AZD4547
(Synonyms: AZD 4547;AZD-4547) 目录号 : GC14005
A selective inhibitor of FGFR tyrosine kinases
Cas No.:1035270-39-3
Sample solution is provided at 25 µL, 10mM.
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AZD4547 is a potent, specific, orally bioavailable fibroblast growth factors receptor (FGFR) tyrosine kinase inhibitor. It inhibits FGFR1, FGFR2, and FGFR3 with IC50 values of 12, 2 and 40 nM, respectively. AZD4547 has also been reported to block FGFR1, FGFR2, and FGFR3 autophosphorylation with IC50 values of 0.2, 2.5, and 1.8 nM, respectively [1].
AZD4547 has been demonstrated to inhibit cell proliferation and inhibit FGFRs and their downstream markers including PLCg and FRS2 phosphorylation in breast cell line Sum52-PE (expressing wild-type FGFR2), multiple myeloma line KMS11 (expressing Y373C mutated FGFR3 protein) and acute myeloid leukemia cell line KG1a (expressing wild-type FGFR1) [1].
Anti-carcinoma effect of AZD4547 has been observed in lung cancer xeonograft mice orally treated with AZD4547. This effect is believed to be via the specifically inhibition of the activity of FGFR but not kinase insert domain receptor (KDR)[1].
References:
[1] Gavine PR1,?Mooney L,?Kilgour E,?Thomas AP,?Al-Kadhimi K,?Beck S,?Rooney C,?Coleman T,?Baker D,?Mellor MJ,?Brooks AN,?Klinowska T. AZD4547: an orally bioavailable, potent, and selective inhibitor of the fibroblast growth factor receptor tyrosine kinase family. Cancer Res.?2012 Apr 15;72(8):2045-56.
| Kinase experiment [1]: | |
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AZD4547 kinase activity |
The ability of AZD4547 to inhibit the human recombinant kinase activities of FGFR1-3 was tested using ATP concentrations at, or just below, the respective Km. |
| Cell experiment [1]: | |
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Cell lines |
KG1a, Sum52-PE, KMS11 and MCF7 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
1 μM; 72 hrs |
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Applications |
AZD4547 affected AKT phosphorylation in Sum52-PE and MCF7 cells, but not in KG1a and KMS11 cells. AZD4547 treatment significantly induced apoptosis in Sum52-PE and KMS11 cells, and dramatically increased G1 arrest but not apoptosis in KG1a cells. In MCF7 cells, AZD4547 showed no effect on cell cycle distribution or apoptosis. |
| Animal experiment [1]: | |
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Animal models |
SCID mice bearing KMS11 tumors |
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Dosage form |
1.5 ~ 12.5 mg/kg, p.o.; q.d. or b.i.d. |
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Applications |
In mice bearing KMS11 tumors, AZD4547 (3 mg/kg, b.i.d.) significantly inhibited tumor growth (53%). AZD4547 treatment at 12.5 mg/kg once daily or 6.25 mg/kg twice daily resulted in complete tumor stasis due to dose-dependent modulation of phospho-FGFR3, and reduced KMS11 cell proliferation. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Gavine PR, Mooney L, Kilgour E, Thomas AP, Al-Kadhimi K, Beck S, Rooney C, Coleman T, Baker D, Mellor MJ, Brooks AN, Klinowska T. AZD4547: an orally bioavailable, potent, and selective inhibitor of the fibroblast growth factor receptor tyrosine kinase family. Cancer Res.2012 Apr 15;72(8):2045-56. | |
| Cas No. | 1035270-39-3 | SDF | |
| 别名 | AZD 4547;AZD-4547 | ||
| 化学名 | N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-4-[(3R,5S)-3,5-dimethylpiperazin-1-yl]benzamide | ||
| Canonical SMILES | CC1CN(CC(N1)C)C2=CC=C(C=C2)C(=O)NC3=NNC(=C3)CCC4=CC(=CC(=C4)OC)OC | ||
| 分子式 | C26H33N5O3 | 分子量 | 463.57 |
| 溶解度 | ≥ 23.2mg/mL in DMSO | 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 | 2.1572 mL | 10.7859 mL | 21.5717 mL |
| 5 mM | 0.4314 mL | 2.1572 mL | 4.3143 mL |
| 10 mM | 0.2157 mL | 1.0786 mL | 2.1572 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: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet