AZD2014
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
AZD2014是mTOR的一种新型的强效高选择性双重抑制剂,针对哺乳动物雷帕霉素蛋白mTORC1和mTORC2的IC50值为2.8 nM。它是一种口服抑制剂,具有潜在的抗肿瘤活性。
在体外和体内原位移植条件下,AZD2014增强胶质母细胞瘤干细胞样细胞(GSCs)对放射的易感性。Kahn J等使用2 μM的AZD2014预处理CD133+和CD15+ GSC细胞1小时,接着放射,然后通过克隆生存分析进行测量[2]。使用体外筛选发现,AZD2014与酪氨酸激酶BTK的抑制剂ibrutinib共同使用,可大幅诱导ABC-亚型DLBCL细胞系的细胞凋亡。AZD2014与BTK抑制剂的结合使用是治疗ABC型DLBCL患者的很有希望的治疗方法[3]。在肝癌细胞中,与雷帕霉素相比,AZD2014对mTORC1有更完整的抑制效果,而mTORC2的抑制阻止AKT信号的反馈激活。与雷帕霉素相比,AZD2014可更有效地诱导细胞凋亡、自噬和细胞周期停滞,可显著抑制细胞增殖[4]。
最近人体药物动力学和药效学研究表明,剂量为50 mg,一天两次(BD),AZD2014可以达到药理学相关的血浆浓度[5]。
参考文献:
[1] 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.
[2] The mTORC1/mTORC2 inhibitor AZD2014 enhances the radiosensitivity of glioblastoma stem-like cells. Neuro Oncol. 2014 Jan;16(1):29-37.
[3] 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.
[4] 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.
[5] 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.
这篇引用文献未标注数字
- 1. Bhola PD, Ahmed E, et al. "High-throughput dynamic BH3 profiling may quickly and accurately predict effective therapies in solid tumors." Sci Signal. 2020;13(636):eaay1451. PMID:32546544
- 2. Xie J, Shen K, et al. "Reciprocal signaling between mTORC1 and MNK2 controls cell growth and oncogenesis." Cell Mol Life Sci. 2020;10.1007/s00018-020-03491-1. PMID:32170339
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 462.54 |
Cas No. | 1009298-59-2 |
Formula | C25H30N6O3 |
Synonyms | AZD 2014;AZD-2014;Vistusertib |
Solubility | ≥23.15 mg/mL in DMSO; insoluble in H2O; ≥4.81 mg/mL in EtOH with ultrasonic |
Chemical Name | 3-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl]-N-methylbenzamide |
SDF | Download SDF |
Canonical SMILES | CC1COCCN1C2=NC(=NC3=C2C=CC(=N3)C4=CC(=CC=C4)C(=O)NC)N5CCOCC5C |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 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。溶液形式一般不宜长期储存,请尽快用完。 |
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. |
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 |
质量控制和MSDS
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