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> MK-2206 (dihydrochloride) [1032350-13-2]

MK-2206 (dihydrochloride) [1032350-13-2]

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Referência HY-10358-10mg

Tamanho : 10mg

Marca : MedChemExpress

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Description

MK-2206 dihydrochloride (MK-2206 2HCl) is an orally active pan-AKT inhibitor, with IC50 values of 8 nM, 12 nM and 65 nM against AKT1, AKT2 and AKT3, respectively. MK-2206 dihydrochloride inhibits the Akt/mTOR signaling pathway and reduces the levels of downstream GSK3β and Mcl-1 via proteasomal degradation. MK-2206 dihydrochloride induces G1-phase cell cycle arrest, apoptosis, epithelial-mesenchymal transition, fibroblast activation and extracellular matrix deposition. MK-2206 dihydrochloride causes transient hyperglycemia and hyperinsulinemia in animals. MK-2206 dihydrochloride can be used in research related to solid tumors, renal fibrosis and hypercholesterolemia[1][2][3][4].

IC50 & Target[1]

Akt1

8 nM (IC50)

Akt2

12 nM (IC50)

Akt3

65 nM (IC50)

In Vitro

MK-2206 dihydrochloride inhibits Akt1 kinase activity in various human cancer cell lines with an IC50 of approximately 20 nM, blocks the downstream signaling pathway of Akt, and exerts potent antiproliferative effects on cancer cell lines with specific PI3K pathway gene defects, while activation of the Ras pathway predicts no response[1].
MK-2206 dihydrochloride exerts additive or synergistic antiproliferative and pro-apoptotic sensitizing effects when combined with various chemotherapeutic agents and targeted inhibitors in relevant human cancer cell lines[1].
MK-2206 (72 h) dihydrochloride potently inhibits the growth of U937, OCI/AML3, MV-4-11 and MOLM-13 acute myeloid leukemia (AML) cell lines, with IC50 values ranging from 0.6 to 2.5 μM, while it exhibits only extremely low cytotoxicity against normal human peripheral blood mononuclear cells (PBMCs)[2].
MK-2206 (1-10 μM; 24 h) dihydrochloride induces dose-dependent G1 cell cycle arrest in OCI/AML3, MOLM-13 and MV-4-11 AML cell lines[2].
MK-2206 (1-10 μM; 24 h) dihydrochloride induces dose-dependent apoptosis in OCI/AML3, MOLM-13 and MV-4-11 acute myeloid leukemia (AML) cell lines, with a significant increase in apoptotic cell populations at higher doses[2].
MK-2206 (0.1-10 μM; 2-24 h) dihydrochloride induces apoptosis in MV-4-11 acute myeloid leukemia (AML) cells via caspase-3 and PARP cleavage, downregulates Mcl-1 protein levels in MV-4-11, OCI/AML3 and U937 AML cells in a dose-dependent manner, and inhibits the phosphorylation of Akt at Ser473 and GSK3β at Ser9 after 2 to 24 h of treatment, respectively[2].
MK-2206 (10 μM; 1-4 h) dihydrochloride induces downregulation of Mcl-1 in MV-4-11 acute myeloid leukemia (AML) cells via a GSK3β-mediated proteasome-dependent mechanism[2].
Combined administration of MK-2206 (200 nM; 72 h) dihydrochloride and Cytarabine (HY-13605) synergistically enhances cytotoxicity in MV-4-11, MOLM-13 and OCI/AML3 acute myeloid leukemia (AML) cell lines (ED50 CI value < 1), but exhibits antagonistic effects in U937 AML cells (ED50 CI value = 1.13)[2].
MK-2206 (0.5-5 μM; 48 h) dihydrochloride inhibits TGF-β1-induced fibrosis, epithelial-mesenchymal transition (EMT), and activation of the Akt/mTOR signaling pathway in HK-2 cells. The effective concentration is 1 μM, which reduces the mRNA expression of Collagen I and Fibronectin, restores E-cadherin levels, and suppresses the expression of mesenchymal markers and phosphorylated Akt/mTOR proteins[3].
MK-2206 (0.5-20 μM; 2-24 h) dihydrochloride upregulates LDLR protein levels in HepG2 cells treated with sterol feeding or sterol starvation. The maximum induction effect is observed in the sterol starvation group treated with 5 μM for 14 h, while that in the sterol feeding group is achieved with 10 μM treatment for 14 h. Moreover, a significant induction effect occurs within 4 h of treatment with 5 μM[4].
MK-2206 (2.5-5 μM; 2-6 h) dihydrochloride inhibits the activity of AKT kinase in sterol-fed HepG2 cells. At concentrations ≥2.5 μM, it reduces the phosphorylation levels of AKT and its downstream target PRAS40 within 2 h[4].
MK-2206 (5 μM; 14 h) dihydrochloride increases cell-surface LDLR expression and stimulates LDL uptake in HepG2 cells under both sterol-fed and sterol-starved conditions[4].
MK-2206 (5-12 μM; 2-24 h) dihydrochloride induces LDLR mRNA expression in sterol-fed HepG2 cells within 2 h through a mechanism that enhances transcription (rather than mRNA stabilization) and is independent of de novo protein synthesis[4].
MK-2206 (5-10 μM; 14 h) dihydrochloride upregulates LDLR protein levels in sterol-fed IHH, HeLa, IMH, and Hepac1c7 cells[4].
MK-2206 (5 μM; 24 h) dihydrochloride inhibits de novo cholesterol biosynthesis in HepG2 cells under sterol starvation conditions[4].
MK-2206 (5 μM; 14 h) dihydrochloride upregulates LDLR protein levels in CHO cells and HMGCR-deficient UT-2 cells, indicating that this effect is independent of HMGCR activity[4].
MK-2206 (0.5-4 μM; 38 h) dihydrochloride enhances the LDLR (low-density lipoprotein receptor)-inducing effect of Mevastatin (HY-17408) in sterol-starved HepG2 cells[4].
MK-2206 (5 μM; 2-24 h) dihydrochloride upregulates the mRNA expression of PCSK9, HMGCR, SREBP-2 and HMGCS1 in sterol-fed HepG2 cells, exerts only minor effects on ACACA, FASN and SCD1, and has no effect on IDOL[4].
MK-2206 (2.5-5 μM; 14-24 h) dihydrochloride stimulates LDLR promoter activity in sterol-fed HepG2 cells in an SRE-1-dependent manner[4].
MK-2206 (5 μM; 14-24 h) dihydrochloride upregulates LDLR mRNA levels in sterol-fed HepG2 cells in an SREBP-2-dependent manner[4].
MK-2206 (5 μM; 2-6 h) dihydrochloride stimulates proteolytic cleavage of FL-SREBP-2 to generate the active NTF-SREBP-2 in sterol-fed HepG2 cells[4].
MK-2206 (2.5-10 μM; 14 h) dihydrochloride upregulates LDLR protein levels in primary adult hepatocytes[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

MK-2206 dihydrochloride Related Antibodies

Solvant et solubilité
In Vitro: 

DMSO : 12.5 mg/mL (26.02 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent 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
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 1.67 mg/mL (3.48 mM); Clear solution

    This protocol yields a clear solution of ≥ 1.67 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (16.7 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: ≥ 1.67 mg/mL (3.48 mM); Clear solution

    This protocol yields a clear solution of ≥ 1.67 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (16.7 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.

For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  20% SBE-β-CD in Saline

    Solubility: 25 mg/mL (52.04 mM); Clear solution; Need ultrasonic
Pureté et documentation
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