MK-2206 2HCl

Catalog No.S1078 Batch:S107811

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Technical Data

Formula

C25H21N5O.2HCl
Molecular Weight 480.39 CAS No. 1032350-13-2
Solubility (25°C)* In vitro DMSO 96 mg/mL (199.83 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description MK-2206 2HCl is a highly selective inhibitor of Akt1/2/3 with IC50 of 8 nM/12 nM/65 nM in cell-free assays, respectively; no inhibitory activities against 250 other protein kinases observed. MK-2206 2HCl induces autophagy and apoptosis in cancer cells. Phase 2.
Targets
Akt1 [1]
(Cell-free assay)		 Akt2 [1]
(Cell-free assay)		 Akt3 [1]
(Cell-free assay)
8 nM 12 nM 65 nM
In vitro MK-2206 is an allosteric inhibitor and is activated by the pleckstrin homology domain. MK-2206 inhibits auto-phosphorylation of both Akt T308 and S473. MK-2206 also prevents Akt-mediated phosphorylation of downstream signaling molecules, including TSC2, PRAS40 and ribosomal S6 proteins. [1] MK-2206 inhibits Ras wild-type (WT) cell lines (A431, HCC827, and NCI-H292) more potently when compared to Ras-mutant cell lines (NCI-H358, NCI-H23, NCI-H1299, and Calu-6). MK-2206 also shows synergistic responses in combination with cytotoxic agents such as erlotinib or lapatinib in lung NCI-H460 or ovarian A2780 tumor cells. [2] MK-2206 or siRNA-mediated Akt inhibition strongly activates autophagy in human glioma cells. However, eukaryotic elongation factor-2 (eEF-2) silencing suppresses MK-2206-induced-autophagy, with a promotion of apoptotic cell death. [3]
In vivo MK-2206 shows 60% TGI and inhibits more than 70 % of phospho-Akt1/2 (T308 and S473) in A2780 ovarian cancer xenografts at a dose of 240 mg/kg. [1] MK-2206 exhibits significant antitumor activity in NCI-H292 xenograft in combination with erlotinib or lapatinib. [2]
Features The first allosteric small molecule inhibitor of Akt to enter clinical development.

Protocol (from reference)

Kinase Assay:

[4]
  • Akt kinases assay

    Akt kinases are assayed by a GSK-derived biotinylated peptide substrate. The extent of peptide phosphorylation is determined by Homogeneous Time Resolved Fluorescence (HTRF) using a lanthanide chelate (Lance)-coupled monoclonal antibody specific for the phosphopeptide in combination with a streptavidin-linked allophycocyanin (SA-APC) fluorophore which will bind to the biotin moiety on the peptide. When the Lance and APC are in proximity, a non-radiative energy transfer takes place from the Lance to the APC, followed by emission of light from APC at 655 nm. Working Solution: 100X protease inhibitor cocktail (PIC): 1mg/mL benzamidine, 0.5 mg/mL pepstatin, 0.5 mg/mL leupeptin, 0.5 mg/mL aprotinin; 10X assay buffer: 500 mM HEPES, pH7.5, 1% PEG, 16.6 mM EDTA, 1 mM EGTA, 1% BSA, 20 mM 9-glycerol phosphate; Quench buffer 50 mM HEPES pH 7.3, 16.6 mM EDTA, 0.1% BSA, 0.1% Triton X-100, 0.17 nM labeled monoclonal antibody, 0.0067 mg/mL SA-APC; ATP/MgCl2 working solution: 1X Assay buffer, 1 mM DTT, 1X PIC, 5% glycerol, active Akt; Peptide working solution: 1X Assay buffer, 1 mM DTT, 1X PIC, 5% glycerol, 2 TM GSK biotinylated peptide. The reaction is assembled by adding 16 µL of ATP/MgCl2 working solution to the appropriate wells. MK-2206 or vehicle (1.0 µL) is added followed by 10 µL of peptide working solution. The reaction is started by adding 13 μL of the enzyme working solution and mixing. The reaction is allowed to proceed for 50 min and then stopped by the addition of 60 µL HTRF quench buffer. The stopped reactions are incubated at room temperature for at least 30 min and then read in the instrument.
Cell Assay:

[2]
  • Cell lines

    A431, HCC827, NCI-H292, NCI-H358, NCI-H23, NCI-H1299, Calu-6 and NCI-H460 cells

  • Concentrations

    0, 0.3, 1 and 3 μM

  • Incubation Time

    72 or 96 hours

  • Method

    MK-2206 is dissolved in DMSO as a stock solution and diluted by culture media before use. Cells are seeded at a density of 2-3 × 103 in 96-well plates and incubated for 24 hours. Then MK-2206 (0, 0.3, 1 and 3 μM) is added to the cells. Cell proliferation is determined after 72 or 96 hours.
Animal Study:

[2]
  • Animal Models

    SK-OV-3, NCI-H292, HCC70, PC-3, and NCI-H460 models in male CD1-nude mice

  • Dosages

    120 mg/kg

  • Administration

    Orally administered

Customer Product Validation

Data from [Data independently produced by Nat Commun, 2015, 6:6943]

Data from [Data independently produced by Leukemia, 2015, 29(1), 169-76]

Data from [Data independently produced by J Exp Med, 2014, 211(9), 1741-58]

Data from [Cancer Cell, 2013, 24, 766-76]

Selleck's MK-2206 2HCl has been cited by 2022 publications

Comprehensive multi-omics analysis reveals WEE1 as a synergistic lethal target with hyperthermia through CDK1 super-activation [ Nat Commun, 2024, 15(1):2089] PubMed: 38453961
AKT1 phosphorylation of cytoplasmic ME2 induces a metabolic switch to glycolysis for tumorigenesis [ Nat Commun, 2024, 15(1):686] PubMed: 38263319
PD-L1-expressing tumor-associated macrophages are immunostimulatory and associate with good clinical outcome in human breast cancer [ Cell Rep Med, 2024, 5(2):101420] PubMed: 38382468
UPP1 enhances bladder cancer progression and gemcitabine resistance through AKT [ Int J Biol Sci, 2024, 20(4):1389-1409] PubMed: 38385072
CUL4B mutations impair human cortical neurogenesis through PP2A-dependent inhibition of AKT and ERK [ Cell Death Dis, 2024, 15(2):121] PubMed: 38331954
Tumor suppressor let-7 acts as a key regulator for pluripotency gene expression in Muse cells [ Cell Mol Life Sci, 2024, 81(1):54] PubMed: 38261036
Hyperfunction of post-synaptic density protein 95 promotes seizure response in early-stage aβ pathology [ EMBO Rep, 2024, none] PubMed: 38413732
Biological and targeting differences between the rare KRAS A146T and canonical KRAS mutants in gastric cancer models [ Gastric Cancer, 2024, 10.1007/s10120-024-01468-8] PubMed: 38261067
PKCiota Inhibits the Ferroptosis of Esophageal Cancer Cells via Suppressing USP14-Mediated Autophagic Degradation of GPX4 [ Antioxidants (Basel), 2024, 13(1)114] PubMed: 38247539
Isoxanthohumol reduces neointimal hyperplasia through the apelin/AKT pathway [ Biochim Biophys Acta Mol Basis Dis, 2024, 1870(4):167099] PubMed: 38428686

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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