Archives of Pharmacal Research

, Volume 35, Issue 4, pp 605–615

Novel small molecule Raf kinase inhibitors for targeted cancer therapeutics


DOI: 10.1007/s12272-012-0403-5

Cite this article as:
Kim, DH. & Sim, T. Arch. Pharm. Res. (2012) 35: 605. doi:10.1007/s12272-012-0403-5


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.

Key words

Raf kinase Molecular-targeted inhibitor Cancer Sorafenib PLX4720/4032 

Copyright information

© The Pharmaceutical Society of Korea and Springer Netherlands 2012

Authors and Affiliations

  1. 1.Chemical Kinomics Research CenterKorea Institute of Science and TechnologySeoulKorea
  2. 2.Future Convergence Research DivisionKorea Institute of Science and TechnologySeoulKorea

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