Kobe0065, Kobe 0065;Kobe0065;Kobe-0065;N-(3-Chloro-4-Methylphenyl)-2-[2,6-dinitro-4-(trifluoroMethyl)phenyl]-hydrazinecarbothioaMide;Kobe-0065 N-(3-Chloro-4-methylphenyl)-2-[2,6-dinitro-4-(trifluoromethyl)pheny 436133-68-5
Kobe0065 is a novel and effective small-molecule compound inhibiting Ras–Raf interaction by SBDD; exhibits potent activity to competitively inhibit the binding of H-Ras·GTP to c-Raf-1 RBD with a Ki value of 46 ± 13 μM.
IC50 value: 46 uM (Ki) [1]
Target: Ras-Raf
These two compounds(Kobe0065 and Kobe2602), added to the culture medium at 2 and 20 μM, effectively reduced the amount of c-Raf-1 associated with H-Ras G12V in NIH 3T3 cells in a dose-dependent manner, indicating the inhibition of the cellular activity of Ras. A rough estimate of the IC50 value for the cellular Ras–Raf-binding inhibition was around 10 μM (Fig. 1B), which was not much different from the Ki values for the in vitro Ras–Raf-binding inhibition considering thequite low cellular concentration of Raf. A similar inhibitory effect was also observed with NIH 3T3 cells overexpressing K-Ras G12V. Both Kobe0065 and Kobe2602 at 20 μM efficiently inhibited the phosphorylation of MEK and ERK, downstream kinases of Raf in NIH 3T3 cells transiently expressing H-Ras G12V, although the effect was slightly weaker than that of 2 μM sorafenib
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