AZD6738
(Synonyms: AZD6738) 目录号 : GC16941
An ATR kinase inhibitor
Cas No.:1352226-88-0
Sample solution is provided at 25 µL, 10mM.
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AZD6738 is a selective ATR (Ataxia Telangiectasia and RAD3-related) inhibitor, with an IC50 of approximately 30 uM to resting CLL cells [1] [2].
ATR is a PI3K-related kinase. It is involved in the repair of DNA damage. During cell division, it is recruited and activated at sites of single strand DNA breaks to help initiate DNA repair [1].
γH2AX acts as a biomarker of DNA damage. In an in vitro model capable of reproducing, over 70 hours after the initiation of the treatment with AZD6738, the γH2AX signal was sustained [1]. Stalled replication forks may collapse the formation of DNA double stranded breaks and the activation of the ataxia telangiectasia mutated (ATM) kinase. As a single agent across cancer cell line panels, AZD6738 is active. In cell lines lacking ATM-pathway, the sensitivity of AZD6738 was enhanced [3].
In ATM-deficient but not ATM-proficient in vivo models, treatment with AZD6738 alone significantly inhibited the activity of tumors in equivalent, tolerated doses. Ionizing radiation (IR) is a DNA damaging inducing agent. When AZD6738 and IR were used together, regression or anti-tumor growth inhibitory activity was observed. In tumor tissue, AZD6738 is associated with a persistent γH2AX staining increase. In normal gut tissue or bone marrow, treatment with AZD6738 only transiently increased the γH2AX staining [3].
References:
[1]. Choi MY, Fecteau JF, Brown J, et al. Induction of proliferation sensitizes chronic lymphocytic leukemia cells to apoptosis mediated by the ATR inhibitor AZD6738. Cancer Research, 2014, 74(19 Supplement): 5485-5485.
[2]. Checkley S, MacCallum L, Yates J, et al. Bridging the gap between in vitro and in vivo: Dose and schedule predictions for the ATR inhibitor AZD6738. Scientific reports, 2015, 5.
[3]. Guichard SM, Brown E, Odedra R, et al. The pre-clinical in vitro and in vivo activity of AZD6738: A potent and selective inhibitor of ATR kinase. Cancer Research, 2013, 73(8 Supplement): 3343-3343.
Cell experiment: | Ceralasertib (AZD6738) is dissolved in DMSO at 30 mM and diluted in DMSO to desired working concentrations. The final DMSO concentration in media for all conditions and controls is 0.1% for Ceralasertib (AZD6738) dose response experiments, 0.05% for Ceralasertib (AZD6738) + chemotherapy viability experiments, and 0.025% for all experiments involving 0.3 μM and 1.0 μM doses of Ceralasertib (AZD6738)[1]. |
Animal experiment: | Mice[1]Ceralasertib (AZD6738) is dissolved in DMSO at a concentration of 25 mg/mL or 50 mg/mL and diluted 1:5 in propylene glycol. Ceralasertib (AZD6738) is administered by oral gavage at 25 mg/kg (H23) or 50 mg/kg (H460) for 14 consecutive days. The dosing volume is 10 mL/kg.[1]. |
References: [1]. Vendetti FP, et al. The orally active and bioavailable ATR kinase inhibitor AZD6738 potentiates the anti-tumor effects of CDDP to resolve ATM-deficient non-small cell lung cancer in vivo. | |
| Cas No. | 1352226-88-0 | SDF | |
| 别名 | AZD6738 | ||
| 化学名 | (R)-3-methyl-4-(6-(1-((R)-S-methylsulfonimidoyl)cyclopropyl)-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)pyrimidin-4-yl)morpholine | ||
| Canonical SMILES | C[C@H]1N(C2=NC(C3=C4C(NC=C4)=NC=C3)=NC(C5([S@](=O)(C)=N)CC5)=C2)CCOC1 | ||
| 分子式 | C20H24N6O2S | 分子量 | 412.51 |
| 溶解度 | ≥ 82 mg/mL in DMSO, ≥ 82.4 mg/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 | 2.4242 mL | 12.1209 mL | 24.2418 mL |
| 5 mM | 0.4848 mL | 2.4242 mL | 4.8484 mL |
| 10 mM | 0.2424 mL | 1.2121 mL | 2.4242 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