LY2857785
目录号 : GC11971
A Cdk9 inhibitor
Cas No.:1619903-54-6
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
LY2857785 was identified as a type I reversible and competitive ATP kinase inhibitor against CDK9 and other transcription kinases CDK8 and CDK7.[1,2]
Cdk7 acts as a Cdk-activating kinase and regulate transcription. Cdk8 and Cdk9 regulate transcription via phosphorylation of the RNA polymerase II carboxyl terminal domain. The Cdk9-related pathway performs an important role in several biological processes, such as cell growth, proliferation, protection from apoptosis and differentiation. These kinases are reported dys-regulation in some cancers. [2]
Transcription activation requires phosphorylation of a carboxyl-terminal domain, by a variety of kinases including CDK7, CDK8, and CDK9. By inhibiting these kinases, LY2857785 has unique transcription inhibitor activity. LY2857785 dramatically inhibited XIAP protein level in MV-4-11 and other hematologic cancer cells. It also can significantly reduce RNAP II CTD phosphorylation and dramatically decreases MCL1 protein levels to result in apoptosis in a variety of leukemia and solid tumor cell lines. [1]
LY2857785 potently inhibits a carboxyl-terminal domain phosphorylation and exhibits antitumor efficacy in orthotopic models of leukemia. LY2857785 inhibits the growth of leukemia cells, including orthotopic leukemia preclinical models as well as in ex vivo acute myeloid leukemia and chronic lymphocytic leukemia patient tumor samples. LY2857785 may be used in treating patients with hematologic tumors, particularly AML and CLL. [1]
References:
[1] Yin T, Lallena MJ, Kreklau EL etal. , A novel CDK9 inhibitor shows potent antitumor efficacy in preclinical hematologic tumor models. Mol Cancer Ther. 2014 Jun;13(6):1442-56.
[2] Romano G1, Giordano A. Role of the cyclin-dependent kinase 9-related pathway in mammalian gene expression and human diseases. Cell Cycle. 2008 Dec;7(23):3664-8.
| Kinase experiment [1]: | |
|
Binding assays |
CDK7 and CDK9 reaction mixtures contained 10 mmol/L Tris-HCl (pH 7.4), 10 mmol/L HEPES, 5 mmol/L DTT, 10 μmol/L ATP, 0.5 μCi 33p-ATP, 10 mmol/L MnCl2, 150 mmol/L NaCl, 0.01% Triton X-100, 2% dimethylsulfoxide (DMSO), 0.05 mmol/L CDK7/9ptide, and 2 nmol/L CDK7/Mat1/cyclin H (14-476M, Upstate), or 2 nmol/L CDK9/cyclin T1 (14-685M, Upstate), respectively. CDK8/cyclin C reaction is performed in HEPES 30 mmol/L, DTT 2 mmol/L, MgCl2 5 mmol/L, 0.015% Triton X-100, 5 μmol/L ATP, and 400 nmol/L of RBER-CHKStide containing 20 nmol/L of enzyme.Compound in DMSO was diluted serially 1:3 for dose response. Reactions were carried out in 96-well polystyrene plates. The reactions were incubated at room temperature for 60 minutes and followed by termination with 10% H3PO4 or 10% trichloroacetic acid (TCA). For the filter binding assay, reactions were transferred to 96-well filter plates and measured by Microbeta scintillation counter. |
| Cell experiment [1]: | |
|
Cell lines |
Human bone marrow myeloid progenitor cells |
|
Preparation method |
This compound is soluble in DMSO. 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. |
|
Reacting condition |
Cells were treated with varying concentrations of compound for varying durations ranging from 4 to 24 hours. |
|
Applications |
LY2857785 inhibited hematologic tumor cell (human bone marrow myeloid progenitor cells) proliferation. |
| Animal experiment [1]: | |
|
Animal models |
Human cancer cells U87MG, MV-4-11, A375, and HCT116 xenograft rat models |
|
Dosage form |
4, 8, 18 mg/kg. i.v. every 3 days. |
|
Application |
LY2857785 demonstrates potent antitumor growth efficacy in preclinical tumor models (U87MG, MV-4-11, A375, and HCT116 xenograft rat models). |
|
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] Yin T, et al. A novel CDK9 inhibitor shows potent antitumor efficacy in preclinical hematologic tumor models. Mol Cancer Ther. 2014 Jun;13(6):1442-56. | |
| Cas No. | 1619903-54-6 | SDF | |
| 化学名 | (1r,4r)-N1-(4-(3-isopropyl-2-methyl-2H-indazol-5-yl)pyrimidin-2-yl)-N4-(tetrahydro-2H-pyran-4-yl)cyclohexane-1,4-diamine | ||
| Canonical SMILES | CN1C(C(C)C)=C(C(C=C2)=N1)C=C2C3=NC(N[C@H]4CC[C@H](NC5CCOCC5)CC4)=NC=C3 | ||
| 分子式 | C26H36N6O | 分子量 | 448.6 |
| 溶解度 | ≥ 13.87mg/mL in EtOH with gentle warming | 储存条件 | Desiccate 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。 |
||
| 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 | 2.2292 mL | 11.1458 mL | 22.2916 mL |
| 5 mM | 0.4458 mL | 2.2292 mL | 4.4583 mL |
| 10 mM | 0.2229 mL | 1.1146 mL | 2.2292 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: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet