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AZD2014

现货
Catalog No.
A8373
新型mTOR抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 850.00
现货
5mg
¥ 700.00
现货
10mg
¥ 1,200.00
现货
50mg
¥ 3,500.00
现货

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Background

AZD2014 is a novel, potent and highly selective dual inhibitor of the mammalian rapamycin (mTORC1 and mTORC2) with an IC50 value of 2.8 nM. It is an oral inhibitor and possesses potential antineoplastic activity.

AZD2014 enhanced susceptibility of glioblastoma stem-like cells (GSCs) to irradiation both in vitro and under orthotopic in vivo conditions. Kahn J et al pretreated CD133+ and CD15+ GSC cells with AZD2014 (2 µM) for 1 hour, followed by irradiation. The effect was then measured by clonogenic survival analysis [2]. Using in vitro screening, they demonstrated that the combination of ibrutinib, an inhibitor of the tyrosine kinase BTK, and AZD2014 could dramatically induce apoptosis in ABC-subtype DLBCL cell lines. Thereby, the combination of AZD2014 with a BTK inhibitor is a promising therapeutic method to cure patients with ABC-type DLBCL [3]. In hepatocellular carcinoma cells, AZD2014 gave rise to a more complete inhibition of mTORC1 than rapamycin, while the inhibition of mTORC2 prevented the feedback activation of AKT signaling. Therefore, AZD2014 was identified to be more efficacious in the induction of apoptosis, autophagy, and cell cycle arrest, resulting in a significant proliferation suppression of the cells, in contrast with rapamycin [4].

In a recent human pharmacokinetic and pharmacodynamic study, a dose of 50mg BD(twice a day)AZD2014 was recommended to achieve pharmacologically relevant plasma concentrations [5].

References:
Optimization of potent and selective dual mTORC1 and mTORC2 inhibitors: the discovery of AZD8055 and AZD2014.  Bioorg Med Chem Lett. 2013 Mar 1;23(5):1212-6.
The mTORC1/mTORC2 inhibitor AZD2014 enhances the radiosensitivity of glioblastoma stem-like cells.  Neuro Oncol. 2014 Jan;16(1):29-37.
Synergistic induction of apoptosis by combination of BTK and dual mTORC1/2 inhibitors in diffuse large B cell lymphoma.  Oncotarget. 2014 Jul 15;5(13):4990-5001.
Dramatic antitumor effects of the dual mTORC1 and mTORC2 inhibitor AZD2014 in hepatocellular carcinoma.  Am J Cancer Res. 2014 Dec 15;5(1):125-39. eCollection 2015.
First-in-human pharmacokinetic and pharmacodynamic study of the dual m-TORC 1/2 inhibitor, AZD2014.  Clin Cancer Res. 2015 Mar 24. pii: clincanres.2422.2014.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt462.54
Cas No.1009298-59-2
FormulaC25H30N6O3
SynonymsAZD 2014; AZD-2014
Solubility≥23.15mg/mL in DMSO
Chemical Name3-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl]-N-methylbenzamide
SDFDownload SDF
Canonical SMILESCC1COCCN1C2=NC(=NC3=C2C=CC(=N3)C4=CC(=CC=C4)C(=O)NC)N5CCOCC5C
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

HCCLM3、Huh-7、SMMC-7721和HepG2细胞

制备方法

在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37 °C加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20 °C可放置数月。

反应条件

10 nM ~ 20 mM;72小时

实验结果

在选择的4种HCC细胞系中,与Rapamycin相比,AZD2014具有更显着的抗增殖活性,IC50值分别为101、441、141和600 nM。SMMC-7721细胞对Rapamycin(甚至在20 μM高浓度下)具有耐药性,但对AZD2014 (141 nM) 高度敏感。

References:

[1]. Dramatic antitumor effects of the dual mTORC1 and mTORC2 inhibitor AZD2014 in hepatocellular carcinoma. Am J Cancer Res. 2014 Dec 15;5(1):125-39. eCollection 2015.

生物活性

Description AZD2014是一种新型的mTOR抑制剂,IC50值为2.8 nM。
靶点 mTOR P-Akt (S473) pS6 (S235/236)      
IC50 2.8 nM 80 nM 200 nM      

质量控制

化学结构

AZD2014