AT7519
(Synonyms: 4-[(2,6-二氯苄基)氨基]-N-4-哌啶1H-吡唑-3-羧胺,AT7519M) 目录号 : GC15870
A Cdk inhibitor
Cas No.:844442-38-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
MM(multiple myeloma) cell lines including MM.1S, MM.1R, RPMI8226 human MM cells ,U266 human MM cells, Melphalan-resistant (LR5) RPMI8266 human MM cells, doxorubicin-resistant RPMI-Dox40 MM cells |
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Preparation method |
Soluble in DMSO > 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 |
0.5 μM for 6, 12 and 24 h |
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Applications |
Anti-MM activity of AT7519 displayed potent cytotoxicity and apoptosis. AT7519 inhibited RNA polymerase II phosphorylation, associated with decreased RNA synthesis. Additionally, AT7519 inhibited glycogen synthase kinase 3 beta (GSK-3β) phosphorylation, suggesting the involvement of GSK-3β in AT7519-induced apoptosis. |
| Animal experiment [2]: | |
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Animal models |
Female ICR severe combined immunodeficient mice bearing HCT116 cells xenografts |
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Dosage form |
4.6 and 9.1 mg/kg/dose, twice in a 24h period, respectively at 0h, 8h, for 9 consecutive days |
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Application |
Suppression of phospho-NPM(nucleophosmin) due to the treating of AT7519 could induce an apoptopic response. AT7519 inhibited tumor growth and induced tumor cell apoptosis in human tumor xenograft models. |
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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]. Santo L1, Vallet S, et al, AT7519, A novel small molecule multi-cyclin-dependent kinase inhibitor, induces apoptosis in multiple myeloma via GSK-3beta activation and RNA polymerase II inhibition. Oncogene. 2010 Apr 22;29(16):2325-36. doi: 10.1038/onc.2009.510. Epub 2010 Jan 25. [2]. Squires M S, Feltell R E, et al. Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines. Molecular cancer therapeutics, 2009, 8(2): 324-332. | |
AT7519 is a small-molecule inhibitor of cyclin-dependent kinases (CDKs) with IC50 values of 210, 47, 100, 13, 170 and <10 nM for CDK1, CDK2, CDK4, CDK5, CDK6 and CDK9, respectively [1].
AT7519 showed no inhibition activity against CDK3, 7 and other non-CDK kinases. It inhibited CDK1 in an ATP- competitive manner with Ki value of 38 nM. AT7519 potently inhibited the proliferation of various human tumor cell lines and this activity is cell cycle related. AT7519 was also effective in cell lines with p53 mutants or suppression, suggesting that the anti-proliferation efficacy is p53-independent. In HCT116 cells, 24 h-treatment of AT7519 resulted in a remarkable induction of G0-G1 and G2-M cell cycle arrest. Besides that, AT7519 at concentrations relating to IC50 induced cell apoptosis (24 h) in HCT116, A2780 and HT29 cells with 52%, 3% and 94% survival, respectively. Moreover, in HCT116 tumor-bearing mice, 10 mg/kg AT7519 with intraperitoneal injection caused inhibition of NPM phosphorylation and induced apoptosis [1, 2].
References:
[1] Squires M S, Feltell R E, Wallis N G, et al. Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines. Molecular cancer therapeutics, 2009, 8(2): 324-332.
[2] Wyatt P G, Woodhead A J, Berdini V, et al. Identification of N-(4-Piperidinyl)-4-(2, 6-dichlorobenzoylamino)-1 H-pyrazole-3-carboxamide (AT7519), a Novel Cyclin Dependent Kinase Inhibitor Using Fragment-Based X-Ray Crystallography and Structure Based Drug Design†. Journal of medicinal chemistry, 2008, 51(16): 4986-4999.
| Cas No. | 844442-38-2 | SDF | |
| 别名 | 4-[(2,6-二氯苄基)氨基]-N-4-哌啶1H-吡唑-3-羧胺,AT7519M | ||
| 化学名 | 4-[(2,6-dichlorobenzoyl)amino]-N-piperidin-4-yl-1H-pyrazole-5-carboxamide | ||
| Canonical SMILES | C1CNCCC1NC(=O)C2=C(C=NN2)NC(=O)C3=C(C=CC=C3Cl)Cl | ||
| 分子式 | C16H17Cl2N5O2 | 分子量 | 382.24 |
| 溶解度 | ≥ 9.55mg/mL in DMSO with gentle warming, ≥ 3.99 mg/mL in EtOH with ultrasonic | 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 | 2.6162 mL | 13.0808 mL | 26.1616 mL |
| 5 mM | 0.5232 mL | 2.6162 mL | 5.2323 mL |
| 10 mM | 0.2616 mL | 1.3081 mL | 2.6162 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。