Kobe0065
目录号 : GC16922
A selective Ras inhibitor
Cas No.:436133-68-5
Sample solution is provided at 25 µL, 10mM.
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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].
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.
Cell experiment: | Cells (2×103) are seeded in a 96-well plate and cultured in DMEM containing 2% (vol/vol) FBS in the presence of one of the compounds. Viable cell numbers are measured by formazan formation using a Cell Counting Kit 8. Apoptotic cells are detected by a standard TUNEL assay using an In Situ Cell Detection kit. |
Animal experiment: | Cells (5×106) are implanted into the right flanks of female athymic nude mice (6-8 wk old). After tumor sizes reached appr 50 mm3 on average, compounds suspended in Cremophor:ethanol:water (1:1:6) are administered orally for five consecutive days per week for 17 d. Tumor volumes (V) are calculated. Dissected tumors after 17-d administration of the 80 mg/kg compounds are fixed in 4% (wt/vol) paraformaldehyde and embedded in paraffin. Their sections are subjected to immunohistochemistry with an anti-ERK1/2 antibody or an anti-CD31 antibody using a HISTMOUSE-PLUS kit. Apoptotic cells are detected by a TUNEL assay. Statistical significance for groups of three or more is determined by one-way ANOVA with Tukey’s test for post hoc analysis. |
References: [1]. Shima, Fumi, 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 of the United States of America (2013), 110(20), 8182-8187, | |
| Cas No. | 436133-68-5 | SDF | |
| 化学名 | N-(3-chloro-4-methylphenyl)-2-(2,6-dinitro-4-(trifluoromethyl)phenyl)hydrazinecarbothioamide | ||
| Canonical SMILES | ClC1=CC(NC(NNC2=C([N+]([O-])=O)C=C(C(F)(F)F)C=C2[N+]([O-])=O)=S)=CC=C1C | ||
| 分子式 | C15H11ClF3N5O4S | 分子量 | 449.79 |
| 溶解度 | ≥ 23.85mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2233 mL | 11.1163 mL | 22.2326 mL |
| 5 mM | 0.4447 mL | 2.2233 mL | 4.4465 mL |
| 10 mM | 0.2223 mL | 1.1116 mL | 2.2233 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet