Ferroptosis is a form of regulated cell death, distinct from apoptosis, necroptosis and autophagy. It is an iron-dependent process that results from the loss of glutathione peroxidase 4 (GPX4) activity, leading to accumulation of lipid peroxidation products and reactive oxygen species (ROS).

Literature (5)
Pathways (1)

Ferroptosis Inhibitors

Cat. No. Product Name / Activity
1761 Baicalein
Inhibits ferroptosis; 5- and 1-lipoxygenase inhibitor
0970 Cycloheximide
Inhibitor of ferroptosis; inhbits protein synthesis
5245 Ebselen
Inhibitor of ferroptosis; glutathione peroxidase mimic
5180 Ferrostatin 1
Selective inhibitor of erastin induced ferroptosis
7162 iFSP1
Ferroptosis inducer; inhibits ferroptosis suppressor protein 1 (FSP1)
6113 Liproxstatin-1 hydrochloride
Potent ferroptosis inhibitor
2850 PD 146176
Inhibits ferroptosis; selective 15-lipoxygenase inhibitor
6002 Trolox
Inhibitor of ferroptosis; antioxidant
3308 Zileuton
Inhibits ferroptosis; 5-LOX inhibitor

Ferroptosis Activators

Cat. No. Product Name / Activity
5449 Erastin
Ferroptosis activator; also mitochondrial VDAC modulator
6280 FIN 56
Ferroptosis activator
0218 L-Glutamic acid
Induces ferroptosis; endogenous, non-selective agonist
6954 L-Buthionine sulfoximine
Induces ferroptosis by inhibiting glutathione synthesis
6429 ML 210
Induces ferroptosis in tumor initiation cells; glutathione peroxidase inhibitor
6118 1S,3R-RSL3
Induces ferroptosis; inhibits glutathione peroxidase 4 (GPX4)
1965 Simvastatin
Induces ferroptosis; also HMG-CoA reductase inhibitor
6814 Sorafenib
Induces ferroptosis; also Raf-1, VEGFR-2, VEGFR-3, PDGFR-β, Flt-3 and cKIT inhibitor
4935 Sulfasalazine
Ferroptosis inducer; cystine-glutamate antiporter inhibitor and inhibitor of NF-κB activation


Cat. No. Product Name / Activity
6687 1R,3R-RSL3
Negative control for 1S,3R-RSL3 (Cat. No. 6118)

Ferroptosis is a form of regulated cell death, distinct from apoptosis, necroptosis and autophagy. It is an iron-dependent process that results from the loss of glutathione peroxidase 4 (GPX4) activity, leading to accumulation of lipid peroxidation products and reactive oxygen species (ROS).

GPX4 is a selenoprotein that reduces hydrogen peroxide and lipid peroxides, while converting reduced glutathione (GSH) to its oxidized form; oxidized glutathione (glutathione disulfide) is recycled by glutathione reductase and NADPH/H+. Depletion of GSH leads to the inactivation of GPX4 with the resultant accumulation of ROS from lipid peroxidation and subsequent ferroptosis. GPX4 inactivation also causes depletion of arachidonic acid and polyunsaturated fatty acids and this also promotes ferroptosis.

Molecular Pathways of Ferroptosis Regulation

Molecular Pathways of Ferroptosis Regulation

Figure 1: Molecular Pathways of Ferroptosis Regulation. DMT1, Divalent metal transporter 1; Glu, Glutamate; GPX4, Glutathione peroxidase 4; GSH, Glutathione; HMG-CoA, 3-hydroxy-3-methyl-glutaryl-CoA reductase; IPP, Isopentenyl pyrophosphate; ROS, Reactive oxygen species; Se, Selenocysteine; System xc-, glutamate/cystine antiporter; TFR1, membrane protein transferrin receptor 1.

Adapted from Yang and Stockwell (2016) Trends Cell Biol. 26 165.

The mevalonate pathway is an important regulator of ferroptosis, as the synthesis of selenoproteins, such as GPX4, is dependent on isopentenyl pyrophosphate, a product of the mevalonate pathway. Isopentenyl pyrophosphate acts as a donor in the incorporation of selenocysteine into selenoproteins by the enzyme tRNA isopentenyl transferase. The glutamate/cysteine antiporter (system Xc-) is also an important regulator of ferroptosis. Inhibition of this transporter, by increased extracellular glutamate for example, depletes the intracellular pool of cysteine, which is a precursor of glutathione synthesis. This in turn depletes glutathione leading to inhibition of GPX4. The MAPK pathway may also have role in ferroptosis regulation.

While iron is a requirement for ferroptosis, its role in the process is not fully understood. It has been proposed that iron-containing enzymes associated with lipid redox regulation are activated during ferroptosis. Excessive iron contributes to ferroptosis, while iron chelators inhibit Erastin-induced ferroptosis.

Ferroptotic cells appear rounded, with no rupture of cell membranes. Mitochondria are smaller than normal, have dense mitochondrial membranes and lack cristae, while the nucleus appears normal. Ferroptosis is involved in many physiological and pathological processes including cancer cell death, neurotoxicity, neurodegenerative disease, acute kidney disease and T-cell immunity, among others. Inhibition of ferroptosis therefore offers a potential therapeutic approach for a variety of conditions.

Literature for Ferroptosis

Tocris offers the following scientific literature for Ferroptosis to showcase our products. We invite you to request* your copy today!

*Please note that Tocris will only send literature to established scientific business / institute addresses.

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