Ferrostatin-1 (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.

Ferrostatin-1是一种有效的铁死亡抑制剂,EC50为60纳摩尔。

Ferrostatin-1是一种分子抑制剂,可以阻止铁死亡。相信Ferrostatins通过防止膜脂质的氧化损伤来发挥作用。 Ferrostatin-1是一种具有抗氧化性能的芳基烷胺,被认为是铁死亡的第一个抑制剂之一。在使用小分子如erastin处理癌细胞时,Ferrostatin-1减轻了氧化、依赖于铁离子的细胞死亡。[3]

Ferrostatin-1是一种抑制铁死亡的药物,其EC50为60 nM（HT-1080）。此外,Ferrostatin-1还能够抑制一种非凋亡性细胞死亡方式——铁死亡。报道了在罗滕酮诱导氧化应激下对多巴胺能神经母细胞瘤细胞（SH-SY5Y）中Ferrostatin-1的神经保护作用。Ferrostatin-1可以抑制SH-SY5Y细胞在罗滕酮刺激下产生的ROS/RNS。确认了Ferrostatin-1在内质网应激介导的凋亡通路激活中的有效作用。此外,报道了Ferrostatin-1缓解罗滕酮诱导α-syn聚集的作用。[1]

Ferrostatin-1是一种特定的铁死亡抑制剂,被用来预防血红蛋白诱导的神经元死亡和减少器官培养海马切片中的铁沉积。给予Ferrostatin-1治疗后,ICH小鼠表现出明显的脑保护作用和改善神经功能。此外,Ferrostatin-1还能够减少脂质活性氧产生,并在体内外减弱PTGS2及其基因产物环氧合酶2表达水平的增加。对于体内实验,将Ferrostatin-1注射到胶原酶注射后立即进入纹状体或在胶原酶注射后2小时注入侧脑室中。侧脑室注射坐标为：相对于bregma点位移动 1.0 mm 横向、0.5 mm 后方、深度为 2.5 mm 。[2]

参考文献：
[1] Kabiraj P等。铁死亡素-1在罗滕酮诱导的多巴胺能神经母细胞瘤细胞氧化应激下的神经保护作用。蛋白质学杂志,2015年10月;34（5）：349-58。
[2] Li Q等。抑制神经元铁死亡可保护出血性脑损伤。JCI Insight. 2017年4月6日;2（7）：e90777. doi: 10.1172/jci.insight.90777。
[3] Hofmans S等。具有改进效力和ADME特性的新型铁死亡素抑制剂。医药化学杂志,2016年3月10日;59（5）：2041-53。