2023年12月6日 · In this work, seeking to diversify EP4R antagonist scaffolds, we computationally dock over 400 million compounds against an EP4R crystal structure and experimentally validate 71 highly ranked, de...

In this review, we summarize the physiological roles of EP4, its molecular structure and intracellular signaling pathways, and how EP4 receptors might be targeted pharmacologically for the benefit of human disease, including vascular and …

研究者通过 分子对接 和实验验证，发现了一种高效抗炎的 EP4R 拮抗剂。 本研究使用 EP4R 的晶体结构，通过分子对接筛选超过 4 亿种化合物。 对排名靠前的 71 新合成分子进行实验验证。 这些分子的筛选基于初始对接结果的结构优化，最终识别出具有 16 纳摩尔的强效选择性拮抗剂。 此外，研究者还发现这种新发现化合物有良好的药代动力学特性，并在多种小鼠临床前疼痛模型中验证了其抗痛觉过敏和抗炎活性。 与传统的 非甾体抗炎药 （NSAIDs）相比，这种拮抗剂通过作 …

The EP 4 receptor is over-expressed in human prostate cancer tissue and a selective EP 4-receptor antagonist inhibits the growth and metastasis of human prostate cancer cell xenografts. An EP 4 receptor antagonist as well EP 4 Gene knockdown inhibit the in vitro proliferation and invasiveness of human breast cancer cells.

Grapiprant is a targeted approach to pain management – it selectively blocks the EP4 receptor, does not interfere with the production of prostanoids, and therefore does not affect the other PG receptor pathways that are affected in animals treated with COX inhibitor NSAIDs.

A possible explanation for the diverse biological functions of EP4 might be the multiple signaling pathways switched on upon EP4 activation. The present review attempts to summarize the EP4 receptor-triggered signaling modules and the possible therapeutic applications of EP4-selective agonists and antagonists.

2021年3月1日 · To prepare an active form of EP4 for biochemical characterization and pharmaceutical application, this study designed a recombinant protein comprising human EP4 fused to the P9 protein (a major envelope protein of phi6 phage) and overexpressed the P9-EP4 fusion protein in the membrane fraction of E. coli.

Here we found that PGE2/EP4 signalling-induced EP4 externalization in dorsal root ganglion (DRG) neurons contributes to nociceptor sensitization and inflammatory pain. In cultured DRG neurons, PGE2 and the EP4 agonist concentration- and …

2022年3月8日 · Importantly, knocking out EP4 in cartilage enhanced stable mature articular cartilage formation instead of fibrocartilage, and reduced joint pain. In addition, we identified a novel selective...

Prostaglandin E (2) (PGE (2)) enhances the Th17 response, exacerbates collagen-induced arthritis (CIA) and promotes inflammatory pain. The current study investigated whether selective antagonism of the PGE (2) EP (4) receptor would suppress Th1/Th17 cell development and inflammatory arthritis in animal models of RA.