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FerroLOXIN-2 is a ferroptosis inhibitor that selectively targets the 15LOX/PEBP1 catalytic complex without affecting the biosynthesis of pro-/anti-inflammatory lipid mediators. FerroLOXIN-2 prevents 0.5 μM GPX4 inhibitor RSL3-induced ferroptosis in HBE cell cultures (IC50 = 97 nM post 20h RSL3 treatment) and rescues mice from total body irradiation (TBI)-induced death in vivo (Cpd administered via 25 mg/kg ip. 20h post 9.25Gy irradiation; survival on day 30 = 80% vs. 0% on day 19 of untreated control). FerroLOXIN-2 does not exert its efficacy via radical scavenging or iron-chelating activity, nor does it prevent cell death by necroptosis, pyroptosis, or apoptosis.
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