Erastin

Erastin is a small molecule capable of initiating ferroptotic cell death.^[1] Erastin binds and activates voltage-dependent anion channels (VDAC) by reversing tubulin's inhibition on VDAC2 and VDAC3,^[2] and functionally inhibits the cystine-glutamate antiporter system X_c⁻.^[3] Cells treated with erastin are deprived of cysteine and are unable to synthesize the antioxidant glutathione. Depletion of glutathione eventually leads to excessive lipid peroxidation and cell death.

Erastin

Legal status
Legal status	Experimental
Identifiers
IUPAC name 2-[1-[4-[2-(4-Chlorophenoxy)acetyl]-1-piperazinyl]ethyl]-3-(2-ethoxyphenyl)-4(3H)-Quinazolinone
CAS Number	571203-78-6
PubChem CID	11214940
ChemSpider	9390002
KEGG	C21478
Chemical and physical data
Formula	C30H31ClN4O4
Molar mass	547.05 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C1N(C2=CC=CC=C2OCC)C(C(C)N3CCN(C(COC4=CC=C(Cl)C=C4)=O)CC3)=NC5=CC=CC=C51
InChI InChI=1S/C30H31ClN4O4/c1-3-38-27-11-7-6-10-26(27)35-29(32-25-9-5-4-8-24(25)30(35)37)21(2)33-16-18-34(19-17-33)28(36)20-39-23-14-12-22(31)13-15-23/h4-15,21H,3,16-20H2,1-2H3 Key:BKQFRNYHFIQEKN-UHFFFAOYSA-N

Erastin was first described in 2003. Its name is short for "eradicator of RAS and ST-expressing cells".^[4]

References

1. Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, et al. (May 2012). "Ferroptosis: an iron-dependent form of nonapoptotic cell death". Cell. 149 (5): 1060–1072. doi:10.1016/j.cell.2012.03.042. PMC 3367386. PMID 22632970.
2. Yagoda N, von Rechenberg M, Zaganjor E, Bauer AJ, Yang WS, Fridman DJ, et al. (June 2007). "RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels". Nature. 447 (7146): 864–868. Bibcode:2007Natur.447..865Y. doi:10.1038/nature05859. PMC 3047570. PMID 17568748.
3. Dixon SJ, Patel DN, Welsch M, Skouta R, Lee ED, Hayano M, et al. (May 2014). "Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis". eLife. 3: e02523. doi:10.7554/elife.02523. PMC 4054777. PMID 24844246.
4. Dolma S, Lessnick SL, Hahn WC, Stockwell BR (March 2003). "Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells". Cancer Cell. 3 (3): 285–296. doi:10.1016/S1535-6108(03)00050-3. PMID 12676586.