Liproxstatin-1 HCl is a potent inhibitor of ferroptosis with IC50 value of 22 nM [1].
Ferroptosis is an iron-dependent non-apoptotic form of cell death induced by small molecules in engineered cells overexpressing oncogenic RAS and specific tumour types [1].
Liproxstatin-1 HCl is a potent ferroptosis inhibitor. Liproxstatin-1 HCl showed inhibition against ferroptosis-inducing agent (FIN) -triggered cell death. In Gpx4-/- cells, Liproxstatin-1 HCl inhibited RSL3-induced BODIPY 581/591 C11 oxidation. In primary human renal proximal tubule epithelial cells (HRPTEpiCs), Liproxstatin-1 HCl inhibited RSL3-induced cell death. Knock down Gpx4 in the immortalized human renal proximal tubule epithelial cell line (HK-2) cells made cells more sensitive to FIN [1].
On TAM treatment of CreERT2; Gpx4fl/fl mice, Liproxstatin-1 HCl significantly extended survival time and reduced number of TUNELC cells, which suggested that Liproxstatin-1 HCl delayed ferroptosis in tubular cells. In a hepatic ischaemia/reperfusion injury model, Liproxstatin-1 HCl mitigated tissue injury induced by ischaemia/reperfusion [1].
Reference:
[1]. Friedmann Angeli JP, Schneider M, Proneth B, et al. Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nat Cell Biol, 2014, 16(12): 1180-1191.
