Sorafenib is an inhibitor of Raf-1 and B-RAF (IC50s = 6 and 22 nM, respectively), as well as several receptor tyrosine kinases, including VEGFR2, VEGFR3, PDGFRbeta, FLT3, and c-Kit (IC50s = 90, 15, 20, 57, and 58 nM, respectively). It poorly inhibits ERK1, MEK1, and several other kinases (IC50s = >10 µM). It inhibits tumor angiogenesis and induces tumor cell apoptosis, particularly in renal cell carcinoma and hepatocellular carcinoma. Sorafenib (10 µM) also induces ferroptotic cell death in HT-1080 fibrosarcoma cells, an effect that can be blocked by the ferroptosis inhibitors ferrostatin-1 (Cay-17729), deferoxamine (Cay-14595), and beta-mercaptoethanol. 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. However, sorafenib induces ferrostatin-1-suppressible ferroptosis only within a narrow range of concentrations in HT-1080 cells (EC50s = 18 and 43 µM without and with ferrostatin-1, respectively) and does not induce ferrostatin-1-suppressible ferroptosis in several other cell lines.