Dabrafenib Mesylate 别名：GSK-2118436B; 甲磺酸达拉非尼
Dabrafenib (GSK2118436)是一种突变型BRAFV600特异性抑制剂，IC50为0.6 nM，作用于B-Raf(wt)和c-Raf效果低4和6倍。此外，Dabrafenib也是RIPK3的抑制剂，可用于肾小管间质纤维化的相关研究。
CAS No.：1195768-06-9
Immunobiology. 2023 Jan;228(1):152311.
化学性质/溶解性/储存
| 分子量 | 615.67 |
| 分子式 | C23H20F3N5O2S2.CH4O3S |
| CAS号 | 1195768-06-9 |
| 中文名称 | 甲磺酸达拉非尼；达帕菲尼甲磺酸盐 |
| 溶解性 | DMSO 22 mg/mL |
| 储存条件 |
粉末型式 -20°C 3年；4°C 2年 溶于溶剂 -80°C 6个月；-20°C 1个月 |
| 运输方式 | 冰袋运输，根据产品的不同，可能会有相应调整。 |
生物活性
实验参考
下述溶液配置方法仅为基于分子量计算出的理论值。不同产品在配置溶液前，需考虑其在不同溶剂中的溶解度限制。
| 浓度/溶剂体积/质量 | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.6242 mL | 8.1212 mL | 16.2425 mL |
| 5 mM | 0.3248 mL | 1.6242 mL | 3.2485 mL |
| 10 mM | 0.1624 mL | 0.8121 mL | 1.6242 mL |
*吸湿的DMSO对产品的溶解度有显著影响，请使用新开封的DMSO；
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。
| 细胞系 | A375P, SKMEL28 and Colo205 cell lines |
| 方法 | A375P-F11 assay: A375P cells were plated in 96-well plates by limiting dilution and single cell-derived clones were harvested and tested for sensitivity to B-Raf inhibitors. The F11 clone was selected for future studies and was named A375P-F11. Cellular pSmad Assay to Measure Anti-TGF-β Activity: Activity of compounds was tested in a mechanistic assay in HepG2 cells. Cells were seeded in 12-well plates at a density of 500,000 cells/well and allowed to adhere overnight at 37℃/5% CO2. Media (BME+10% serum) was removed and compound in serum free media was added to the cells for 45 minutes at 37oC/5% CO2. Cells were stimulated with 1 ng/ml TGF-β (R&D systems) for 60 minutes. Cells were lysed in buffer (25 mM Tris-HCl ph: 7.5, 2 mM EDTA, 2 mM EGTA,1% Triton X-100, 0.1 % SDS, 50 mM sodium-β-glycerophosphate, 2 mM sodium orthovanadate, 12.5 mM sodium pyrophosphate, protease and phosphatase inhibitor cocktails) for 30 minutes, scraped, collected, clarified by centrifugation and prepared for western blots in LDS/reducing reagent (Invitogen). Samples were resolved on 4-12% Bis-Tris gels, transferred to PVDF, and probed for total and phospho-Smad2 using antibodies from Cell Signaling. Gels were imaged using the odyssey blot scanner (Licor) and quantified using Licor software. Phospho:total Smad2 ratios were determined and the IC50 was defined as the concentration of compound which decreased the phospho:total ratio by 50%. |
| 浓度 | 0~10 nM |
| 处理时间 |
* 上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。
建议您制定动物给药及实验方案时，尽量参考已发表的相关实验文献（溶剂种类及配比众多，简单地溶解目的化合物，并不能解决动物给药依从性、体内生物利用度、组织分布等相关问题，未必能保证目的化合物在动物体内充分发挥生物学效用）。
体内实验的工作液，建议您现用现配，当天使用；如在配制过程中出现沉淀、析出现象，可以通过超声和（或）加热的方式助溶。
切勿一次性将产品全部溶解。
请在下面的计算器中，输入您的动物实验相关数据并点击计算，即可得到该实验的总需药量和工作液终浓度。
例如您给药剂量是10 mg/kg，平均每只动物的体重为20 g，每只动物的给药体积是100 μL，动物数量为20只，则该动物实验的总需药量为4 mg，工作液终浓度为2 mg/mL。
1：鉴于实验过程的损耗，建议您至少多配1-2只动物的量；
2：为该产品最终给药时的浓度。
| 动物模型 | A375P F11 Melanoma Xenograft in nude mice |
| 配制 | 0.5% hydroxypropylmethylcellulose (Sigma) and 0.2% Tween-80 in distilled water pH 8.0 |
| 剂量 | 0.2 mL/20g daily |
| 给药处理 | oral gavage |
* 上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。
其他相关的Raf产品
参考文献
