产品描述:
FA16 is a ferroptosis inducer and an inhibitor of the system xc- cystine/glutamate transporter.{66712} It reduces the viability of various cancer cell lines, including HT-1080 fibrosarcoma and A375 melanoma cells (IC50s = 1.26 and 2.31 µM, respectively), 786-O renal cell carcinoma cells (IC50 = 0.7 µM), and MDA-MB-231 breast cancer cells (IC50 = 4.34 µM) but not several non-cancer cell lines at 20 µM. FA16-induced death of HT-1080 cells can be blocked by the ferroptosis inhibitors ferrostatin-1 (Item No. 17729), Trolox (Item No. 10011659), and deferoxamine (DFO; Item No. 14595) and potentiated by ferric ammonium citrate or ferric citrate. FA16-induced death of HT-1080 cells can also be blocked by β-mercaptoethanol, which prevents cell death induced by system xc- cystine/glutamate transporter inhibition by increasing intracellular cystine bioavailability. FA16 (5 µM) increases the production of reactive oxygen species (ROS) in HT-1080 cells, an effect that can be blocked by ferrostatin-1, and inhibits glutamate release from HT-1080 cells in an enzyme-coupled glutamate release assay. FA16 (15 and 30 mg/kg) reduces tumor growth and increases intratumoral levels of 4-hydroxy nonenal (4-HNE; Item No. 32100) and malondialdehyde (MDA), markers of lipid peroxidation, in a HepG2 mouse xenograft model. It also has an increased half-life and slower clearance than the ferroptosis inducer erastin (Item No. 17754) in human and rat liver microsomes.