GPX4 represents a promising {yet|however|but} difficult-to-drug therapeutic target for the {treatment|therapy|remedy} of, {among|amongst} {others|other people|other individuals|other folks}, drug-resistant cancers. {While|Whilst|Although|Even though|When|Though} most GPX4 inhibitors {rely on|depend on} a chloroacetamide moiety to modify covalently the protein’s catalytic selenocysteine residue, the discovery and mechanistic elucidation of structurally diverse GPX4-inhibiting molecules has uncovered novel electrophilic warheads that bind and inhibit GPX4. {Here|Right here} we report our discovery that diacylfuroxans can act as masked nitrile oxides that inhibit GPX4 covalently. These observations illuminate a novel molecular mechanism of action for biologically active furoxans {and also|as well as} {suggest|recommend} that nitrile oxides {may|might|could|may possibly|may well|may perhaps} be uniquely suited to targeting GPX4. Formula of 3,5-Dichloropyrido[3,4-b]pyrazine Buy1354952-28-5 PMID:24103058
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