Erastin is a ferroptosis activator acting on mitochondrial VDAC. It induces ferroptotic cell death in vitro.

Treatment of NRAS-mutant HT-1080 fibrosarcoma cells with the RSL molecule erastin (10 μM) resulted in a time-dependent increase in cytosolic and lipid ROS beginning at 2 hours [1]. A lung carcinoma cell line (Calu-1) with an activating mutation in KRAS was sensitive to erastin (IC50 = 4 μM); when infected with lentiviral constructs expressing two different shRNAs targeting KRAS, these cells exhibited resistance to erastin [2]. Erastin exerted potent cytotoxic effects against multiple human colorectal cancer cell lines, possibly via inducing oxidative stress and caspase-9 dependent cell apoptosis. Further, mitochondrial permeability transition pore (mPTP) opening was observed in erastin-treated cancer cells [3].

Intraperitoneal injection of erastin at well-tolerated doses dramatically inhibited HT-29 xenograft growth in severe combined immunodeficient (SCID) mice [3].

BJeLR cells were plated at 100,000 cells/dish in 35 mm tissue culture dishes. After 12h cells were treated with vehicle (DMSO; 10 hrs), erastin (37 μM; 10 hrs), staurosporine (750 nM; 8 hrs), hydrogen peroxide (16 mM; 1 hr) or rapamycin (100 nM; 24 hrs). Cells were fixed with 2.5% glutaraldehyde in 0.1 M Sorenson's buffer (0.1 M H2PO4, 0.1 M HPO4 (pH 7.2)) for at least 1 h, and then treated with 1% OsO4 in 0.1 M Sorenson's buffer for 1 h. Enblock staining used 1% tannic acid. After dehydration through an ethanol series, cells were embedded in Lx-112 and Embed-812 (EMS). Thin sections were cut on an MT-7000 ultramicrotome, stained with 1% uranyl acetate and 0.4% lead citrate, and examined under a Jeol JEM-1200 EXII electron microscope. Pictures were taken on an ORCA-HR digital camera at 5,000-50,000-fold magnification [1].

Tumor growth studies were performed in severe combined immunodeficient (SCID) mice xenograft model. Briefly, 2×10^6 viable HT-29 cells in 100 μL of growth medium (per mouse) were subcutaneously inoculated, and mice bearing ~100 mm3 tumors were randomly divided into three groups with 10 mice per group. Mice were treated daily with 10 or 30 mg/kg body weight of erastin (intraperitoneal injection, for 4 weeks) or vehicle control (Saline). Tumor volumes were calculated by the modified ellipsoid formula: (π / 6) ×AB2, where A is the longest and B is the shortest perpendicular axis of a tumor mass. Mice body weights were also recorded every week. Humane endpoints were always utilized to minimize mice suffering. Animals were observed on daily bases. Signs such as significant-reduced locomotion, severe diarrhea, severe piloerection or a sudden weight loss (> 20%) were recorded. If animals reached these endpoints they were euthanized by exsanguination under 2,2,2-tribromoethanol anesthesia (4 mg/10 g body weight). All injections were performed under the 2,2,2-tribromoethanol anesthesia method [3].

571203-78-6

C30H31ClN4O4

547.05

Erastin

[1]Yagoda N, et al. RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels. Nature. 2007 Jun 14;447(7146):864-8. [2]Dixon SJ, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012 May 25;149(5):1060-72. [3]Li H, Shi W, Li X, et al. Ferroptosis is Accompanied by? OH Generation and Cytoplasmic Viscosity Increase Revealed via Dual-Functional Fluorescence Probe[J]. Journal of the American Chemical Society. 2019. [4]Yan B, Ai Y, Sun Q, et al. Membrane Damage during Ferroptosis Is Caused by Oxidation of Phospholipids Catalyzed by the Oxidoreductases POR and CYB5R1[J]. Molecular Cell. 2020 [5]Huo H, et al. Erastin Disrupts Mitochondrial Permeability Transition Pore (mPTP) and Induces Apoptotic Death of Colorectal Cancer Cells. PLoS One. 2016 May 12;11(5):e0154605. [6]Wu Z, Geng Y, Lu X, et al. Chaperone-mediated autophagy is involved in the execution of ferroptosis[J]. Proceedings of the National Academy of Sciences. 2019 Feb 19;116(8):2996-3005.

[1]Yan R, Xie E, Li Y, et al. The structure of erastin-bound xCT–4F2hc complex reveals molecular mechanisms underlying erastin-induced ferroptosis. Cell Research. 2022-32（7）P1-4 [2]Zheng Y, Kong F, Liu S, et al. Membrane protein-chimeric liposome-mediated delivery of triptolide for targeted hepatocellular carcinoma therapy. Drug delivery. 2021 [3]Zhou Y, Wu H, Wang F, et al. GPX7 Is Targeted by miR-29b and GPX7 Knockdown Enhances Ferroptosis Induced by Erastin in Glioma. Frontiers in oncology. 2021, 11: 802124-802124. [4]Tan Q, Fang Y, Peng X, et al. A new ferroptosis inhibitor, isolated from Ajuga nipponensis, protects neuronal cells via activating NRF2-antioxidant response elements (AREs) pathway. Bioorganic Chemistry. 2021: 105177. [5]Zhu, Lizhe, et al. A novel ferroptosis-related gene signature for overall survival prediction in patients with breast cancer. Frontiers in Cell and Developmental Biology. 9 (2021) [6]Ning X, Qi H, Yuan Y, et al. Identification of a new small molecule that initiates ferroptosis in cancer cells by inhibiting the system Xc? to deplete GSH. European Journal of Pharmacology. 2022: 175304. [7]Kong R, Wang N, Han W, et al. IFNγ‐mediated repression of system xc? drives vulnerability to induced ferroptosis in hepatocellular carcinoma cells. Journal of Leukocyte Biology. 2021, 110(2): 301-314. [8]Kong R, Wang N, Han W, et al. IFNγ‐mediated repression of system xc? drives vulnerability to induced ferroptosis in hepatocellular carcinoma cells. Journal of Leukocyte Biology. 2021, 110(2): 301-314. [9]Peng X, Tan Q, Wu L, et al. Ferroptosis Inhibitory Aromatic Abietane Diterpenoids from Ajuga decumbens and Structural Revision of Two 3, 4-Epoxy Group-Containing Abietanes. Journal of Natural Products. 2022 [10]Yan B, Ai Y, Sun Q, et al. Membrane Damage during Ferroptosis Is Caused by Oxidation of Phospholipids Catalyzed by the Oxidoreductases POR and CYB5R1. Molecular Cell. 2020

Ethanol:<1 mg/mL
H2O:<1 mg/mL
DMSO:16 mg/mL (29.2 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years