AZD0156
目录号 : GC11593
An ATM kinase inhibitor
Cas No.:1821428-35-6
Sample solution is provided at 25 µL, 10mM.
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AZD0156 is an ATM kinase inhibitor.
Ataxia telangiectasia mutant (ATM), a serine/threonine protein kinase from the phosphatidylinositol 3-kinase-related kinase (PIKK) family of protein kinases, plays a critical role in the cellular DNA damage response signalling activated by DNA double strand breaks. Activated ATM can promote DNA repair and S/G1-cell cycle checkpoints to prevent premature mitosis, maintain genomic integrity as well as promote appropriate cell survival or death pathways. Thus, ATM inhibitor can represent a promosing clinical opportunity to hyper-sensitize tumors to chemo/radiotherapy.
In vitro: AZD0156 was identified as a first in class orally available ATM inhibitor, showing sub-nanomolar potency in cell based assays of ATM inhibition. Moreover, AZD0156 had selectivities of greater than 1000 fold over other members of the PIKK family enzymes [1].
In vivo: In animal study, AZD0156 displayed excellent preclinical PK properties including oral bioavailability. Additionally, in mouse xenograft models, AZD0156 showed robust efficacy after oral administration when combined with double strand breaks (DSB) inducing agents [1].
Clinical trial: AZD0156 is now undergoing early clinical assessment to investigate the safety and preliminary efficacy at increasing doses alone or in combination with other anti-cancer treatment in patients with advanced cancer [2].
References:
[1] Kurt G. Pike. Identifying high quality, potent and selective inhibitors of ATM kinase: Discovery of AZD0156. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4859.
[2] https://clinicaltrials. gov/ct2/show/NCT02588105 term=AZD0156&rank=1
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Cell experiment: |
HT29 cells are seeded into 384 well assay plates at a density of 6000 cells/well in 40 μL EMEM medium containing 1% L glutamine and 10% FBS and allowed to adhere overnight. The following morning compound of Formula (I) in 100% DMSO is added to assay plates by acoustic dispensing. After lh incubation at 37°C and 5% C02, 40 nL of 3 mM 4NQO in 100% DMSO is added to all wells by acoustic dispensing, except minimum control wells which are left untreated with 4NQO to generate a null response control. Plates are returned to the incubator for a further lh. Then cells are fixed by adding 20 μL of 3.7% formaldehyde in PBS solution and incubating for 20 mins at r.t.. Then 20 μL of 0.1% Triton XI 00 in PBS is added and incubated for 10 minutes at r.t., to permeabalise cells. Then the plates are washed once with 50 μL/well PBS, using a Biotek EL405 plate washer. |
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References: [1]. Imidazo[4,5-c]quinolin-2-one compounds and their use in treating cancer. |
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| Cas No. | 1821428-35-6 | SDF | |
| 化学名 | 8-(6-(3-(dimethylamino)propoxy)pyridin-3-yl)-3-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinolin-2(3H)-one | ||
| Canonical SMILES | O=C(N1C2CCOCC2)N(C)C3=C1C4=CC(C5=CC=C(OCCCN(C)C)N=C5)=CC=C4N=C3 | ||
| 分子式 | C26H31N5O3 | 分子量 | 461.56 |
| 溶解度 | ≥ 23.1mg/mL in DMSO with gentle warming, ≥ 5.49mg/mL in EtOH | 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 | 2.1666 mL | 10.8328 mL | 21.6657 mL |
| 5 mM | 0.4333 mL | 2.1666 mL | 4.3331 mL |
| 10 mM | 0.2167 mL | 1.0833 mL | 2.1666 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