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LEE011

现货
Catalog No.
A8641
CDK4/6抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 880.00
现货
5mg
¥ 800.00
现货
10mg
¥ 1,260.00
现货
25mg
¥ 2,000.00
现货
50mg
¥ 2,500.00
现货

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Background

LEE011 (NVP-LEE011) is a highly specific inhibitor of CDK4/CDK6 and functions via decreasing in phosphorylated RB and FOXM1 [1]. When tested with 17 human neuroblastoma cell lines, 12 of them were sensitive to LEE011 treatment with mean IC50=306±68 nM [2].
CDK4/6 could increase G1-S phase cell cycle progression and ultimately cellular proliferation via phosphorylating tumor suppressor protein RB. CDK4/6 signaling also could senescence suppression by regulating FOXM1 transcription[3]. Numerous studies have shown that over-expression of CDK4/CDK6 correlated with tumorigenesis and disease progression [4].
LEE011 is a novel inhibitor for CDK4/CDK6. When subjected to human liposarcoma cell lines, treated with LEE011 could dramatically decrease cell growth via arresting cell cycle G0-G1 [1]. In 12 of 17 human neuroblastoma-derived cell lines, treatment with LEE011 could significantly reduce cell proliferation [2].
In a mouse model with human liposarcoma xerography, continued treating the mouse with LEE011 orally could inhibit tumor growth or induce regression without detrimental effects on mouse weight [1]. In mice xerography with neuroblastoma cells, treated with LEE011 could inhibit the tumor growth [2].
References:
1.Zhang, Y.X., et al., Antiproliferative effects of CDK4/6 inhibition in CDK4-amplified human liposarcoma in vitro and in vivo. Mol Cancer Ther, 2014. 13(9): p. 2184-93.
2.Rader, J., et al., Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma. Clin Cancer Res, 2013. 19(22): p. 6173-82.
3.Paternot, S., et al., The CDK4/CDK6 inhibitor PD0332991 paradoxically stabilizes activated cyclin D3-CDK4/6 complexes. Cell Cycle, 2014. 13(18): p. 2879-88.
4.Dickson, M.A., Molecular pathways: CDK4 inhibitors for cancer therapy. Clin Cancer Res, 2014. 20(13): p. 3379-83.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt434.54
Cas No.1211441-98-3
FormulaC23H30N8O
Solubility≥10.88mg/mL in DMSO
Chemical Name7-cyclopentyl-N,N-dimethyl-2-[(5-piperazin-1-ylpyridin-2-yl)amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide
SDFDownload SDF
Canonical SMILESCN(C)C(=O)C1=CC2=CN=C(N=C2N1C3CCCC3)NC4=NC=C(C=C4)N5CCNCC5
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。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。

试验操作

细胞实验 [1]:

细胞系

神经母细胞瘤细胞系

溶解方法

该化合物在DMSO中的溶解度大于10.9 mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。

反应条件

IC50: 306 ± 68 nM,24小时

应用

在12/17种神经母细胞瘤细胞系中,LEE011显著抑制了底物贴壁生长,其平均IC50为306±68 nM。 LEE011抑制CDK4/6敏感性的两个神经母细胞瘤细胞系(BE2C和IMR5),以剂量依赖性方式增加G0/G1期细胞数目。

动物实验 [1]:

动物模型

BE2C或NB-1643异种移植小鼠模型

给药剂量

口服,200 mg/kg,每天一次,21天

应用

每日口服200 mg/kg剂量的LEE011显著延迟携带BE2C或NB-1643异种移植物的小鼠的肿瘤生长,没有伴随体重减轻或其他毒性迹象。

注意事项

由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。

References:

[1]. Rader J A, Russell M R, Hart L S, et al. Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma[J]. Clinical cancer research, 2013, 19(22): 6173-6182.

生物活性

描述 LEE011是一种可口服的和高度特异性的CDK4/6抑制剂。
靶点 CDK4 CDK6        
IC50            

质量控制

化学结构

LEE011