现货大促销,价格低至8折起,量大更优惠,详细咨询客服
全部分类
全部分类
  • Dabrafenib Mesylate (GSK-2118436)
Dabrafenib Mesylate (GSK-2118436)的可视化放大

Dabrafenib Mesylate (GSK-2118436)

A Raf kinase inhibitor

原价
¥625-2250
价格
500-1800
Dabrafenib Mesylate (GSK-2118436)的二维码

所有产品仅用于科学研究,我们不为任何个人用途提供产品和服务

询价有惊喜,量大更优惠 点击这里给我发消息

  • 库存: 现货
可选包装 >>>
首页
  • 货号: ajci9214
  • CAS: 1195768-06-9
  • 别名: 甲磺酸达拉非尼; GSK2118436 Mesylate; GSK 2118436B
  • 分子式: C24H24F3N5O5S3
  • 分子量: 615.67
  • 纯度: >98%
  • 溶解度: ≥ 30.75 mg/mL in DMSO, ≥ 2.74 mg/mL in EtOH with ultrasonic and warming
  • 储存: Store at -20°C
  • 库存: 现货

Background

GSK2118436 is a selective BRAF V600E inhibitor. BRAF encodes a proto-oncogene B-Raf also known as serine/threonine protein kinase B-Raf. It is critical in regulating the MAPK/ERK signaling pathway. BRAF mutations frequently occur in many human cancers. [1, 2] BRAF V600E mutant is constitutively active, allowing MAPK/ERK activation independent of upstream cues. [3]


GSK2118436 binds to Raf family kinases and inhibits their activity. It is highly selective against B-Raf V600E with IC50 of 0.8 nM, compared to wild type B-Raf and c-Raf with IC50s of 3.2 nM and 5.0 nM, respectively. [4]


GSK2118436 treatment shows selective inhibition of MAPK/ERK activation, proliferation, transformation and tumorigenicity. FDA approved GSK2118436 as a single agent treatment for advanced melanoma with BRAF V600E mutation on May 30, 2013.


GSK2118436 can be taken orally.

参考文献:
[1]Namba H, Nakashima M, Hayashi T, Hayashida N, Maeda S, Rogounovitch TI, Ohtsuru A, Saenko VA, Kanematsu T, Yamashita S. Clinical implication of hot spot BRAF mutation, V599E, in papillary thyroid cancers. J. Clin. Endocrinol. Metab. 2003; 88 (9): 4393–7.
[2]Tan YH, Liu Y, Eu KW, Ang PW, Li WQ, Salto-Tellez M, Iacopetta B, Soong R. Detection of BRAF V600E mutation by pyrosequencing. Pathology 2008; 40 (3): 295–8.
[3]Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature. 2002; 417: 949-954.
[4]Ma XH, Piao SF, Dey S, McAfee Q, Karakousis G, Villanueva J, Hart LS, Levi S, Hu J, Zhang G, Lazova R, Klump V, Pawelek JM, Xu X, Xu W, Schuchter LM, Davies MA, Herlyn M, Winkler J, Koumenis C, Amaravadi RK. Targeting ER stress-induced autophagy overcomes BRAF inhibitor resistance in melanoma. J Clin Invest. 2014; 124(3): 1406-17.

Protocol

Cell experiment [1]:

Cell lines

M257 wild-type BRAF, LCP BRAFV600R and WM266 BRAFV600D melanoma cell lines.

Preparation method

Soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reaction Conditions

3-100 nM; 72 h

Applications

Dabrafenib remarkably inhibits cell proliferation and phosphorylated ERK in both melanoma cell lines carrying a mutated BRAF.

Animal experiment [2]:

Animal models

Female CD1 nu/nu mice xenografted BRAFV600E (A375P) human tumor.

Dosage form

30 mg/kg; 14 days; dosed orally once daily.

Preparation method

0.5% hydroxypropylmethylcellulose, 0.2% Tween 80 in pH 8.0 distilled water; 0.2 mL per 20 g of bodyweight.

Applications

Dabrafenib is orally bioavailable, reduces pERK and inhibits tumor growth. Dabrafenib reduces pERK and Ki67 by 89% and 28% respectively and increases p27 by 54%.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

参考文献:

[1]. Gentilcore G, Madonna G, Mozzillo N, et al. Effect of dabrafenib on melanoma cell lines harbouring the BRAF(V600D/R) mutations. BMC Cancer, 2013, 13: 17.


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

动态评分

0.0

没有评分数据
没有评价数据
一键回到顶部
展开 收缩
安捷凯在线客服