piperazine erastin

Piperazine erastin is a more soluble and metabolically stable analogue of erastin, a pioneering small-molecule inducer of ferroptosis. It functions by inhibiting the cystine/glutamate transporter (System Xc-), specifically targeting the SLC7A11 subunit. This inhibition prevents the uptake of cystine, a critical precursor for glutathione (GSH) synthesis, leading to the depletion of intracellular GSH and the subsequent inactivation of glutathione peroxidase 4 (GPX4). The resulting accumulation of iron-dependent lipid peroxides triggers ferroptotic cell death. Developed to overcome the poor pharmacological properties of erastin, piperazine erastin is widely used in preclinical oncology research to study ferroptosis sensitivity in various cancers, including lymphoma and renal cell carcinoma. It has also been utilized as a tool to identify ferroptosis-specific biomarkers, such as the transferrin receptor (TfR1). However, its efficacy can be compromised by the multidrug resistance transporter P-glycoprotein (P-gp), which recognizes it as a substrate and can confer resistance.

Other names

PEerastin-piperazine