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AZD-3463

现货
Catalog No.
A8620
ALK/IGF1R抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,100.00
现货
5mg
¥ 950.00
现货
10mg
¥ 1,500.00
现货
50mg
¥ 3,640.00
现货
100mg
¥ 5,320.00
Ship with 10-15 days

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Background

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.

文献引用

1. Wilson C, Nimick M, et al. "ALK and IGF-1R as independent targets in crizotinib resistant lung cancer." Sci Rep. 2017 Oct 24;7(1):13955. PMID:29066738
2. Hawkinson JE, Sinville R, et al."Potent Pyrimidine and Pyrrolopyrimidine Inhibitors of Testis-Specific Serine/Threonine Kinase 2 (TSSK2)." ChemMedChem. 2017 Sep 26. PMID:28952188
3. Wang Y, Wang L, et al. "Novel ALK inhibitor AZD3463 inhibits neuroblastoma growth by overcoming crizotinib resistance and inducing apoptosis." Sci Rep. 2016 Jan 20;6:19423. PMID:26786851

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt448.95
Cas No.1356962-20-3
FormulaC24H25ClN6O
Solubility≥11.22mg/mL in DMSO
Chemical NameN-[4-(4-aminopiperidin-1-yl)-2-methoxyphenyl]-5-chloro-4-(1H-indol-3-yl)pyrimidin-2-amine
SDFDownload SDF
Canonical SMILESCOC1=C(C=CC(=C1)N2CCC(CC2)N)NC3=NC=C(C(=N3)C4=CNC5=CC=CC=C54)Cl
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验[1]:

细胞系

ALK野生型细胞系(SK-N-AS,IMR-32,NGP,NB-19)和ALK突变体细胞系(LA-N-6(D1091N)和SH-SY5Y(WT/F1174L))

溶解方法

在DMSO中的溶解度> 11.2mg/mL。为了获得更高浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

0~50 μM,72小时

应用

AZD-3463通过阻断ALK介导的PI3K/AKT/mTOR通路,可有效抑制野生型ALK和ALK活化突变体神经母细胞瘤细胞系的增殖,最终诱导细胞凋亡和自噬。

动物实验[1]:

动物模型

原位神经母细胞瘤小鼠模型

剂量

腹腔注射15mg/kg,每日一次,持续2天。

应用

AZD-3463在原位异种移植小鼠模型中对野生型和突变激活ALK的神经母细胞瘤肿瘤的生长表现出显著的抑制作用。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

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.

生物活性

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)          

质量控制

化学结构

AZD-3463

相关生物数据

AZD-3463

相关生物数据

AZD-3463

相关生物数据

AZD-3463