LY2835219
(Synonyms: LY2835219 methanesulfonate) 目录号 : GC16822A dual inhibitor of CDK4 and CDK6
Cas No.:1231930-82-7
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Kinase experiment [1]: | |
Binding assays |
CDK4 and CDK6 activity was determined by radiometric-filter binding assay using a c-terminus fragment of the human Rb protein (containing amino acids 773 to 928) as a substrate. Human CDK4/cyclin D1 and CDK6/cyclin D1 complexes were expressed in insect cells and purified as described. LY2835219 were serially diluted 1:3 in 20 % DMSO to create a 10-point curve at a starting concentration of 20 μM. 20 % DMSO buffer alone was employed as a control; 500 mM EDTA was used to determine the level of background in the absence of enzyme activity. A 4-parameter logistic curve fit was used to generate the IC50 values using ActivityBase software (IDBS). For kinetic analysis, a range of ATP concentrations was used and Ki for both CDK4/cyclin D1 and CDK6/cyclin D1 complexes was determined by fitting to the Michaelis-Menten equation for a competitive inhibitor using GraphPad Prism. |
Cell experiment [1]: | |
Cell lines |
Colo-205 colorectal cells, MDA-MB-361 and MCF10A breast cancer cell lines, MV4-11 AML cells. |
Preparation method |
The solubility of this compound in DMSO is >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. |
Reaction Conditions |
24 h |
Applications |
LY2835219 is a selective and orally available dual cyclin-dependent kinases 4/6 (CDK4/6) inhibitor. LY2835219 (6000 nM) inhibits Rb phosphorylation with IC50 value of 120 nM and a corresponding arrest of cells in G1 (2 N DNA content) with EC50 value of 72 nM. |
Animal experiment [1]: | |
Animal models |
Mice bearing colo-205 xenograft tumors. |
Dosage form |
12.5 mg/kg, 25 to 100mg/kg |
Preparation method |
Formulated in 1 % hydroxyethyl cellulose + 0.1 % antifoam in 25 mM PB pH 2 and administered orally by gavage (final volume 0.2 mL). |
Applications |
LY2835219 mediates CDK4/6 inhibition, cell-cycle arrest and tumor growth inhibition (TGI) in colo-205 and inhibits Rb phosphorylation by CDK4/6. LY2835219 significantly inhibits tumor growth, doses up to 100 mg/kg are well tolerated with no loss of body weight or other signs of toxicity during or after treatment. |
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. |
References: [1]. Gelbert LM, Cai S, Lin X, et al. Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine. Invest New Drugs, 2014, 32(5): 825-837. |
LY2835219 is a selective and orally available dual cyclin-dependent kinases 4/6 (CDK4/6) inhibitor that potently inhibits the activities of CDK4 and CDK6 with the half maximal inhibition concentration IC50 values of 2 nM and 10 nM respectively [1].
LY2835219 has also been found to inhibit Rb phosphorylation both in vivo and in vitro leading to specific cell arrest at G1 phase as well as the inhibition of tumor growth [1].
Since the blood brain barrier (BBB) is a major obstacle for the effective treatment of primary brain tumors and brain metastases, LY2835219, which is able to cross the BBB, has the potential to inhibit intracranial tumor growth alone or in combination with other agents [1].
References:
[1] Concepcion Sanchez-Martinez, Lawrence M. Gelbert, Harlan Shannon, Alfonso De Dios, Brian A. Staton, Rose T. Ajamie, Geri Sawada, Graham N. Wishart and Thomas J. Raub. LY2835219, a potent oral inhibitor of the cyclin-dependent kinases 4 and 6 (CDK4/6) that crosses the blood-brain barrier and demonstrates in vivo activity against intracranial human brain tumor xenografts [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B234.
Cas No. | 1231930-82-7 | SDF | |
别名 | LY2835219 methanesulfonate | ||
化学名 | N-[5-[(4-ethylpiperazin-1-yl)methyl]pyridin-2-yl]-5-fluoro-4-(7-fluoro-2-methyl-3-propan-2-ylbenzimidazol-5-yl)pyrimidin-2-amine;methanesulfonic acid | ||
Canonical SMILES | CCN1CCN(CC1)CC2=CN=C(C=C2)NC3=NC=C(C(=N3)C4=CC5=C(C(=C4)F)N=C(N5C(C)C)C)F.CS(=O)(=O)O | ||
分子式 | C27H32F2N8.CH4O3S | 分子量 | 602.7 |
溶解度 | ≥ 30.15mg/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 | |||
1 mg | 5 mg | 10 mg | |
1 mM | 1.6592 mL | 8.296 mL | 16.592 mL |
5 mM | 0.3318 mL | 1.6592 mL | 3.3184 mL |
10 mM | 0.1659 mL | 0.8296 mL | 1.6592 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。