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MK-2206

Cat. No. M1837
MK-2206 Structure
Synonym:

MK-2206 2HCl

Size Price Availability Quantity
10mg USD 100 In stock
50mg USD 280 In stock
100mg USD 400 In stock
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Quality Control
Biological Activity

MK-2206 is a novel allosteric inhibitor of Akt with IC50 values of 8 nM, 12 nM and 65 nM for Akt1, Akt2 and Akt3, respectively. An Akt inhibitor may be particularly useful for cancers in which increased Akt signaling is associated with reduced sensitivity to cytotoxic agents or receptor tyrosine kinase inhibitors. In vitro, MK-2206 synergistically inhibited cell proliferation of human cancer cell lines in combination with molecular targeted agents such as erlotinib (an epidermal growth factor receptor inhibitor) or lapatinib (a dual epidermal growth factor receptor/human epidermal growth factor receptor 2 inhibitor). In vivo, MK-2206 in combination with these agents exerted significantly more potent tumor inhibitory activities than each agent in the monotherapy setting.

Protocol
Cell Experiment
Cell lines CNE-1,CNE-2,HONE-1,SUNE-1
Preparation method 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.
Concentrations 0,0.08,0.16,0.31,0.63,1.25,2.5,5,10μM
Incubation time 72 or 96 hours
Animal Experiment
Animal models CNE-2 model in male BALB/c nude mice
Formulation Formulated in 30% Captisol
Dosages MK-2206 (240 mg/kg, three times a week), MK-2206 (480 mg/kg, once a week), and 30% Captisol (Cydex) diluents
Administration Oral gavage for 2 weeks
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 480.39
Formula C25H21N5O.2HCl
CAS Number 1032349-77-1
Purity 100.00%
Solubility DMSO ≥90 mg/mL
Water ≥90 mg/mL
Storage at -20°C
Customer Product Validations & Biological Datas
Source Fakultät für Mathematik (2017). Figure 3.35. MK-2206 (AbMole Bioscience, Kowloon, HK, China)
Method Scratch assay
Cell Lines
Concentrations 5 μM
Incubation Time
Results Signifikante Unterschiede sind entsprechend ihrem Signifikanzniveau mit einem oder mehreren * gekennzeichnet.
Rating
Source Fakultät für Mathematik (2017). Figure 3.34. MK-2206 (AbMole Bioscience, Kowloon, HK, China)
Method Westernblot
Cell Lines
Concentrations 5 μM
Incubation Time
Results Die Gesamtproteinmenge von AKT wurde durch keine der Behandlungen signifikant beeinflusst.
Rating
Source Am J Pathol (2017). Figure 3. MK-2206 (Abmole Bioscience)
Method Western blot
Cell Lines Human keratinocytes
Concentrations 2 or 5 mmol/L
Incubation Time 3 h
Results 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).
Rating
Source J Cancer (2015). MK220- Figure 6. (AbMole Bio Science (Kowloon, Hongkong, China)
Method
Cell Lines In HepG2R cells
Concentrations 2 μM
Incubation Time
Results 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.
Rating
Source J Cancer (2015). MK220- Figure 5. (AbMole Bio Science (Kowloon, Hongkong, China)
Method
Cell Lines HCC cell lines
Concentrations 2 μM
Incubation Time 72 h
Results 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
Rating
Source J Cancer (2015). MK220- Figure 3. (AbMole Bio Science (Kowloon, Hongkong, China)
Method western blot
Cell Lines HCC cell lines
Concentrations 2 μM
Incubation Time
Results "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)."
Rating
Source J Cancer (2015). MK220- Figure 2. (AbMole Bio Science (Kowloon, Hongkong, China)
Method
Cell Lines HCC cell lines
Concentrations 2 μM
Incubation Time 24 h
Results 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.
Rating
Source J Cancer (2015). MK220- Figure 1. (AbMole Bio Science (Kowloon, Hongkong, China)
Method
Cell Lines HCC cell lines
Concentrations
Incubation Time 72 h
Results 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.
Rating
Source Invest New Drugs (2014). MK-2206, Figure 5. (AbMole BioScience, Kowloon, Hongkong, China)
Method
Cell Lines EGI-1R and TFK-1R cells
Concentrations
Incubation Time 72 h
Results 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.
Rating
Source Invest New Drugs (2014). MK-2206, Figure 4. (AbMole BioScience, Kowloon, Hongkong, China)
Method
Cell Lines TFK-1 SCR and TFK-1 AKT1/2 knock-down cells
