iFSP1

iFSP1 (CAS No.: 150651-39-1) is a potent, selective, and glutathione-independent small-molecule inhibitor of ferroptosis suppressor protein 1 (FSP1/AIFM2), a key regulator of lipid peroxidation defense pathways distinct from the canonical GPX4-dependent system, and is widely utilized in ferroptosis research and oncology-focused drug discovery. By targeting FSP1-mediated CoQ10 reduction and antioxidant activity, iFSP1 disrupts cellular redox homeostasis and promotes iron-dependent lipid peroxidation, thereby selectively inducing ferroptotic cell death in models characterized by GPX4 deficiency and FSP1 overexpression. It exhibits biological activity in the nanomolar range, with reported EC50 values around low nanomolar levels, and demonstrates the ability to decrease viability in engineered cell systems such as Pfa1 and HT1080 cells in a ferroptosis-dependent manner, an effect reversible by ferroptosis inhibitors such as liproxstatin-1. In addition, iFSP1 sensitizes a broad spectrum of human cancer cell lines to ferroptosis inducers, including GPX4 inhibitors, highlighting its utility in combination treatment strategies aimed at overcoming resistance to oxidative cell death. This compound is commonly applied in mechanistic studies of ferroptosis regulation, validation of FSP1 as a therapeutic target, and screening platforms for redox-modulating agents, with experimental concentrations tailored to specific cellular contexts and assay designs.