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Book synopsis

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. 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.

Book details

Book category Books in English Technology, engineering, agriculture Technology: general issues Engineering: general

• Full title: RAF Kinases
• Author: Armin Robubi
• Language: English
• Binding: Paperback
• Number of pages: 96
• EAN: 9783639056655
• ISBN: 3639056655
• ID: 04333995
• Publisher: VDM Verlag
• Weight: 141 g
• Dimensions: 229 × 152 × 5 mm
• Date of publishing: 05. December 2008

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