Sorafenib is a multi-kinase inhibitor that inhibits Raf-1 and B-RAF (IC50s = 6 and 22 µM, respectively), as well as the receptor tyrosine kinases VEGFR2, VEGFR3, PDGFR?, FLT3, and c-Kit (IC50s = 90, 15, 20, 57, and 58 nM, respectively).{19941,19945} It is selective for these kinases over 12 other kinases, including ERK1, MEK1, EGFR, and HER2 (IC50s = >10 µM for all).{19945} Sorafenib inhibits proliferation of PLC/PRF/5 and HepG2 cells (IC50s = 6.3 and 4.5 µM, respectively) and induces apoptosis in these cells.{19940} It completely inhibits tumor growth in a PLC/PRF/5 mouse xenograft model when administered at a dose of 30 mg/kg and reduces basic FGF-induced angiogenesis in a Matrigel™ assay in vivo.{19940,58180} Sorafenib (10 µM) induces ferroptotic cell death in HT-1080 fibrosarcoma cells, an effect that can be blocked by the ferroptosis inhibitors ferrostatin-1 (Item No. 17729), deferoxamine (Item No. 14595), and ?-mercaptoethanol, but does not induce ferroptosis in a variety of other cancer cell lines.{43340,62293} It inhibits glutamate release by the system xc- cystine/glutamate transporter in HT-1080 cells when used at concentrations ranging from 2.5 to 10 µM, decreases glutathione levels, and increases lipid peroxidation.{43340} Sorafenib also inhibits replication of hepatitis C virus (HCV) in Huh7.5 cells (IC50 = 7.2 µM).{58181} Formulations containing sorafenib have been used in the treatment of hepatocellular, renal cell, and thyroid carcinomas.