Kobe2602

Research use only, not for human use.

kobe2602 is a novel and effective small-molecule compound inhibiting Ras–Raf interaction by SBDD.

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.

Kobe2602 (2-20 μM; 1 hour) exhibits Ras-Raf-binding inhibition in NIH 3T3 cells.Kobe2602 has IC50 value of approximately 10 μM for the cellular Ras-Raf-binding inhibition.Kobe2602 (20 μM) efficiently inhibits the phosphorylation of MEK and ERK, downstream kinases of Raf in NIH 3T3 cells transiently expressing H-RasG12V.Kobe2602 inhibits Ras?GTP but not Ras?GDP.Kobe2602 (20 μM) inhibits the anchorage-dependent proliferation of H-RasG12V-transformed cells. Cell Proliferation Assay Cell Line:H-rasG12V-transformed NIH 3T3 cells Concentration:20 μM Incubation Time:24 hours , 48 hours, 72 hours Result:Efficiently inhibited colony formation in soft agar in a dose-dependent manner.Western Blot Analysis Cell Line:NIH 3T3 cells Concentration:2 μM, 20 μM Incubation Time:1 hour Result:Effectively reduced the amount of c-Raf-1 associated with H-RasG12V in NIH 3T3 cells in a dose-dependent manner, indicating the inhibition of the cellular activity of Ras.

Kobe2602 (80 mg/kg; p.o.; five consecutive days per week; for 17 days) exhibits antitumor activity on a xenograft of human colon carcinoma SW480 cells carrying the K-RasG12V gene. Animal Model:Female athymic nude mice (6-8 wk old), with SW480 cells xenograft Dosage:80 mg/kg Administration:Oral administration, five consecutive days per week, for 17 days Result:Caused inhibition of the tumor growth.

Kobe2602 | Kobe 2602 | Kobe-2602

MAPK/ERK Signaling

Raf

Ras-Raf

Cancer

——

454453-49-7

419.31

C14H9F4N5O4S

>98% (HPLC)

DMSO: 10 mM

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

2-(2,6-dinitro-4-(trifluoromethyl)phenyl)-N-(4-fluorophenyl)hydrazinecarbothioamide

(-20℃)

With Ice Pack

≥ 2 years