规格 | 价格 | 库存 | 数量 |
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25mg |
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50mg |
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100mg |
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250mg |
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500mg |
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1g |
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Other Sizes |
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靶点 |
B-Raf (V600E) (IC50 = 0.7 nM); B-Raf (IC50 = 5.2 nM); C-Raf (IC50 = 6.3 nM)
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体外研究 (In Vitro) |
Dabrafenib 在酶和细胞机制测定以及 B-RafV600E 驱动的黑色素瘤系 SKMEL28 和 A375P F11(IC50 分别 = 3 和 8 nM)和结直肠癌系 Colo205(IC50 = 7纳米)。对于具有野生型 B-Raf 的细胞和缺乏激活的 B-RafV600E 突变的肿瘤细胞,达拉非尼在体外几乎没有作用 (HFF IC50 = 3.0 μM)。与大多数筛选的激酶相比,B-RafV600E 的选择性高出 500 倍。该组中的激酶之一 Alk5 显示出显着的活性(<100 倍选择性),但 GSK2118436 在抑制 SMAD2/3 磷酸化 (IC50 = 3.7 μM) 方面的效果明显低于抑制 ERK 磷酸化 (IC50 = 4) 的效果nM)在细胞环境中[1]。达拉非尼降低细胞中 BRAFV600E 激酶的活性,进而导致 MEK 和 ERK 磷酸化减少,以及 G1 细胞周期停滞和细胞死亡。
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体内研究 (In Vivo) |
在含有 BRAFV600E 的人类黑色素瘤异种移植模型中,口服达拉非尼可阻止 ERK 激活、下调 Ki67 并上调 p27,从而抑制肿瘤生长。达拉非尼具有口服生物利用度,多次给药后不会显着蓄积,并且在给药 7 天和 14 天后会降低 pERK[2]。这种作用在给药后可持续长达 18 小时。
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细胞实验 |
对于长期增殖测定,将细胞置于含有 10% FBS 的 RMPI-1640 中 12 天,并用单一化合物或化合物组合进行处理。该测定涉及至少一种化合物治疗替代。 12 天后,使用 50% 乙醇中的 0.5% 亚甲蓝对细胞进行染色。使用平板扫描仪拍摄照片。
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动物实验 |
The 26 10-week-old, time-mated, virus-antibody-free SD (Crl:CD[SD]) female rats that were chosen as the test system gave birth to the rat pups. From Day 20 to Day 23 postpartum, mated females are monitored for spontaneous deliveries (the day parturition is complete is designated PND 0). When parturition is complete, on PNDs 3 and 6, litter examinations are carried out. These examinations include external morphologic examinations, gender determination, and individual pup weights. Clinical signs and body weights are used to select parturient dams and their litters for the study, and selected dams and their litters are then randomly assigned to study groups based on clinical observations and PND 3 litter mean body weights. On PND 3 or 4, litters are reduced to four or five males and females, with only a small amount of fostering required to achieve the desired sex ratio. This helps to preserve natural litter sizes as much as possible. Records of the pups raised by the original and foster dams are kept. Paw tattoos are used to identify each puppy. Nonlittermates are placed in subsets to the greatest extent possible. DAB is administered to young male and female rats by oral gavage at a dose volume of 5 ml/kg, based on daily body weight, in a suspension of vehicle, 0.5% hydroxypropylmethylcellulose K15M, and 0.1% (v/v) Tween80 in purified water.
