LEE011 hydrochloride
(Synonyms: 瑞博西尼盐酸盐; LEE011 hydrochloride) 目录号 : GC15922
A selective cyclin D1/CDK4 and cyclin D3/CDK6 inhibitor
Cas No.:1211443-80-9
Sample solution is provided at 25 µL, 10mM.
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Ribociclib hydrochloride (LEE011 hydrochloride) is a highly specific CDK4/6 inhibitor with IC50 values of 10 nM and 39 nM, respectively, and is over 1,000-fold less potent against the cyclin B/CDK1 complex.
Treating a panel of 17 neuroblastoma cell lines with Ribociclib (LEE011) across a four-log dose range (10 to 10,000 nM). Treatment with Ribociclib significantly inhibits substrate adherent growth relative to the control in 12 of the 17 neuroblastoma cell lines examined (mean IC50=306±68 nM, considering sensitive lines only, where sensitivity is defined as an IC50 of less than 1 μM. Ribociclib treatment of two neuroblastoma cell lines (BE2C and IMR5) with demonstrated sensitivity to CDK4/6 inhibition results in a dose-dependent accumulation of cells in the G0/G1 phase of the cell cycle. This G0/G1 arrest becomes significant at Ribociclib concentrations of 100 nM (p=0.007) and 250 nM (p=0.01), respectively[2].
CB17 immunodeficient mice bearing BE2C, NB-1643 (MYCN amplified, sensitive in vitro), or EBC1 (non-amplified, resistant in vitro) xenografts are treated once daily for 21 days with Ribociclib (LEE011; 200 mg/kg) or with a vehicle control. This dosing strategy is well tolerated, as no weight loss or other signs of toxicity are observed in any of the xenograft models. Tumor growth is significantly delayed throughout the 21 days of treatment in mice harboring the BE2C or 1643 xenografts (both, p<0.0001), although growth resumed post-treatment[2].
References:
[1]. VanArsdale T, et al. Molecular Pathways: Targeting the Cyclin D-CDK4/6 Axis for Cancer Treatment. Clin Cancer Res. 2015 Jul 1;21(13):2905-10.
[2]. Rader J, et al. Dual CDK4/CDK6 Inhibition Induces Cell-Cycle Arrest and Senescence in Neuroblastoma. Clin Cancer Res. 2013 Nov 15;19(22):6173-82.
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Cell experiment: |
Cells are grown for 24 hours in 35 mm plates, treated with 500 nM Ribociclib for 6 days, and then fixed and stained overnight. Cells are then imaged for SA-β-gal using an Axio Observer D.1 phase contrast microscope. The percentage of SA-β-gal positive cells is determined by counting the number of positive cells present in three separate microscope frames, and then normalizing to the control. To assess apoptotic activity, cells are plated in triplicate in 96 well plates, treated with Ribociclib, and assayed for caspase 3/7 activation 16 hours after treatment with Caspase-Glo 3/7. Cells treated with SN-38 are used as a positive control[2]. |
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Animal experiment: |
Mice[2] The BE2C, NB-1643, or EBC1 cell line-derived xenografts are implanted subcutaneously into the right flank of CB17 SCID-/- mice. Animals bearing engrafted tumors of 200-600 mm3 are then randomized to oral treatment with 200 mg/kg Ribociclib in 0.5 % methylcellulose (n=10) or vehicle (n=10) daily for a total of 21 days. Tumor burden is determined periodically throughout treatment according to the formula (π/6)×d2, where d represents the mean tumor diameter obtained by caliper measurement. |
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References: [1]. VanArsdale T, et al. Molecular Pathways: Targeting the Cyclin D-CDK4/6 Axis for Cancer Treatment. Clin Cancer Res. 2015 Jul 1;21(13):2905-10. |
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| Cas No. | 1211443-80-9 | SDF | |
| 别名 | 瑞博西尼盐酸盐; LEE011 hydrochloride | ||
| 化学名 | (E)-7-cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)imino)-3,7-dihydro-2H-pyrrolo[2,3-d]pyrimidine-6-carboxamide hydrochloride | ||
| Canonical SMILES | CN(C(C(N1C2CCCC2)=CC(C1=N/3)=CNC3=N/C4=NC=C(N5CCNCC5)C=C4)=O)C.Cl | ||
| 分子式 | C23H31ClN8O | 分子量 | 471 |
| 溶解度 | DMSO : 94mg/mL; Water : 94mg/mL | 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 | 2.1231 mL | 10.6157 mL | 21.2314 mL |
| 5 mM | 0.4246 mL | 2.1231 mL | 4.2463 mL |
| 10 mM | 0.2123 mL | 1.0616 mL | 2.1231 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: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet