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RAF Kinases

RAF Kinases


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About the Book

The Ras/RAF/MEK/ERK cascade is a central cellular signal transduction pathway involved in cell proliferation, differentiation, and survival where RAF kinases are pivotal kinases implicated in cancer. The development of specific irreversible kinase inhibitors is a rewarding but difficult aim. A novel synthetic approach including a lyophilization step allowed us the synthesis of a diphenyl urea compound with an epoxide moiety (compound 1). Compound 1 possessed inhibitory activity in vitro. In cell culture experiments, a strong activation of the RAF signaling pathway was observed, an effect which is known from several other RAF kinase inhibitors and is here reported for the first time for a diphenyl urea compound. Furthermore, we developed a mathematical model of the Ras/RAF/MEK/ERK cascade demonstrating how stimuli induce different signal patterns and thereby different cellular responses, depending on the ratio between B-RAF and C-RAF. Additionally the effect of the tumor suppressor DiRas3 (also known as Noey2 or ARHI) on RAF signaling was studied. I could show that DiRas3 down-regulates the mitogenic pathway by inhibition of MEK.


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Product Details
  • ISBN-13: 9783639056655
  • Publisher: VDM Verlag
  • Binding: Paperback
  • Height: 229 mm
  • No of Pages: 96
  • Spine Width: 5 mm
  • Weight: 190 gr
  • ISBN-10: 3639056655
  • Publisher Date: 05 Dec 2008
  • Depth: 6
  • Language: English
  • Returnable: N
  • Sub Title: Pathway, Modulation and Modeling
  • Width: 152 mm


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