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参考文献 |
分子式 |
C24H24F3N5O5S3
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分子量 |
615.66
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元素分析 |
C, 46.82; H, 3.93; F, 9.26; N, 11.38; O, 12.99; S, 15.62
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CAS号 |
1195768-06-9
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相关CAS号 |
Dabrafenib;1195765-45-7
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外观&性状 |
Solid powder
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SMILES |
CC(C)(C)C1=NC(=C(S1)C2=NC(=NC=C2)N)C3=C(C(=CC=C3)NS(=O)(=O)C4=C(C=CC=C4F)F)F.CS(=O)(=O)O
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InChi Key |
YKGMKSIHIVVYKY-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C23H20F3N5O2S2.CH4O3S/c1-23(2,3)21-30-18(19(34-21)16-10-11-28-22(27)29-16)12-6-4-9-15(17(12)26)31-35(32,33)20-13(24)7-5-8-14(20)25;1-5(2,3)4/h4-11,31H,1-3H3,(H2,27,28,29);1H3,(H,2,3,4)
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化学名 |
N-[3-[5-(2-aminopyrimidin-4-yl)-2-tert-butyl-1,3-thiazol-4-yl]-2-fluorophenyl]-2,6-difluorobenzenesulfonamide;methanesulfonic acid
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别名 |
GSK2118436A Mesylate; GSK 2118436A Mesylate; GSK-2118436A; GSK2118436B ( Dabrafenib Mesylate); GSK-2118436B Mesylate; GSK 2118436B. Trade name: Tafinlar.
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HS Tariff Code |
2934.99.9001
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存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
运输条件 |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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溶解度 (体外) |
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溶解度 (体内) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.06 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.06 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.06 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 2.5 mg/mL (4.06 mM) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 5: ≥ 2.5 mg/mL (4.06 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 6: 30% PEG400+0.5% Tween80+5% Propylene glycol: 8 mg/mL 1、请先配制澄清的储备液(如:用DMSO配置50 或 100 mg/mL母液(储备液)); 2、取适量母液,按从左到右的顺序依次添加助溶剂,澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明,并不一定代表此产品 的实际溶解配方): 10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline); 假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀/澄清;向上述体系中加入50 μL Tween-80,混合均匀/澄清;然后继续加入450 μL ddH2O (或 saline)定容至 1 mL; 3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例; 4、 如产品在配制过程中出现沉淀/析出,可通过加热(≤50℃)或超声的方式助溶; 5、为保证最佳实验结果,工作液请现配现用! 6、如不确定怎么将母液配置成体内动物实验的工作液,请查看说明书或联系我们; 7、 以上所有助溶剂都可在 Invivochem.cn网站购买。 |
制备储备液 | 1 mg | 5 mg | 10 mg | |
1 mM | 1.6243 mL | 8.1214 mL | 16.2427 mL | |
5 mM | 0.3249 mL | 1.6243 mL | 3.2485 mL | |
10 mM | 0.1624 mL | 0.8121 mL | 1.6243 mL |
1、根据实验需要选择合适的溶剂配制储备液 (母液):对于大多数产品,InvivoChem推荐用DMSO配置母液 (比如:5、10、20mM或者10、20、50 mg/mL浓度),个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息,或者很难将产品溶解在溶液中,请联系我们;
3、建议使用下列计算器进行相关计算(摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等);
4、母液配好之后,将其分装到常规用量,并储存在-20°C或-80°C,尽量减少反复冻融循环。
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)。如该浓度超过该批次药物DMSO溶解度,请首先与我们联系。
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 ddH2O,混匀澄清。
(1) 请确保溶液澄清之后,再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶;
(2) 一定要按顺序加入溶剂 (助溶剂) 。
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT04439292 | Active Recruiting |
Drug: Dabrafenib Mesylate Drug: Trametinib Dimethyl Sulfoxide |
Advanced Lymphoma Refractory Lymphoma |
National Cancer Institute (NCI) |
August 12, 2015 | Phase 2 |
NCT02447939 | Active Recruiting |
Drug: Dabrafenib Drug: Trametinib |
Melanoma | GlaxoSmithKline | May 2017 | Phase 1 |
NCT01738451 | Active Recruiting |
Drug: GSK2118436 75 mg Drug: Placebo |
Cancer | GlaxoSmithKline | January 22, 2013 | Phase 1 |
NCT02083354 | Completed | Drug: Dabrafenib Drug: Trametinib |
Cancer Melanoma |
Novartis Pharmaceuticals | March 18, 2014 | Phase 2 |
NCT01336634 | Completed | Drug: Dabrafenib Drug: Trametinib |
Cancer | Novartis Pharmaceuticals | August 5, 2011 | Phase 2 |