Uses
N-(3-Chloro-4-methylphenyl)-2-[2,6-dinitro-4-(trifluoromethyl)phenyl]-hydrazinecarbothioamide is used in the preparation of pyrazolidine or pyrazole compounds which exhibit mild antimicrobial effects against various strains of bacteria.
Biological Activity
kobe0065 is a small-molecule inhibitor of ras with ki value of 46 μm for the binding of h-ras.gtp to c-raf-1 [1].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 μm. besides that, 20 μm 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 μm. kobe0065 also showed effect on other cancer cells carrying activated ras oncogenes, such as panc-1(k-rasg12v), ht1080 (n-rasq61l) and hct116 (h-rasg13d). moreover, in mice bearing sw480 xenografts, administration of kobe0065 resulted in 40-50% inhibition of the tumor growth at dose of 80 mg/kg. this effect turned to be more distinct when the dose was up to 160 mg/kg [1].
in vivo
Kobe0065 and Kobe2602 exhibit antitumor activity on a xenograft of human colon carcinoma SW480 cells carrying the K-ras(G12V) gene by oral administration[1].
References
[1] shima f, yoshikawa y, ye m, 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, 2013, 110(20): 8182-8187.
