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PD173955

现货
Catalog No.
A8812
Src/Abl激酶双重抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,740.00
现货
5mg
¥ 1,380.00
现货
25mg
¥ 4,880.00
Ship with 10-15 days

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Background

PD173955 is a potent inhibitor of Bcr-Abl, Src and Yes with IC50 value of 1-2 nM, 300 nM and 175 nM, respectively [1-3].

Bcr-Abl is a protein tyrosine kinase which has oncogenic potential. Src is an enzyme and plays an important role in a variety of cancer cells survival, angiogenesis, proliferation and invasion pathways. Yes is a proto-oncogene tyrosine-protein kinase smf belongs to the Src kinase family [1-3].

PD173955 is a potent Bcr-Abl, Src and Yes inhibitor. When tested with CML CD34+ GM progenitors, PD173955 inhibited KL-dependent proliferation at an IC50 value of 50 nM and GM-CSF-dependent cell growth at an IC50 value of 1μM and the maximum inhibition was achieved at the dose of 25 nM. It was shown that PD173955 reduced the fractions of cells in G2-M phase and increased the cells in G1 phase with significant difference [2]. In HT29 cells, PD173955 treatment inhibited Src auot-phosphorylation in a dose dependent manner. Further, PD173955 showed inhibition on cell growth with IC50 value of 800 nM without morphologic changes and high concentrations arrested cell cycle at the M phase [1]. When tested with Bcr-Abl-depedent cell lines K562 and RWLeu4, PD173955 showed inhibition on cell proliferation with the IC50 value of 35 and 10 nM, respectively and arrested cell cycle in G1 phase at the low nanomolar [3].

References:
[1].  Windham, T.C., et al., Src activation regulates anoikis in human colon tumor cell lines. Oncogene, 2002. 21(51): p. 7797-807.
[2].  Strife, A., et al., Direct evidence that Bcr-Abl tyrosine kinase activity disrupts normal synergistic interactions between Kit ligand and cytokines in primary primitive progenitor cells. Mol Cancer Res, 2003. 1(3): p. 176-85.
[3].  Wisniewski, D., et al., Characterization of potent inhibitors of the Bcr-Abl and the c-kit receptor tyrosine kinases. Cancer Res, 2002. 62(15): p. 4244-55.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt443.35
Cas No.260415-63-2
FormulaC21H16Cl2N4OS
Solubility≥22.15mg/mL in DMSO with gentle warming
Chemical Name6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one
SDFDownload SDF
Canonical SMILESCN1C2=NC(=NC=C2C=C(C1=O)C3=C(C=CC=C3Cl)Cl)NC4=CC(=CC=C4)SC
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]:

体外Bcr-Abl激酶实验

在维持对数期的培养条件下,使Bcr-Abl和SHIP2复合物从K562细胞裂解物中免疫沉淀出来。使用蛋白质A-琼脂糖收集复合物,在裂解缓冲液中将复合物清洗3次,再用abl激酶缓冲液 [50 mM Tris (pH 8.0),10 mM MgCl2,1 mM DTT,2 mM对硝基苯酚磷酸盐和2 μM ATP] 清洗2次。加入或不加入指定浓度的药物,再将10 μM [γ-32P]ATP加入每个样品中。反应于30 °C下进行15 ~ 60分钟。加入SDS-PAGE样品缓冲液,将混合物置于100 °C加热10分钟,终止上述反应。使用7.5% SDS聚丙烯酰胺凝胶分离蛋白,凝胶于真空下干燥,通过放射自显影观察X-ray胶片,从而评估磷酸化程度。

细胞实验 [1]:

细胞系

Bcr-Abl阳性细胞系K562和RWLeu4

制备方法

该化合物在DMSO中的溶解度有限。若配制更高浓度的溶液,一般步骤如下:请将试管置于37 °C加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20 °C可放置数月。

反应条件

10和35 nM;3天

实验结果

在Bcr-Abl阳性红白血病细胞系K562和Bcr-Abl阳性骨髓单核细胞系RWLeu4中,PD173955抑制细胞增殖,其IC50值分别为35 nM和10 nM。在低纳摩尔浓度下,PD173955使细胞阻滞于G1期。

References:

[1]. Wisniewski, D., et al., Characterization of potent inhibitors of the Bcr-Abl and the c-kit receptor tyrosine kinases. Cancer Res, 2002. 62(15): p. 4244-55.

生物活性

Description PD173955是一种ATP竞争性的Src/Abl激酶双重抑制剂。
靶点 Bcr-Abl Src        
IC50 1-2 nM 22 nM        

质量控制

质量控制和MSDS

批次:

化学结构

PD173955