Kobe0065

Research use only, not for human use.

Kobe0065 is a novel and effective small-molecule compound inhibiting Ras–Raf interaction by SBDD.

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.

Kobe0065-family compounds bind to Ras?GTP and exhibit antiproliferative activity toward cancer cells carrying the activated ras oncogenes. The compounds efficiently inhibit the interaction of Ras?GTP with their multiple effectors including Raf, PI3K, and RalGDS and a regulator/effector Sos and show rather broad binding specificity toward various Ras family small GTPases, which may account for their higher potency at the cellular level compared with that of the in vitro binding inhibition. The phosphorylation of downstream kinases MEK and ERK is effectively attenuated by 20 μM Kobe0065 and Kobe2602 in NIH3T3 cells transiently expressing H-RasG12V.

Kobe0065 and Kobe2602 exhibit antitumor activity on a xenograft of human colon carcinoma SW480 cells carrying the K-ras(G12V) gene by oral administration.

Kobe0065 | Kobe 0065 | Kobe0065

MAPK/ERK Signaling

Raf

Ras-Raf

Cancer

——

436133-68-5

449.79

C15H11ClF3N5O4S

>98% (HPLC)

DMSO: 10 mM

FC(C1=CC([N+]([O-])=O)=C(NNC(NC2=CC=C(C)C(Cl)=C2)=S)C([N+]([O-])=O)=C1)(F)F

N-(3-chloro-4-methylphenyl)-2-(2,6-dinitro-4-(trifluoromethyl)phenyl)hydrazinecarbothioamide.

(-20℃)

With Ice Pack

≥ 2 years