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This study aimed to identify novel hit compounds targeting soluble epoxide hydrolase (sEH) for the development of lead molecules that could be used in the treatment of chronic inflammatory diseases. While numerous sEH inhibitors have been reported, none have reached clinical use due to high plasma protein binding and suboptimal pharmacokinetic profiles. The sEH enzyme regulates inflammation by converting protective endogenous epoxylipids produced through cytochrome-mediated epoxidation of fatty acids into inactive diols. Thus, there is a significant therapeutic potential for small compounds that selectively inhibit sEH to retain these epoxylipids. We targeted the identification of small molecules exhibiting strong sEH...