AZD4547
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mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
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Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
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Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
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Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
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SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
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Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
AZD4547是一种有效的、特异性的和可口服的成纤维细胞生长因子受体(FGFR)酪氨酸激酶抑制剂。AZD4547抑制FGFR1、FGFR2和FGFR3,IC50值分别为12、2和40 nM。据报道,AZD4547阻断FGFR1、FGFR2和FGFR3的自磷酸化,IC50值分别为0.2、2.5和1.8 nM[1]。
在乳腺癌细胞系Sum52-PE(表达野生型FGFR2)、多发性骨髓瘤细胞系KMS11(表达Y373C突变的FGFR3蛋白)和急性骨髓性白血病细胞系KG1a(表达野生型FGFR1)中,AZD4547抑制细胞增殖,并抑制FGFRs及其下游标记物(包括PLCg和FRS2)的磷酸化[1]。
在肺癌异种移植小鼠中观察到了AZD4547口服治疗的抗癌效果,这种效应被认为是通过特异性抑制FGFR,而非激酶插入域受体(KDR)的活性[1]。
参考文献:
[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.
- 1. Hugh A. Nicholson, Lynne Sawers, et al. "Fibroblast growth factor signalling influences homologous recombination-mediated DNA damage repair to promote drug resistance in ovarian cancer." Br J Cancer. 2022 Oct;127(7):1340-1351. PMID: 35778553
- 2. Day EK, Sosale NG, et al. "Glioblastoma Cell Resistance to EGFR and MET Inhibition Can Be Overcome via Blockade of FGFR-SPRY2 Bypass Signaling." Cell Rep. 2020;30(10):3383-3396.e7. PMID: 32160544
- 3. Else Driehuis. "Organoids as a tool for fundamental and translational oncology research: Can organoids guide clinical decision making?" Universiteit Utrecht. 2019.
- 4. Driehuis E, Kolders S, et al. "Oral Mucosal Organoids as a Potential Platform for Personalized Cancer Therapy." Cancer Discov. 2019 Jul;9(7):852-871. PMID: 31053628
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 463.57 |
Cas No. | 1035270-39-3 |
Formula | C26H33N5O3 |
Synonyms | AZD 4547;AZD-4547 |
Solubility | ≥23.2 mg/mL in DMSO; insoluble in H2O; ≥6.33 mg/mL in EtOH |
Chemical Name | N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-4-[(3R,5S)-3,5-dimethylpiperazin-1-yl]benzamide |
SDF | Download SDF |
Canonical SMILES | CC1CN(CC(N1)C)C2=CC=C(C=C2)C(=O)NC3=NNC(=C3)CCC4=CC(=CC(=C4)OC)OC |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 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。溶液形式一般不宜长期储存,请尽快用完。 |
激酶实验 [1]: | |
AZD4547激酶活性 |
使用等于或稍低于Km的ATP浓度测定AZD4547对FGFR1-3人重组激酶活性的抑制能力。 |
细胞实验 [1]: | |
细胞系 |
KG1a、Sum52-PE、KMS11和MCF7细胞 |
制备方法 |
在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃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℃可放置数月。 |
反应条件 |
1 μM;72小时 |
实验结果 |
AZD4547影响Sum52-PE和MCF7细胞AKT磷酸化,但不影响KG1a和KMS11细胞AKT磷酸化。AZD4547处理显著诱导Sum52-PE和KMS11细胞凋亡,并显著增加KG1a细胞G1期阻滞,但不诱导细胞凋亡。在MCF7细胞中,AZD4547对细胞周期分布或细胞凋亡没有影响。 |
动物实验 [1]: | |
动物模型 |
携带KMS11肿瘤的SCID小鼠 |
给药剂量 |
1.5 ~ 12.5 mg/kg,口服给药;每日1次或每日2次 |
实验结果 |
在携带KMS11肿瘤的小鼠中,AZD4547(3 mg/kg,每日2次)显著抑制肿瘤生长 (53%)。AZD4547(12.5 mg/kg,每日1次;6.25 mg/kg,每日2次)呈剂量依赖性调节磷酸化FGFR3,从而完全抑制肿瘤生长。此外,AZD4547抑制KMS11细胞增殖。 |
其它注意事项 |
请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。 |
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. |
描述 | AZD4547是一种新型选择性的FGFR抑制剂,作用于FGFR1/2/3,IC50值分别为0.2 nM/2.5 nM/1.8 nM,对FGFR4和VEGFR2(KDR)具有较弱的活性,而对IGFR、CDK2和p38几乎没有活性。 | |||||
靶点 | FGFR1 | FGFR2 | FGFR3 | |||
IC50 | 0.2 nM | 2.5 nM | 1.8 nM |
质量控制和MSDS
- 批次:
化学结构
![AZD4547](http://www.apexbt.com//media/diy/images/struct/A8350.png)
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