In Vivo-Active Soluble Epoxide Hydrolase-Targeting PROTACs with Improved Potency and Stability

Soluble epoxide hydrolase (sEH) is a bifunctional enzyme involved in fatty acid metabolism and a promising drug target. We previously reported first-generation sEH proteolysis-targeting chimeras (PROTACs) with limited degradation potency and low aqueous and metabolic stability. Herein, we report the development of next-generation sEH PROTAC molecules with improved stability and degradation potency. One of the most potent molecules (compound