ホームページ PI3K/Akt/mTOR GSK-3 inhibitor CHIR-98014 For research use only.

CHIR-98014

別名：CT98014

CHIR-98014 (CT98014) is a potent GSK-3α/β inhibitor with IC50 of 0.65 nM/0.58 nM in cell-free assays, with the ability to distinguish GSK-3 from its closest homologs Cdc2 and ERK2.

CHIR-98014化学構造

CAS No. 252935-94-7

サイズ 価格(税別) 在庫状況
10mM (1mL in DMSO) JPY 29500 国内在庫あり
JPY 22000 国内在庫あり
JPY 59500 国内在庫あり
JPY 134500 国内在庫あり
JPY 520500 国内在庫なし(納期7~10日)

代表番号: 045-509-1970|電子メール：sales@selleck.co.jp
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製品安全説明書

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CHIR-98014関連製品

シグナル伝達経路

GSK-3 Signaling Pathways

GSK-3シグナル伝達経路

GSK-3阻害剤の選択性比較

阻害剤 Citation GSK-3 GSK-3α GSK-3β その他
Laduviglusib (CHIR-99021) HCl 704
SB216763 90
AT7519 52 CDK9/CyclinT,CDK5/p35,CDK2/CyclinA
CHIR-98014 53
TWS119 53
Tideglusib 28
SB415286 21
BIO 36 TYK2,CDK5/p35,CDK2/CyclinA
Laduviglusib (CHIR-99021) 943
AZD2858 8
AZD1080 6
AR-A014418 20
TDZD-8 8
LY2090314 30
WAY-119064 0
RGB-286638 free base 0 cyclin T1-CDK9,cyclin B1-CDK1,cyclin E-CDK2
PF-04802367 0
(E/Z)-GSK-3β inhibitor 1 0
KY19382 (A3051) 0 CXXC5–DVL
BRD0705 0
Alsterpaullone 0 caspase-9,CDK2/cyclin A,CDK1/cyclin B
BIO-acetoxime 5
IM-12 17
1-Azakenpaullone 16
Indirubin (NSC 105327) 8 CDK2/CyclinA,CDK5/p35,CDK1/CyclinB
Cu(II)GTSM 0
Indirubin-3′-oxime 0 JNK1
Resibufogenin 2 RIP3,PI3K,cyclin E
Elraglusib 0
5-Bromoindole 0
CP21R7 13
Bikinin 3
もっと見る
1. "+" indicates inhibitory effect. Increased inhibition is marked by a higher "+" designation. 2. "✔" indicates inhibitory effect, but without specific value.

Cell Data

Cell Lines Assay Type Concentration Incubation Time 活性情報 PMID
BGC-823 Proliferation assay 50 nM 48 h abrogated rLMO3 protein-induced proliferation 29436606
HGC-27 Proliferation assay 50 nM 48 h abrogated rLMO3 protein-induced proliferation 29436606
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
他の多くの細胞株試験データをご覧になる場合はこちらをクリックして下さい

生物活性

製品説明 CHIR-98014 (CT98014) is a potent GSK-3α/β inhibitor with IC50 of 0.65 nM/0.58 nM in cell-free assays, with the ability to distinguish GSK-3 from its closest homologs Cdc2 and ERK2.
Targets
GSK-3β [1]
(Cell-free assay)		 GSK-3α [1]
(Cell-free assay)
0.58 nM 0.65 nM
In Vitro
In vitro CHIR-98014 inhibits human GSK-3β with Ki of 0.87 nM. CHIR-98014 is very effective in preventing murine and rat GSK-3. Although CHIR-98014 acts as a simple competitive inhibitor of ATP binding, it displays from 500-fold to >1000-fold selectivity for GSK-3 versus 20 other protein kinases including Cdc2, ERK2, Tie-2 and KDR. CHIR-98014 prevents Cdc2 with IC50 of 3.7 μM. However, CHIR 98014 reveals similar ptoency against the highly homologous ɑ and β isoforms of GSK-3, it is noteworthy that it stronly discriminated between GSK-3 and its closest homologs CDC2 and ERK2. Exposure of insulin receptor-expressing CHO-IR cells or primary rat hepatocytes to increasing concentrations of inhibitor CHIR98014 results in a two- to three-fold stimulation of the GS activity ratio above basal. The concentrations of CHIR-98014 giving rise to half-maximal GS stimulation (EC50) is 106 nM and 107 nM for CHO-IR and rat hepatocytes, respectively. [1]
Kinase Assay Kinase assays
Polypropylene 96-well plates are filled with 300 μL/well buffer (50 mM tris HCl, 10 mM MgCl2, 1 mM EGTA, 1 mM dithiothreitol, 25 mM β-glycerophosphate, 1 mM NaF, 0.01% BSA, pH 7.5) containing kinase, peptide substrate, and any activators. CHIR-98014 or controls are added in 3.5 μL of DMSO, followed by 50 μL of ATP stock to yield a final concentration of 1 μM ATP in all cell-free assays. After incubation, triplicate 100-μL aliquots are transferred to Combiplate eight plates containing 100 μL/well 50 μM ATP and 20 mM EDTA. After 1 hour, the wells are rinsed five times with PBS, filled with 200 μL of scintillation fluid, sealed, left 30 min, and counted in a scintillation counter. All steps are performed at room temperature.
細胞実験 細胞株 CHO-IR cells
濃度 0.01-10 μM
反応時間 30 min
実験の流れ

