Description

Erastin, named for eradicator of RAS and small T (ST) antigen-expressing cells, is a ferroptosis inducer. It induces ferroptotic cell death in vitro, an effect that can be blocked by the ferroptosis inhibitors ciclopirox olamine, Trolox , ferrostatin-1 , U-0126 , cycloheximide , and β-mercaptoethanol. Erastin (5 μM) inhibits cystine uptake by the system x_c^- cystine-glutamate transporter in HT-1080 fibrosarcoma and Calu-1 lung carcinoma cells and inhibits glutamate release in an enzyme-coupled fluorescence assay (EC₅₀ = 1.2 μM). It also selectively induces cell death in cells expressing the SV40 small T oncoprotein and oncogenic Ras (IC₅₀s = 1.25-5 μg/ml).

Uses

Erastin, named for eradicator of RAS and ST-expressing cells, is an irreversible antitumor agent that selectively kills cells expressing the small T oncoprotein and oncogenic Ras (IC50s = 1.25-5 μg/ml). It produces non-apoptotic tumor cell death by altering mitochondrial voltage-dependent anion channel gating, allowing cations to enter mitochondria and leading to release of oxidative species causing oxidative cell death.[Cayman Chemical]

Uses

Erastin has been used:

• as a positive control for inducing ferroptosis in hepatic stellate cell (HSC)
• to induce ferroptosis and in transferrin internalization assay of human fibrosarcoma HT1080 cells
• to induce ferroptosis of muscle-derived cell lines

Definition

ChEBI: Erastin is a member of the class of quinazolines that is quinazolin-4(3H)-one in which the hydrogens at positions 2 and 3 are replaced by 1-{4-[(4-chlorophenoxy)acetyl]piperazin-1-yl}ethyl and 2-ethoxyphenyl groups, respectively. It is an inhibitor of voltage-dependent anion-selective channels (VDAC2 and VDAC3) and a potent ferroptosis inducer. It has a role as a ferroptosis inducer, an antineoplastic agent and a voltage-dependent anion channel inhibitor. It is a member of quinazolines, a member of monochlorobenzenes, an aromatic ether, a N-acylpiperazine, a N-alkylpiperazine, a diether and a tertiary carboxamide.

General Description

Erastin is a cell-permeable piperazinyl-quinazolinone. It interacts with antiporter system Xc^-.

Biochem/physiol Actions

Erastin is an antitumor agent selective for tumor cells bearing oncogenic RAS (i.e. HRAS, KRAS). Erastin produces ferroptosis, a non-apoptotic tumor cell death, by altering mitochondrial voltage-dependent anion channel (VDAC) gating allowing cations to enter mitochondria and leading to release of oxidative species causing oxidative cell death.

storage

Store at -20°C

References

[1] SONAM DOLMA. Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells.[J]. Cancer Cell, 2003, 3 3: 285-296. DOI:10.1016/s1535-6108(03)00050-3
[2] SCOTT J DIXON. Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis.[J]. ACS Applied Nano Materials, 2014: e02523. DOI:10.7554/elife.02523
[3] MAMI SATO. The ferroptosis inducer erastin irreversibly inhibits system xc- and synergizes with cisplatin to increase cisplatin’s cytotoxicity in cancer cells.[J]. Scientific Reports, 2018: 968. DOI:10.1038/s41598-018-19213-4
[4] NICHOLAS YAGODA. RAS–RAF–MEK-dependent oxidative cell death involving voltage-dependent anion channels[J]. Nature, 2007, 447 7146: 865-869. DOI:10.1038/nature05859