AT7519
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
AT7519是细胞周期蛋白依赖性激酶(CDKs)的小分子抑制剂,对CDK1、CDK2、CDK4、CDK5、CDK6和CDK9的IC50值分别为210、47、100、13、170和小于10 nM[1]。
AT7519对CDK3和7及其他非CDK激酶无抑制活性。它以ATP竞争性的方式抑制CDK1,Ki值为38 nM。AT7519有效抑制多种人肿瘤细胞系的增殖,这种抑制活性与细胞周期相关。AT7519对含有p53突变或抑制的细胞系也有效,说明其抗增殖效果是p53不依赖的。在HCT116细胞中,AT7519处理24小时,显著诱导G0-G1和G2-M期的细胞周期阻滞。除此之外,在HCT116、A2780和HT29细胞中,IC50浓度下的AT7519诱导细胞凋亡(24 h),细胞存活率分别为52%、3%和94%。而且,在HCT116肿瘤小鼠中,腹腔注射10 mg/kg的AT7519,抑制NPM磷酸化和诱导细胞凋亡[1,2]。
参考文献:
[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.
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 382.24 |
Cas No. | 844442-38-2 |
Formula | C16H17Cl2N5O2 |
Solubility | insoluble in H2O; ≥3.99 mg/mL in EtOH with ultrasonic; ≥9.55 mg/mL in DMSO with gentle warming |
Chemical Name | 4-[(2,6-dichlorobenzoyl)amino]-N-piperidin-4-yl-1H-pyrazole-5-carboxamide |
SDF | Download SDF |
Canonical SMILES | C1CNCCC1NC(=O)C2=C(C=NN2)NC(=O)C3=C(C=CC=C3Cl)Cl |
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。 |
细胞实验 [1]: | |
细胞系 |
MM(多发性骨髓瘤)细胞系,包括MM.1S, MM.1R, RPMI8226人源 MM细胞, U266人源MM细胞, Melphalan抵抗的RPMI8266人源MM细胞, doxorubicin抵抗的RPMI-Dox40 MM细胞 |
溶解方法 |
在DMSO中的溶解度>10 mM。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月 |
反应时间 |
0.5 μM 作用6, 12和24 h |
应用 |
AT7519的抗MM活性表现出细胞毒性和凋亡诱导。AT7519能够抑制RNA聚合酶II的磷酸化,它与RNA的合成降低密切相关。并且,AT7519能够抑制GSK-3β(糖原合成酶激酶3β)磷酸化,这意味着在AT7519诱导的凋亡中GSK-3β的参与。 |
动物实验[2]: | |
动物模型 |
携带HCT116细胞移植物的严重联合免疫缺陷雌性ICR小鼠 |
剂量 |
4.6 和9.1 mg/kg/剂,24h内两次,分别在0h, 8h,连续9天 |
应用 |
AT7519的使用导致磷酸化NPM(核仁磷酸蛋白)的抑制,从而诱导凋亡反应。在人源肿瘤异种移植物模型中,AT7519能够抑制肿瘤生长并且诱导肿瘤细胞凋亡。 |
注意事项 |
请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。 |
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. |
Description | AT7519是CDK1、2、4、5、6和9的抑制剂,IC50值为10-210 nM。 | |||||
靶点 | CDK9/CyclinT | CDK5/p35 | CDK2/CyclinA | GSK-3β | CDK4/CyclinD1 | CDK6/CyclinD3 |
IC50 | <10 nM | 13 nM | 47 nM | 89 nM | 100 nM | 170 nM |