A novel inhibitor of soluble epoxide hydrolase that adducts C521 is cardioprotective.

ABSTRACT: The lipid electrophile nitro-oleic acid (NO₂-OA) and inhibitors of soluble epoxide hydrolase (sEH) limit injury during myocardial ischemia and reperfusion (IR). We investigated if cardioprotection by NO₂-OA was mediated by inhibitory adduction of this electrophile to C521 of the hydrolase. Indeed, administering NO₂-OA to wild type (WT) isolated perfused hearts prior to IR limited infarction, but this protection was absent in C521S sEH knock-in (KI) mice - demonstrating the critical importance of this cysteine. To identify more potent and selective inhibitors, we screened a library of electrophiles for their ability to inhibit sEH. A compound, we termed RLC14, had an IC₅₀ of 6.8x10^-9 M and protected WT, but not KI, isolated hearts from

SUBMITTER: Charles RL 

PROVIDER: S-EPMC12768880 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature