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The canonical GPX4 inhibitors RSL3 and ML162, which belong to the chloroacetamide class of compounds, were originally designed to covalently engage the catalytic selenocysteine residue (Sec46) through their reactive alkyl chloride groups ( 50 ) of 338.3 mg/kg ( Ferroptosis fundamentally diverges from classical apoptosis, exhibiting unique morphological, biochemical, and genetic characteristics ( - by compounds like Erastin and sulfasalazine (SSZ) blocks cellular cystine import, initiating a cascade of intracellular cysteine depletion, glutathione (GSH) exhaustion, GPX4 dysfunction, and consequent ferroptotic cell death ( SOX13 exerts transcriptional control over SCAF1, facilitating the reorganization of electron transport chain complexes into superassemblies that enhance mitochondrial energetics and cellular resilience against ferroptosis ( This conclusion was reached via an integrated multi-omics approach, incorporating metabolomic and transcriptomic profiling, alongside validation in a lung epithelial-specific Cpt1a-deficient murine model and corroborating clinical data

21 Recent studies showed that CPTIC was localized both in endoplasmic reticulum and mitochondria, but its presence in endoplasmic reticulum is predominant

PubMed Sigalos JT, et al