Dabrafenib (GSK2118436)是一种突变型BRAFV600特异性抑制剂，IC50为0.8 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。
别名：GSK-2118436B
Dabrafenib (GSK2118436)是一种突变型BRAFV600特异性抑制剂，IC50为0.8 nM，作用于B-Raf(wt)和c-Raf效果低4和6倍。Dabrafenib对Raf激酶具有选择性，对B-Raf的活性比其它测试过的91%的激酶高400倍。 Dabrafenib抑制B-RafV600E激酶，导致ERK磷酸化降低和抑制细胞的增值，在特异性编码突变的B-RafV600E的癌细胞中细胞停滞在G1期。Dabrafenib（口服）抑制B-RafV600E突变的黑色素瘤（A375P）的生长，在免疫受损小鼠中皮下注射结肠癌（Colo205），Dabrafenib（口服）同样能抑制肿瘤生长。
Immunobiology. 2023 Jan;228(1):152311.
| 体外实验* | |
|---|---|
| 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。
| 体内实验* | |
|---|---|
| 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。
| 分子量 | 615.67 |
| 分子式 | C23H20F3N5O2S2.CH4O3S |
| CAS号 | 1195768-06-9 |
| 溶解性（25°C） | DMSO 36 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。 |
*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。
| Concentration / Solvent Volume / Mass | 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 |
| 小鼠 | 大鼠 | 兔 | 豚鼠 | 仓鼠 | 狗 | |
| 重量 (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| 体表面积 (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km 系数 | 3 | 6 | 12 | 8 | 5 | 20 |
| 动物 A (mg/kg) = 动物 B (mg/kg) × | 动物 B的Km系数 |
| 动物 A的Km系数 |
例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。
| 其他相关的Raf产品 |
|---|
| Cyclorasin 9A5
Cyclorasin 9A5 是一种具有11个残基的细胞渗透环肽，抑制 Ras-Raf 蛋白的相互作用，其 IC50 值为 120 nM。 |
| R18
R18 是 14-3-3 的肽拮抗剂，其 KD 值为 70-90 nM。 |
| PROTAC RAF degrader 1
PROTAC RAF degrader 1 是一种 PROTAC RAF 降解剂。 |
| B-Raf IN 15
BRAF V600E/CRAF-IN-3 是一种 BRAF 抑制剂。 |
| Raf inhibitor 3
Raf inhibitor 3 是一种 Raf 抑制剂。 |
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