Clinical Paths for Soluble Epoxide Hydrolase Inhibitors and Epoxide-Based Therapeutics

Soluble epoxide hydrolase (sEH) is an enzyme that contributes importantly to metabolism of endogenous, biologically active lipids including epoxides of arachidonic acid (EETs). Soluble epoxide hydrolase inhibitors (sEHIs) were developed to increase lipid epoxides including EETs and epoxides of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Interestingly, EETs, EPA and DHA epoxides, and sEHIs reduce blood pressure, improve insulin sensitivity, and decrease inflammation. Further sEHI development led to initial clinical trials for hypertension, diabetes, and chronic obstructive pulmonary disease (COPD). These initial clinical trials demonstrated improved endothelial function in smokers with COPD highlighting sEHI therapeutic potential.

There has been significant expansion of the potential clinical paths for sEHIs and epoxide-based therapeutics in recent years. Additionally, recent work has turned toward multi-target drug strategies. Dual-acting molecules that combine sEHI with additional activities such as peroxisome proliferator activated receptor-gamma (PPARγ) agonism, farnesoid X receptor (FXR) activation, or inhibition of other fatty acid metabolizing enzymes have demonstrated additive or synergistic effects in models of metabolic syndrome, non-alcoholic steatohepatitis (NASH), kidney fibrosis, and cardiovascular disease. This Research Topic seeks to capture the increasingly broad scope for the potential applications of sEHIs, epoixde-based drugs, and multi-target drugs covering cardiovascular, pulmonary, kidney, diabetes, metabolic diseases, and neural pathologies.

We invite contributions ranging from basic mechanistic studies and preclinical models to translational drug development and early-phase clinical trials in this evolving therapeutic field. Submissions from both academic and industry groups are encouraged, with the aim of fostering a comprehensive overview of how manipulation of epoxide pathways via sEHI, epoxide mimics, or multi-target approaches can be harnessed to improve human health.

_{Topic Editor John D. Imig has several patents and is on the Scientific Advisory Boards of the following organizations: Synthia, OROX Biosciences, Lumaired. He is also the founding inventor of Nephraegis Therapeutics. All other Topic Editors declare no competing interests with regards to the Research Topic subject.}