N6F11

N6F11 is an inducer of ferroptosis.¹ It increases the thermal stability of the ubiquitin ligase TRIM25 in a cellular thermal shift assay (CETSA) using PANC-1 pancreatic cancer cells when used at a concentration of 10 µM and enhances TRIM25-dependent ubiquitination of glutathione peroxidase 4 (GPX4) in a cell-free assay at 0.1 and 1 µM. N6F11 (5 µM) induces lipid peroxidation and ferroptosis, as well as degradation of GPX4, an effect that can be reversed by the proteasome inhibitors carfilzomib (Item No. 17554) or bortezomib (Item No. 10008822), in PANC-1 cells. It selectively induces cytotoxicity in HT-1080, PANC-1, MiaPaCa-2, and Calu-1 cancer cells over neutrophils, dendritic cells, natural killer (NK) cells, and CD8⁺ T cells. N6F11 (10 mg/kg) decreases tumor volume in a KPC murine pancreatic ductal adenocarcinoma (PDAC) model, which can be inhibited by the ferroptosis inhibitor liproxstatin-1 (Item No. 17730) or an anti-CD8 antibody.

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1. Li, J., Liu, J., Zhou, Z., et al. Tumor-specific GPX4 degradation enhances ferroptosis-initiated antitumor immune response in mouse models of pancreatic cancer. Sci. Transl. Med. 15(720), eadg3049 (2023).