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MK-2206 2HCl

目录号 M1837 所有产品仅供科研使用,严禁用于人或动物的治疗等任何其他用途,不为任何个人提供产品和服务  


MK-2206是一种高度选择性的Akt1/2/3抑制剂,IC50分别为8 nM/12 nM/65 nM;对250种其他蛋白激酶没有抑制活性。

MK-2206 2HCl结构式

别名:MK-2206 dihydrochloride

包装 价格 库存状态
10mM*1mL 原价 ¥ 950
促销价 ¥ 902.5
中国库存现货
5mg 原价 ¥ 800
促销价 ¥ 760
中国库存现货
10mg 原价 ¥ 1100
促销价 ¥ 1045
中国库存现货
50mg 原价 ¥ 2800
促销价 ¥ 2660
中国库存现货
100mg 原价 ¥ 4800
促销价 ¥ 4560
中国库存现货
其他规格数量报价?

质量控制及产品安全说明书
生物活性

MK-2206是一种高度选择性的Akt1/2/3抑制剂,IC50分别为8 nM/12 nM/65 nM;对250种其他蛋白激酶没有抑制活性。MK-2206抑制Akt的苏氨酸308位点和丝氨酸473位点的自身磷酸化作用。另外,MK-2206阻止Akt调节的下游信号分子(包括TSC2, PRAS40,及核糖体S6蛋白)的磷酸化作用。与抑制Ras 突变型细胞系(如NCI-H358, NCI-H23, NCI-H1299, 和Calu-6)相比,MK-2206 更有效地抑制Ras野生型细胞系(如A431, HCC827, 和NCI-H292)。MK-2206和细胞毒素药剂如erlotinib 和lapatinib联用作用于肺部NCI-H460肿瘤细胞或者卵巢A2780肿瘤细胞,MK-2206也显示出协同效应。

实验操作 来自于公开的文献,仅供相同实验参考(如实验材料、目的不同,请参考其他文献)
细胞实验
细胞系 CNE-1,CNE-2,HONE-1,SUNE-1
方法 MK-2206 is dissolved in DMSO as a stock solution and diluted by culture media before use. Cells are seeded at an appropriate density per well in 96-well plates and incubated for 24 hours. Then MK-2206 (0~10μM) is added to the cells. Cell proliferation is determined after 72 or 96 hours.
浓度 0,0.08,0.16,0.31,0.63,1.25,2.5,5,10μM
处理时间 72 or 96 hours
动物实验
动物模型 CNE-2 model in male BALB/c nude mice
配制 Formulated in 30% Captisol
剂量 MK-2206 (240 mg/kg, three times a week), MK-2206 (480 mg/kg, once a week), and 30% Captisol (Cydex) diluents
给药处理 Oral gavage for 2 weeks
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)
小鼠 大鼠 豚鼠 仓鼠
重量 (kg) 0.02 0.15 1.8 0.4 0.08 10
体表面积 (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km 系数 3 6 12 8 5 20
动物 A (mg/kg) = 动物 B (mg/kg) ×  动物 B的Km系数
动物 A的Km系数

例如,依据体表面积折算法,将白藜芦醇用于小鼠的剂量22.4 mg/kg 换算成大鼠的剂量,需要将22.4 mg/kg 乘以小鼠的Km系数(3),再除以大鼠的Km系数(6),得到白藜芦醇用于大鼠的等效剂量为11.2 mg/kg。

化学数据
分子量 480.39
分子式 C25H21N5O.2HCl
CAS号 1032350-13-2
纯度 100.00%
溶解性(25°C) 12mg/mL in DMSO
储存和运输条件 固体粉末: -20°C 冷藏长期储存
常温运输及临时存放
储备液配制

以下数据基于产品分子量,对于特殊产品,请参照COA中的储备液配制条件和说明进行操作。

Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 2.0816 mL 10.4082 mL 20.8164 mL
5 mM 0.4163 mL 2.0816 mL 4.1633 mL
10 mM 0.2082 mL 1.0408 mL 2.0816 mL
使用AbMole产品发表的文献
客户产品验证及相关生物数据
数据来源 Int J Biol Sci (2018 Oct). Figure 6. MK-2206 (Abmole Bioscience, Houston, USA)
方法 oral
细胞系 mice
浓度 240 mg/kg
处理时间 -
实验结果 We identified downstream pathways that might specifically affect the regulation of MK-2206 resistance or sensitivity.
数据来源 Int J Biol Sci (2018 Oct). Figure 4. MK-2206 (Abmole Bioscience, Houston, USA)
方法 oral
细胞系 mice
浓度 240 mg/kg
处理时间 -
实验结果 Three weeks after the initiation of treatment, the volume of tumors in vehicle-treated mice had increased ~5.8-fold relative to baseline, whereas tumors in MK-2206-treated mice were significantly smaller, exhibiting only an approximate 2.8-fold increase.
数据来源 Int J Biol Sci (2018 Oct). Figure 5. MK-2206 (Abmole Bioscience, Houston, USA)
方法 oral
细胞系 mice
浓度 240 mg/kg
处理时间 -
实验结果 The overall RTVs (treated vs. non-treated tumors) for mice bearing Brca1-mutant tumor allografts were 60.8% and 62.6% for mice treated with MK-2206 and olaparib, respectively.
数据来源 Am J Pathol (2017). Figure 3. MK-2206 (Abmole Bioscience)
方法 Western blot
细胞系 Human keratinocytes
浓度 2 or 5 mmol/L
处理时间 3 h
实验结果 To investigate whether indeed decreased p-AKT activity can result in impaired scratch WH under our low calcium conditions we inhibited AKT phosphorylation by using MK-2206 (Figure 3E). This resulted in significantly impaired scratch WH in a dose-dependent manner (Figure 3F).
数据来源 J Cancer (2015). MK220- Figure 6. (AbMole Bio Science (Kowloon, Hongkong, China)
方法
细胞系 In HepG2R cells
浓度 2 μM
处理时间
实验结果 In HepG2R cells only the combination of MK-2206 and AZD8055 resulted in a stronger inhibition of proliferation, whereas the combination of AZD6244 with MK-2206, or AZD8055, even had strong antagonistic effects compared to MK-2206 or AZD8055 alone.
数据来源 J Cancer (2015). MK220- Figure 5. (AbMole Bio Science (Kowloon, Hongkong, China)
方法
细胞系 HCC cell lines
浓度 2 μM
处理时间 72 h
实验结果 As shown in Figure 5B, combined MK2206 or knockdown of AKT1/2 with AZD8055 results in an additional inhibition of proliferation compared to inhibition of mTOR or AKT alone
数据来源 J Cancer (2015). MK220- Figure 3. (AbMole Bio Science (Kowloon, Hongkong, China)
方法 western blot
细胞系 HCC cell lines
浓度 2 μM
处理时间
实验结果 "Neither the AKT inhibitor MK-2206, nor the mTOR inhibitor AZD8055 alone were able to significantly reduce the level of pGSK3β (S9) in any of the cell lines analyzed, even though both had a distinct impact on pAKT (S473)."
数据来源 J Cancer (2015). MK220- Figure 2. (AbMole Bio Science (Kowloon, Hongkong, China)
方法
细胞系 HCC cell lines
浓度 2 μM
处理时间 24 h
实验结果 The combination of MK-2206 and AZD8055, which has shown the most robust impact on proliferation, caused an almost complete reduction of cells in S and G2 phase in Hep3B and Huh-7.
数据来源 J Cancer (2015). MK220- Figure 1. (AbMole Bio Science (Kowloon, Hongkong, China)
方法
细胞系 HCC cell lines
浓度
处理时间 72 h
实验结果 Combined targeting of AKT and MEK synergistically inhibited proliferation of all HCC cell lines, although the synergistic effect appears less prominent in HepG2 cell line because of its high susceptibility to AZD6244.
数据来源 Invest New Drugs (2014). MK-2206, Figure 5. (AbMole BioScience, Kowloon, Hongkong, China)
方法
细胞系 EGI-1R and TFK-1R cells
浓度
处理时间 72 h
实验结果 Surprisingly, combining MEK and AKT, or MEK and mTOR inhibition was highly synergistic, and completely reversed the acquired resistance against AZD6244 in these cells. Furthermore, combining MK-2206 and AZD8055 was still highly effective in these cells.
数据来源 Invest New Drugs (2014). MK-2206, Figure 4. (AbMole BioScience, Kowloon, Hongkong, China)
方法
细胞系 TFK-1 SCR and TFK-1 AKT1/2 knock-down cells
浓度 2 μM
处理时间 72 h
实验结果 Synergistic effects of MK-2206 and AZD8055 were confirmed when AKT1/2 knockdown cells or control cells, were counted after incubationwith AZD8055, MK-2206, or the combination of both for 72 h, as indicated in Fig. 4.
数据来源 Invest New Drugs (2014). MK-2206, Figure 2. (AbMole BioScience, Kowloon, Hongkong, China)
方法 Western blot
细胞系 CCA cell lines
浓度 2 μM
处理时间 24 h
实验结果 MK-2206, AZD6244 and AZD8055 clearly suppress the phosphorylation of their respective targets or downstream effectors, i.e.
数据来源 Invest New Drugs (2014). MK-2206, Figure 1. (AbMole BioScience, Kowloon, Hongkong, China)
方法 MTT assay
细胞系 CCA cell lines
浓度
处理时间 72 h
