Ferrostatin-1

Biological Activity

Ferrostatin-1 (Fer-1) is a potent and selective inhibitor of ferroptosis with EC50 of 60 nM. Ferrostatin-1 (2 μM) prevents erastin-induced ferroptosis in cancer cells, as well as glutamate-induced cell death in postnatal rat brain slices. Ferrostatin-1 is a lipid ROS scavenger, with the N-cyclohexyl moiety serving as a lipo-philic anchor within biological membranes. Ferrostatin-1 does not inhibit extracellular signal -regulated kinase (ERK) phos-phorylation or arrest the proliferation of HT-1080 cells, suggesting that it does not inhibit the MEK/ERK pathway, chelate iron, or inhibit protein synthesis. Ferrostatin-1 does, however, prevent erastin-induced accumulation of cytosolic and lipid ROS. Ferrostatin-1 readily oxidizes the stable radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) under cell-free conditions.

Product Citations

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  Toxicol Appl Pharmacol. 2024 Jan;116825.

  Anti-NOTCH1 therapy with OMP-52 M51 inhibits salivary adenoid cystic carcinoma by depressing epithelial-mesenchymal transition (EMT) process and inducing …
  Ferrostatin-1 purchased from AbMole

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  Oxid Med Cell Longev. 2023 Jan 14;2023:6896790.

  Curcumin Induces Ferroptosis in Follicular Thyroid Cancer by Upregulating HO-1 Expression
  Ferrostatin-1 purchased from AbMole

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  Cancer Cell Int. 2023 Jan 13;23(1):5.

  Heat shock protein 27 deficiency promotes ferrous ion absorption and enhances acyl-Coenzyme A synthetase long-chain family member 4 stability to promote
  Ferrostatin-1 purchased from AbMole

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  Apoptosis. 2023 Apr;28(3-4):607-626.

  Inhibition of ferroptosis by icariin treatment attenuates excessive ethanol consumption-induced atrial remodeling and susceptibility to atrial fibrillation, role of SIRT1
  Ferrostatin-1 purchased from AbMole

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  J Cancer Res Clin Oncol. 2023 Apr 29.

  Apatinib combined with olaparib induces ferroptosis via a p53-dependent manner in ovarian cancer
  Ferrostatin-1 purchased from AbMole

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  Oxid Med Cell Longev. 2022 Apr 16;2022:4505513.

  Nrf2-Mediated Ferroptosis Inhibition Exerts a Protective Effect on Acute-on-Chronic Liver Failure
  Ferrostatin-1 purchased from AbMole

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  Food Funct. 2022 Oct 3;13(19):10210-10224.

  Vitamin D3 Attenuates Cisplatin-Induced Intestinal Injury by Inhibiting Ferroptosis, Oxidative Stress, and ROS-mediated Excessive Mitochondrial Fission
  Ferrostatin-1 purchased from AbMole

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  Food Chem Toxicol. 2022 Jun;164:113046.

  DEHP induces ferroptosis in testes via p38α-lipid ROS circulation and destroys the BTB integrity
  Ferrostatin-1 purchased from AbMole

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  Anat Rec (Hoboken). 2020 Jan 21.

  Resibufogenin inhibited colorectal cancer cell growth and tumorigenesis through triggering ferroptosis and ROS production mediated by GPX4 inactivation
  Ferrostatin-1 purchased from AbMole

Protocol (for reference only)

Cell Experiment
Cell lines	BEAS-2B cells
Preparation method	Cell viability assay In brief, BEAS-2B cells were seeded into a 96-well plate at the concentration of 5 × 104 cells/well. The cells were cultured for 24 h, then treated with LPS (Sigma) and Fer-1 (Sigma) in different concentrations for 16 h followed by the addition of 20 μl of CCK-8 solution directly into the medium (200 μl per well) and incubation at 37 °C for 4 h. The absorbances (Abs) in different groups were detected at 450 nm (n = 3). In the blank group, the well only contained medium, and the cells without any treatment were used as the control group. Herein, the cell viability = (Abs of experimental group-Abs of blank group)/(Abs of control group-Abs of blank group) × 100%.
Concentrations	2 μM
Incubation time	16 h

Animal Experiment
Animal models	male C57BL/6 mice
Formulation	The Fer-1 was dissolved in DMSO first, and diluted with 0.9% NaCl. The final concentration of Fer-1 and DMSO was 0.2 mg/ml and 0.1% respectively.
Dosages	0.8 mg/kg
Administration	via tail vein injection

Chemical Information

Molecular Weight	262.35
Formula	C15H22N2O2
CAS Number	347174-05-4
Solubility (25°C)	DMSO ≥ 50 mg/mL
Storage	-20°C, protect from light, dry, sealed

Conversion of different model animals based on BSA (PMID: 27057123)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Wanting Shu, et al. Redox Biol. Ferrous but not ferric iron sulfate kills photoreceptors and induces photoreceptor-dependent RPE autofluorescence

[2] Pengfei Liu, et al. Cell Mol Biol Lett. Ferrostatin-1 alleviates lipopolysaccharide-induced acute lung injury via inhibiting ferroptosis