Ferrostatin1

Ferrostatin-1 is a cell-permeable small molecule that inhibits ferroptosis, a form of regulated, iron-dependent cell death driven by lipid peroxidation. It was first described in 2012 by Dixon and colleagues as a potent inhibitor of ferroptosis, widely used as a tool to study this pathway in vitro.

Mechanism and action: Ferrostatin-1 functions as a lipophilic radical-trapping antioxidant that intercepts lipid peroxyl radicals in cellular membranes, thereby preventing the propagation of lipid peroxidation. By limiting the accumulation of lipid hydroperoxides, it protects cells from ferroptotic death in various contexts. Its protective effect can be observed in cells subjected to GPX4 inhibition, system Xc− blockade, or cystine deprivation, indicating that its action targets lipid peroxidation rather than acting as a general antioxidant.

Use in research: In laboratory settings, ferrostatin-1 is widely used to determine whether cell death is ferroptotic. It is typically effective at low micromolar concentrations in cell culture and is usually delivered as a DMSO stock solution. Although it can rescue cells from ferroptosis induced by GPX4 inhibitors or cystine deprivation, its pharmacokinetic properties in vivo are limited, and researchers sometimes employ related compounds such as liproxstatin-1 for in vivo studies.

Chemical and distribution notes: Ferrostatin-1 is a small, lipophilic molecule. It is often sensitive to oxidation and light, particularly in aqueous solutions, and is generally prepared fresh or protected from light and air. As a prototypical ferroptosis inhibitor, it remains a common reference compound for experiments investigating lipid peroxidation and ferroptotic pathways.