- AP26113
- (R)-Crizotinib
- ALK inhibitor 2
- ASP3026
| AZD-3463ALK/IGF1R inhibitor |
Sample solution is provided at 25 µL, 10mM.
Quality Control & MSDS
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- Purity = 98.10%
- COA (Certificate Of Analysis)
- HPLC(Retest)
- NMR (Nuclear Magnetic Resonance)
- MSDS (Material Safety Data Sheet)
- Datasheet
Chemical structure
Related Biological Data
Related Biological Data
Related Biological Data
| Description | AZD3463 is a novel orally bioavailable inhibitor of ALK with a Ki value of 0.75 nM. | |||||
| Targets | ALK | |||||
| IC50 | 0.75 nM(Ki) | |||||
| Cell experiment [1]: | |
Cell lines | ALK wild type cell lines (SK-N-AS, IMR-32, NGP, NB-19) and ALK mutant cell lines (LA-N-6 (D1091N) and SH-SY5Y (WT/F1174L)) |
Preparation method | The solubility of this compound in DMSO is >11.2mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
Reacting condition | 0~50 μM, 72h |
Applications | AZD-3463 effectively suppressed the proliferation of neuroblastoma cell lines with wild type ALK as well as ALK activating mutations by blocking the ALK-mediated PI3K/AKT/mTOR pathway and ultimately induced apoptosis and autophagy. |
| Animal experiment [1]: | |
Animal models | Orthotopic Neuroblastoma Mouse Model |
Dosage form | 15 mg/kg intraperitoneal injection once daily for 2 days. |
Application | AZD-3463 exhibited significant therapeutic efficacy on the growth of the neuroblastoma tumors with WT and F1174L activating mutation ALK in orthotopic xenograft mouse models. |
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] Wang Y, Wang L, Guan S, Cao W, Wang H, Chen Z, et al. Novel ALK inhibitor AZD3463 inhibits neuroblastoma growth by overcoming crizotinib resistance and inducing apoptosis. Sci Rep. 2016;6:19423. | |
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| Cas No. | 1356962-20-3 | SDF | Download SDF |
| Synonyms | N/A | ||
| Chemical Name | N-[4-(4-aminopiperidin-1-yl)-2-methoxyphenyl]-5-chloro-4-(1H-indol-3-yl)pyrimidin-2-amine | ||
| Canonical SMILES | COC1=C(C=CC(=C1)N2CCC(CC2)N)NC3=NC=C(C(=N3)C4=CNC5=CC=CC=C54)Cl | ||
| Formula | C24H25ClN6O | M.Wt | 448.95 |
| Solubility | ≥11.22mg/mL in DMSO | Storage | Store at -20°C |
| Physical Appearance | A solid | Shipping Condition | Evaluation sample solution : ship with blue ice.All other available size:ship with RT , or blue ice upon request |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. | ||
Target: ALK, IGF1R
IC50: 0.75 nM(Ki)
AZD3463 is a novel orally bioavailable ALK/IGF1R inhibitor with Ki value of 0.75 nM. ALK expression is largely restricted to neurons and upregulated in neuroblastoma. Activated ALK has been shown to promote cell survival and growth. High ALK expression or mutations in the ALK gene correlates with adverse outcomes in neuroblastoma. Therefore, ALK receptor tyrosine kinase is an important therapeutic target for drug development against neuroblastoma [1].
In vitro: AZD3463 (5, 10, 20, and 50 μM) effectively inhibited the proliferation of neuroblastoma cell lines with wild type ALK (WT) and ALK activating mutations (F1174L and D1091N) via targeting the ALK-mediated PI3K/AKT/mTOR pathway and ultimately induced apoptosis and autophagy in vitro. Moreover, AZD3463 (1 μM) significantly enhanced the cytotoxic effects of doxorubicin (1 μM) on neuroblastoma cells [1]. AZD3463 simultaneously inhibited STAT3 and AKT to augment the cytotoxic effects of temozolomide and further reduce cell growth [2].
In vivo: AZD3463 (15 mg/kg, i.p. injection) showed significant therapeutic efficacy on the growth of the neuroblastoma tumors with WT and F1174L oncogenic mutant ALK in orthotopic xenograft mouse models [1].
References:1. Wang Y, Wang L, Guan S, Cao W, Wang H, Chen Z, et al. Novel ALK inhibitor AZD3463 inhibits neuroblastoma growth by overcoming crizotinib resistance and inducing apoptosis. Sci Rep. 2016;6:19423. 2. Sampson VB, Vetter NS, Kamara DF, Collier AB, Gresh RC, Kolb EA. Vorinostat Enhances Cytotoxicity of SN-38 and Temozolomide in Ewing Sarcoma Cells and Activates STAT3/AKT/MAPK Pathways. PLoS One. 2015;10(11):e0142704.
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二、限制性内切酶消化样品DNA
三、凝胶电泳分离消化产物
四、如果靶序列>5kb，在0.25M的HCl中进行震荡脱嘌呤10min，ddH2O洗一次
五、用变性液震荡处理30min，ddH2O洗一次
六、中和液震荡处理30min
七、裁取合适大小的尼龙膜或硝酸纤维素膜进行转膜操作，可用真空转膜仪或者搭滤纸桥，需要20×SSC
八、制备探针，可用地高辛标记（以地高辛为例）
九、将膜放入杂交瓶，42°C预杂交30min
十、倒掉预杂交液，加入杂交液，适当的温度进行杂交4h至过夜
十一、洗膜，先用2×SSC+0.1%SDS，20-25°C洗2×5min，再用0.5×SSC+0.1%SDS洗2×15min。然后用washing buffer洗1-5min，接着用blocking solution洗30min后，用antibody solution洗30min，再用washing buffer洗2×15min，再用detection buffer洗2-5min后，取出膜，放于保鲜膜上，在结合有DNA的一面滴加CSPD ready-to-use后，立刻盖上保鲜膜，让CSPD ready-to-use均匀的布满膜表面，室温放置5min后，37°C温育10min以上
十二、放射自显影，可用成像系统信号累积模式显影或用X-ray显影
我用Bio-rda转膜仪，转膜2分钟就停止，然后机器上显示“noloaddetected“。各位知道这是为什么吗？？
第一次出现这种情况，同样的条件，之前一直没有问题。
