iFSP1

iFSP1 is a potent and selective small molecule inhibitor of Ferroptosis Suppressor Protein 1 (FSP1), also known as Apoptosis-Inducing Factor Mitochondria-Associated 2 (AIFM2). FSP1 is a key component of a glutathione-independent ferroptosis surveillance pathway that operates in parallel with the GPX4-glutathione system. FSP1 functions by reducing Coenzyme Q10 (CoQ10) to its antioxidant form, ubiquinol, using NAD(P)H, thereby preventing lipid peroxidation. By inhibiting FSP1, iFSP1 triggers lipid ROS accumulation and sensitizes cancer cells to ferroptotic cell death. Research indicates that iFSP1 can enhance the efficacy of BCL-2 inhibitors like venetoclax in treating Acute Myeloid Leukemia (AML), particularly in resistant cell lines, by activating the ferroptosis pathway.