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Ferrostatin-1 (Fer-1)

Catalog No.GC10380

Ferrostatin-1 (Fer-1) Chemical Structure

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

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10mM (in 1mL DMSO)
$46.00
In stock
5mg
$32.00
In stock
25mg
$117.00
In stock
50mg
$227.00
In stock
100mg
$404.00
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Sample solution is provided at 25 µL, 10mM.

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Protocol

Cell experiment [1]:

Cell lines

SH-S5Y

Preparation Method

Soluble in DMSO (up to 100 mg/ml) or in Ethanol (up to 100 mg/ml).

Reaction Conditions

1 μM, 24 h

Applications

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. Besides, Ferrostatin-1 inhibited the ROS/RNS generated under rotenone insult in SH-SY5Y cells.

Animal experiment [2]:

Animal models

C57BL/6 (ICH, Intracerebral hemorrhage)

Preparation Method

10 μM Ferrostatin-1 in 1 μl 0.01% DMSO in saline

Dosage form

1 pmol of Ferrostatin-1, collagenase injection

Applications

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.

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.

Background

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, Han X, 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.

Chemical Properties

Cas No. 347174-05-4 SDF
Synonyms N/A
Chemical Name N/A
Canonical SMILES NC1=C(NC2CCCCC2)C=CC(C(OCC)=O)=C1
Formula C15H22N2O2 M.Wt 262.35
Solubility ≥ 9.8 mg/mL in DMSO, ≥ 99.6 mg/mL in EtOH with ultrasonic Storage 4°C, protect from light
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
Shipping Condition Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request

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Research Update

Ferrostatin-1 alleviates lipopolysaccharide-induced acute lung injury via inhibiting ferroptosis

Cell Mol Biol Lett2020 Feb 27;25:10.PMID: 32161620DOI: 10.1186/s11658-020-00205-0

Background: Ferroptosis is a newly recognized type of cell death, which is different from traditional necrosis, apoptosis or autophagic cell death. However, the position of ferroptosis in lipopolysaccharide (LPS)-induced acute lung injury (ALI) has not been explored intensively so far. In this study, we mainly analyzed the relationship between ferroptosis and LPS-induced ALI.
Methods: In this study, a human bronchial epithelial cell line, BEAS-2B, was treated with LPS and ferrostatin-1 (Fer-1, ferroptosis inhibitor). The cell viability was measured using CCK-8. Additionally, the levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and iron, as well as the protein level of SLC7A11 and GPX4, were measured in different groups. To further confirm the in vitro results, an ALI model was induced by LPS in mice, and the therapeutic action of Fer-1 and ferroptosis level in lung tissues were evaluated.
Results: The cell viability of BEAS-2B was down-regulated by LPS treatment, together with the ferroptosis markers SLC7A11 and GPX4, while the levels of MDA, 4-HNE and total iron were increased by LPS treatment in a dose-dependent manner, which could be rescued by Fer-1. The results of the in vivo experiment also indicated that Fer-1 exerted therapeutic action against LPS-induced ALI, and down-regulated the ferroptosis level in lung tissues.
Conclusions: Our study indicated that ferroptosis has an important role in the progression of LPS-induced ALI, and ferroptosis may become a novel target in the treatment of ALI patients.

