Liproxstatin-1

Liproxstatin-1 is a ferroptosis inhibitor. It inhibits ferroptotic cell death (IC₅₀ = 22 nM) and lipid peroxidation in mouse embryonic fibroblasts (MEFs) with an inducible knockdown of glutathione peroxidase 4 (Gpx4^-/- MEFs) when used at a concentration of 50 nM. Liproxstatin-1 also inhibits ferroptosis induced by the ferroptosis-inducing agents L-buthionine sulphoximine (BSO), erastin , and (1S,3R)-RSL3 in a concentration-dependent manner in MEFs, but does not inhibit necroptosis, apoptosis, or necrosis. It inhibits cell death and lipid peroxidation induced by (1S,3R)-RSL3 in human renal proximal tubule epithelial cells. Liproxstatin-1 (10 mg/kg) increases survival and decreases TUNEL⁺ kidney cells in inducible Gpx4^-/- mice and reduces tissue injury in a mouse model of hepatic ischemia/reperfusion injury. It is also an antioxidant that inhibits autooxidation of lipids by trapping peroxyl radicals.

Liproxstatin-1 has been used as a cell death inhibitor in the cell viability assay and for the determination of lipid peroxidation.

Liproxstatin-1 is a potent inhibitor of ferroptosis, a non-apoptotic form of cell death characterized by iron-dependent accumulation of lethal lipid reactive oxygen species (ROS). Liproxstatin-1 suppressed ferroptosis in human cells and in an ischaemia/reperfusion-induced tissue injury model in mice. Knockout of glutathione peroxidase 4 (Gpx4) Has been shown to cause cell death by ferroptosis. Liproxstatin-1 was able to suppress ferroptosis in Gpx4 knock-out mice.