LEE011
(Synonyms: 瑞博西尼; LEE011) 目录号 : GC10842
A selective cyclin D1/CDK4 and cyclin D3/CDK6 inhibitor
Cas No.:1211441-98-3
Sample solution is provided at 25 µL, 10mM.
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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.
| Cell experiment [1]: | |
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Cell lines |
Neuroblastoma cell lines |
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Preparation method |
The solubility of this compound in DMSO is >10.9mg/mL. 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 |
IC50: 306 ± 68 nM, 24 hours |
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Applications |
Treatment with LEE011 significantly inhibited substrate adherent growth relative to the control in 12 of the 17 neuroblastoma cell lines with mean IC50 of 306 ± 68 nM. LEE011 treatment of two neuroblastoma cell lines (BE2C and IMR5) with demonstrated sensitivity to CDK4/6 inhibition resulted in a dose-dependent accumulation of cells in the G0/G1 phase of the cell cycle. |
| Animal experiment [1]: | |
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Animal models |
Mice bearing BE2C, or NB-1643 xenografts |
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Dosage form |
Oral administration, 200 mg/kg, once daily for 21 days |
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Application |
LEE011 (200 mg/kg daily, p.o.) significantly delayed tumor growth in mice harboring the BE2C or NB-1643 xenografts with no weight loss or other signs of toxicity. |
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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]. 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. | |
| Cas No. | 1211441-98-3 | SDF | |
| 别名 | 瑞博西尼; LEE011 | ||
| 化学名 | 7-cyclopentyl-N,N-dimethyl-2-[(5-piperazin-1-ylpyridin-2-yl)amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide | ||
| Canonical SMILES | CN(C)C(=O)C1=CC2=CN=C(N=C2N1C3CCCC3)NC4=NC=C(C=C4)N5CCNCC5 | ||
| 分子式 | C23H30N8O | 分子量 | 434.54 |
| 溶解度 | ≥ 10.88mg/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 | 2.3013 mL | 11.5064 mL | 23.0128 mL |
| 5 mM | 0.4603 mL | 2.3013 mL | 4.6026 mL |
| 10 mM | 0.2301 mL | 1.1506 mL | 2.3013 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