Erastin
Erastin is a cell-permeable ferroptosis activatior and an antitumor agent that is selective for cell expressing oncogene RAS.
Ferroptosis is a unique iron-dependent form of nonapoptotic cell death. It is triggered by oncogenic RAS-selective lethal small molecule erastin. Acitvation of ferroptosis lead to nonapoptotic destruction of cancer cells.
In BJ-TERT/LT/ST/RASV12 cells, Erastin activated a rapid, oxidative and non-apoptotic cell death process. It exerted lethality in human cancer cells with HRAS, KRAs or BRAF oncogenic mutation involving the RAS-RAF-MEF pathway and acted via modulating VDAC (volatage-dependent anion channels). [1] In HT 1080 cells, Erastin-induced death triggered the cytosolic ROS accumulation and the induced oxidative death was iron dependent. Erastin also inhibited the activity of independent cystine/glutamate antiporter, system xc−. [2]
References:
[1] Yagoda N, von Rechenberg M, Zaganjor E, Bauer AJ, Yang WS, Fridman DJ, Wolpaw AJ, Smukste I, Peltier JM, Boniface JJ, Smith R, Lessnick SL, Sahasrabudhe S, Stockwell BR. RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels. Nature. 2007 Jun 14;447(7146):864-8.
[2] Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, Morrison B 3rd, Stockwell BR. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012 May 25;149(5):1060-72.
- 1. Xin Li, Yanan Hu, et al. "Exosomal let-7a-5p derived from human umbilical cord mesenchymal stem cells alleviates coxsackievirus B3-induced cardiomyocyte ferroptosis via the SMAD2." J Zhejiang Univ Sci B. 2024 May 15;25(5):422-437. PMID: 38725341
- 2. Elizabeth Jose, Woody March-Steinman, et al. "Temporal coordination of the transcription factor response to H2O2 stress." Nat Commun. 2024 Apr 23;15(1):3440. PMID: 38653977
- 3. Chenyang Fan, Xiaohong Guo, et al. "BRD4 inhibitors broadly promote erastin-induced ferroptosis in different cell lines by targeting ROS and FSP1." Discov Oncol. 2024 Apr 3;15(1):98. PMID: 38565708
- 4. Chen-Yi Wang, Mu-Yu Li, et al. "Rack1‐mediated ferroptosis affects hindgut development in rats with anorectal malformations: Spatial transcriptome insights." Cell Prolif. 2024 Mar 25:e13618. PMID: 38523594
- 5. Miaomiao Shao, Kangwei Qi, et al. "E3 ubiquitin ligase CHIP interacts with transferrin receptor 1 for degradation and promotes cell proliferation through inhibiting ferroptosis in hepatocellular carcinoma." Cell Signal. 2024 Jun:118:111148. PMID: 38521179
- 6. Hong-Feng Gu, et al. "A* ameliorates cognitive decline by inhibiting hippocampal neuronal ferroptosis via Nrf2 activation in T2DM mice." Mol Med. 2024 Mar 7;30(1):35. PMID: 38454322
- 7. Charles C. Hong, et al. "GPR68-ATF4 signaling is a novel prosurvival pathway in glioblastoma activated by acidic extracellular microenvironment." Exp Hematol Oncol. 2024 Jan 31;13(1):13. PMID: 38291540
- 8. Zhi-Jun Ou, et al. "The oxidized phospholipid PGPC impairs endothelial function by promoting endothelial cell ferroptosis via FABP3." J Lipid Res. 2024 Feb;65(2):100499. PMID: 38218337
- 9. Yang Wang, Hongmei Ding, et al. "Alleviated NCOA4-mediated ferritinophagy protected RA FLSs from ferroptosis in lipopolysaccharide-induced inflammation under hypoxia." Inflamm Res. 2024 Mar;73(3):363-379. PMID: 38189810
- 10. Krishan Kumar Saini, Priyank Chaturvedi, et al. "Loss of PERK function promotes ferroptosis by downregulating SLC7A11 (System Xc⁻) in colorectal cancer." Redox Biol. 2023 Sep;65:102833. PMID: 37536085
- 11. Qingyu Zhang, Ning Li, et al. "ACSL1-induced ferroptosis and platinum resistance in ovarian cancer by increasing FSP1 N-myristylation and stability." Cell Death Discov. 2023 Mar 8;9(1):83. PMID: 36882396
- 12. Dong S, Zheng L, et al. "Loss of Lactate/Proton Monocarboxylate Transporter 4 Induces Ferroptosis via the AMPK/ACC Pathway and Inhibition of Autophagy on Human Bladder Cancer 5637 Cell Line" J Oncol 2023;2023 PMID: 36718218
- 13. Li J, Li W, et al. "Development and validation of a novel ferroptosis‑related lncRNA prognostic signature for pancreatic adenocarcinoma." Mol Med Rep 2023 Feb;27(2) PMID: 36660936
- 14. Yang Liu, Libo He, et al. "Pharmacological inhibition of sphingolipid synthesis reduces ferroptosis by stimulating the HIF-1 pathway." iScience. 2022 Jun 6;25(7):104533. PMID: 35784791
