GPX4-IN-14 (compound 2c) acts as a GPX4 inhibitor, exhibiting both free radical scavenging activity (with a maximum scavenging rate of 72.52%) and anti-tumor proliferation activity in vitro. This compound targets GPX4 protein, elevating lipid peroxide and intracellular Reactive Oxygen Species (ROS) levels, which induces ferroptosis and contributes to its anti-tumor proliferation effects.

GPX4-IN-14 (100 μM, 30 min) 展现出了72.52%的最高自由基清除效率。对于多种肿瘤细胞如SW480、HCT116、HepG2和MCF-7，GPX4-IN-14显示出显著的抗增殖作用，其IC 50 分别为5.61 μM，6.59 μM，18.23 μM和9.73 μM;而对LO2细胞的IC 50 则为11.64 μM。此外，GPX4-IN-14 (3.3, 6.6, 13.2 μM, 24 h) 在HCT116细胞中通过剂量依赖方式抑制GPX4通路，并诱导细胞内ROS及脂质ROS的积累，导致铁死亡并抑制线粒体膜电位。同样的实验条件下，该化合物还使HCT116细胞内铁水平呈剂量依赖性增高。