| 名称 | AZD-8055 |
| 描述 | AZD-8055 is an orally bioavailable, highly selective, ATP-competitive mTOR kinase inhibitor that directly binds to the ATP-binding pocket of the mTOR kinase domain, while potently inhibiting both mTORC1 and mTORC2 complexes (IC50 values of 0.8 nM and 0.1 nM, respectively). AZD-8055 is suitable for research in oncology, metabolic diseases, and fibrotic disorders. |
| 细胞实验 | For growth inhibition and acridine staining, cells were exposed to increasing concentrations of AZD8055 for 72 to 96 h and stained for cell nuclei (0.03 mg/mL Hoechst 33342) and acidic vesicles (1 μg/mL acridine orange). Images were captured at 450 and 536 nm on an ArrayScan II platform, and the percentage of acidic vesicles and the number of cells were quantified. For LC3 assessment, cells were exposed to e64d/pepstatin (10 μg/mL) for 30 to 90 min before incubation with AZD8055. Cells were lysed on ice and analyzed by immunoblotting [1]. |
| 激酶实验 | The activity of mTOR was assayed using the recombinant mTOR technique described above. For inhibition experiments, AZD8055 was added to the reaction mixture and preincubated for 10 min before addition of ATP. Inhibition was performed at 1 to 3,000 nmol/L of AZD8055 in varying concentrations of ATP (40–200 μmol/L) [1]. |
| 动物实验 | Tumor cells (10^6 for U87-MG, 5 × 10^6 for A549) were injected s.c. in a volume of 0.1 mL, and mice were randomized into control and treatment groups when tumor size reached 0.2 cm^3. AZD8055 was formulated in 30% (w/v) captisol (pH 3.0). The control group received the vehicle only. Tumor volumes (measured by caliper), animal body weight, and tumor condition were recorded twice weekly for the duration of the study. The tumor volume was calculated (taking length to be the longest diameter across the tumor and width to be the corresponding perpendicular diameter) using the following formula: (length × width) × √(length × width) × (π/6) [1]. |
| 体外活性 | 方法：Huh7 人肝癌细胞转染 HPCAL1 敲低 （shRNA），转染后加入梯度浓度 AZD-8055 （0， 10， 50， 100， 500 nM） ，药物处理 72 小时，CCK-8 法检测细胞活力。
结果：HPCAL1 敲低细胞对 AZD-8055 的敏感性增加（细胞活力更低）。[1]
方法：葡萄膜黑色素瘤细胞系：92.1， Mel202， MP38， MP41，加入 AZD-8055 （1 μM）和罗米地辛（25 ng/mL），罗米地辛处理 6 小时后更换新鲜培养基，继续培养至 48 小时，流式细胞术（Annexin V/SYTOX Green 染色）检测细胞凋亡。
结果：AZD-8055 与罗米地辛联合在所有四种细胞系中均诱导了最高水平的凋亡，效果优于其他组合。[2] |
| 体内活性 | 方法：通过 hydrodynamic tail-vein injection 构建的 MYC/Trp53⁻/⁻ 肝癌模型，同时使用 CRISPR/Cas9 敲除 Hpcal1(sgHpcal1)或对照(sgCON)，构建成功后腹腔注射 AZD-8055 (10 mg/kg/天，每日一次)，持续给药 30 天。
结果：AZD-8055 治疗使 sgHpcal1 小鼠的肿瘤负荷显著降低，效果优于 sgCON 组。[1] |
| 存储条件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | Ethanol : 3 mg/mL (6.44 mM), Sonication is recommended.
H2O : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 91 mg/mL (195.47 mM), Sonication is recommended.
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 4.5 mg/mL (9.67 mM), Solution.
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| 关键字 | mTOR | Mammalian target of Rapamycin | Inhibitor | inhibit | AZD-8055 | AZD8055 | AZD 8055 | Autophagy | Apoptosis |
| 相关产品 | Urea | Formamide | Guanidine hydrochloride | Naringin | Aceglutamide | Alginic acid | Dextran sulfate sodium salt (MW 5000) | Hemin | Hydroxychloroquine | Stavudine | Tamoxifen | Paeonol |
| 相关库 | 抑制剂库 | 经典已知活性库 | 抗癌活性化合物库 | 抗癌化合物库 | 已知活性化合物库 | 激酶抑制剂库 | 高选择性抑制剂库 | 抗衰老化合物库 | 免疫/炎症分子化合物库 | 药物功能重定位化合物库 | 抗癌临床化合物库 | 抗癌药物库 |