实验结果 We then analyzed the effect of combined AKT and mTOR inhibition by combiningMK-2206 and AZD8055 (Fig. 1).We observed strong synergistic effects, with CI values below 0.3 in all cell lines tested.
数据来源 Biochem Pharmacol (2015). MK-2206, Figure 5. (Abmole Bioscience Kowloon, Hong Kong, China)
方法 western blot
细胞系 CD4+ T cells
浓度 20 mM
处理时间 24 h
实验结果 Similar results were obtained with AKT inhibitor MK-2206, which abolished the activation of AKT as well as mTORC1-mediated RPS6 phosphorylation.
数据来源 Oncotarget (2016). Figure 11. Inhibitors of PI3K (LY294002), Akt (MK-2206), Src (PP2), FAK (PF573228) and mTOR (rapamycin) were purchased from Abmole Bioscience (Houston, TX, USA).
方法 western blot
细胞系 MDA-MB-231 cells
浓度 PI3K (10 µM LY294002), Akt (10 µM MK-2206) or mTOR (10 µM rapamycin)
处理时间 1h
实验结果 As shown in Figure 11. Pretreating MDA-MB-231 cells with the specific inhibitors of PI3K (10 µM LY294002), Akt (10 µM MK-2206) and mTOR (10 µM rapamycin) completely abolished the LSS-induced MT1-MMP expression, indicating that the PI3K/Akt/mTOR pathway is required for LSS-induced MT1-MMP expression.
数据来源 Oncotarget (2016). Figure 1. Inhibitors of PI3K (LY294002), Akt (MK-2206), Src (PP2), FAK (PF573228) and mTOR (rapamycin) were purchased from Abmole Bioscience (Houston, TX, USA).
方法 Cell motility assay
细胞系 MDA-MB-231 cells
浓度 PI3K (10 μM LY294002), Akt (20 μM MK-2206), mTOR (10 μM rapamycin, Rap), FAK (10 μM PF573228) or Src (10 μM PP2)
处理时间 1h
实验结果 "Notably, inhibitors of PI3K (LY294002), Akt (MK-2206) and mTOR (rapamycin) markedly decreased the LSS-induced wound closure activity. However, pretreatment with inhibitors of FAK (PF573228) and Src (PP2) has no effect on the LSS-induced cell motility (Figure 1B). It is suggested that PI3K, Akt and mTOR might be participated LSS-induced cell motility in an FAK and Src-independent manner. "
数据来源 Biochemical Pharmacology (2015). Figure 7. LY294002, MK-2206 and GSK1120212 were gifts from Abmole Bioscience (Kowloon, Hong Kong).
方法 Western blot
细胞系 Purified CD4+ T cells
浓度 20 mM LY294002, 10 mM MK-2206 as well as 10 mM GSK1120212
处理时间 3 h
实验结果 Arctigenin could inhibit mTORC1 activation via a way independent of PI3K/AKT and ERK.
数据来源 Int J Cancer (2013). Figure 3.MK-2206 was obtained from AbMole BioScience (Kowloon, Hongkong)
方法 Western blotting, Brdu proliferation assay,
细胞系 CCA cells
浓度 1.7µM
处理时间 24 or 72h
实验结果 The novel AKT inhibitor MK-2206 augments the antiproliferative effect of RAD001 in CCA cell lines.
数据来源 Invest New Drugs (2014). Figure 2.MK-2206 was obtained from AbMole BioScience (Kowloon, Hongkong)
方法 Cell cycle analysis, Cell Death Detection ELISA, western blot
细胞系 EGI-1, Sk-ChA-1, TFK-1 cells
浓度 2µM
处理时间 24 or 48h
实验结果 Treating CCA cell lines with a combination of two inhibitors significantly increased the amount of cells in G1-phase compared to each respective compound alone. A significant induction of apoptosis was observed in TFK-1 cells for the treatment with AZD6244 in combination with either MK-2206 or AZD8055. MK-2206, AZD6244 and AZD8055 clearly suppress the phosphorylation of their respective targets or downstream effectors, i.e. AKT, ERK and pS6.
数据来源 Invest New Drugs (2014). Figure 1.MK-2206 was obtained from AbMole BioScience (Kowloon, Hongkong)
方法 BrdU proliferation assay
细胞系 EGI-1, Sk-ChA-1, TFK-1 cells
浓度 0,7,21,62,185,556,1667, 5000nM / 0, 6.3, 12.5, 25, 50, 75, 100nM
处理时间 72h
实验结果 Combined targeting of AKT and MEK as well as AKT and mTOR is highly synergistic in CCA cell lines.
数据来源 Cellular Signalling 27 (2015) 2191–2200.Figure 4. MK-2206 was obtained from AbMole BioScience (Kowloon, HongKong).
方法 Cell viability was analyzed by using Alamar blue assay(EGI-1).
细胞系 MDA-MB-231/MDA-MB-231R, A375/A375R
浓度 2µM
处理时间 72 hours
实验结果 Treatment of resistant cells with a combination of AKTi MK-2206 and mTORi AZD8055 was unable to suppress migration. However, adding low dose AZD6244 (500 nM) to the combination of MK-2206 and AZD8055 significantly suppresses both, migration and proliferation.
数据来源 Cellular Signalling 27 (2015) 2191–2200.Figure 1. MK-2206 was obtained from AbMole BioScience (Kowloon, HongKong).
方法 Cell viability was analyzed by using MTT or Alamar blue assay(EGI-1).
细胞系 MDA-MB-231(HTB-26), EGI-1, HT-29, A549, HCT116, A375 and SW480
浓度 5µM
处理时间 72 hours
实验结果 Acquired resistance in these cell lines was independent of AKT and mTOR signaling. However, both parental and resistant cell lines were highly susceptible to mTORi AZD8055 and even more to the combination of MK-2206 and AZD8055.
参考文献

Phosphatidylinositol 3-Kinase/Akt Signaling Pathway Activates the WNK-OSR1/SPAK-NCC Phosphorylation Cascade in Hyperinsulinemic db/db Mice.
Nishida et al. Hypertension. 2012 Sep 4. PMID: 22949526.

Biomarkers of Response to Akt Inhibitor MK-2206 in Breast Cancer.
Sangai et al. Clin Cancer Res. 2012 Aug 29. PMID: 22932669.

Inhibition of AKT with the Orally Active Allosteric AKT Inhibitor, MK-2206, Sensitizes Endometrial Cancer Cells to Progestin.
Pant et al. PLoS One. 2012;7(7):e41593. PMID: 22911820.

Harnessing the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia: Eliminating activity by targeting at different levels.
Bressanin et al. Oncotarget. 2012 Aug 9. PMID: 22885370.

A novel PKB/Akt inhibitor, MK-2206, effectively inhibits insulin-stimulated glucose metabolism and protein synthesis in isolated rat skeletal muscle.
Lai et al. Biochem J. 2012 Jul 13. PMID: 22793019.

Cytotoxic activity of the novel Akt inhibitor, MK-2206, in T-cell acute lymphoblastic leukemia.
Simioni et al. Leukemia. 2012 May 22. PMID: 22614243.

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