FINO₂

FINO₂ is a ferroptosis-inducing peroxide compound that indirectly inhibits glutathione peroxidase 4 (GPX4) and oxidizes iron.¹ It decreases GPX4 activity and protein levels in vitro but does not act as an active site, allosteric, or covalent inhibitor 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 lipid 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 cell growth (mean GI₅₀ = 5.8 µM) and induces lethality (mean LC₅₀ = 46 µM) in the NCI-60 panel of cancer cell lines.² It is selective for oncogenically transformed BJ-ELR cells over noncancerous BJ-hTERT cells when used at concentrations of 15 and 20 µM. FINO₂ (6 µM) induces oxidative stress, including lipid peroxidation, in RS4;11 B-lymphoblastic leukemia cells. It induces iron-dependent cell death, an effect that can be blocked by pretreatment with the lipophilic antioxidants ferrostatin-1 (Item No. 17729) and liproxstatin-1 (Item No. 17730), and does not induce markers of apoptosis, necrosis, or autophagy in RS4;11 cells.

WARNING This product is not for human or veterinary use.

1. Gaschler, M.M., Andia, A.A., Liu, H., et al. FINO2 initiates ferroptosis through GPX4 inactivation and iron oxidation. Nat. Chem. Biol. 14(5), 507-515 (2018).

2. Abrams, R.P., Carroll, W.L., and Woerpel, K.A. Five-membered ring peroxide selectively initiates ferroptosis in cancer cells. ACS Chem. Biol. 11(5), 1305-1312 (2016).

Nakamura, T., Hipp, C., Mourão, A.S.D., et al. Phase separation of FSP1 promotes ferroptosis. Nature 619, 371-377 (2023).

Mishima, E., Ito, J., Wu, Z., et al. A non-canonical vitamin K cycle is a potent ferroptosis suppressor. Nature 608(7924), 778-783 (2022).

Kremer, D.M., Nelson, B.S., Lin, L., et al. GOT1 inhibition primes pancreatic cancer for ferroptosis through the autophagic release of labile iron. bioRxiv (2020).