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WH-4-023

现货
Catalog No.
B8003
Lck/Src抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,000.00
现货
5mg
¥ 800.00
现货
10mg
¥ 1,200.00
现货
50mg
¥ 4,000.00
现货
100mg
¥ 6,500.00
Ship with 10-15 days

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Background

WH-4-023 is a potent and selective Lck and Src inhibitor with IC50 values of 2 and 6 nM, respectively [1]. It is also an inhibitor of IC50 values of 10, 22 and 60 nM for SIK 1, 2 and 3, respectively [2].

Lck and Src are cytoplasmic tyrosine kinases of the Src family expressed in T cells and NK cells [1]. SIKs restrict the formation of regulatory macrophages and that their inhibition greatly stimulates the production of IL-10 and other anti-inflammatory molecules [2].

WH-4-023 inhibited a number of protein tyrosine kinases that possess a Thr residue at the gatekeeper site, such as FGF and Ephrin receptors, Src family members (Src, Lck, and Yes) and BTK. WH-4-023 also inhibited the SIKs and did not inhibit any other member of the AMPK-related kinase subfamily, which all possess a large hydrophobic residue (Met or Leu) at the gatekeeper site. WH-4-023 inhibited SIK 1, 2 and 3 with IC50 values of 10, 22 and 60 nM, respectively. Also, WH-4-023 increased LPS-stimulated IL-10 production and greatly suppressed proinflammatory cytokine secretion [2].

References:
[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].  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.

Chemical Properties

Physical AppearanceA solid
StorageDesiccate at -20°C
M.Wt568.67
Cas No.837422-57-8
FormulaC32H36N6O4
Solubility≥56.9mg/mL in DMSO
Chemical Name2,6-dimethylphenyl (2,4-dimethoxyphenyl)(2-((4-(4-methylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)carbamate
SDFDownload SDF
Canonical SMILESCN1CCN(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

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.

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