A. Chemical structure of sorafenib. B. Cellular targets of sorafenib. Sorafenib blocks auto-phosphorylation of multiple RTKs, including VEGFR1/2, PDGFR, FLT3 and RET. It is also a direct inhibitor of RAF-1, wild-type BRAF and the mutant V600E BRAF. RTK, receptor tyrosine kinase; RET, ret proto-oncogene; RAF, rapidly accelerated fibrosarcoma; MEK, mitogen-activated protein kinase kinase; ERK, extracellular signal-regulated kinase; PTEN, phosphatase and tensin homolog, PI3K, phosphoinositide 3-kinase; mTOR, mechanistic target of rapamycin.