Erastin Explained

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

Notes and References

1. Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, Morrison B, Stockwell BR . 6 . Ferroptosis: an iron-dependent form of nonapoptotic cell death . Cell . 149 . 5 . 1060–1072 . May 2012 . 22632970 . 3367386 . 10.1016/j.cell.2012.03.042 .
2. 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 . 6 . RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels . Nature . 447 . 7146 . 864–868 . June 2007 . 17568748 . 3047570 . 10.1038/nature05859 . 2007Natur.447..865Y .
3. Dixon SJ, Patel DN, Welsch M, Skouta R, Lee ED, Hayano M, Thomas AG, Gleason CE, Tatonetti NP, Slusher BS, Stockwell BR . 6 . Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis . eLife . 3 . e02523 . May 2014 . 24844246 . 4054777 . 10.7554/elife.02523 . free .
4. Dolma S, Lessnick SL, Hahn WC, Stockwell BR . Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells . Cancer Cell . 3 . 3 . 285–296 . March 2003 . 12676586 . 10.1016/S1535-6108(03)00050-3 . free .