FA16

FA16 is a ferroptosis inducer and an inhibitor of the system xc- cystine/glutamate transporter. 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 (Cay-17729), Trolox (Cay-10011659), and deferoxamine (DFO, Cay-14595) and potentiated by ferric ammonium citrate or ferric citrate. FA16-induced death of HT-1080 cells can also be blocked by beta-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, Cay-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 (Cay-17754) in human and rat liver microsomes.Formal Name: N,N-dimethyl-4-(4-((2-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)methyl)piperidin-1-yl)benzenesulfonamide. Molecular Formula: C22H25F3N4O2S. Formula Weight: 466.5. Purity: >95%. Formulation: (Request formulation change), A solid. Solubility: DMSO: Slightly soluble: 0.1-1 mg/ml, Ethanol: Slightly soluble: 0.1-1 mg/ml, PBS (pH 7.2): Slightly soluble: 0.1-1 mg/ml. SMILES: FC(F)(F)C1=NC2=CC=CC=C2N1CC3CCN(C4=CC=C(S(N(C)C)(=O)=O)C=C4)CC3. InChi Code: InChI=1S/C22H25F3N4O2S/c1-27(2)32(30,31)18-9-7-17(8-10-18)28-13-11-16(12-14-28)15-29-20-6-4-3-5-19(20)26-21(29)22(23,24)25/h3-10,16H,11-15H2,1-2H3. InChi Key: JIYXEVFXCPXAIH-UHFFFAOYSA-N.