Sorafenib (Bay 43-9006) is a novel bi-aryl urea compound that inhibits cell proliferation by targeting the ERK pathway and angiogenesis by targeting the receptor tyrosine kinases VEGFR-2 and PDGFR-b and their associated signaling cascades. Although sorafenib was initially developed as a Raf kinase inhibitor (IC50=6nM), it has since been shown to have activity against many receptor tyrosine kinases involved in tumorigenesis and angiogenesis including FGFR-1, wt BRAF and V599E mutant BRAF, as well as members of the so-called "split kinase" family: VEGFR-2, VEGFR-3, PDGFR-b, c-KIT, and Flt3. However, sorafenib is not active against erbB1, erbB2, ERK-1, MEK-1, EGFR, HER-2, IGFR-1, c-MET, c-yes, PKB, PKA, cdk1/cyclinB, PKC, and pim-1. In cellular mechanistic assays, sorafenib decreased basal phosphorylation of the ERK pathway in melanoma, breast, colon, and pancreatic tumor cell lines.