PD173955
(Synonyms: 6-(2,6-二氯苯基)-8-甲基-2-[[3-(甲硫基)苯基]氨基]吡啶并[2,3-D]嘧啶-7(8H)-酮) 目录号 : GC13592
A tyrosine kinase inhibitor
Cas No.:260415-63-2
Sample solution is provided at 25 µL, 10mM.
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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.
| Kinase experiment [1]: | |
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In vitro Bcr-Abl kinase assays |
Bcr-Abl complexed to SHIP2 was immunoprecipitated from cell lysates of K562 cells maintained in log-phase culture conditions. Complexes were collected on protein A-Sepharose, and complexes were washed three times in lysis buffer and then washed twice in abl kinase buffer [50 mM Tris (pH 8.0), 10 mM MgCl2, 1 mM DTT, 2 mM p-nitrophenylphosphate, and 2 μM ATP]. Kinase assays were performed with 10 μM [γ-32P]ATP/sample for 15 ~ 60 mins at 30 °C in the presence or absence of the indicated concentrations of drug. The reaction was stopped by the addition of SDS-PAGE sample buffer and heated at 100 °C for 10 mins. Proteins were separated on 7.5% SDS-polyacrylamide gels, gels were dried under vacuum, and phosphorylation was visualized by autoradiography on X-ray film. |
| Cell experiment [1]: | |
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Cell lines |
Bcr-Abl-positive cell lines K562 and RWLeu4 |
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Preparation method |
This compound in DMSO is limited. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
|
Reacting condition |
10 and 35 nM; 3 days |
|
Applications |
In the Bcr-Abl-positive erythroleukemia cell line K562 and the Bcr-Abl-positive myelomonocytic cell line RWLeu4, PD173955 inhibited cell proliferation with the IC50 values of 35 and 10 nM, respectively. At the low nanomolar, PD173955 arrested cell cycle in G1 phase. |
|
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. | |
| Cas No. | 260415-63-2 | SDF | |
| 别名 | 6-(2,6-二氯苯基)-8-甲基-2-[[3-(甲硫基)苯基]氨基]吡啶并[2,3-D]嘧啶-7(8H)-酮 | ||
| 化学名 | 6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one | ||
| Canonical SMILES | CN1C2=NC(=NC=C2C=C(C1=O)C3=C(C=CC=C3Cl)Cl)NC4=CC(=CC=C4)SC | ||
| 分子式 | C21H16Cl2N4OS | 分子量 | 443.35 |
| 溶解度 | ≥ 22.15mg/mL in DMSO with gentle warming | 储存条件 | Store at -20° C |
| General tips | 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°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2556 mL | 11.2778 mL | 22.5555 mL |
| 5 mM | 0.4511 mL | 2.2556 mL | 4.5111 mL |
| 10 mM | 0.2256 mL | 1.1278 mL | 2.2556 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet