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Novel small molecule Raf kinase inhibitors for targeted cancer therapeutics

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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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Authors and Affiliations

  1. Chemical Kinomics Research Center, Korea Institute of Science and Technology, Seoul, 130-650, Korea

    Do-Hee Kim & Taebo Sim

  2. Future Convergence Research Division, Korea Institute of Science and Technology, Seoul, 130-650, Korea

    Taebo Sim

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  1. Do-Hee Kim
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  2. Taebo Sim
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Correspondence to Taebo Sim.

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Kim, DH., Sim, T. Novel small molecule Raf kinase inhibitors for targeted cancer therapeutics. Arch. Pharm. Res. 35, 605–615 (2012). https://doi.org/10.1007/s12272-012-0403-5

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  • DOI: https://doi.org/10.1007/s12272-012-0403-5

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