Multiple additional sorafenib kinase targets

Multiple additional sorafenib kinase targets refers to the broad inhibitory profile of the drug sorafenib, which extends beyond a single protein to include a variety of receptor tyrosine kinases (RTKs) and serine/threonine kinases. Sorafenib is a small-molecule multi-kinase inhibitor primarily recognized for its ability to block the Raf/MEK/ERK signaling pathway through the inhibition of RAF proto-oncogene serine/threonine-protein kinase (C-Raf) and B-Raf proto-oncogene, serine/threonine kinase (B-Raf), including the oncogenic B-Raf V600E mutant (Wilhelm et al., 2004, Nature Reviews Drug Discovery). Additionally, it targets several cell surface receptors involved in angiogenesis and tumor progression, such as Vascular endothelial growth factor receptor 1, 2, and 3 (VEGFR-1, VEGFR-2, VEGFR-3) and Platelet-derived growth factor receptor beta (PDGFR-beta) (Adnane et al., 2006, Methods in Enzymology). It also demonstrates activity against other kinases like Mast/stem cell growth factor receptor Kit (KIT), Receptor-type tyrosine-protein kinase FLT3 (FLT-3), and Proto-oncogene tyrosine-protein kinase receptor Ret (RET) (PubChem, CID 216239). This multi-targeted approach allows sorafenib to simultaneously inhibit tumor cell proliferation and the development of tumor-associated vasculature, making it a standard treatment for advanced hepatocellular carcinoma, renal cell carcinoma, and differentiated thyroid carcinoma (FDA, Nexavar Prescribing Information). However, the inhibition of these diverse targets is also responsible for a distinct profile of adverse effects, such as hand-foot skin reaction and hypertension (Escudier et al., 2007, New England Journal of Medicine).

Other names

Sorafenib multi-kinase profileNexavar targetsSorafenib-inhibited kinasesVEGFR-1/2/3, PDGFR-beta, KIT, FLT-3, RET, and Raf kinases

Sorafenib acts as a multi-kinase inhibitor that targets several serine/threonine and receptor tyrosine kinases. It inhibits the Raf/MEK/ERK pathway by targeting C-Raf and B-Raf, and it also inhibits receptor tyrosine kinases involved in neo-angiogenesis and tumor progression, including Vascular endothelial growth factor receptor 1, 2, and 3, Platelet-derived growth factor receptor beta, Mast/stem cell growth factor receptor Kit, Receptor-type tyrosine-protein kinase FLT3, and Proto-oncogene tyrosine-protein kinase receptor Ret (Wilhelm et al., 2004, Nature Reviews Drug Discovery; Adnane et al., 2006, Methods in Enzymology).