ABSTRACT

Introduction

Biological effects mediated by the CYP450 arm of arachidonate cascade implicate the enzyme-soluble epoxide hydrolase (sEH) in hydrolyzing anti-inflammatory epoxy fatty acids to pro-inflammatory diols. Hence, inhibiting the sEH offers a therapeutic approach to treating inflammatory diseases. Over three decades of work has shown the role of sEH inhibitors (sEHis) in treating various disorders in rodents and larger veterinary subjects. Novel chemical strategies to enhance the efficacy of sEHi have now appeared.

Areas covered

A comprehensive review of patent literature related to soluble epoxide hydrolase inhibitors in the last decade (2010–2021) is provided.

Expert opinion

Soluble epoxide hydrolase (sEH) is an important enzyme that metabolizes the bioactive epoxy fatty acids (EFAs) in the arachidonic acid signaling pathway and converts them to vicinal diols, which appear to be pro-inflammatory. Inhibition of sEH hence offers a mechanism to increase in vivo epoxyeicosanoid levels and resolve pro-inflammatory pathways in disease states. Significant efforts in the field have led to potent single target as well as multi-target inhibitors with promising in vitro and widely encompassing in vivo activities. Successful clinical translation of compounds targeting sEH inhibition will further validate the promised therapeutic potential of this pathway in treating human diseases.

中文翻译：

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可溶性环氧化物水解酶抑制剂：过去十年的概述和专利审查

摘要

介绍

由花生四烯酸级联的 CYP450 臂介导的生物学效应表明酶可溶性环氧化物水解酶 (sEH) 在将抗炎环氧脂肪酸水解为促炎二醇。因此，抑制 sEH 为治疗炎症性疾病提供了一种治疗方法。三十多年的工作表明 sEH 抑制剂 (sEHis) 在治疗啮齿动物和大型兽医受试者的各种疾病中的作用。现在已经出现了提高 sEHi 功效的新化学策略。

涵盖的领域

提供了过去十年（2010-2021 年）与可溶性环氧化物水解酶抑制剂相关的专利文献的全面回顾。

专家意见

可溶性环氧化物水解酶 (sEH) 是一种重要的酶，可代谢花生四烯酸信号通路中的生物活性环氧脂肪酸 (EFA)，并将其转化为似乎具有促炎作用的连位二醇。因此，抑制 sEH 提供了一种增加体内环氧类二十烷酸水平和解决疾病状态中的促炎途径的机制。在该领域的重大努力已经产生了有效的单靶点和多靶点抑制剂，这些抑制剂具有有希望的体外和广泛的体内活性。靶向 sEH 抑制的化合物的成功临床转化将进一步验证该途径在治疗人类疾病中的潜在治疗潜力。