |
Dosage form | 16mg/kg, 50mg/kg, and 150mg/kg; p.o.; Daily for 14 days. |
Applications | EP4 receptor antagonist 1 administration significantly inhibited tumor growth in a dose-dependent manner and enhanced infiltration of CD8+ T cells in the tumor microenvironment without causing significant body weight loss. |
References: | |
| Cas No. | 2287259-07-6 | SDF | |
| Canonical SMILES | C[C@@H](C1=CC=C(C=C1)C(O)=O)NC(C2=C(/C=C/C)N=NN2CC3=CC=C(C(F)(F)F)C=C3)=O | ||
| 分子式 | C23H21F3N4O3 | 分子量 | 458.4 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,DMSO:PBS (pH 7.2) (1:6): 0.14 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1815 mL | 10.9075 mL | 21.815 mL |
| 5 mM | 436.3 μL | 2.1815 mL | 4.363 mL |
| 10 mM | 218.2 μL | 1.0908 mL | 2.1815 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
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- Purity: >98.00% Appearance: A solid
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