| CAS NO: | 1009298-09-2 |
| 包装 | 价格(元) |
| 10mM (in 1mL DMSO) | 电议 |
| 10mg | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 465.54 |
| Cas No. | 1009298-09-2 |
| Formula | C25H31N5O4 |
| Solubility | ≥23.3 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH |
| Chemical Name | [5-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl]-2-methoxyphenyl]methanol |
| Canonical SMILES | CC1COCCN1C2=NC(=NC3=C2C=CC(=N3)C4=CC(=C(C=C4)OC)CO)N5CCOCC5C |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 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。溶液形式一般不宜长期储存，请尽快用完。 |
AZD8055是一种选择性mTOR激酶抑制剂，IC50值为0.8 nM[1]，可与ATP竞争性结合mTOR的ATP结合裂口。与密切相关的激酶PI3K亚型和ATM/DNA-PK相比，对mTOR具有约1000倍的选择性。此外，10 μM AZD8055对其他260种激酶无显著活性[1]。
临床前研究表明AZD8055具有潜在抗肿瘤活性。mTOR磷酸化和活化转录因子，从而调节细胞生长、增殖、运动和存活。AZD8055可抑制mTORC1和mTORC2复合体下游的信号[1]。AZD8055可抑制肺癌、宫颈癌和喉癌以及急性髓性白血病细胞系的增殖[1-4]。异种移植模型研究表明AZD8055可抑制胶质母细胞瘤、乳腺癌、肺癌、结肠癌、前列腺癌、子宫癌和头颈癌的肿瘤生长[1，5]。此外，AZD8055还可增强HDAC 抑制剂和MEK抑制剂的功效[6-8]。AZD8055已在I期临床实验中进行检测，具有最小的临床获益[9，10]。
参考文献：
[1] Chresta CM, Davies BR, Hickson I et al. AZD8055 is a potent, selective, and orally bioavailable ATP-competitive mammalian target of rapamycin kinase inhibitor with in vitro and in vivo antitumor activity. Cancer Res 2010; 70: 288-298.
[2] Li S, Li Y, Hu R et al. The mTOR inhibitor AZD8055 inhibits proliferation and glycolysis in cervical cancer cells. Oncol Lett 2013; 5: 717-721.
[3] Willems L, Chapuis N, Puissant A et al. The dual mTORC1 and mTORC2 inhibitor AZD8055 has anti-tumor activity in acute myeloid leukemia. Leukemia 2012; 26: 1195-1202.
[4] Zhao L, Teng B, Wen L et al. mTOR inhibitor AZD8055 inhibits proliferation and induces apoptosis in laryngeal carcinoma. Int J Clin Exp Med 2014; 7: 337-347.
[5] Li Q, Song XM, Ji YY et al. The dual mTORC1 and mTORC2 inhibitor AZD8055 inhibits head and neck squamous cell carcinoma cell growth in vivo and in vitro. Biochem Biophys Res Commun 2013; 440: 701-706.
[6] Shao H, Gao C, Tang H et al. Dual targeting of mTORC1/C2 complexes enhances histone deacetylase inhibitor-mediated anti-tumor efficacy in primary HCC cancer in vitro and in vivo. J Hepatol 2012; 56: 176-183.
[7] Holt SV, Logie A, Davies BR et al. Enhanced apoptosis and tumor growth suppression elicited by combination of MEK (selumetinib) and mTOR kinase inhibitors (AZD8055). Cancer Res 2012; 72: 1804-1813.
[8] Renshaw J, Taylor KR, Bishop R et al. Dual blockade of the PI3K/AKT/mTOR (AZD8055) and RAS/MEK/ERK (AZD6244) pathways synergistically inhibits rhabdomyosarcoma cell growth in vitro and in vivo. Clin Cancer Res 2013; 19: 5940-5951.
[9] Asahina H, Nokihara H, Yamamoto N et al. Safety and tolerability of AZD8055 in Japanese patients with advanced solid tumors; a dose-finding phase I study. Invest New Drugs 2013; 31: 677-684.
[10] Naing A, Aghajanian C, Raymond E et al. Safety, tolerability, pharmacokinetics and pharmacodynamics of AZD8055 in advanced solid tumours and lymphoma. Br J Cancer 2012; 107: 1093-1099.
| 细胞实验[1]: | |
细胞系 | TamR和MCF7-X细胞 |
制备方法 | 该化合物在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℃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℃可放置数月。 |
反应条件 | 100 nM，3 days |
实验结果 | 使用MIB1 Ki67染色监测AZD8055对TamR和MCF-7-X细胞增殖的影响。用50 nM AZD8055处理三天，在TamR和MCF7-X细胞中Ki67染色均减少，用100 nM 处理后，40％至50％的细胞为MIB1阴性，表明细胞退出细胞周期。 |
| 动物实验: [2] | |
动物模型 | 雌性C57BL/6小鼠 |
给药剂量 | 腹腔注射，10 mg/kg |
实验结果 | 过夜禁食的小鼠中，腹腔注射载体或AZD8055。AZD8055注射后3小时，血液取样用于血浆胰岛素和脂肪酸（FA）测定。AZD8055注射后3和6小时，小鼠中的葡萄糖水平升高，与对照小鼠中注射后24小时的葡萄糖含量相似。随着药物处理后3小时葡萄糖水平的升高，AZD8055处理小鼠的血浆胰岛素水平增高3倍，血浆FA降低。 |
注意事项 | 请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同，但仍处于实验系统误差的允许范围内。 |
References: [1] Jordan NJ, Dutkowski CM, Barrow D, Mottram HJ, Hutcheson IR, Nicholson RI, Guichard SM, Gee JM. Impact of dual mTORC1/2 mTOR kinase inhibitor AZD8055 on acquired endocrine resistance in breast cancer in vitro. Breast Cancer Res. 2014 Jan 23;16(1):R12. [2] Kleinert M, Sylow L, Fazakerley DJ, Krycer JR, Thomas KC, Oxb?ll AJ, Jordy AB, Jensen TE, Yang G, Schjerling P, Kiens B, James DE, Ruegg MA, Richter EA. Acute mTOR inhibition induces insulin resistance and alters substrate utilization in vivo. Mol Metab. 2014 Jun 27;3(6):630-41. | |
| Description | AZD8055是一种新型ATP竞争性mTOR抑制剂，IC50值为0.8 nM，具有优异的选择性，与PI3K亚型和ATM/DNA-PK相比，对mTOR具有约1000倍的选择性。 | |||||
| 靶点 | mTOR (full length) | mTOR (truncated) | ||||
| IC50 | 0.8 nM | 0.13 nM | ||||
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