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Dabrafenib

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Chemical Structure| 1195765-45-7 同义名 : 达拉菲尼 ;GSK2118436A;GSK2118436
CAS号 : 1195765-45-7
货号 : A484347
分子式 : C23H20F3N5O2S2
纯度 : 98%
分子量 : 519.562
MDL号 : -
存储条件：

粉末 Keep in dark place,Inert atmosphere,Room temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 35 mg/mL(67.36 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

2% DMSO+45% PEG 300+2% Tween 80+water 5 mg/mL

生物活性
靶点

  • B-Raf

    B-Raf, IC50:5.2 nM

    B-Raf (V600E), IC50:0.7 nM

  • C-Raf/Raf-1

    C-Raf, IC50:6.3 nM
描述 The RAS/RAF signaling pathway is an important mediator of tumor cell proliferation and angiogenesis. Among them, B-RAF is the most frequently mutated protein kinase in human cancers. Dabrafenib is a potent, selective and efficacious inhibitor of B-RafV600E with IC50 value of 0.7 nM, and less potent to B-Raf and C-Raf with IC50 values of 5.2 nM and 6.3 nM (measured by enzymatic activity), respectively. Consistent with the in vitro kinase assay, Dabrafenib displayed compelling inhibitory on p-ERK in SKMEL28 cells with IC50 value of 4 nM, as well as on cell proliferation of B-RafV600E-driven melanoma lines such as SKMEL28 and A375P F11 (IC50=3 nM and 8 nM, respectively) and colorectal carcinoma line Colo205 (IC50=7 nM). Meanwhile, Dabrafenib had a minimal effect on cells with wild-type B-Raf (HFF IC50=3.0 μM) and in tumor cells not harboring the activating B-RafV600E mutation. Oral administration of Dabrafenib at doses of 0.1, 1, 10, and 100 mg/kg once daily for 14 days dose-dependently reduce tumor growth with notable pharmacodynamic response, measured by pERK levels after a single oral dose, in CD1 nu/nu mice bearing A375P F11 (B-RafV600E) tumors. Dabrafenib is currently in phase III clinical development for the treatment of activating B-Raf mutant tumors[1].
作用机制 Dabrafenib binding to BRAF is ATP-competitive.[2]
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
22Rv1 10 μM Growth Inhibition Assay 72 h IC50=10 μM 23844038
647-V 10 μM Growth Inhibition Assay 72 h IC50=10 μM 23844038
786-O 10 μM Growth Inhibition Assay 72 h IC50=10 μM 23844038
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.92mL

0.38mL

0.19mL

9.62mL

1.92mL

0.96mL

19.25mL

3.85mL

1.92mL
参考文献

[1]Rheault TR, Stellwagen JC, et al. Discovery of Dabrafenib: A Selective Inhibitor of Raf Kinases with Antitumor Activity against B-Raf-Driven Tumors. ACS Med Chem Lett. 2013 Feb 7;4(3):358-62.

[2]King AJ, Arnone MR, et al. Dabrafenib; preclinical characterization, increased efficacy when combined with trametinib, while BRAF/MEK tool combination reduced skin lesions. PLoS One. 2013 Jul 3;8(7):e67583.

[3]Tafinlar