| 名稱 | MK-2206 dihydrochloride |
| 描述 | MK-2206 dihydrochloride (MK-2206 2HCl) is a variant Akt inhibitor that inhibits Akt1, Akt2, and Akt3 (IC50=8/12/65 nM) with orally active, highly potent and selective potency. MK-2206 dihydrochloride exhibits antitumor activity. |
| 細胞實驗 | Cells were seeded at a density of 2 to 3 × 103 per well in 96-well plates. Twenty-four hours after plating, varying concentrations of the drug, either as a single agent or in combination, were added to the wells. Cell proliferation was determined by using the CellTiter-Glo assay at 72 or 96 hours after dosing. The nature of the drug interaction was evaluated by using the combination index (CI) according to the method of Chou and Talalay. A commercial software package was obtained from Calcusyn. In combination with docetaxel, we tested three treatment sequences: (a) MK-2206 followed by docetaxel—cells were exposed to MK-2206 for 24 hours, and then after washout of MK-2206, cells were treated with docetaxel for an additional 72 hours; (b) docetaxel followed by MK-2206—cells were exposed to docetaxel for 24 hours, and then after washout of docetaxel, cells were treated with MK-2206 for an additional 72 hours; and (c) concurrent treatment—cells were exposed to both MK-2206 and docetaxel for 72 hours [2]. |
| 動物實驗 | When the mean tumor size reached 0.13 cm3 for the SK-OV-3 or 0.2 cm3 for the NCI-H292, HCC70, PC-3, and NCI-H460 models, the mice were randomized into control and treatment groups with approximately equivalent ranges of tumor volume between groups (n = 5 animals per group). The following vehicles were used to dose the compounds: 30% Captisol (Cydex) for MK-2206; 0.5% methylcellulose + 0.1% Tween 80 for erlotinib; distilled water for lapatinib; 0.73% ethanol in saline for docetaxel; and saline for carboplatin and gemcitabine. The control group received vehicle only. Tumor volume was measured with calipers twice a week. Animal body weight and physical signs were monitored during the experiments. Tumor volume was calculated, taking length to be the longest diameter across the tumor and width to be the perpendicular diameter, by using the following formula: (length × width)2 × 0.5. Relative tumor volume was assessed by dividing the tumor volume on different observation days with the starting tumor volume. Statistical significance was evaluated by using the two-way repeated ANOVA test followed by Dunnett's test or an unpaired t-test [2]. |
| 體外活性 | 方法：14 種腫瘤細胞用 MK-2206 dihydrochloride 處理 72 h，使用 CellTiter-Glo assay 檢測細胞活力。
結果：MK-2206 dihydrochloride 抑制腫瘤細胞生長，IC50 在 0.1-28.6 μmol/L之間。[1]
方法：人鼻咽癌細胞系 CNE-2、HONE-1 用 MK-2206 dihydrochloride (0.625-10 μM) 處理 24-48 h，使用 Flow Cytometry 方法檢測細胞周期情況。
結果：MK-2206 dihydrochloride 導致 G0/G1 期細胞百分比的劑量依賴性增加和 S 期細胞數(shù)量的減少。MK-2206 dihydrochloride 誘導細胞周期停滯于 G1 期。[2] |
| 體內(nèi)活性 | 方法：為檢測體內(nèi)抗腫瘤活性，將 MK-2206 dihydrochloride (120 mg/kg 每周三次或 360 mg/kg 每周一次，30% Captisol) 和 erlotinib (50 mg/kg 每周五次，0.5% methylcellulose + 0.1% Tween 80) 口服給藥給攜帶人肺癌腫瘤 NCI-H292 的 CD1 小鼠，持續(xù)兩周。
結果：每周三次的 MK-2206 單藥治療無效，每周一次的方案僅介導中等的抗腫瘤療效。盡管 erlotinib 單獨介導了顯著的腫瘤生長抑制，但與 MK-2206 的聯(lián)合治療顯著增強了其抗腫瘤療效，包括腫瘤消退。[1]
方法：為檢測體內(nèi)抗腫瘤活性，將 MK-2206 dihydrochloride (120 mg/kg in 30% captisol) 灌胃給藥給攜帶人子宮內(nèi)膜癌腫瘤的 NSG 小鼠，每周兩次，持續(xù)三周。
結果：MK-2206 dihydrochloride 治療使 3 種不同類型和等級的 PDX 腫瘤的生長都受到顯著抑制。[3] |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | Ethanol : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 7.5 mg/mL (15.61 mM)
10% DMSO+90% Saline : 0.75 mg/mL (1.56 mM), Please add co-solvents sequentially, clarifying the solution as much as possible before adding the next one. Dissolve by heating and/or sonication if necessary. Working solution is recommended to be prepared and used immediately.
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| 關鍵字 | Apoptosis | mutant | Inhibitor | MK 2206 | cancer | inhibit | MK-2206 (2HCl) | MK2206 dihydrochloride | PIK3CA | selective | MK-2206 Dihydrochloride | Autophagy | Protein kinase B | Akt | loss | PKB | PTEN | sensitive | oral | MK 2206 Dihydrochloride | breast | MK-2206 | MK2206 | MK 2206 dihydrochloride | MK2206 Dihydrochloride |
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