Powder: -20°C for 3 years | In solvent: -80°C for 1 year
AZD1390 是一种可口服的,可渗透脑的ATM 高度选择性抑制剂,IC50为 0.78 nM。
规格 | 价格/CNY | 货期 | 数量 | |
---|---|---|---|---|
1 mg | ¥ 678 | 现货 | ||
2 mg | ¥ 980 | 现货 | ||
5 mg | ¥ 1,450 | 现货 | ||
10 mg | ¥ 2,320 | 现货 | ||
25 mg | ¥ 3,930 | 现货 | ||
50 mg | ¥ 5,390 | 现货 | ||
100 mg | ¥ 6,570 | 现货 | ||
1 mL * 10 mM (in DMSO) | ¥ 1,520 | 现货 |
产品描述 | AZD1390 is an exceptionally potent inhibitor of ATM in cells (IC50: 0.78 nM) with >10,000-fold selectivity over closely related members of the PIKK family of enzymes. |
靶点活性 | ATM:0.78 nM (cell based) |
体外活性 | ATM autophosphorylation inhibition by AZD1390 occurred at 4 hours after treatment, and 3 nM produced strong inhibition of ATM in LN18 GBM cells. Other DDR inhibitors tested under the same conditions at relevant IC50 concentrations did not affect pATM levels. A dose-dependent increase in G2 accumulation occurred after 24 hours following AZD1390 and irradiation at 2 Gy indicative of cells not arresting in S and accumulating in G2 or experiencing problems during mitosis. |
体内活性 | In in vivo syngeneic and patient-derived glioma as well as orthotopic lung-brain metastatic models, AZD1390 dosed in combination with daily fractions of IR (whole-brain or stereotactic radiotherapy) significantly induced tumor regressions and increased animal survival compared to IR treatment alone. |
细胞实验 | Cells were seeded in six-well plates to a density of 50 to 60% and incubated at 37°C for 24 hours. Cells were pretreated with AZD1390, the ATR inhibitor AZD6738, the Wee1 inhibitor AZD1775, the poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor olaparib, or the DNA-PK inhibitor KU-0060648 at indicated concentrations for 1 hour and subsequently irradiated at 2 Gy using the Faxitron CellRad (130-kV, 5-mA, 0.5-mm Al). In washout experiments, the cell culture medium was immediately replaced and cells were incubated with or without the compound for 1, 6, and 24 hours. In all other experiments, proteins were collected at indicated time points following irradiation. Proteins were harvested by scraping the cells in radioimmunoprecipitation assay (RIPA) lysis buffer supplemented with protease and phosphatase inhibitors. Protein content was quantified using the BCA Protein Assay Kit according to manufacturing conditions. Proteins were separated by SDS–polyacrylamide gel electrophoresis on 4 to 12% bis-tris or 3 to 8% Tris-acetate gels and transferred onto nitrocellulose membranes using the iBlot Dry Blotting System. Membranes were briefly washed with water and Tris-buffered saline (TBS) with 0.05% Tween 20 (TBST) once and incubated in blocking solution, followed by primary antibodies diluted in TBST with 5% (w/v) nonfat dry milk or 3% bovine serum albumin (BSA) overnight at 4°C with shaking. Membranes were then washed three times and incubated for 1.5 hours with horseradish peroxidase (HRP)–conjugated antibodies and/or LI-COR fluorescent antibodies CW700-800 in TBST with 5% (w/v) nonfat dry milk. Membranes were washed five times with TBST, and proteins were visualized with the Fuji or Syngene G:BOX Imaging System or Film Developer after enhanced chemiluminescence substrate addition. |
动物实验 | Bioluminescence signaling of implanted 3 × 10^5 NCI-H2228-Luc cells was measured using an IVIS Xenogen imaging machine to monitor tumor growth. When the signal reached the range of 10^7 to 10^8, the mice were randomized into different treatment groups and treated orally with either vehicle or AZD1390 QD or BID + IR at 2.5 Gy daily for four consecutive days. AZD1390 or vehicle was dosed at 1 hour before IR on each dosing day. The bioluminescence signals and body weight of the mice were measured once weekly, and the raw data were recorded according to their study number and measurement date in the in vivo database. TGI from the start of treatment was assessed by comparison of the mean change in bioluminescence intensity for the control and treated groups and presented as % of TGI. The calculation of inhibition and regression was based on the geometric mean of relative tumor volume (RTV) in each group. "CG" means the geometric mean of RTV of the control group, whereas "TG" means the geometric mean of RTV of the treated group. On specific day, for each treated group, the inhibition value was calculated using the following formula: Inhibition% = (CG ? TG) * 100/(CG ? 1). CG should use the corresponding control group of the treated group during calculation. If inhibition was >100%, then regression was calculated using the following formula: Regression = 1 – TG. Statistical significance was evaluated using a one-tailed t-test. Survival benefit was measured by Kaplan-Meier plots at the end of the study. |
分子量 | 477.57 |
分子式 | C27H32FN5O2 |
CAS No. | 2089288-03-7 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
DMSO: 20 mg/mL, sonification/heating is recommended.
对于不同动物的给药剂量换算,您也可以参考 更多...
请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。
母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。
体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。
您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。
azd1390 2089288-03-7 DNA Damage/DNA Repair PI3K/Akt/mTOR signaling ATM/ATR azd-1390 ATM and RAD3 related AZD 1390 inhibit Inhibitor Ataxia telangiectasia mutated inhibitor