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...

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 …

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 …

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.

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...

2018年12月3日 · Prostaglandin E receptor EP4, a G-protein-coupled receptor, is involved in disorders such as cancer and autoimmune disease. Here, we report the crystal structure of human EP4 in complex with...

Prostaglandin E(2) (PGE(2)) is both an inflammatory mediator released at the site of tissue inflammation and a neuromodulator that alters neuronal excitability and synaptic processing. The effects of PGE(2) are mediated by four G-protein-coupled EP receptors (EP1-EP4). Here we show that the EP4 rece …

2013年6月17日 · The EP4 prostanoid receptor is one of four receptor subtypes for prostaglandin E2. It belongs to the family of G protein-coupled receptors. It was originally identified, similar to the EP2 receptor as a G(s)α-coupled, adenylyl cyclase-stimulating receptor. EP4 signaling plays a variety of roles thro …

Prostaglandin E2 (PGE 2) receptor 4 (EP4) is one of four EP receptors commonly upregulated in the tumor microenvironment and plays vital roles in stimulating cell proliferation, invasion, and metastasis. Biochemical blockade of the PGE 2 –EP4 signaling pathway is a promising strategy for controlling inflammatory and immune related disorders ...