MK-8776(SCH-900776)
(Synonyms: 6-溴-3-(1-甲基-1H-吡唑-4-基)-5-(3R)-3-哌啶基吡唑并[1,5-A]嘧啶-7-胺,MK-8776) 目录号 : GC16374
A selective Chk1 inhibitor
Cas No.:891494-63-6
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');)
;)
SCH 900776 is a potent and selective inhibitor of cell cycle checkpoint kinase 1 (Chk1), Chk2 and Cdk3 with IC50 value of 3 nM, 1.5µM and 0.16 µM, respectively.
Chk is s serine/threonine kinase that senses signal of DNA damage and stalls DNA replication, and also plays an essential role in the maintenance of replication fork viability during exposure to DNA antimetabolites.
In vitro, SCH 900776 blocked accumulation of the Chk1 pS296 autophosphorylation in a dose-dependent manner. Treatment of proliferating WS1 cells with SCH 900776 was found to be associated with rapid, dose-dependent accumulation of Chk1 pS345, indicating that cycling populations of normal cells induce Chk1 pS345 in response to the inhibition of SCH 900776 as part of a futile cycle 1.
In BALB/c mice, administration of SCH 900776 at a dosage of 8mg/kg after gemcitabine treatment can sufficiently induce enhanced tumor pharmacodynamic and regression responses as compared to gemcitabine or SCH 900776 alone 1.
Reference:
1. Guzi TJ, Paruch K, Dwyer MP, et al. Targeting the replication checkpoint using SCH 900776, a potent and functionally selective CHK1 inhibitor identified via high
content screening. Molecular cancer therapeutics. 2011;10(4):591-602.
| Cell experiment [1]: | |
|
Cell lines |
U2OS cells |
|
Preparation method |
The solubility of this compound in DMSO is >18.8mg/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. |
|
Reacting condition |
2h |
|
Applications |
In U2OS cells, SCH 900776 induced a dose-dependent loss of DNA replication capability 24 hours after hydroxyurea exposure. SCH 900776 enhanced apoptosis for at least 48 hours following release from hydroxyurea blockade. |
| Animal experiment [1]: | |
|
Animal models |
BALB/c mice bearing A2780 xenografts |
|
Dosage form |
4-32 mg/kg |
|
Application |
SCH-900776 (8 mg/kg) led to enhanced tumor pharmacodynamic and regression responses. SCH 900776 (16 and 32 mg/kg) induced incremental improvements in tumor response. |
|
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] Guzi T J, Paruch K, Dwyer M P, et al. Targeting the replication checkpoint using SCH 900776, a potent and functionally selective CHK1 inhibitor identified via high content screening[J]. Molecular cancer therapeutics, 2011, 10(4): 591-602. |
|
| Cas No. | 891494-63-6 | SDF | |
| 别名 | 6-溴-3-(1-甲基-1H-吡唑-4-基)-5-(3R)-3-哌啶基吡唑并[1,5-A]嘧啶-7-胺,MK-8776 | ||
| 化学名 | (R)-6-bromo-3-(1-methyl-1H-pyrazol-4-yl)-5-(piperidin-3-yl)pyrazolo[1,5-a]pyrimidin-7-amine | ||
| Canonical SMILES | BrC(C([C@@H]1CCCNC1)=N2)=C(N)N3C2=C(C4=CN(C)N=C4)C=N3 | ||
| 分子式 | C15H18BrN7 | 分子量 | 376.25 |
| 溶解度 | ≥ 18.8mg/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。 |
||
| 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 | 2.6578 mL | 13.289 mL | 26.5781 mL |
| 5 mM | 0.5316 mL | 2.6578 mL | 5.3156 mL |
| 10 mM | 0.2658 mL | 1.3289 mL | 2.6578 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