- 15. Weilin Liu, Hongqi Chen, et al. "Ferroptosis Inducer Improves the Efficacy of Oncolytic Virus-Mediated Cancer Immunotherapy." Biomedicines. 2022 Jun 15;10(6):1425. PMID: 35740445
- 16. Xinxin Ren, Xiang Wang, et al. "Integrative bioinformatics and experimental analysis revealed TEAD as novel prognostic target for hepatocellular carcinoma and its roles in ferroptosis regulation." Aging (Albany NY). 2022 Jan 25;14(2):961-974. PMID: 35077390
- 17. Zixin Zhu, Ya Zhang, et al. "Thymosin beta 4 alleviates non-alcoholic fatty liver by inhibiting ferroptosis via up-regulation of GPX4." Eur J Pharmacol. 2021 Oct 5;908:174351. PMID: 34280397
- 18. Zongbo Wei, Caili Hao, et al. "Aging lens epithelium is susceptible to ferroptosis." Free Radic Biol Med. 2021 May 1;167:94-108. PMID: 33722625
- 19. Xinzhi Yang, Jiangang Liu, et al. "miR-18a promotes glioblastoma development by down-regulating ALOXE3-mediated ferroptotic and anti-migration activities." Oncogenesis. 2021 Feb 12;10(2):15. PMID: 33579899
- 20. Ali Ghoochani, En-Chi Hsu, et al. "Ferroptosis inducers are a novel therapeutic approach for advanced prostate cancer." Cancer Res. 2021 Mar 15;81(6):1583-1594. PMID: 33483372
- 21. Zhijun Liu, Himani Nailwal, et al. "A class of viral inducer of degradation of the necroptosis adaptor RIPK3 regulates virus-induced inflammation." Immunity. 2021 Feb 9;54(2):247-258.e7. PMID: 33444549
- 22. Qi Wang, Yaxun Guo, et al. "RNA binding protein DAZAP1 promotes HCC progression and regulates ferroptosis by interacting with SLC7A11 mRNA." Exp Cell Res. 2021 Feb 1;399(1):112453. PMID: 33358859
- 23. Hu Z, Zhang H, et al. "VDR activation attenuate cisplatin induced AKI by inhibiting ferroptosis." Cell Death Dis. 2020;11(1):73. Published 2020 Jan 29. PMID: 31996668
- 24. Zhou HH, Chen X, et al. "Erastin Reverses ABCB1-Mediated Docetaxel Resistance in Ovarian Cancer." Front Oncol, 9, 1398 2019 Dec PMID: 31921655
- 25. Wang H, Liu C, et al. "Inhibition of LONP1 protects against erastin-induced ferroptosis in Pancreatic ductal adenocarcinoma PANC1 cells." Biochem Biophys Res Commun. 2019 Dec 7. pii: S0006-291X(19)32315-0. PMID: 31822343
| Physical Appearance | A solid |
| Storage | Store at -20°C The product is not stable in solution, please dissolve it immediately before use. |
| M.Wt | 547.04 |
| Cas No. | 571203-78-6 |
| Formula | C30H31ClN4O4 |
| Solubility | insoluble in H2O; insoluble in EtOH; ≥10.92 mg/mL in DMSO with gentle warming |
| Chemical Name | 2-[1-[4-[2-(4-chlorophenoxy)acetyl]piperazin-1-yl]ethyl]-3-(2-ethoxyphenyl)quinazolin-4-one |
| SDF | Download SDF |
| Canonical SMILES | O=C1N(C2=CC=CC=C2OCC)C(C(N3CCN(C(COC4=CC=C(Cl)C=C4)=O)CC3)C)=NC5=C1C=CC=C5 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1, 2]: | |
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Cell lines |
Engineered human tumour cells (BJ-TERT/LT/ST/RAS V12 cells), HT-1080 fibrosarcoma cell line |
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Preparation method |
The solubility of this compound in DMSO is >27.4mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
10 μM, 24h, |
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Applications |
Erastin activates a rapid, oxidative, non-apoptotic cell death process. Erastin exhibits greater lethality in human tumour cells harbouring mutations in the oncogenes HRAS, KRAS or BRAF. Erastin treatment of cells harbouring oncogenic RAS causes the appearance of oxidative species and subsequent death through an oxidative, non-apoptotic mechanism. 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 |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Yagoda N, von Rechenberg M, Zaganjor E, Bauer AJ, Yang WS, Fridman DJ, Wolpaw AJ, Smukste I, Peltier JM, Boniface JJ, Smith R, Lessnick SL, Sahasrabudhe S, Stockwell BR. RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels. Nature. 2007 Jun 14;447(7146):864-8. [2] Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, Morrison B 3rd, Stockwell BR. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012 May 25;149(5):1060-72. |
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Quality Control & MSDS
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