Dabrafenib (GSK2118436A) 是ATP竞

Dabrafenib  (Synonyms: 达拉非尼; GSK2118436A; GSK2118436)

Dabrafenib (GSK2118436A) 是ATP竞争型的 Raf 抑制剂，抑制 C-Raf 和 B-Raf^V600E 的 IC₅₀ 分别为 5 nM 和 0.6 nM。

美国medchemexpress（MCE)浙江省一级代理:杭州昊鑫生物科技股份有限公司
MCE中国是全球领先的科研化学品和生物活性化合物供应商，总部位于美国新泽西。我们的产品范围覆盖各种抑制剂、激动剂、API和化合物库。专业、高效的企业灵魂铸造了在行业的卓越地位。热情和充满活力的研发团队拥有着大量的化学和生物科学家。专注于生物活性化合物，拥有着多年的发展历程和丰富的行业经验。

生物活性    
Dabrafenib (GSK2118436A) is an ATP-competitive inhibitor of Raf with IC50s of 5 nM and 0.6 nM for C-Raf and B-RafV600E, respectively[4].

体外研究(In Vitro)    
Dabrafenib (GSK2118436, 1 μM) with 0.01 μM GSK1120212 inhibits more than 90% of cell growth in the NRAS mutant clones. GSK2118436 is sufficient to reduce S6P phosphorylation in A375[1]. Dabrafenib suppresses the PolyP-mediated vascular barrier permeability, upregulation of inflammatory biomarkers, adhesion/migration of leukocytes, and activation and/or production of nuclear factor-κB, tumor necrosis factor-α, and interleukin-6[2]. Dabrafenib inhibits the release of HMGB1 and downregulates HMGB1-dependent inflammatory responses by enhancing the expressions of cell adhesion molecules (CAMs) in human endothelial cells[3].

体内研究(In Vivo)    
Dabrafenib-treated females have mostly immature reproductive tracts with no evidence of ovulation, similar to age-matched controls; however, DAB-treated females have keratinized and histologically open vaginas[5].

分子量    
519.56

性状    
Solid

Formula    
C23H20F3N5O2S2

CAS 号    
1195765-45-7

中文名称    
达拉非尼

运输条件    
Room temperature in continental US; may vary elsewhere.

储存方式    
Powder    -20°C    3 years
4°C    2 years
In solvent    -80°C    2 years
-20°C    1 year
溶解性数据    
In Vitro: 
DMSO : ≥ 33 mg/mL (63.52 mM)

* "≥" means soluble, but saturation unknown.

配制储备液    
浓度溶剂体积质量    1 mg    5 mg    10 mg
1 mM    1.9247 mL    9.6235 mL    19.2471 mL
5 mM    0.3849 mL    1.9247 mL    3.8494 mL
10 mM    0.1925 mL    0.9624 mL    1.9247 mL
*
请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 2 years; -20℃, 1 year。-80℃ 储存时，请在 2 年内使用， -20℃ 储存时，请在 1 年 内使用。

In Vivo:
请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.
请依序添加每种溶剂： 30% PEG400  0.5% Tween80  5% Propanediol  64.5%H2O

Solubility: 5 mg/mL (9.62 mM); Suspended solution; Need ultrasonic

2.
请依序添加每种溶剂： 0.5%HPMC

Solubility: 2.5 mg/mL (4.81 mM); Suspended solution; Need ultrasonic

3.
请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

Solubility: ≥ 2.5 mg/mL (4.81 mM); Clear solution

4.
请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

Solubility: ≥ 2.5 mg/mL (4.81 mM); Clear solution

5.
请依序添加每种溶剂： 10% DMSO    90% corn oil

Solubility: ≥ 2.5 mg/mL (4.81 mM); Clear solution

6.
请依序添加每种溶剂： 5% DMSO    40% PEG300    5% Tween-80    50% saline

Solubility: 2.5 mg/mL (4.81 mM); Suspended solution; Need ultrasonic

7.
请依序添加每种溶剂： 5% DMSO    95% (20% SBE-β-CD in saline)

Solubility: ≥ 2.5 mg/mL (4.81 mM); Clear solution
 

参考文献

[1]. Greger JG, et al. Combinations of BRAF, MEK, and PI3K/mTOR inhibitors overcome acquired resistance to the BRAF inhibitor GSK2118436 dabrafenib, mediated by NRAS or MEK mutations. Mol Cancer Ther, 2012, 11(4), 909-920.  [Content Brief] [2]. Lee S, et al. Anti-inflammatory effects of dabrafenib on polyphosphate-mediated vascular disruption. Chem Biol Interact. 2016 Jul 22.  [Content Brief] [3]. Jung B, et al. Anti-septic effects of dabrafenib on HMGB1-mediated inflammatory responses. BMB Rep. 2016 Apr;49(4):214-9.  [Content Brief] [4]. Alexander M Menzies, et al. Dabrafenib and its potential for the treatment of metastatic melanoma. Drug Des Devel Ther. 2012; 6: 391–405.  [Content Brief] [5]. Posobiec LM, et al. Early Vaginal Opening in Juvenile Female Rats Given BRAF-Inhibitor Dabrafenib Is Not Associated with Early Physiologic Sexual Maturation. Birth Defects Res B Dev Reprod Toxicol. 2015 Dec;104(6):244-52.  [Content Brief]