imidazole ketone erastin

Imidazole ketone erastin (IKE) is a potent, metabolically stable small molecule inducer of ferroptosis, a form of iron-dependent regulated cell death. It was developed as an optimized analog of erastin to overcome the latter's poor metabolic stability and solubility, making it suitable for in vivo research and potential therapeutic use. IKE's primary mechanism of action is the inhibition of System xc-, a cystine-glutamate antiporter, by targeting its functional subunit SLC7A11 (also known as xCT). By blocking the uptake of cystine, IKE depletes the intracellular pool of glutathione (GSH), which is a critical cofactor for the antioxidant enzyme glutathione peroxidase 4 (GPX4). The resulting loss of GPX4 activity leads to the uncontrolled accumulation of lipid reactive oxygen species (ROS) and lipid peroxidation, ultimately triggering ferroptotic cell death. IKE is extensively used in preclinical studies to investigate ferroptosis as a strategy for treating various malignancies, including lung, breast, and bladder cancers, as well as for sensitizing tumors to immunotherapy and radiotherapy.

Other names

IKEimidazole-ketone erastin