WH-4-023
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
WH-4-023是一种有效的和选择性的Lck和Src抑制剂,IC50值分别为2和6 nM[1]。
淋巴细胞特异性激酶(Lck)是一种酪氨酸激酶,在淋巴细胞的细胞内信号途径中起重要作用。Src是一种非受体酪氨酸激酶蛋白,参与胚胎发育和细胞生长的调控[1]。据报道,Lck和Src的异常表达与多种癌症相关[2]。
在巨噬细胞中,WH-4-023不仅抑制在门控位点含有Thr残基的多种蛋白酪氨酸激酶,如FGF和Ephrin受体,还作用于Src家族成员(Src、Lck和Yes)和BTK。而且,WH-4-023抑制SIK 1、2和3,IC50值分别为10、22和60 nM,而对AMPK相关激酶亚家族的任何其它成员均没有抑制活性,而这些成员在门控位点均没有大的疏水残基(Met或Leu)[3]。
据报道,WH-4-023增加LPS刺激的IL-10的产生,极大抑制促炎细胞因子的分泌[2]。
参考文献:
[1]. Martin MW, Newcomb J, Nunes JJ, et al. Novel 2-aminopyrimidine carbamates as potent and orally active inhibitors of Lck: synthesis, SAR, and in vivo antiinflammatory activity. J Med Chem, 2006, 49(16): 4981-4991.
[2]. Lin YL, Roux B. Computational analysis of the binding specificity of Gleevec to Abl, c-Kit, Lck, and c-Src tyrosine kinases [J]. J Am Chem Soc, 2013, 135(39):14741-14753.
[3]. Clark K, MacKenzie KF, Petkevicius K, et al. Phosphorylation of CRTC3 by the salt-inducible kinases controls the interconversion of classically activated and regulatory macrophages. Proc Natl Acad Sci U S A, 2012, 109(42): 16986-16991.
Physical Appearance | A solid |
Storage | Desiccate at -20°C |
M.Wt | 568.67 |
Cas No. | 837422-57-8 |
Formula | C32H36N6O4 |
Solubility | ≥56.9 mg/mL in DMSO; insoluble in H2O; ≥2.42 mg/mL in EtOH with gentle warming and ultrasonic |
Chemical Name | 2,6-dimethylphenyl (2,4-dimethoxyphenyl)(2-((4-(4-methylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)carbamate |
SDF | Download SDF |
Canonical SMILES | CN1CCN(C2=CC=C(NC3=NC(N(C4=CC=C(OC)C=C4OC)C(OC5=C(C)C=CC=C5C)=O)=CC=N3)C=C2)CC1 |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 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。溶液形式一般不宜长期储存,请尽快用完。 |
激酶实验[1]: | |
Lck激酶实验 |
采用激酶实验检测WH-4-023对Lck的抑制作用。Lck均相时间分辨荧光激酶实验涉及有或无WH-4-023存在条件下胃泌素的生物素化底物肽的ATP依赖性磷酸化。ATP、胃泌素和Lck的终浓度分别为0.5 μM、1.2 μM和250 pM。缓冲液配置如下:50 mM HEPES pH=7.5,2 mM DTT,5 mM MnCl2,20 mM MgCl2,50 mM NaCl,0.05% BSA。加入160 μL检测试剂猝灭终止反应,检测试剂配置如下:50 mM Tris,pH=7.5,3 mM EDTA,100 mM NaCl,0.05% BSA,0.1% Tween-20。读数之前加入终浓度为0.4 μg/mL的链霉亲和素别藻蓝蛋白和0.025 nM的抗磷酸酪氨酸抗体,在激发光320 nm,发射光615和655 nm的条件下读取酶联板的数据。 |
细胞实验[2]: | |
细胞系 |
人原始多能细胞 |
溶解方法 |
在DMSO中的溶解度大于10 mM。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。 |
反应条件 |
1 μM |
应用 |
WH-4-023是一个强效的选择性Src和Lck抑制剂,对Src和Lck的IC50分别为6 nM和2 nM[1]。在含有WH-4-023的培养基中培养人原始多能细胞,WH-4-023可提高活GFP+ 细胞的比例,若去掉WH-4-023,细胞形态改变,OCT4-DPE-GFP报告基因活性有轻微的下降[2]。 |
References: [1]. Martin M W, Newcomb J, Nunes J J, et al. Novel 2-aminopyrimidine carbamates as potent and orally active inhibitors of Lck: synthesis, SAR, and in vivo antiinflammatory activity[J]. Journal of medicinal chemistry, 2006, 49(16): 4981. [2]. Theunissen T W, Powell B E, Wang H, et al. Systematic Identification of Defined Conditions for Induction and Maintenance of Naive Human Pluripotency[J]. Cell stem cell, 2014, 15(4): 471. |
质量控制和MSDS
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