Liproxstatin-1

Description

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.

The Uses of Liproxstatin-1

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

Definition

ChEBI: Liproxstatin-1 is an azaspiro compound that is 1'H-spiro[piperidine-4,2'-quinoxaline] in which the hydrogen at position 3' is replaced by a (3-chlorobenzyl)amino group. It is a potent inhibitor of ferroptosis. It has a role as a ferroptosis inhibitor, a radical scavenger, an antioxidant and a cardioprotective agent. It is a member of monochlorobenzenes, a secondary amino compound, an azaspiro compound and an organic heterotricyclic compound.

Biochem/physiol Actions

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.

References

Angeli et al. (2014), Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice; Nat. Chem. Biol. 16 1180 Feng et al. (2019), Liproxstatin-1 protects the mouse myocardium against ischemia/reperfusion injury by decreasing VDAC1 levels and restoring GPX4 levels; Biochem. Biophys. Res. Commun. 520 606 Zilka et al. (2017), On the mechanism of Cytoprotection by Ferrostatin-1 and Liproxstatin-1 and the Role of Lipid Peroxidation in Ferroptotic Cell Death; ACS Cent. Sci. 3 232