Inhibitor of several Tyrosine protein kinases (VEGFR and PDGFR) and Raf kinases (more avidly C-Raf t
REVIEW Sorafenib 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-β and their associated signaling cascades. Although sorafenib was initially developed as a Raf kinase inhibitor (IC50 = 6 nM), 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-β, 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.
M. Danielle Bareford, Margaret A. Park, Adly Yacoub, Hossein A. Hamed, Yong Tang, Nichola Cruickshanks, Patrick Eulitt, Nisan Hubbard, Gary Tye, Matthew E. Burow, Paul B. Fisher, Richard G. Moran, Kenneth P. Nephew, Steven Grant, and Paul Dent.:Sorafenib Enhances Pemetrexed Cytotoxicity through an Autophagy-Dependent Mechanism in Cancer Cells.Cancer Res., Jul 2011; 71: 4955 - 4967.
Eulitt PJ, Park MA, Hossein H, Cruikshanks N, Yang C, Dmitriev IP, Yacoub A, Curiel DT, Fisher PB, Dent P.Enhancing mda-7/IL-24 therapy in renal carcinoma cells by inhibiting multiple protective signaling pathways using sorafenib and by Ad.5/3 gene delivery.Cancer Biol Ther. 2011 Jan 12;10(12):1290-305. Epub 2010 Dec 15.
M Danielle Bareford,1 Hossein A Hamed,1 Yong Tang,1 Nichola Cruickshanks,1 Matthew E Burow,7 Paul B Fisher,4,5 Richard G Moran,2 Kenneth P Nephew,6 Steven Grant,3,5 and Paul Dent.Sorafenib enhances pemetrexed cytotoxicity through an autophagy- dependent mechanism in cancer cellsPublished online 2011 October 1. doi: 10.4161/auto.7.10.17029