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KMID : 0043320120350040605
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Archives of Pharmacal Research
2012 Volume.35 No. 4 p.605 ~ p.615
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Novel small molecule Raf kinase inhibitors for targeted cancer therapeutics
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Kim Do-Hee
Sim Tae-Bo
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Abstract
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Aberrant activation of Raf signaling pathway is frequently found in various human tumors, it has been considered as distinct and promising molecular target for cancer therapeutics. B-Raf is most attractive drug target out of three Raf isoforms (A-Raf, B-Raf and C-Raf) because it exhibits high kinase activity due to frequent mutations in human tumors. However, most recently, it has been reported that Raf isoforms show the cross-activation in the presence of specific B-Raf inhibitors, which brings about the paradoxical p-ERK activation as well as tumor promoting effect. According to these findings, it remains controversy whether pan-Raf kinase inhibitor is more valuable and promising rather than specific B-Raf inhibitor under certain conditions in terms of cancer therapeutics. In this short review, novel Raf kinase inhibitors undergoing clinical investigation are introduced. Moreover, the paradoxical p-ERK activation is discussed with specific B-Raf inhibitors, PLX4032/4720 compounds.
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KEYWORD
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Raf kinase, Molecular-targeted inhibitor, Cancer, Sorafenib, PLX4720/4032
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