Insight into the mechanism of ferroptosis inhibition by ferrostatin-1

Redox Biol2020 Jan;28:101328.PMID: 31574461DOI: 10.1016/j.redox.2019.101328

Ferroptosis is a form of cell death primed by iron and lipid hydroperoxides and prevented by GPx4. Ferrostatin-1 (fer-1) inhibits ferroptosis much more efficiently than phenolic antioxidants. Previous studies on the antioxidant efficiency of fer-1 adopted kinetic tests where a diazo compound generates the hydroperoxyl radical scavenged by the antioxidant. However, this reaction, accounting for a chain breaking effect, is only minimally useful for the description of the inhibition of ferrous iron and lipid hydroperoxide dependent peroxidation. Scavenging lipid hydroperoxyl radicals, indeed, generates lipid hydroperoxides from which ferrous iron initiates a new peroxidative chain reaction. We show that when fer-1 inhibits peroxidation, initiated by iron and traces of lipid hydroperoxides in liposomes, the pattern of oxidized species produced from traces of pre-existing hydroperoxides is practically identical to that observed following exhaustive peroxidation in the absence of the antioxidant. This supported the notion that the anti-ferroptotic activity of fer-1 is actually due to the scavenging of initiating alkoxyl radicals produced, together with other rearrangement products, by ferrous iron from lipid hydroperoxides. Notably, fer-1 is not consumed while inhibiting iron dependent lipid peroxidation. The emerging concept is that it is ferrous iron itself that reduces fer-1 radical. This was supported by electroanalytical evidence that fer-1 forms a complex with iron and further confirmed in cells by fluorescence of calcein, indicating a decrease of labile iron in the presence of fer-1. The notion of such as pseudo-catalytic cycle of the ferrostatin-iron complex was also investigated by means of quantum mechanics calculations, which confirmed the reduction of an alkoxyl radical model by fer-1 and the reduction of fer-1 radical by ferrous iron. In summary, GPx4 and fer-1 in the presence of ferrous iron, produces, by distinct mechanism, the most relevant anti-ferroptotic effect, i.e the disappearance of initiating lipid hydroperoxides.

Ferrostatin-1 alleviates lipopolysaccharide-induced cardiac dysfunction

Bioengineered2021 Dec;12(2):9367-9376.PMID: 34787054DOI: 10.1080/21655979.2021.2001913

Cardiac dysfunction is a common complication of sepsis, and is attributed to severe inflammatory responses. Ferroptosis is reported to be involved in sepsis-induced cardiac inflammation. Therefore, we speculated that ferrostatin-1 (Fer-1), a ferroptosis inhibitor, improves cardiac dysfunction caused by sepsis. An intraperitoneal injection of lipopolysaccharide (LPS) was performed to induce a rat cardiac dysfunction model. Echocardiography, cardiac histopathology, biochemical and western blot results were analyzed. Twelve hours after the LPS injection, LPS-treated rats exhibited deteriorating cardiac systolic function, increased levels of cardiac injury markers and levels of ferroptosis markers prostaglandin endoperoxide synthase 2 (PTGS2). Additionally, LPS increased iron deposition in the myocardium, with downregulating ferroportin (FPN, SLC40A1) and transferrin receptor (TfR)expression, and upregulating ferritin light chain (FTL) and ferritin heavy chain (FTH1) expression. Meanwhile, LPS also increased lipid peroxidation in the rat heart by decreasing the expression of glutathione peroxidase 4 (GPX4). Moreover, the expression of inflammatory cytokines, such as tumor necrosis-alpha (TNF-α), interleukin-1 (IL-1β), and interleukin-6 (IL-6), and inflammatory cell infiltration were also increased following LPS challenge. Finally, the abovementioned adverse effects of LPS were relieved by Fer-1 except for TfR expression. Mechanistically, Fer-1 significantly reduced the levels of toll-like receptor 4 (TLR4), phospho-nuclear factor kappa B (NF-κB), and phospho-inhibitor of kappa Bα (IκBα) in LPS-treated rats. In summary, these findings imply that Fer-1 improved sepsis-induced cardiac dysfunction at least partially via the TLR4/NF-κB signaling pathway.

Ferrostatin-1 protects HT-22 cells from oxidative toxicity

Neural Regen Res2020 Mar;15(3):528-536.PMID: 31571665DOI: 10.4103/1673-5374.266060

