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WZ4003

现货
Catalog No.
B1374
NUAK1/2抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,100.00
现货
5mg
¥ 680.00
现货
50mg
¥ 3,990.00
现货

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Background

WZ4003 is a potent and selective inhibitor of NUAK1 and NUAK2 with IC50 values of 20 and 100 nM, respectively [1].

NUAK family SNF1-like kinase-1 (NUAK1) and the related NUAK2 belong to the AMP-activated protein kinase (AMPK) family and are activated by liver kinase B1 (LKB1) tumour suppressor protein kinase [1].

WZ4003 is a potent and selective NUAK1/2 inhibitor. In HEK-293 cells, WZ4003 inhibited the phosphorylation of myosin phosphate-targeting subunit 1 (MYPT1), which was phosphorylated by NUAK1 at Ser445. In HEK-293 cells overexpressing inhibitor-resistant NUAK1[A195T], WZ4003 didn’t inhibit the phosphorylation of MYPT1 at Ser445. In mouse embryonic fibroblasts (MEFs), WZ4003 significantly inhibited migration in a wound-healing assay and inhibited MEFs proliferation. In a cell invasion assay, WZ4003 inhibited the invasive potential of U2OS cells [1]. In U2OS cells, WZ4003 (10 μM) inhibited phosphorylation of MYPT1 and reduced the cells in S-phase by 50%. Also, WZ4003 prevented cells from entering into mitosis [2].

References:
[1].  Banerjee S, Buhrlage SJ, Huang HT, et al. Characterization of WZ4003 and HTH-01-015 as selective inhibitors of the LKB1-tumour-suppressor-activated NUAK kinases. Biochem J, 2014, 457(1): 215-225.
[2].  Banerjee S, Zagórska A, Deak M, et al. Interplay between Polo kinase, LKB1-activated NUAK1 kinase, PP1βMYPT1 phosphatase complex and the SCFβTrCP E3 ubiquitin ligase. Biochem J, 2014, 461(2): 233-245.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt496.99
Cas No.1214265-58-3
FormulaC25H29ClN6O3
Solubility≥7.85mg/mL in DMSO with gentle warming
Chemical NameN-[3-[5-chloro-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]oxyphenyl]propanamide
SDFDownload SDF
Canonical SMILESCCC(=O)NC1=CC(=CC=C1)OC2=NC(=NC=C2Cl)NC3=C(C=C(C=C3)N4CCN(CC4)C)OC
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

酶学实验[1]:

激酶检测

使用Cerenkov,通过定量Sakamototide底物肽中来自于[γ-32P]ATP的放射性32P的数量来测量纯化的GST-NUAK1的体外活性。反应在30℃、50μl反应体积进行30分钟,通过将40μl反应混合物点样到P81纸上并立即浸入50mM正磷酸中终止反应。样品在50mM正磷酸中洗涤三次,随后用丙酮冲洗一次,空气干燥。通过Cerenkov计数定量激酶介导的从[γ-32P]ATP中掺入Sakamototide底物肽的32P。

细胞实验[1]:

细胞系

U2OS细胞系

溶解方法

在DMSO中的溶解度> 7.85mg/mL。为了获得更高浓度,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

10 μM作用16小时

应用

WZ4003在3D细胞侵袭试验中降低了U2OS细胞的侵袭潜力,效果与NUAK1敲低相同,这表明WZ4003可作为阐述NUAK激酶生物学作用的化学探针。

References:

[1] Banerjee S, Buhrlage SJ, Huang HT, et al. Characterization of WZ4003 and HTH-01-015 as selective inhibitors of the LKB1-tumour-suppressor-activated NUAK kinases. Biochem J, 2014, 457(1): 215-225.

质量控制

质量控制和MSDS

批次:

化学结构

WZ4003