2-[1-[4-[2-(4-Chlorophenoxy)acetyl]-1-piperazinyl]ethyl]-3-(2-ethoxyphenyl)-4(3H)-Quinazolinone Property

Boiling point:

721.9±70.0 °C(Predicted)

Density 

1.28±0.1 g/cm3(Predicted)

storage temp. 

-20°C

solubility 

DMSO: soluble5mg/mL, clear (warmed)

form 

White solid

pka

5.54±0.10(Predicted)

color 

white to beige

Stability:

Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.

CAS DataBase Reference

571203-78-6

Safety

Hazard Codes 

T

Risk Statements 

25

Safety Statements 

45

RIDADR 

UN 2811 6.1/PG 3

WGK Germany 

3

HS Code 

2933599590

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

2-[1-[4-[2-(4-Chlorophenoxy)acetyl]-1-piperazinyl]ethyl]-3-(2-ethoxyphenyl)-4(3H)-Quinazolinone Chemical Properties,Usage,Production

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 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

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]

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) Dolma et al. (2003), Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells; Cancer Cell, 3 285 2) Dixon et al. (2014), Pharmacological inhibition of cysteine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis; Elife, 3 e02523 3) Sato et al. (2018), The ferroptosis inducer erastin irreversibly inhibits system xc-and synergizes with cisplatin to increase cisplatin’s cytotoxicity in cancer cells; Sci. Rep., 8 968 4) Yagoda et al. (2007), RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels; Nature, 447 864