Kobe0065

• CAT Number: I003549
• CAS Number: 436133-68-5
• Molecular Formula: C15H11ClF3N5O4S
• Molecular Weight: 449.789
• Purity: ≥95%
• Target: Ras
• Solubility: DMSO: ≥ 42.5 mg/mL
• Storage: Store at -20C
• IC50: 46 uM (Ki) [1]
• IUPAC Name: 1-(3-chloro-4-methylphenyl)-3-[2,6-dinitro-4-(trifluoromethyl)anilino]thiourea
• InChI: InChI=1S/C15H11ClF3N5O4S/c1-7-2-3-9(6-10(7)16)20-14(29)22-21-13-11(23(25)26)4-8(15(17,18)19)5-12(13)24(27)28/h2-6,21H,1H3,(H2,20,22,29)
• InChIKey: KSJVAYBCXSURMQ-UHFFFAOYSA-N
• SMILES: CC1=C(C=C(C=C1)NC(=S)NNC2=C(C=C(C=C2[N+](=O)[O-])C(F)(F)F)[N+](=O)[O-])Cl

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-RafThese 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.

Reference

[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, S8182/1-S8182/10.