KOBE-2602
中文名称:
KOBE-2602
中文同义词:
2-[2,6-二硝基-4-(三氟甲基)苯基]-N-(4-氟苯基)肼基硫代甲酰胺;H-RAS·GTP与C-RAF-1RBD结合抑制剂(KOBE2602)
英文名称:
kobe-2602
英文同义词:
kobe 2602;kobe2602;kobe-2602;2-[2,6-Dinitro-4-(trifluoroMethyl)phenyl]-N-(4-fluorophenyl)hydrazinecarbothioaMide;kobe-2602 2-[2,6-Dinitro-4-(trifluoromethyl)phenyl]-N-(4-fluorophenyl)hydrazinecarbothioamide;Kobe 2602, >=98%;kobe2602, >96%;CS-1280
CAS号:
454453-49-7
分子式:
C14H9F4N5O4S
分子量:
419.31
EINECS号:
相关类别:
小分子抑制剂;小分子抑制剂，天然产物;细胞生物学试剂;Inhibitors;Aromatics, Miscellaneous Reagents, Pharmaceuticals, Intermediates Fine Chemicals
Mol文件:
454453-49-7.mol
沸点
450.8±55.0 °C(Predicted)
密度
1.691±0.06 g/cm3(Predicted)
酸度系数(pKa)
9.35±0.70(Predicted)
生物活性
Kobe2602是选择性Ras抑制剂，抑制H-Ras GTP与c-Raf-1结合，Ki值为149 μM。
靶点
Target Value
Ras
() 149 μM(Ki)
Target
Value
Ras
()
149 μM(Ki)
体外研究
Kobe2602 (2-20 μM; 1 hour) exhibits Ras-Raf-binding inhibition in NIH 3T3 cells.
Kobe2602 has IC 50 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-Ras G12V .
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-ras G12V -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-Ras G12V in NIH 3T3 cells in a dose-dependent manner, indicating the inhibition of the cellular activity of Ras.
Cell Line:
H-ras G12V -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.
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-Ras G12V in NIH 3T3 cells in a dose-dependent manner, indicating the inhibition of the cellular activity of Ras.
体内研究
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-ras G12V 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.
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.
