The ovarian tumor domain-containing protein 4 (OTUD4)-targeted ferroptosis inhibitor Maclekarpine E attenuates ulcerative colitis

This study aimed to evaluate the therapeutic effect of ME against UC and to elucidate its underlying molecular mechanism and potential target. ME was semi-synthesized on a gram scale via a biomimetic route. Its activity was assessed in an LPS-induced RAW264.7 macrophage model in vitro and a DSS-induced mouse UC model in vivo. Mechanistic studies employed TMT-based proteomics profiling , an RSL3-induced ferroptosis model, and target identification using DIA-based SPIA proteomics profiling combined with cycloheximide chase and co-immunoprecipitation assays.