Erastin is a small molecule capable of initiating ferroptotic cell death. Erastin binds and activates

voltage-dependent anion channel Voltage-dependent anion channels, or mitochondrial porins, are a class of porin ion channel located on the outer mitochondrial membrane. There is debate as to whether or not this channel is expressed in the cell surface membrane. This major pro ...

s (VDAC) by reversing tubulin's inhibition on

VDAC2 Voltage-dependent anion-selective channel protein 2 is a protein that in humans is encoded by the ''VDAC2'' gene on chromosome 10. This protein is a voltage-dependent anion channel and shares high structural homology with the other VDAC isoforms. ...

and

VDAC3 Voltage-dependent anion-selective channel protein 3 (VDAC3) is a protein that in humans is encoded by the ''VDAC3'' gene on chromosome 8. The protein encoded by this gene is a voltage-dependent anion channel and shares high structural homology wi ...

, and functionally inhibits the cystine-glutamate antiporter system X_c⁻. Cells treated with erastin are deprived of

cysteine Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, sometime ...

and are unable to synthesize the antioxidant

glutathione Glutathione (GSH, ) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources such as reactive oxygen species, free radicals, pero ...

. Depletion of glutathione eventually leads to excessive

lipid peroxidation Lipid peroxidation is the chain of reactions of oxidative degradation of lipids. It is the process in which radical (chemistry), free radicals "steal" electrons from the lipids in cell membranes, resulting in cell damage. This process proceeds by ...

and

cell death Cell death is the event of a biological cell ceasing to carry out its functions. This may be the result of the natural process of old cells dying and being replaced by new ones, as in programmed cell death, or may result from factors such as dis ...

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

References

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