Molecular Formula | C14H9F4N5O4S |
Molar Mass | 419.31 |
Density | 1.691±0.06 g/cm3(Predicted) |
Boling Point | 450.8±55.0 °C(Predicted) |
pKa | 9.35±0.70(Predicted) |
Storage Condition | 2-8℃ |
In vitro study | 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. |
In vivo study | 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. |
1mg | 5mg | 10mg | |
---|---|---|---|
1 mM | 2.385 ml | 11.924 ml | 23.849 ml |
5 mM | 0.477 ml | 2.385 ml | 4.77 ml |
10 mM | 0.238 ml | 1.192 ml | 2.385 ml |
5 mM | 0.048 ml | 0.238 ml | 0.477 ml |
biological activity | Kobe2602 is a selective Ras inhibitor, inhibiting the binding of H-Ras GTP to c-Raf-1 with a Ki value of 149 μM. |
target | TargetValue Ras () 149 μ m (Ki) |
Target | Value |
Ras () | 149 μM(Ki) |
in vitro study | Kobe2602 (2-20μM; 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 RasGTP but not RasGDP. Kobe2602 (20 μ M) inhibits the anchorage-dependent proliferation of H-rasG12V-transformed cells. Cell Proliferation Assay Cell Line: H-ras G12V-transformed NIH 3T3 cells Concentration: 20 μ M 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 μ M, 20 μ M 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 NIH 3T3 cells |
Concentration: | 20 μM 2 μM, 20 μM |
Incubation Time: | 24 hours , 48 hours, 72 hours 1 hour |
Result: | Efficiently inhibited colony formation in soft agar in a dose-dependent manner. 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. Caused inhibition of the tumor growth. |
in vivo study | 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: used 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 |