Ferroptosis is a type of programmed cell death dependent on iron. It is different from other forms of cell death such as apoptosis, classic necrosis and autophagy. Ferroptosis is involved in many neurodegenerative diseases. The role of ferroptosis in glutamate-induced neuronal toxicity is not fully understood. To test its toxicity, glutamate (1.25-20 mM) was applied to HT-22 cells for 12 to 48 hours. The optimal experimental conditions occurred at 12 hours after incubation with 5 mM glutamate. Cells were cultured with 3-12 μM ferrostatin-1, an inhibitor of ferroptosis, for 12 hours before exposure to glutamate. The cell viability was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Autophagy was determined by monodansylcadaverine staining and apoptosis by caspase 3 activity. Damage to cell structures was observed under light and by transmission electron microscopy. The release of lactate dehydrogenase was detected by the commercial kit. Reactive oxygen species were measured by flow cytometry. Glutathione peroxidase activity, superoxide dismutase activity and malondialdehyde level were detected by the appropriate commercial kit. Prostaglandin peroxidase synthase 2 and glutathione peroxidase 4 gene expression was detected by real-time quantitative polymerase chain reaction. Glutathione peroxidase 4 and nuclear factor erythroid-derived-like 2 protein expression was detected by western blot analysis. Results showed that ferrostatin-1 can significantly counter the effects of glutamate on HT-22 cells, improving the survival rate, reducing the release of lactate dehydrogenase and reducing the damage to mitochondrial ultrastructure. However, it did not affect the caspase-3 expression and monodansylcadaverine-positive staining in glutamate-injured HT-22 cells. Ferrostatin-1 reduced the levels of reactive oxygen species and malondialdehyde and enhanced superoxide dismutase activity. It decreased gene expression of prostaglandin peroxidase synthase 2 and increased gene expression of glutathione peroxidase 4 and protein expressions of glutathione peroxidase 4 and nuclear factor (erythroid-derived)-like 2 in glutamate-injured HT-22 cells. Treatment of cultured cells with the apoptosis inhibitor Z-Val-Ala-Asp (OMe)-fluoromethyl ketone (2-8 μM), autophagy inhibitor 3-methyladenine (100-400 μM) or necrosis inhibitor necrostatin-1 (10-40 μM) had no effect on glutamate induced cell damage. However, the iron chelator deferoxamine mesylate salt inhibited glutamate induced cell death. Thus, the results suggested that ferroptosis is caused by glutamate-induced toxicity and that ferrostatin-1 protects HT-22 cells from glutamate-induced oxidative toxicity by inhibiting the oxidative stress.

Ferrostatin-1 alleviates angiotensin II (Ang II)- induced inflammation and ferroptosis in astrocytes

Int Immunopharmacol2021 Jan;90:107179.PMID: 33278745DOI: 10.1016/j.intimp.2020.107179

Background and purpose: Inflammation and ferroptosis in astrocytes can be induced by external injuries, which results in excessive production of inflammatory factors and further injury on neurons. Alleviating ferroptosis might be an effective way to protect the brain from external injuries. The present study aims to explore the protective effects of Ferrostatin-1 against ferroptosis induced by Angiotensin II and the underlying mechanism.
Methods: The mouse primary astrocytes were isolated from the cortices of mice. The astrocytes were stimulated using 10 µM angiotensin II in the presence or absence of 1 or 2 μM Ferrostatin-1. The gene expression levels of AT1R, IL-6, IL-1β, COX-2, GFAP, and GPx4 were evaluated using qRT-PCR. Western Blot was used to determine the protein levels of AT1R, COX-2, GFAP, GPx4, Nrf2, and HO-1 and ELISA was used to detect the concentrations of IL-6, IL-1β, and PGE2. The ROS levels were evaluated using DHE staining and the reduced GSH level was determined using GSH detection kits.
Results: The expression levels of AT1R, IL-6, IL-1β, COX-2, and GFAP in the astrocytes were significantly elevated by stimulation with Ang II and greatly suppressed by the introduction of Ferrostatin-1 in a dose-dependent manner. The promoted ROS level and inhibited GSH level in the astrocytes by the stimulation with Ang II were significantly reversed by Ferrostatin-1. Down-regulated GPx4, Nrf2, and HO-1 in the astrocytes induced by Ang II were extremely up-regulated by the treatment of Ferrostatin-1 in a dose-dependent manner.
Conclusion: Ferrostatin-1 alleviates angiotensin II (Ang II)- induced inflammation and ferroptosis by suppressing the ROS levels and activating the Nrf2/HO-1 signaling pathway.

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