Imidazole Ketone Erastin is an effective and metabolically stable system xc- inhibitor and ferroptosis inducer. Ferroptosis is a regulated form of cell death that can be induced by inhibiting the cystine-glutamate antiporter system xc- [1].
In vitro, Imidazole Ketone Erastin (0.1 nM-100 µM; 24 h) effectively reduces the number of DLBCL cells by inducing lipid peroxidation and ferroptosis, with 18 DLBCL cell lines displaying varying sensitivities to the inhibition by Imidazole Ketone Erastin [1]. Imidazole Ketone Erastin (1-250 nM; 24 h) depletes reduced glutathione in a dose-dependent manner, with an IC50 of 34 nM in SUDHL 6 cells, and also increases lipid ROS [1].
In vivo, Imidazole Ketone Erastin (23, 40 mg/kg/d; i.p.) inhibits tumor growth in a mouse model of diffuse large B cell lymphoma, leading to a significant reduction in tumor growth and body weight loss starting from day 9 [1]. Imidazole Ketone Erastin (40 mg/kg; i.p.) administered every other day for 22 days to mice with a model of chronic arthritis significantly alleviates symptoms of synovitis and promotes the rapid resolution of inflammation [2].
References:
[1]Zhang, Y., Tan, H., Daniels, J.D., et al. Imidazole ketone erastin induces ferroptosis and slows tumor growth in a mouse lymphoma model. Cell Chem. Biol. 26(5), 623-633 (2019).
[2] TNF antagonist sensitizes synovial fibroblasts to ferroptotic cell death in collagen-induced arthritis mouse models[J]. Nature Communications[2024-03-08].
Imidazole Ketone Erastin是一种有效的、代谢稳定的系统xc- 抑制剂和铁凋亡诱导剂。铁凋亡是一种受调节的细胞死亡形式,其可通过抑制胱氨酸-谷氨酸反向转运蛋白系统xc- 而诱导[1]。
在体外,Imidazole Ketone Erastin (0.1 nM-100 µM; 24 h) 通过诱导脂质过氧化和铁凋亡可以有效减少DLBCL细胞数量,18种DLBCL细胞系均显示出对Imidazole Ketone Erastin抑制的不同敏感性[1]。Imidazole Ketone Erastin(1-250 nM; 24 h)以剂量依赖性方式消耗还原型谷胱甘肽,在SUDHL 6细胞中IC50 为34 nM,还增加脂质ROS[1]。
在体内,Imidazole Ketone Erastin (23, 40 mg/kg/d; i.p.) 抑制弥漫性大 B 细胞淋巴瘤小鼠模型中的肿瘤生长,从第9天开始导致肿瘤生长和体重减轻显着减少[1]。Imidazole Ketone Erastin(40 mg/kg; i.p.)每两天一次对慢性关节炎模型小鼠进行治疗,持续22天,显著减轻了滑膜炎症状,促进了炎症的迅速消退[2]。