Laduviglusib (CHIR-99021) HCl

別名：CT99021 HCl

製品コード：S2924 純度：99.97%

ラドゥビグルシブ塩酸塩 (Laduviglusib (CHIR-99021; CT99021) HCl) は CHIR-99021 の塩酸塩で、GSK-3α/β 阻害剤 (IC50 = 10 nM/6.7 nM) です。 CHIR-99021 は、最も近縁なホモログである Cdc2 および ERK2 と比較して、GSK-3 に対して 500 倍を超える選択性を示します。 CHIR-99021 は、Wnt/β-カテニン シグナル伝達経路の強力な薬理学的活性化因子です。 CHIR-99021 は、光誘発されるオートファジー (autophagy) を大幅にレスキューし、GR、RORα、およびオートファジー関連タンパク質量を増大します。

CAS No. 1797989-42-4

サイズ	価格(税別)	在庫状況
5mg	JPY 25500	国内在庫あり
25mg	JPY 85500	国内在庫あり
100mg	JPY 145500	国内在庫あり
1g	JPY 295500	国内在庫なし(納期7~10日)

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文献中Selleckの製品使用例（706）

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製品安全説明書

現在のバッチを見る：純度： 99.97%

99.97

Laduviglusib (CHIR-99021) HClと併用されることが多い化合物

Y-27632 2HCl

Laduviglusib HCl and Y-27632 2HCl, along with a combination of other small molecules, promote the neuronal induction of mesenchymal stem cells (MSCs) derived from both adult and neonatal sources.

Cortés-Medina LV, et al. Stem Cells Int. 2019 Apr 1;2019:7627148.

IWR-1-endo

Laduviglusib HCl treatment upregulates total and active β-catenin, while IWR1-endo reduces active β-catenin expression in cardiac atrial appendage stem cells (CASCs) and SW480 cells.

Willems L, et al. Int J Mol Sci. 2020 May 30;21(11):3931.

MG132

Laduviglusib HCl and MG132 play a crucial role in identifying regulators of short half-life proteins when used as part of a protein stability probe.

Hickman KA, et al. Cytometry A. 2020;97(4):363-377.

IWP-2

Laduviglusib HCl and IWP-2 play a crucial role in the differentiation of human induced pluripotent stem cells (hiPSC) into cardiomyocytes.

Debus JD, et al. J Mol Cell Cardiol. 2019;129:303-313.

Laduviglusib (CHIR-99021) HCl関連製品

関連ターゲット	GSK-3α GSK-3β	もっと見る
関連製品	Laduviglusib (CHIR-99021) SB216763 TWS119 CHIR-98014 BIO LY2090314 Tideglusib SB415286 AR-A014418 1-Azakenpaullone IM-12 CP21R7 TDZD-8 Indirubin (NSC 105327) AZD2858 AZD1080 BIO-acetoxime Bikinin	もっと見る
関連化合物ライブラリー	Kinase Inhibitor Library PI3K/Akt Inhibitor Library Apoptosis Compound Library Cell Cycle compound library NF-κB Signaling Compound Library	もっと見る

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

阻害剤	Citation	GSK-3	GSK-3α	GSK-3β	その他
Laduviglusib (CHIR-99021) HCl	705		+++	+++
SB216763	90		++	++
AT7519	52			+	CDK9/CyclinT,CDK5/p35,CDK2/CyclinA
CHIR-98014	53		++++	++++
TWS119	53			++
Tideglusib	28			++
SB415286	22		+	+
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	✔

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
ES-CCE	Function Assay	5 μM	3 d	Strongly induces the activity of Wnt/beta-catenin pathway	24779365
ES-D3	Function Assay	5 μM	3 d	Strongly induces the activity of Wnt/beta-catenin pathway	24779365
ES-CCE	Cytotoxic Assay	10 μM	3 d	Induces moderate cytotoxicity	24779365
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

