AZD7762
(Synonyms: 3-[(氨基羰基)氨基]-5-(3-氟苯基)-N-(3S)-3-哌啶基-2-噻吩羧胺) 目录号 : GC10546
A selective checkpoint kinase inhibitor
Cas No.:860352-01-8
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');)
;)
AZD7762 is a novel ATP competitive inhibitor of checkpoint kinases. Chk family checkpoint kinases include Chk1 and Chk2. They are activated in response to DNA damage and phosphorylate CDC25A, CDC25C protein phosphatases, which delay cell cycle progression. Therefore, Chk activation initiates cell cycle checkpoint, causes cell cycle arrest, and allows DNA repair.
AZD7762 is a potent selective inhibitor of Chk1. It binds to the ATP binding pocket and compete ATP binding in a reversible manner. AZD7762 inhibits Chk1 phosphorylation of CDC25C peptide with an IC50 of 5 nM. The Ki is 3.6 nM. It is equally potent against Chk2 but less potent against CAM, Yes, Fyn, Lyn, Hck and Lck. [1]
AZD7762 prevents cell cycle arrest and DNA repair in DNA damaged tumor cells, causing tumor cell apoptosis. Hence, it potentiates the antitumor activity of DNA damaging agents and can be used as a chemosensitizing agent. [2]
Half life of AZD7762 is 1-2 hours in mice [3]
References:
[1]Zabludoff SD, et al. AZD7762, a novel checkpoint kinase inhibitor, drives checkpoint abrogation and potentiates DNA-targeted therapies. Mol Cancer Ther, 2008, 7(9): 2955-2966.
[2]Landau HJ, et al. The checkpoint kinase inhibitor AZD7762 potentiates chemotherapy-induced apoptosis of p53-mutated multiple myeloma cells. Mol Cancer Ther. 2012, 11(8): 1781-1788
[3]Goteti K, et al. Preclinical pharmacokinetic/pharmacodynamic models to predict synergistic effects of co-administered anti-cancer agents. Cancer Chemother Pharmacol. 2010, 66(2): 245-254.
| Cell experiment: [1] | |
|
Cell lines |
T47D and MCF7 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 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
|
Reaction Conditions |
100 nM, 24 hours |
|
Applications |
A clearly enhanced radiosensitization of AZD7762 was observed in the p53 mutant T47D cells but not in the wild-type p53 MCF7 cells. In the p53 mutant T47D cells, the cytotoxicity produced by AZD7762 in combination with radiation was significantly greater than that caused by the radiation alone. In the wild-type p53 MCF7 cells, although there was a trend for AZD7762 to sensitize cells to radiation, this difference did not reach a statistical significance. |
| Animal experiment: [2] | |
|
Animal models |
Female athymic nude mice injected with HT-29 cells |
|
Dosage form |
Intraperitoneal injection, 25 mg/kg, given immediately after radiation treatment and 8 hours later |
|
Applications |
AZD7762 treatment alone had little effect on tumor growth, whereas fractionated radiation delayed tumor growth. The time for tumors to reach thrice the initially measured tumor volume relative to the control for AZD7762 alone, fractionated radiation, and AZD7762 plus fractionated radiation was 2.3 (P < 0.53), 7.4 (P < 0.07), and 18.7 (P < 0.00014) days, respectively. Relative to fractionated radiation alone, the combination of AZD7762 and fractionated radiation was also highly significant. Thus, the combination of AZD7762 and fractionated radiation showed a greater tumor growth delay than the sum of the individual treatments alone. |
|
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] Ma Z, Yao G, Zhou B, et al. The Chk1 inhibitor AZD7762 sensitises p53 mutant breast cancer cells to radiation in vitro and in vivo. Molecular medicine reports, 2012, 6(4): 897-903. [2] Mitchell J B, Choudhuri R, Fabre K, et al. In vitro and in vivo radiation sensitization of human tumor cells by a novel checkpoint kinase inhibitor, AZD7762. Clinical Cancer Research, 2010, 16(7): 2076-2084. | |
| Cas No. | 860352-01-8 | SDF | |
| 别名 | 3-[(氨基羰基)氨基]-5-(3-氟苯基)-N-(3S)-3-哌啶基-2-噻吩羧胺 | ||
| 化学名 | 3-(carbamoylamino)-5-(3-fluorophenyl)-N-[(3S)-piperidin-3-yl]thiophene-2-carboxamide | ||
| Canonical SMILES | C1CC(CNC1)NC(=O)C2=C(C=C(S2)C3=CC(=CC=C3)F)NC(=O)N | ||
| 分子式 | C17H19FN4O2S | 分子量 | 362.42 |
| 溶解度 | ≥ 18.1mg/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 | 2.7592 mL | 13.7961 mL | 27.5923 mL |
| 5 mM | 0.5518 mL | 2.7592 mL | 5.5185 mL |
| 10 mM | 0.2759 mL | 1.3796 mL | 2.7592 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