MK-2206 Dihydrochloride

製品コードS1078 バッチS107813

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₂₅H₂₁N₅O.2HCl

分子量

480.39

CAS No.

1032350-13-2

Solubility (25°C)*

体外

DMSO

96 mg/mL (199.83 mM)

Water (warmed with 50ºC water bath)

10 mg/mL (20.81 mM)

Ethanol

Insoluble

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	4.800mg/ml (9.99mM)	Taking the 1 mL working solution as an example, add 50 μL of 96 mg/ml clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% corn oil この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	0.400mg/ml (0.83mM)	Taking the 1 mL working solution as an example, add 50 μL of 8 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	MK-2206 2HCl は高い選択性をもつ Akt1/2/3 阻害剤であり、cell-free assay における IC50 はそれぞれ 8 nM/ 12 nM/ 65 nM です。一方で、他の250種におよぶキナーゼ (kinases) に対しては活性が検出されていません。MK-2206 2HCl はがん細胞におけるオートファジー (autophagy) やアポトーシス (apoptosis) に関与します。臨床第2相試験中
in vitro	MK-2206 2HCl is an allosteric inhibitor and is activated by the pleckstrin homology domain. This compound inhibits auto-phosphorylation of both Akt T308 and S473. It also prevents Akt-mediated phosphorylation of downstream signaling molecules, including TSC2, PRAS40 and ribosomal S6 proteins. ^[1] This chemical 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). It also shows synergistic responses in combination with cytotoxic agents 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 this compound-induced-autophagy, with a promotion of apoptotic cell death. ^[3]
in vivo	MK-2206 2HCl 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] This compound exhibits significant antitumor activity in NCI-H292 xenograft in combination. ^[2]
特徴	The first allosteric small molecule inhibitor of Akt to enter clinical development.

プロトコル(参考用のみ)

キナーゼアッセイ	Akt kinases assay
キナーゼアッセイ	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. 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 2HCl 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.
細胞アッセイ	細胞株	A431, HCC827, NCI-H292, NCI-H358, NCI-H23, NCI-H1299, Calu-6 and NCI-H460 cells
	濃度	0, 0.3, 1 and 3 μM
	反応時間	72 or 96 hours
	実験の流れ	MK-2206 2HCl 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 this compound (0, 0.3, 1 and 3 μM) is added to the cells. Cell proliferation is determined after 72 or 96 hours.
動物実験	動物モデル	SK-OV-3, NCI-H292, HCC70, PC-3, and NCI-H460 models in male CD1-nude mice
	投薬量	120 mg/kg
	投与方法	Orally administered

参考

http://cancerres.aacrjournals.org/content/69/9_Supplement/DDT01-1
https://pubmed.ncbi.nlm.nih.gov/20571069/
https://pubmed.ncbi.nlm.nih.gov/21307130/

http://worldwide.espacenet.com/publicationDetails/biblio?CC=WO&NR=2008070016A2&KC=A2&FT=D&ND=5&date=

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カスタマーフィードバック

: 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]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Lysosomal EGFR acts as a Rheb-GEF independent of its kinase activity to activate mTORC1 [ Cell Res, 2025, 10.1038/s41422-025-01110-x]	PubMed: 40259053
Oncogenic RAS induces a distinctive form of non-canonical autophagy mediated by the P38-ULK1-PI4KB axis [ Cell Res, 2025, 10.1038/s41422-025-01085-9]	PubMed: 40055523
Chromosome mis-segregation triggers cell cycle arrest through a mechanosensitive nuclear envelope checkpoint [ Nat Cell Biol, 2025, 27(1):73-86]	PubMed: 39779939
Nucleus-translocated glucokinase functions as a protein kinase to phosphorylate TAZ and promote tumour growth [ Nat Commun, 2025, 16(1):7156]	PubMed: 40759645
RIOK3 mediates the degradation of 40S ribosomes [ Mol Cell, 2025, 85(4):802-814.e12]	PubMed: 39947183
CD24 Regulates the Formation of Ectosomes in B Lymphocytes [ J Extracell Vesicles, 2025, 14(5):e70093]	PubMed: 40415253
PIP5K1A Suppresses Ferroptosis and Induces Sorafenib Resistance by Stabilizing NRF2 in Hepatocellular Carcinoma [ Adv Sci (Weinh), 2025, 12(30):e04372]	PubMed: 40405713
EGFR TKIs suppress MUC1 glycosylation through the PI3K/AKT/SP1/C1GALT1 pathway to enhance TnMUC1 CAR-T efficacy in EGFR-mutant NSCLC [ Cell Rep Med, 2025, S2666-3791(25)00272-1]	PubMed: 40562040
The PLEKHA1-TACC2 fusion gene drives tumorigenesis via vascular mimicry formation in esophageal squamous-cell carcinoma [ Cell Death Differ, 2025, 10.1038/s41418-025-01536-1]	PubMed: 40615663
Ferroptosis in acute liver Failure: Unraveling the hepcidin-ferroportin axis and therapeutic interventions [ Redox Biol, 2025, 84:103657]	PubMed: 40393152

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。