Ferrostatin-1 (Fer-1) (Synonyms: Fer-1)

Ferrostatin-1 is a potent inhibitor of ferroptosis with an EC50 of 60 nM.

Ferrostatin-1, as an molecular inhibitor, can block ferroptosis. Ferrostatins are believed to act by preventing oxidative damage to membrane lipids. Ferrostatin-1, an arylalkylamine with antioxidative properties, was identified as one of the first inhibitors of ferroptosis. Ferrostatin-1 attenuates oxidative, iron-dependent cell death in cancer cells treated with small molecules such as erastin. [3]

Ferrostatin-1, an inhibitor of ferroptosis, has an EC₅₀ of 60 nM (HT-1080). Besides, Ferrostatin-1 was able to inhibit a non-apoptotic cell death named ferroptosis. The neuroprotective role of Ferrostatin-1 under rotenone-induced oxidative stress in dopaminergic neuroblastoma cells (SH-SY5Y) was reported. Ferrostatin-1 inhibited the ROS/RNS generated under rotenone insult in SH-SY5Y cells. The effective role of Ferrostatin-1 in ER stress mediated activation of apoptotic pathway was confirmed. Additionally, Ferrostatin-1 mitigated rotenone-induced α-syn aggregation was also reported.[1]

Ferrostatin-1, a specific inhibitor of ferroptosis, was Administrated to prevent neuronal death and reduced iron deposition induced by hemoglobin in organotypic hippocampal slice cultures (OHSCs). Mice treated with ferrostatin-1 after ICH exhibited marked brain protection and improved neurologic function. Additionally, Ferrostatin-1 reduced lipid reactive oxygen species production and attenuated the increased expression level of PTGS2 and its gene product cyclooxygenase-2 ex vivo and in vivo. For in vivo experiments, Ferrostatin-1 was injected 1 pmol (10 μM Ferrostatin-1 in 1 μl 0.01% DMSO in saline) into the striatum immediately after collagenase injection or into the cerebral ventricle 2 hours after collagenase injection. The coordinates for cerebral ventricle injection were: 1.0 mm lateral, 0.5 mm posterior, and 2.5 mm in depth relative to the bregma. [2]

References:
[1] Kabiraj P, et al. The neuroprotective role of ferrostatin-1 under rotenone-induced oxidative stress in dopaminergic neuroblastoma cells. Protein J. 2015 Oct;34(5):349-58.
[2] Li Q, et al. Inhibition of neuronal ferroptosis protects hemorrhagic brain. JCI Insight. 2017 Apr 6;2(7):e90777. doi: 10.1172/jci.insight.90777.
[3] Hofmans S, et al. Novel Ferroptosis Inhibitors with Improved Potency and ADME Properties. J Med Chem. 2016 Mar 10;59(5):2041-53.