Novel small molecule Raf kinase inhibitors for targeted cancer therapeutics

Archives of Pharmacal Research
Do-Hee Kim, Taebo Sim

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.

References

Apr 1, 1997·Current Opinion in Cell Biology·M J Robinson, M H Cobb
Mar 31, 2000·Trends in Cell Biology·J M ShieldsC J Der
Sep 22, 2001·Endocrine-related Cancer·J F LyonsG Bollag
Oct 9, 2002·Current Pharmaceutical Design·Timothy B LowingerRoger A Smith
Feb 28, 2004·Expert Reviews in Molecular Medicine·Walter KolchPetra Janosch
Mar 24, 2004·Cell·Paul T C WanUNKNOWN Cancer Genome Project
Jun 23, 2004·Oncogene·Maria KarasaridesRichard Marais
Sep 28, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Tanya Ahmad, Tim Eisen
Oct 9, 2004·The Journal of Clinical Endocrinology and Metabolism·Giuliana SalvatoreMassimo Santoro
Oct 19, 2004·Cancer Cell·Mathew J Garnett, Richard Marais
Nov 2, 2005·Bioorganic & Medicinal Chemistry Letters·Andrew K TakleDavid M Wilson
Mar 15, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Giuliana SalvatoreMassimo Santoro
Jun 20, 2006·Nature Chemical Biology·Yi Liu, Nathanael S Gray
Aug 2, 2006·British Journal of Cancer·T EisenM J Ratain
Oct 31, 2006·The American Journal of Pathology·Danielle A MurphyWilliam M F Lee
Jan 6, 2007·Leukemia·D AuclairS M Wilhelm
Jun 5, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Teresa GuidaFrancesca Carlomagno
Nov 21, 2007·Expert Opinion on Therapeutic Targets·Vladimir KhazakErica A Golemis
Dec 14, 2007·Proceedings of the National Academy of Sciences of the United States of America·Ultan McDermottJeffrey Settleman
Jan 31, 2008·Journal of the National Cancer Institute·Weiguo ZhangMichael Andreeff
Feb 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·James TsaiGideon Bollag
Jun 19, 2008·Cancer Research·Clara MontagutJeffrey Settleman
Jan 14, 2009·Molecular Cancer Therapeutics·Hung HuynhKhee Chee Soo
Feb 17, 2009·Cancer Letters·Clara Montagut, Jeff Settleman
May 26, 2009·Hematology/oncology Clinics of North America·Nathalie Dhomen, Richard Marais
Mar 4, 2010·Molecular Cancer Therapeutics·Shengbing Huang, Frank A Sinicrope
Mar 20, 2010·Nature·Karen Cichowski, Pasi A Jänne
Mar 31, 2010·Biochemical Pharmacology·Claudia Wellbrock, Adam Hurlstone
May 15, 2010·Future Oncology·Alvaro Moreno-Aspitia

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Citations

Jan 16, 2014·European Journal of Medicinal Chemistry·Hala Bakr El-Nassan
Jul 10, 2012·The Journal of Clinical Endocrinology and Metabolism·Mingzhao Xing
Jan 29, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Michael N Vansaun
Nov 19, 2015·International Journal of Molecular Sciences·Huiding XieJijun Fu
Sep 27, 2012·Biochemical and Biophysical Research Communications·Tatsiana PakladokFlorian Lang
Nov 22, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Nan JiangXin Zhai
Nov 5, 2014·Integrative Biology : Quantitative Biosciences From Nano to Macro·Ling YuZhisong Lu
Aug 3, 2019·Expert Opinion on Therapeutic Patents·Ruo-Jun ManHai-Liang Zhu
May 15, 2020·Clinical Microbiology Reviews·Naveen KumarBarry T Rouse
Feb 13, 2013·Journal of Medicinal Chemistry·Melissa M VasbinderMinwei Ye

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