Discovery of soluble epoxide hydrolase inhibitors through DNA-encoded library technology (ELT)

Inhibition of soluble epoxide hydrolase (sEH) has recently emerged as a new approach to treat cardiovascular disease and respiratory disease. Inhibitors based on 1,3,5-triazine chemotype were discovered through affinity selection against two triazine-based DNA-encoded libraries. The structure and activity relationship study led to the expansion of the original 1,4-cycloalkyl series to related aniline, piperidine, quinoline, aryl-ether and benzylic series. The 1,3-cycloalkyl chemotype led to the discovery of a clinical candidate (GSK2256294) for COPD.

Automated summary

The inhibition of soluble epoxide hydrolase (sEH) has emerged as a new approach to treat cardiovascular and respiratory diseases. Through structure-activity relationship studies, inhibitors based on 1,3,5-triazine chemotype have been discovered, leading to the identification of a clinical candidate for COPD.