Ferroptosisinducer-8 is a ferroptosis (iron-dependent cell death) inducer with high selectivity against other cell death pathways. It induces ferroptosis by affecting ACSL4, GPX4, and FTH1, disrupting intracellular iron homeostasis and the GSH/GPX4 antioxidant defense system, leading to the accumulation of lipid peroxides. Ferroptosisinducer-8 also stimulates ROS production and can inhibit tumor growth, making it useful for research in triple-negative breast cancer (TNBC).

Ferroptosis inducer-8, also known as Compound B23, interacts with GPX4, reducing its thermal stability. This compound exhibits cytotoxicity in tumor cells over 48 hours, with IC50 values of 0.08 μM for MCF-7, 0.04 μM for MDA-MB-231, 0.04 μM for MDA-MB-468, 0.05 μM for HT29, 2.81 μM for A549, 0.06 μM for MPC-3, and 2.23 μM for normal cells (MCF-10A). At 1 μM over 48 hours, Ferroptosis inducer-8 selectively induces ferroptosis in MDA-MB-231 and MDA-MB-468 cells, instead of other cell death mechanisms such as apoptosis, necrosis, or autophagy. Additionally, at concentrations of 20-60 nM for 7 hours, it induces iron metabolism disorders, enhances lipid peroxidation, and stimulates reactive oxygen species (ROS) production in MDA-MB-231 cells over 10 hours. When used at 20-60 nM for 8 hours, it upregulates the expression of ACSL4 and downregulates FTH1 and GPX4 expressions in MDA-MB-231 cells.

Ferroptosis inducer-8, administered intravenously at a dose of 1-4 mg/kg once daily for a 21-day period, has demonstrated anti-tumor activity in xenograft models.