N6F11

N6F11 is a ferroptosis inducer (0.5-10 µM for 24h) that causes cellular glutathione peroxidase 4 (GPX4) degradation (5 µM for 6-12h, 0.0625-5 µM for 12h) via ubiquitin-proteasome system (UPS) by inducing TRIM25-mediated ubiquitination. N6F11 causes ferroptotic cancer cell death that initiates HMGB1-dependent antitumor immunity mediated by CD8+ T-cells. When administered together with CD274 neutralizing antibody (clone 10F.9G2), N6F11 prolongs the average life expectancy of KPC mice, an orthotopic pancreatic ductal adenocarcinoma (PDA) model in vivo (10 mg N6F11/kg, 20 mg αCD274/kg via i.p.). Unlike RSL3, Fin56, and erastin, autophagy is dispensable of N6F11-induced ferroptosis.