Soluble epoxide hydrolase inhibitors: an overview and patent review from the last decade

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.

Automated summary

Soluble epoxide hydrolase (sEH) plays an important role in metabolizing bioactive epoxy fatty acids (EFAs) and converting them to pro-inflammatory vicinal diols in the arachidonic acid signaling pathway. Inhibition of sEH offers a potential therapeutic approach to increase the levels of epoxyeicosanoids and resolve pro-inflammatory pathways in diseases. Significant progress has been made in developing potent single and multi-target inhibitors with promising in vitro and in vivo activities. Successful clinical translation of compounds targeting sEH inhibition will further validate the therapeutic potential of this pathway in treating human diseases.