Imidazole ketone erastin

Imidazole ketone erastin is a potent, selective, and metabolically stable inhibitor of the cystine-glutamate antiporter, system x_c^- and an activator of ferroptosis. Imidazole ketone erastin has anti-tumor activity^[1]. IC50 & Target:System X_c^-, ferroptosis^[1] In Vitro:Imidazole ketone erastin (IKE) (0.1 nM-100 μM; 24 h) potently reduces diffuse large B cell lymphoma (DLBCL) cell number by lipid peroxidation and ferroptosis^[1].
IKE (1-250 nM; 24 h) depletes reduced glutathione (GSH) in a dose-dependent manner with an IC₅₀ of 34 nM in SUDHL6 cells^[1].
IKE (125-500 nM) increases lipid ROS in a dose-dependent manner in SUDHL-6 cells^[1].
IKE (500 nM; 5-360 min) increases the system x_c component SLC7A11, prostaglandin-endoperoxide synthase 2 (PTGS2), and ChaC glutathione-specific gamma-glutamylcyclotransferase 1 (CHAC1) expression in SUDHL-6 cells^[1].
IKE (500 nM and 1 μM) changes the relative abundance of 62 lipid species including lysophosphatidylcholines (LPC), phosphatidylcholines (PC), phosphatidylethanolamines (PE), and triglycerides (TAGs) in SUDHL6 cells^[1].
IKE (500 nM) activates de novo lipid biosynthesis pathways, phospholipid remodeling pathways, and arachidonic acid oxidation pathways in SUDHL6 cells^[1]. In Vivo:IKE (23-40 mg/kg; i.p. once daily for 13 d) inhibits tumor growth in mice^[1].
IKE (50 mg/kg; a single i.p) depletes GSH significantly starting from 4 h, and increases in the relative abundance of free fatty acids, phospholipids, and diacylglycerols (DAG) in mice^[1].
IKE (50 mg/kg) exhibits half-life (1.82, 1.31, and 0.96 h) and C_max (19515, 11384, and 5203 ng/mL) following different administration (i.p., i.v., and p.o. respectively) in mice^[1].