Table 2 Action mechanism of ferroptosis activators

Targeting MAPK signaling pathway

Lapatinib + Siramesine

Blocking iron transport and increasing intracellular unstable iron, leading to increased ROS.

[118]

Vorinostat

Inhibits system Xc⁻ activity, affects GSH synthesis, enhances the effect of ferroptosis inducers.

[119]

Cetuximab + β-elemene

ROS accumulation, GSH depletion.

[120]

Targeting AMPK signaling pathway

DHA

Accelerate the degradation of ferritin, increase the content of unstable iron pool, promote the accumulation of ROS in AML cells and ultimately lead to ferroptosis.

[121, 122]

IMCA

Inhibits system Xc⁻ activity, affects GSH synthesis, and leads to ROS accumulation.

[91]

Targeting system Xc-

sorafenib

Inhibits system Xc⁻ activity, affects GSH synthesis, and leads to ROS accumulation.

[17, 123]

erastin

Inhibits system Xc⁻ activity, affects GSH synthesis, and leads to ROS accumulation.

[16]

PE

Inhibits system Xc- activity, affects GSH synthesis, and leads to ROS accumulation.

[14]

IKE

Inhibits system Xc⁻ activity, affects GSH synthesis, and leads to ROS accumulation.

[124]

SAS

Inhibits system Xc⁻ activity, affects GSH synthesis, and leads to ROS accumulation.

[122, 125]

LP

Inhibits system Xc⁻ activity, affects GSH synthesis, and leads to ROS accumulation.

[126]

Glutamate

Inhibits system Xc⁻ activity, affects GSH synthesis, and leads to ROS accumulation.

[2]

Ibuprofen

Inhibits system Xc⁻ activity, affects GSH synthesis, and leads to ROS accumulation.

[127]

Targeting GPX4

RSL3

Covalently binding GPX4 at the selenocysteine site to inactivates GPX4.

[10, 128]

FIN56

Induces GPX4 degradation, binds to and activates SQS resulting in loss of CoQ10.

[14]

Targeting p53

APR-246

Induce ferroptosis in cells by disrupting the GSH/ROS balance.

[129]

ART

Increases iron levels and accumulation of lipid peroxidation products, reduces GSH content.

[130, 131]