AR-A014418

AR-A014418 (GSK-3β Inhibitor VIII) is an ATP-competitive, and selective GSK3β inhibitor with IC50 and K_i of 104 nM and 38 nM in cell-free assays, without significant inhibition on 26 other kinases tested.

CAS No. 487021-52-3

サイズ	価格(税別)	在庫状況
10mg	JPY 22000	国内在庫あり
50mg	JPY 55500	国内在庫あり
1g	JPY 448500	国内在庫なし(納期7~10日)

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（17）

カスタマーフィードバック2个实验数据

製品安全説明書

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シグナル伝達経路

GSK-3シグナル伝達経路

GSK-3阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Incubation Time	活性情報	PMID
human BxPC3 cells	Growth inhibition assay	72 h	Growth inhibition of human BxPC3 cells after 72 hrs by MTS assay, IC50=14 μM	19338355
human HUPT3 cells	Growth inhibition assay	72 h	Growth inhibition of human HUPT3 cells after 72 hrs by MTS assay, IC50=22 μM	19338355
human MIAPaCa2 cells	Growth inhibition assay	72 h	Growth inhibition of human MIAPaCa2 cells after 72 hrs by MTS assay, IC50=29 μM	19338355
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生物活性

製品説明

AR-A014418 (GSK-3β Inhibitor VIII) is an ATP-competitive, and selective GSK3β inhibitor with IC50 and K_i of 104 nM and 38 nM in cell-free assays, without significant inhibition on 26 other kinases tested.

特性

Cell-permeable GSK3-selective inhibitor.

Targets

GSK-3β ^[1] (Cell-free assay)	GSK-3β ^[1] (Cell-free assay)
38 nM(Ki)	38 nM(Ki)

In Vitro
In vitro	AR-A014418 inhibits tau phosphorylation at a GSK3-specific site (Ser-396) in 3T3 fibroblasts expressing human four-repeat tau protein with IC50 of 2.7 μM, and protects cultured N2A cells from death induced by blocking PI3K/PKB pathway. In hippocampal slices, AR-A014418 inhibits neurodegeneration mediated by beta-amyloid peptide. ^[1] While in NGP and SH-5Y-SY cells, AR-A014418 reduces neuroendocrine markers and suppresses neuroblastoma cell growth. ^[2]
Kinase Assay	GSK3 Scintillation Proximity Assay
Kinase Assay	The competition experiments are carried out in duplicate with 10 concentrations of the inhibitor in clear-bottomed microtiter plates. The biotinylated peptide substrate, biotin-AAEELDSRAGS(PO3H2)PQL, is added at a final concentration of 2 μM in an assay buffer containing 6 milliunits of recombinant human GSK3 (equal mix of both α and β), 12 mM MOPS, pH 7.0, 0.3 mM EDTA, 0.01% β-mercaptoethanol, 0.004% Brij 35, 0.5% glycerol, and 0.5 μg of bovine serum albumin/25 μl and preincubated for 10-15 min. The reaction is initiated by the addition of 0.04 μCi of [γ-³³P]ATP and unlabeled ATP in 50 mM Mg(Ac)₂ to a final concentration of 1 μM ATP and assay volume of 25 μl. Blank controls without peptide substrate are used. After incubation for 20 min at room temperature, each reaction is terminated by the addition of 25 μl of stop solution containing 5 mM EDTA, 50 μM ATP, 0.1% Triton X-100, and 0.25 mg of streptavidin-coated SPA beads corresponding to ∼35 pmol of binding capacity. After 6 h the radioactivity is determined in a liquid scintillation counter. Inhibition curves are analyzed by non-linear regression using GraphPad Prism.
細胞実験	細胞株	N2A cells
	濃度	~50 μM
	反応時間	24 h
	実験の流れ	Cell viability is assessed by calcein/propidium iodide uptake. Calcein AM is taken up and cleaved by esterases present within living cells, yielding yellowish-green fluorescence, whereas PI is only taken up by dead cells, which become orange-red fluorescent. In brief, N2A cells are cultured for 2 days in vitro and then treated with 50 μM LY-294002 in the presence of AR-A014418 or vehicle (DMSO) for 24 h. Subsequently, N2A cells are incubated for 30 min with 2 μM PI and 1 μM calcein-AM. The cultures are then rinsed three times with Hanks' buffered saline solution containing 2 mM CaCl₂, and the cells are visualized by fluorescence microscopy using a Zeiss Axiovert 135 microscope. Three fields (selected at random) are analyzed per well (∼300 cells/field) in at least three different experiments. Cell death is expressed as percentage of PI-positive cells from the total number of cells. In every experiment, specific cell death is obtained after subtracting the number of dead cells present in vehicle-treated cultures.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	β-catenin β-catenin / GSK3α / GSK3β / Notch1 TAK1 / TAB1 / TAB2 / p-p65 / p65		26292722
	Growth inhibition assay	Cell viability		26292722

In Vivo
In Vivo	In ALS mouse model with the G93A mutant human SOD1, AR-A014418 (0-4 mg/kg, i.p.) delays the onset of symptoms, improves motor activity, slows down disease progression, and postpons the endpoint of the disease. ^[3] In addition, AR-A014418 produces inhibition effect on acetic acid- and formalin-induced nociception in mice by modulating NMDA and metabotropic receptor signaling as well as TNF-α and IL-1β transmission in the spinal cord. ^[4]
動物実験	動物モデル	ALS mouse model with the G93A mutant human SOD1
	投与量	~4 mg/kg
	投与経路	i.p.

参考
[1] Bhat R, et al. J Biol Chem. 2003, 278(46), 45937-45945. [2] Carter YM, et al. Cancer Biol Ther. 2014, 15(5). [3] Koh SH, et al. Exp Neurol. 2007, 205(2), 336-346. [4] Martins DF, et al. J Pain. 2011, 12(3), 315-322. + 展開

参考

[4] Martins DF, et al. J Pain. 2011, 12(3), 315-322.

+ 展開

化学情報

分子量	308.31	化学式	C₁₂H₁₂N₄O₄S
CAS No.	487021-52-3	SDF	Download AR-A014418 SDFをダウンロードする
Smiles	COC1=CC=C(C=C1)CNC(=O)NC2=NC=C(S2)[N+](=O)[O-]
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

In vitro
Batch:

DMSO : 61 mg/mL ( (197.85 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Water : Insoluble

Ethanol : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):