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生物活性
AZD8055 is a selective inhibitor of mTOR kinase with IC50 of 0.8 nM. It competes with ATP at the ATP-binding cleft of mTOR. AZD8055 showed ~1000 fold selectivity against closely related kinases PI3K isoforms and ATM/DNA-PK. Furthermore, it had no significant activity against a panel of 260 kinases at 10 μM. AZD8055 inhibits the phosphorylation of mTORC1 substrates p70S6K and 4E-BP1 as well as phosphorylation of the mTORC2 substrate AKT and downstream proteins. AZD8055 fully inhibits the rapamycin-resistant T37/46 phosphorylation sites on 4E-BP1, resulting in significant inhibition of cap-dependent translation. AZD8055 inhibits proliferation and induces autophagy in H838 and A549 cells.
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体外研究
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体内研究
dissolve in captisol (CyDex, pH 3.0)
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激酶实验
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细胞实验
0.001-1.0 μM
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动物实验
2.5-20 mg/kg 口服饲喂，每天1到2次
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不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）
|  动物 A (mg/kg) = 动物 B (mg/kg)×动物 B的Km系数/动物 A的Km系数 |
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例如，已知某工具药用于小鼠的剂量为88 mg/kg , 则用于大鼠的剂量换算方法：将88 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到该药物用于大鼠的等效剂量44 mg/kg。
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参考文献
[1] Chresta CM, et al. Cancer Res, 2010, 70(1), 288-298.
[2] García-Martínez JM, et al. Effect of PI3K- and mTOR-specific inhibitors on spontaneous B-cell follicular lymphomas in PTEN/LKB1-deficient mice. Br J Cancer, 2011, 104(7), 1116-1
分子式
C25H31N5O4 |
分子量
465.54 |
CAS号
1009298-09-2 |
储存方式
﹣20 ℃冷藏长期储存。冰袋运输 |
溶剂（常温）
|
DMSO
70 mg/mL |
Water
<1 mg/mL |
Ethanol
3 mg/mL |
体内溶解度
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Clinical Trial Information ( data from http://clinicaltrials.gov )
| NCT Number | Conditions | Interventions | Sponsor/Collaborators | Phases | Start Date | Last Updated |
| NCT00973076 | Cancer|Solid Tumors|Advanced Solid Malignancies | Drug: AZD8055 | AstraZeneca | Phase 1 | 2009-08-01 | 2011-06-14 |
| NCT01316809 | Glioblastoma Multiforme|Anaplastic Astrocytoma|Anaplastic Oligodendroglioma|Malignant Glioma|Brainstem Glioma | Drug: AZD8055 | National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) | Phase 1 | 2011-03-04 | 2017-01-26 |
| NCT00999882 | Cancer|Advanced Hepatocellular Carcinoma | Drug: AZD8055 | AstraZeneca | Phase 1 | 2009-10-01 | 2012-07-09 |
| NCT00731263 | Solid Tumors | Drug: AZD8055 | AstraZeneca | Phase 1 | 2008-07-01 | 2012-07-10 |
| NCT01194193 | Cancer|Advanced Solid Tumours|Lymphomas | Drug: AZD8055 | AstraZeneca | Phase 1 | null | 2011-05-13 |
注：以上所有数据均来自公开文献，并不保证对所有实验均有效，数据仅供参考。
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