title: Novel small molecule Raf kinase inhibitors for targeted cancer therapeutics.
abstract: 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.
authors.affiliation: Chemical Kinomics Research Center, Korea Institute of Science and Technology, Seoul, 130-650, Korea.
authors.forename: Do-Hee
authors.initials: DH
authors.lastname: Kim
authors.forename: Taebo
authors.initials: T
authors.lastname: Sim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001665:Binding Sites; D049109:Cell Proliferation / Q000187:drug effects; D002986:Clinical Trials as Topic; D055808:Drug Discovery; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D015398:Signal Transduction / Q000187:drug effects; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D048490:raf Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D054852:Small Molecule Libraries; D048490:raf Kinases