Concentrations 2 μM
Incubation Time 72 h
Results 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.
Rating
Source Invest New Drugs (2014). MK-2206, Figure 2. (AbMole BioScience, Kowloon, Hongkong, China)
Method Western blot
Cell Lines CCA cell lines
Concentrations 2 μM
Incubation Time 24 h
Results MK-2206, AZD6244 and AZD8055 clearly suppress the phosphorylation of their respective targets or downstream effectors, i.e.
Rating
Source Invest New Drugs (2014). MK-2206, Figure 1. (AbMole BioScience, Kowloon, Hongkong, China)
Method MTT assay
Cell Lines CCA cell lines
Concentrations
Incubation Time 72 h
Results 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.
Rating
Source Biochem Pharmacol (2015). MK-2206, Figure 5. (Abmole Bioscience Kowloon, Hong Kong, China)
Method western blot
Cell Lines CD4+ T cells
Concentrations 20 mM
Incubation Time 24 h
Results Similar results were obtained with AKT inhibitor MK-2206, which abolished the activation of AKT as well as mTORC1-mediated RPS6 phosphorylation.
Rating
Source 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).
Method western blot
Cell Lines MDA-MB-231 cells
Concentrations PI3K (10 µM LY294002), Akt (10 µM MK-2206) or mTOR (10 µM rapamycin)
Incubation Time 1h
Results 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.
Rating
Source 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).
Method Cell motility assay
Cell Lines MDA-MB-231 cells
Concentrations PI3K (10 μM LY294002), Akt (20 μM MK-2206), mTOR (10 μM rapamycin, Rap), FAK (10 μM PF573228) or Src (10 μM PP2)
Incubation Time 1h
Results "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. "
Rating
Source Biochemical Pharmacology (2015). Figure 7. LY294002, MK-2206 and GSK1120212 were gifts from Abmole Bioscience (Kowloon, Hong Kong).
Method Western blot
Cell Lines Purified CD4+ T cells
Concentrations 20 mM LY294002, 10 mM MK-2206 as well as 10 mM GSK1120212
Incubation Time 3 h
Results Arctigenin could inhibit mTORC1 activation via a way independent of PI3K/AKT and ERK.
Rating
Source Int J Cancer (2013). Figure 3.MK-2206 was obtained from AbMole BioScience (Kowloon, Hongkong)
Method Western blotting, Brdu proliferation assay,
Cell Lines CCA cells
Concentrations 1.7µM
Incubation Time 24 or 72h
Results The novel AKT inhibitor MK-2206 augments the antiproliferative effect of RAD001 in CCA cell lines.
Rating
Source Invest New Drugs (2014). Figure 2.MK-2206 was obtained from AbMole BioScience (Kowloon, Hongkong)
Method Cell cycle analysis, Cell Death Detection ELISA, western blot
Cell Lines EGI-1, Sk-ChA-1, TFK-1 cells
Concentrations 2µM
Incubation Time 24 or 48h
Results 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.
Rating
Source Invest New Drugs (2014). Figure 1.MK-2206 was obtained from AbMole BioScience (Kowloon, Hongkong)
Method BrdU proliferation assay
Cell Lines EGI-1, Sk-ChA-1, TFK-1 cells
Concentrations 0,7,21,62,185,556,1667, 5000nM / 0, 6.3, 12.5, 25, 50, 75, 100nM
Incubation Time 72h
Results Combined targeting of AKT and MEK as well as AKT and mTOR is highly synergistic in CCA cell lines.
Rating
Source Cellular Signalling 27 (2015) 2191–2200.Figure 4. MK-2206 was obtained from AbMole BioScience (Kowloon, HongKong).
Method Cell viability was analyzed by using Alamar blue assay(EGI-1).
Cell Lines MDA-MB-231/MDA-MB-231R, A375/A375R
Concentrations 2µM
Incubation Time 72 hours
Results 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.
Rating
Source Cellular Signalling 27 (2015) 2191–2200.Figure 1. MK-2206 was obtained from AbMole BioScience (Kowloon, HongKong).
Method Cell viability was analyzed by using MTT or Alamar blue assay(EGI-1).
Cell Lines MDA-MB-231(HTB-26), EGI-1, HT-29, A549, HCT116, A375 and SW480
Concentrations 5µM
Incubation Time 72 hours
Results 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.
Rating
Product Citations
References

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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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: MK-2206, MK-2206 2HCl supplier, Akt, inhibitors

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