Kos2602

kobe2602 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 149 ± 55 μM.IC50 value: 149 ± 55 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 expressingH-Ras G12V, although the effect was slightly weaker than that of2 μM sorafenib.

Signaling Pathways >> GPCR/G Protein >> Ras

Research Areas >> Cancer

[1]. Shima, Fumi, et al. In silico discovery of small-molecule Ras inhibitors that display antitumor activity by blocking the Ras-effector interaction. Proceedings of the National Academy of Sciences of the United States of America (2013), 110(20), 8182-8187,

ARS-853 | ARS-1620 | NSC 23766 | ML 141 | Salirasib | Pan-RAS-IN-1 | Rhosin hydrochloride | CASIN | EHT 1864 | EHop-016 | 1A-116 | CCG 1423 | K-Ras(G12C) inhibitor 12 | ZCL 278 | Y16