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Description: Kobe0065 (Kobe 0065) is novel and potent inhibitor of the H-Ras-cRaf1 interaction which exhibits potent activity to competitively inhibit the binding of H-Ras·GTP to c-Raf-1 RBD with a Ki value of 46 +/- 13 uM. Kobe0065 is a compound screened out by an in silico screen method as a potent inhibitor of the Ras–Raf interaction. It showed favorite efficacy to inhibit the binding of M-Ras.GTP and H-Ras.GTP to the Ras-binding domain of c-Raf-1. Kobe0065 also dose-dependently inhibited the binding of H-RasG12V to c-Raf-1 in NIH 3T3 cells with a rough IC50 value of 10 uM. Besides that, 20 uM of Kobe0065 effectively suppressed the phosphorylation of down-stream kinases of Raf, including MEK and ERK. In NIH 3T3 cells transfected with H-rasG12V, Kobe0065 inhibited the colony formation with IC50 value of 0.5 uM.
References: Proc Natl Acad Sci U S A. 2013 May 14; 110(20):8182-7.
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