Targets

GSK-3β ^[1] (Cell-free assay)	GSK-3α ^[1] (Cell-free assay)
6.7 nM	10 nM

In Vitro
In vitro	CHIR-99021 shows greater than 500-fold selectivity for GSK-3 versus its closest homologs CDC2 and ERK2, as well as other protein kinases. Furthermore, CHIR-99021 shows only weak binding to a panel of 22 pharmacologically relevant receptors and little inhibitory activity against a panel of 23 nonkinase enzymes. CHIR-99021 induces the activation of glycogen synthase (GS) in insulin receptor-expressing CHO-IR cells with EC50 of 0.763 μM. ^[1] In addition to simulating the actions of insulin, inhibition of GSK-3 by CHIR-99021 (3 μM) increases free cytosolic β-catenin by 1.9-fold, mimicking the canonical Wnt signaling pathway in 3T3-L1 preadipocytes. During any of the first 3 days of differentiation, CHIR-99021 treatment inhibits the preadipocyte differentiation with IC50 of 0.3 μM by blocking induction of CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ). ^[2] Unlike lithium chloride and AR-A014418, CHIR-99021 treatment does not reduce the viability of INS-1E cells even at high concentrations. Instead, CHIR-99021 robustly increases the rate of proliferation of INS-1E cells in a dose-dependent manner, and significantly inhibits INS-E cell death induced by high glucose and high palmitate in a concentration-dependent manner. CHIR-99021 promotes primary beta cell replication in isolated rat islets at concentrations as low as 1 μM, with 2-3 fold increase of cell replication at 5 μM of CHIR-99021 treatment. ^[3]
Kinase Assay	Cell-free kinase assays
Kinase Assay	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 27 nM GSK-3α or 29 nM GSK-3β, and 0.5 μM biotin-CREB peptide substrate. Various concentrations of CHIR-99021 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 minutes, and counted in a scintillation counter. All steps are performed at room temperature.
細胞実験	細胞株	INS-1E
	濃度	Dissolved in DMSO, final concentrations ~ 20 μM
	反応時間	1, or 4 days
	実験の流れ	Cells are maintained for 24 hours in starvation medium (culture medium with only 5 mM glucose, 1% fetal calf serum). Then cells are exposed to various concentrations of CHIR-99021 for 1, or 4 days. Cell number is measured by staining of cellular DNA with CyQuant dye, which becomes fluorescent when bound to DNA. Fluorescence is measured after 30 minutes of incubation using the FLUOstar Optima reader. Cell replication is determined by BrdUrd incorporation. BrdUrd labeling solution is added to the medium for the last 4 hours before the cells are fixed using FixDenat solution and incubated with monoclonal anti-BrdUrd-POD antibodies. After substrate solution is added to each well, the light emission is measured in a microplate luminometer using the Analyst HT detection system.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	Cleaved PARP / CD31 / VE-Cadherin / α-SMA / vimentin CTNNB1 β-catenin		30709379
	Growth inhibition assay	Cell viability		22039301
	Immunofluorescence	SOX10 / EdU Oct3/4		28174705

In Vivo
In Vivo	Oral administration of CHIR-99021 at 30 mg/kg enhances glucose metabolism in a rodent model of type 2 diabetes, with a maximal plasma glucose reduction of nearly 150 mg/dl 3-4 hours after administration, while plasma insulin remains at or below control levels. Oral administration of CHIR-99021 at 16 or 48 mg/kg 1 hour before oral glucose challenges in ZDF rats significantly improves glucose tolerance with 14% and 33% reduction in plasma glucose at 16 mg/kg and 48 mg/kg, respectively, and the higher dose of CHIR-99021 also reduces hyperglycemia before the oral glucose challenge. ^[1]
動物実験	動物モデル	Female db/db mice or male ZDF rats with type 2 diabetes
	投与量	~48 mg/kg
	投与経路	Orally

参考
[1] Ring DB, et al. Diabetes, 2003, 52(3), 588-595. [2] Bennett CN, et al. J Biol Chem, 2002, 277(34), 30998-31004. [3] Mussmann R, et al. J Biol Chem, 2007, 282(16), 12030-12037.

参考

化学情報

分子量	501.8	化学式	C₂₂H₁₈Cl₂N_8.HCl
CAS No.	1797989-42-4	SDF	Download Laduviglusib (CHIR-99021) HCl SDFをダウンロードする
Smiles	CC1=CN=C(N1)C2=CN=C(N=C2C3=C(C=C(C=C3)Cl)Cl)NCCNC4=NC=C(C=C4)C#N.Cl
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ケ月-20°Cin solvent

In vitro
Batch:

DMSO : 100 mg/mL ( (199.28 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。)

Ethanol : 10 mg/mL

Water : 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

Saline

10.0mg/ml (19.93mM)

Taking the 1 mL working solution as an example, add 10 mg of this product to 1 ml of physiological saline (0.9% NaCL solution), mix evenly to make it clear, 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
=	×	×

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。

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よくある質問（FAQ）

質問1:
How about the half-life of this compound? If it is necessary for daily treatment when the compound is used in long-term experiment?

回答
Please change the culture medium each day to add the new comound in it if the duration is more than 72h.

質問2:
What is the difference between S2924 and S1263? Which one is better for differentiation?

回答
S1263 is the free base format of Chir-99021, while S2924 is the HCl salt format. They have the same biological activity but are slightly different in solubility.

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):