Liproxstatin-1 Chemical Properties

Boiling point:

581.4±50.0 °C(Predicted)

Density 

1.32±0.1 g/cm3(Predicted)

storage temp. 

-20°C

solubility 

Soluble in DMSO (15 mg/ml)

form 

powder

pka

9.45±0.40(Predicted)

color 

white to light brown

Stability:

Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 2 month.

InChI

InChI=1S/C19H21ClN4/c20-15-5-3-4-14(12-15)13-22-18-19(8-10-21-11-9-19)24-17-7-2-1-6-16(17)23-18/h1-7,12,21,24H,8-11,13H2,(H,22,23)

InChIKey

YAFQFNOUYXZVPZ-UHFFFAOYSA-N

SMILES

N1CCC2(C(NCC3=CC=CC(Cl)=C3)=NC3=C(N2)C=CC=C3)CC1

Liproxstatin-1 Usage And Synthesis

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.

Uses

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.

in vivo

References

[1] JOSE PEDRO FRIEDMANN ANGELI. Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice[J]. Nature Cell Biology, 2014, 16 12: 1180-1191. DOI:10.1038/ncb3064
[2] YANSHENG FENG . Liproxstatin-1 protects the mouse myocardium against ischemia/reperfusion injury by decreasing VDAC1 levels and restoring GPX4 levels[J]. Biochemical and biophysical research communications, 2019, 520 3: Pages 606-611. DOI:10.1016/j.bbrc.2019.10.006
[3] OMKAR ZILKA. On the Mechanism of Cytoprotection by Ferrostatin-1 and Liproxstatin-1 and the Role of Lipid Peroxidation in Ferroptotic Cell Death[J]. ACS Central Science, 2017, 3 3: 232-243. DOI:10.1021/acscentsci.7b00028

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