CHO-IR cells expressing human insulin receptor are grown to 80% confluence in Hamm’s F12 medium with 10% fetal bovine serum and without hypoxanthine. Trypsinized cells are seeded in 6-well plates at 1 × 106 cells/well in 2 mL of medium without fetal bovine serum. After 24 hours, medium is replaced with 1 mL of serum-free medium containing GSK-3 inhibitor CHIR 98014 or control (final DMSO concentration 0.1%) for 30 min at 37 °C. Cells are lysed by freeze/thaw in 50 mM tris (pH 7.8) containing 1 mM EDTA, 1 mM DTT, 100 mM NaF, 1 mM phenylmethylsulfonyl fluoride, and 25 μg/mL leupeptin (buffer A) and centrifuged 15 min at 4 °C/14000 g. The activity ratio of GS is calculated as the GS activity in the absence of glucose-6-phosphate divided by the activity in the presence of 5 mM glucose-6-phosphate.
実験結果図 Methods Biomarkers 結果図 PMID
Western blot p-AKT / AKT / p-GSK3β / GSK3β / β-catenin 28415692
Growth inhibition assay Cell viability 24779365
In Vivo
In Vivo GSK-3 inhibitor CHIR-98014 activates the GS activity ratio in isolated type I skeletal muscle from insulin-sensitive lean Zucker and from insulin-ressitant ZDF rats. Soleus muscle isolated from ZDF rats shows significant resistance to insulin for activation of GS but responded to 500 nM CHIR-98014 to the same extent (40% increase) as muscle from lean Zucker rats. Notably, GS activation by insulin plus CHIR-98014 is additive in muscle from lean Zucker rats and greater than additive in muscle from the ZDF rats. Total GS activity is not altered by either CHIR-98014 or insulin in these cells and muscles. Meanwhile, CHIR-98014 does not influence the insulin dose-response in muscle from lean animals. The reduction in hyperglycemia and improved glucose disposal are not limited to db/db mice and ZDF rats, as similar results are observed with ob/ob mice, diet-induced diabetic C57BL/6 mice, and glucose-intolerant SHHF rats treated with CHIR-98014. [1] Additionally, CHIR-98014 decreases the phosphorylation (Ser396) of tau protein in the cortex and hippocampus of postnatal rats. [2]
動物実験 動物モデル db/db mice with 8-9 weeks
投与量 30 mg/kg
投与経路 Subcutaneously

化学情報

分子量 486.31 化学式

C20H17Cl2N9O2
CAS No. 252935-94-7 SDF Download CHIR-98014 SDFをダウンロードする
Smiles C1=CC(=C(C=C1Cl)Cl)C2=NC(=NC=C2N3C=CN=C3)NCCNC4=NC(=C(C=C4)[N+](=O)[O-])N
保管

In vitro
Batch:

DMSO : 10 mg/mL ( (20.56 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
Clear solution
10%DMSO 90%Corn oil
1.1mg/ml (2.26mM) Taking the 1 mL working solution as an example, add 100 μL of 11 mg/ml clear DMSO stock solution to 900 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 

実験計算

モル濃度計算器

質量 濃度 体積 分子量

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）

mg/kg g μL 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。

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