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- W2000902711 abstract "The RAS/RAF/MEK/ERK signaling pathway plays a central role in the regulation of many cellular processes including proliferation, survival, differentiation, apoptosis, motility and metabolism. This pathway is activated by a diverse group of extracellular signals including integrins, growth factor receptors [i.e. epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor (PDGFR)], or cytokines. While RAS, RAF and MEK activity appear restricted to only one class of substrates, ERK activates more than 70 substrates including nuclear transcription factors. Agents targeting the RAS/RAF/MEK/ERK pathway may therefore inhibit oncogenic signaling in tumor cells. However, most pharmacological agents directed against these targets have not been successful in the clinic. The only small molecule in this class to be approved for cancer therapy is sorafenib, which is not a pure RAF kinase inhibitor. To be successful, one may have to approach this pathway from a multi-pronged approach and also tailor therapy according to which component might be the one playing a pivotal role in a particular system. Relatively selective raf kinase inhibitors are entering clinical trials, and one MEK inhibitor, AZD6244 is in phase II clinical trials." @default.
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- W2000902711 date "2008-10-01" @default.
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- W2000902711 title "584 POSTER Novel inhibitors of BRAF based on a 2,6-disubstituted pyrazine scaffold" @default.
- W2000902711 doi "https://doi.org/10.1016/s1359-6349(08)72518-7" @default.
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