FINO2

Биологическая активность

FINO2 is a ferroptosis-inducing peroxide compound that indirectly inhibits glutathione peroxidase 4 (GPX4) and oxidizes iron. It decreases GPX4 activity and protein levels in vitro but does not act as an active site, allosteric, or covalent ингибитор of GPX4 or alter GPX homeostasis. It also oxidizes iron in vitro, leading to degradation of the endoperoxide moiety, but does not affect the protein levels of iron regulatory proteins, such as IRP2, FTL1, or TFR. FINO2 induces липид peroxidation of a large subset of the lipidome in HT-1080 cells when used at a concentration of 10 μM and induces ferroptosis in an arachidonic acid lipoxygenase-independent manner. It inhibits клетка growth and induces lethality in the NCI-60 panel of cancer клетка lines. It is селективный for oncogenically transformed BJ-ELR cells over noncancerous BJ-hTERT cells. FINO2 induces oxidative stress, including липид peroxidation, in RS4;11 B-lymphoblastic leukemia cells. It induces iron-dependent клетка death, an effect that can be blocked by pretreatment with the lipophilic antioxidants ferrostatin-1 and liproxstatin-1 and does not induce markers of apoptosis, necrosis, or autophagy in RS4;11 cells.