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Dabrafenib (GSK2118436)

现货
Catalog No.
B1407
BRAF(V600)突变抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 550.00
现货
10mg
¥ 700.00
现货
50mg
¥ 1,500.00
现货
100mg
¥ 2,400.00
现货

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Background

Dabrafenib is a specific inhibitor of BRAF V600 mutants with IC50 values of 0.5nM, 0.6nM and 1.9nM against V600E, V600K and V600D, respectively [1].

BRAF plays a central role in regulating MAPK signaling pathway which regulates cell growth, division and differentiation. The V600E mutation of BRAF increases the kinase activity and is involved in metastatic melanomas. Dabrafenib is an ATP-competitive and reversible inhibitor of BRAF mutants. It potently inhibits BRAFV600E, BRAFV600K and BRAFV600D with IC50 values of 0.5nM, 0.6nM and 1.9nM, respectively. Dabrafenib is currently approved by FDA and is widely used in cancer patients harboring BRAF mutations. It is reported that treatment of dabrafenib shrinks the overall size of brain metastases in patients. It also has an impressive 60% response rate for melanomas outside of the brain. Dabrafenib provides a significant survival benefit in patients with metastatic melanoma [1, 2].

References:
[1] Hong S, Hong S. Overcoming metastatic melanoma with BRAF inhibitors. Archives of pharmacal research, 2011, 34(5): 699-701.
[2] Hong D S, Vence L, Falchook G, et al. BRAF (V600) inhibitor GSK2118436 targeted inhibition of mutant BRAF in cancer patients does not impair overall immune competency. Clinical Cancer Research, 2012, 18(8): 2326-2335.

文献引用

1. Cheriyan VT, Alsaab H, et al. "A CARP-1 functional mimetic compound is synergistic with BRAF-targeting in non-small cell lung cancers." Oncotarget. 2018 Jul 3;9(51):29680-29697. PMID:30038713
2. Azimi A, Caramuta S, et al. "Targeting CDK2 overcomes melanoma resistance against BRAF and Hsp90 inhibitors." Mol Syst Biol. 2018 Mar 5;14(3):e7858. PMID:29507054
3. Sieber J, Wieder N, et al. "GDC-0879, a BRAF(V600E) Inhibitor, Protects Kidney Podocytes from Death." Cell Chem Biol. 2017 Dec 6. PMID:29249695

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt519.56
Cas No.1195765-45-7
FormulaC23H20F3N5O2S2
Solubility≥26mg/mL in DMSO, ≥2.59 mg/mL in EtOH with ultrasonic and warming, <2.58 mg/mL in H2O
Chemical NameN-[3-[5-(2-aminopyrimidin-4-yl)-2-tert-butyl-1,3-thiazol-4-yl]-2-fluorophenyl]-2,6-difluorobenzenesulfonamide
SDFDownload SDF
Canonical SMILESCC(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
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1, 2]:

细胞系

编码突变的B-RafV600E的黑色素瘤细胞(SKMEL28和A375P F11)、结肠癌细胞Colo205与 HT29细胞

溶解方法

该化合物在DMSO中的溶解度> 10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应时间

10 μM处理24小时

应用

Dabrafenib有效抑制编码突变的B-RafV600E的黑色素瘤细胞(SKMEL28和A375P F11)、结肠癌细胞Colo205细胞增殖,其IC50值分别为3 nM、8 nM和7 nM。同时,Dabrafenib能选择性地抑制RIP3并且抑制RIP3介导的HT29细胞坏死。

动物实验 [1, 2]:

动物模型

A375P F11 (B-RafV600E)肿瘤CD1 nu/nu小鼠模型

剂量

0.1、1、10和100 mg/kg,口服,每日一次,持续14天或口服300 mg/kg、100 mg/kg dabrafenib

应用

Dabrafenib以剂量相关的方式抑制B-RafV600E突变的黑色素瘤(A375P F11)的生长并且降低人源黑色素瘤组织的pERK表达水平;同时,Dabrafenib能缓解对乙酰氨基酚诱导的鼠肝损伤。

注意事项

请于室内测试所有化合物的溶解度。实际溶解度和理论值可能略有不同,这是由实验系统的误差引起的,属于正常现象。

References:

1. Rheault, T. R., Stellwagen, J. C., Adjabeng, G. M., Hornberger, K. R., Petrov, K. G., Waterson, A. G., Dickerson, S. H., Mook, R. A., Jr., Laquerre, S. G., King, A. J., Rossanese, O. W., Arnone, M. R., Smitheman, K. N., Kane-Carson, L. S., Han, C., Moorthy, G. S., Moss, K. G. and Uehling, D. E. (2013) Discovery of Dabrafenib: A Selective Inhibitor of Raf Kinases with Antitumor Activity against B-Raf-Driven Tumors. ACS Med Chem Lett. 4, 358-362

2. Li, J. X., Feng, J. M., Wang, Y., Li, X. H., Chen, X. X., Su, Y., Shen, Y. Y., Chen, Y., Xiong, B., Yang, C. H., Ding, J. and Miao, Z. H. (2014) The B-Raf(V600E) inhibitor dabrafenib selectively inhibits RIP3 and alleviates acetaminophen-induced liver injury. Cell Death Dis. 5, e1278

生物活性

描述 Dabrafenib(GSK2118436)是突变BRAFV600的特异性抑制剂,IC50值为0.8 nM。
靶点 B-Raf (V600E) B-Raf C-Raf      
IC50 0.8 nM 3.2 nM 5.0 nM      

质量控制

化学结构

Dabrafenib (GSK2118436)

相关生物数据

Dabrafenib (GSK2118436)

相关生物数据

Dabrafenib (GSK2118436)