AZD-7648
目录号 : GC64938
An inhibitor of DNA-PK
Cas No.:2230820-11-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
AZD 7648 is an inhibitor of DNA-dependent protein kinase (DNA-PK; IC50 = 0.63 nM in an enzyme assay).1 It is selective for DNA-PK over TTK (IC50 = 5.012 μM), as well as JAK1, JAK2, JAK3, Aurora A, and Aurora B (IC50s = >10 μM for all). AZD 7648 reduces tumor growth in a FaDu ATM KO pharynx cancer mouse xenograft model when administered at doses of 37.5 or 75 mg/kg twice per day and induces tumor regression at these doses when administered in combination with the PARP inhibitor olaparib .
1.Finlay, M., and Verschoyle, R.Amino-triazolopyridine compounds and their use in treating cancer(2018)
| Cas No. | 2230820-11-6 | SDF | Download SDF |
| 分子式 | C18H20N8O2 | 分子量 | 380.4 |
| 溶解度 | DMSO : 5 mg/mL (13.14 mM; ultrasonic and warming and heat to 80°C) | 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 | 2.6288 mL | 13.1441 mL | 26.2881 mL |
| 5 mM | 0.5258 mL | 2.6288 mL | 5.2576 mL |
| 10 mM | 0.2629 mL | 1.3144 mL | 2.6288 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。
Discovery of novel 7,8-dihydropteridine-6(5H)-one-based DNA-PK inhibitors as potential anticancer agents via scaffold hopping strategy
Eur J Med Chem 2022 Jul 5;237:114401.PMID:35468512DOI:10.1016/j.ejmech.2022.114401.
DNA-dependent protein kinase (DNA-PK) is an essential element in the DNA damage response (DDR) pathway and has been regarded as a druggable target for antineoplastic agents. Starting from AZD-7648, a potent DNA-PK inhibitor being investigated in phase II clinical trials for advanced cancer treatment, two series of DNA-PK inhibitors were rationally designed via scaffold hopping strategy, synthesized, and assessed for their biological activity. Most compounds exhibited potent biochemical activity on DNA-PK enzymatic assay with IC50 values below 300 nM. Among these compounds, DK1 showed the best DNA-PK-inhibitory potency (IC50 = 0.8 nM), slightly better than that of AZD-7648 (IC50 = 1.58 nM). Mode of action studies revealed that compound DK1 decreased the expression levels of γH2A.X and demonstrated synergistic antiproliferative activity against a series of cancer cell lines when used in combination with doxorubicin. Moreover, DK1 showed reasonable in vitro drug-like properties and favorable in vivo pharmacokinetics as an oral drug candidate. Importantly, the combination therapy of DK1 with DNA double-strand break (DSB)-inducing agent doxorubicin showed synergistic anticancer efficacy in the HL-60 xenograft model with a tumor growth inhibition (TGI) of 52.4% and 62.4% for tumor weight and tumor volume, respectively. In conclusion, DK1 is a novel DNA-PK inhibitor with great promise for further study.