Sorafenib

Sorafenib (Nexavar) is a novel, small molecular inhibitor of several tyrosine protein kinases (VEGFR and PDGFR) and RAF/MEK/ERK cascade inhibitor with an IC50 of 6, 22, 38 nM for Raf-1, wt BRAF and V599E mutant BRAF. It does not significantly inhibit MEK-1 or ERK-1 activity (IC50,>10 µM). MDA-MB-231 human breast carcinoma cells were the most sensitive cell line identified for inhibition of the MAPK pathway by BAY 43-9006 (IC50, 90nM). Several other cell lines responded to BAY 43-9006 treatment, including the LOX human melanoma (IC50, 880 nM), BxPC3 human pancreatic (IC50, 1200 nM), and the HCT 116, DLD-1, and Colo-205 human colon carcinoma cells (IC50s ranging between 2000 and 4000 nmol/L). It interacts synergistically with bortezomib to induce apoptosis in a broad spectrum of neoplastic cell lines and show an important role for the Akt and JNK pathways in mediating synergism.