human ep4 receptor

EP4 receptor antagonist 1 是一种有效的特异性前列腺素 EP4受体拮抗剂，对人和小鼠 EP4受体的 IC50分别为6.1 nM 和16.2 nM。 EP4 receptor antagonist 1 可用于癌症免疫治疗的研究。

KAG-308 is an effective selective and orally active agonist of the EP4 receptor (Ki: 2.57 nM and EC50: 17 nM for human EP4 receptor), more selective over EP1, EP2, EP3, and IP receptor. KAG-308 suppresses colitis and promotes histological mucosal healing,

PF-04418948 是一种可口服的，选择性的前列腺素EP2受体拮抗剂，IC50为16 nM。

CJ-42794 (CJ-042794)是前列腺素受体 EP4的选择性拮抗剂, 抑制[3H]-PGE2与 EP4受体结合的平均 pKi 为8.5, 对 EP4选择性比 EP1, EP2和 EP3高200多倍。

The prostaglandin E receptor 4 (EP4) is one of four G protein-coupled receptors that mediate the actions of prostaglandin E2 . Binding of PGE2 to the EP4 receptor causes an increase in intracellular cyclic AMP, which plays important roles in bone formation and resorption, cancer, and atherosclerosis. KMN-80 is a substituted γ-lactam (pyrrolidinone) derivative of PGE1 that acts as a selective and potent agonist of EP4 with an IC50 value of 3 nM (IC50 = 1.4 μM for EP3 and > 10 μM for all other prostanoid receptors). In functional assays it has been shown to stimulate secreted alkaline phosphatase gene reporter activity in EP4-transfected HEK293 cells with an EC50 value of 0.19 nM, demonstrating >5,000 and 50,000-fold selectivity against EP2 and TP, respectively. KMN-80 can induce the differentiation of bone marrow stem cells from both young and aged rats into osteoblasts in vitro (EC50s = 20 and 153 nM, respectively) and exhibits favorable tolerability up to at least 10 μM, whereas the EP4 agonist L-902,688 is highly cytotoxic at similar concentrations in these cells. KMN-80 has been used to repair calvarial defects in an in vivo rat craniomaxillofacial reconstruction model (rate of reduction in defect size equivalent to BMP-2 treated rats) and to promote bone formation in a rat incisor tooth socket model.

EP4 receptor antagonist 4 是一种EP4受体激动剂 (human pEC50 = 6.3)。

CR6086 is a novel, potent EP4 antagonist showing favourable immunomodulatory properties, striking DMARD effects in rodents, and anti-inflammatory activity targeted to immune-mediated inflammatory diseases and distinct from the general effects of cyclooxygenase inhibitors. CR6086 showed selectivity and high affinity for the human EP4 receptor (Ki = 16.6 nM) and functioned as a pure antagonist (half-maximal inhibitory concentration, 22 nM) on PGE2-stimulated cAMP production.

MF-592 is a potent and selective antagonists of the EP4 receptor. MF-592 demonstrated good functional potency (hEP4 IC50 = 3 nM) and potent inhibition of PGE2 modulated TNFa release in LPS stimulated human whole blood (hWB) (IC50 = 78nM). In addition, it showed an excellent oral pharmacokinetic (PK) profile and in vivo efficacy in a rat chronic adjuvant-induced-arthritis model (ED50 = 0.1 mg kg day).. MF-592 has a desirable overall preclinical profile that suggests it is suitable for further development.

EP4 antagonist 14是一种前列腺素E2（PGE2）受体亚型EP4的拮抗剂，其在使用表达人源受体的HEK293细胞的报告基因测定中的IC50值为1.1 nM。它还能抑制PGE2诱导的同种细胞中的β-阿雷斯汀招募（IC50 = 0.9 nM）。EP4 antagonist 14（10 µM）能减少RAW 264.7巨噬细胞中PGE2诱导的mRNA表达，这些mRNA编码Il-4、巨噬细胞甘露糖受体1（Mrc1）、几丁质酶样蛋白3（Chil3）、趋化因子（C-X-C）基序配体1（Cxcl1）、表达在髓样细胞上的触发受体2（Trem2）和精氨酸酶-1（Arg1）。在体内，EP4 antagonist 14（每天30 mg/kg），结合抗PD-1抗体，能够在CT26小鼠结肠癌模型中抑制肿瘤生长并增加CD8+ T细胞对肿瘤的浸润。

(R)-Vorbipiprant ((R)-CR6086) 作为口服前列腺素 E2 (EP4) 受体拮抗剂，绑定 EP4 受体的能力强，Ki 值为 16.6 nM。该化合物能有效抑制 PGE2 诱导的 cAMP 生成，IC50 值达 22 nM，显示出显著的免疫调节和抗血管生成特性，对小鼠胶原诱导性关节炎的改善效果显著。