1. PI3K/Akt/mTOR Stem Cell/Wnt
  2. GSK-3
  3. CHIR-98014

CHIR-98014 

Cat. No.: HY-13076 Purity: ≥98.0%
COA Handling Instructions

CHIR-98014 is a potent, cell-permeable GSK-3 inhibitor with IC50s of 0.65 and 0.58 nM for GSK-3α and GSK-3β, respectively; it shows less potent activities against cdc2 and erk2.

For research use only. We do not sell to patients.

CHIR-98014 Chemical Structure

CHIR-98014 Chemical Structure

CAS No. : 252935-94-7

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10 mM * 1 mL in DMSO
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Based on 3 publication(s) in Google Scholar

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Description

CHIR-98014 is a potent, cell-permeable GSK-3 inhibitor with IC50s of 0.65 and 0.58 nM for GSK-3α and GSK-3β, respectively; it shows less potent activities against cdc2 and erk2.

IC50 & Target[1]

GSK-3β

0.58 nM (IC50)

GSK-3α

0.65 nM (IC50)

cdc2

3700 nM (IC50)

In Vitro

CHIR 98014 inhibits human GSK-3β with Ki value of 0.87 nM. CHIR 98014 causes GS stimulation in CHO-IR cells and rat hepatocytes, with EC50s of 106 nM and 107 nM, respectively[1]. CHIR-98014 (1 μM) reduces the viability of ES-CCE cells by 52%, with IC50 of 1.1 μM. Moreover, CHIR-98014 in combination with CHIR-99021 results in a significant activation of the Wnt/beta-catenin pathway in ES-D3 cells. In CHIR-98014 treated cells, the T gene expression is induced up to 2,500-fold. CHIR-98014 (1 μM) also yields around 50% Brachyury-positive cells, with EC50 of 0.32 μM[2]. CHIR98014 (10 μM) prevents loss of neurites caused by 20 μM PrP1-30 in cortical and hippocampal neurons, and substantially decreases the amount of dead cells[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

CHIR 98014 (30 mg/kg, i.p.) exhibits a significant reduction in fasting hyperglycemia within 4 h of treatment and shows improved glucose disposal during an ipGTT in markedly diabetic and insulin-resistant db/db mice[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Molecular Weight

486.31

Formula

C20H17Cl2N9O2

CAS No.
Appearance

Solid

Color

Light yellow to yellow

SMILES

ClC1=CC(Cl)=CC=C1C2=NC(NCCNC3=CC=C([N+]([O-])=O)C(N)=N3)=NC=C2N4C=CN=C4

Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 2 years
-20°C 1 year
Solvent & Solubility
In Vitro: 

DMSO : 12.5 mg/mL (25.70 mM; ultrasonic and warming and heat to 60°C)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.0563 mL 10.2815 mL 20.5630 mL
5 mM 0.4113 mL 2.0563 mL 4.1126 mL
10 mM 0.2056 mL 1.0282 mL 2.0563 mL
*Please refer to the solubility information to select the appropriate solvent.
Purity & Documentation

Purity: ≥98.0%

References
Kinase Assay
[1]

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. Information on the kinase concentration, peptide substrate, and activator for these assays is as follows: GSK-3α (27 nM, and 0.5 μM biotin-CREB peptide); GSK-3β (29 nM, and 0.5 μM biotin-CREB peptide); cdc2 (0.8 nM, and 0.5 μM biotin histone H1 peptide); erk2 (400 units/mL, and myelin basic protein-coated Flash Plate); PKC-α (1.6 nM, 0.5 μM biotin-histone H1 peptide, and 0.1 mg/mL phosphatidylserine + 0.01 mg/mL diglycerides); PKC-ζ (0.1 nM, 0.5 μM biotin-PKC-86 peptide, and 50 μg/mL phosphatidylserine + 5 μg/mL diacylglycerol); akt1 (5.55 nM, and 0.5 μM biotin phospho-AKT peptide); p70 S6 kinase (1.5 nM, and 0.5 μM biotin-GGGKRRRLASLRA); p90 RSK2 (0.049 units/mL, and 0.5 μM biotin-GGGKRRRLASLRA); c-src (4.1 units/mL, and 0.5 μM biotin-KVEKIGEGTYGVVYK); Tie2 (1 μg/mL, and 200 nM biotin-GGGGAPEDLYKDFLT); flt1 (1.8 nM, and 0.25 μM KDRY1175 [B91616] biotin-GGGGQDGKDYIVLPI-NH2); KDR (0.95 nM, and 0.25 μM KDRY1175 [B91616] biotin-GGGGQDGKDYIVLPI-NH2); bFGF receptor tyrosine kinase (RTK; 2 nM, and 0.25 μM KDRY1175 [B91616] biotin-GGGGQDGKDYIVLPI-NH2); IGF1 RTK (1.91 nM, and 1 μM biotin-GGGGKKKSPGEYVNIEFG-amide); insulin RTK (using DG44 IR cells); AMP kinase (470 units/mL, 50 μM SAMS peptide, and 300 μM AMP); pdk1 (0.25 nM, 2.9 nM unactivated Akt, and 20 μM each of DOPC and DOPS + 2 μM PIP3); CHK1 (1.4 nM, and 0.5 μM biotin-cdc25 peptide); CK1-ε (3 nM, and 0.2 μM biotin-peptide); DNA PK (see 31); and phosphatidylinositol (PI) 3-kinase (5 nM, and 2 μg/mL PI). Test compounds 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 h, 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. Inhibition is calculated as 100% × (inhibited − no enzyme control)/(DMSO control − no enzyme control)[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[2]

The viability of the mouse ES cells is determined after exposure to different concentrations of GSK3 inhibitors for three days using the MTT assay. The decrease of MTT activity is a reliable metabolism-based test for quantifying cell viability; this decrease correlates with the loss of cell viability. 2,000 cells are seeded overnight on gelatine-coated 96-well plates in LIF-containing ES cell medium. On the next day the medium is changed to medium devoid of LIF and with reduced serum and supplemented with 0.1-1 μM BIO, or 1-10 μM SB-216763, CHIR-99021 or CHIR-98014. Basal medium without GSK3 inhibitors or DMSO is used as control. All tested conditions are analyzed in triplicates[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

Blood is obtained by shallow tail snipping at lidocaine-anesthetized tips. Blood glucose is measured directly or heparinized plasma is collected for measurement of glucose or insulin. Animals are prebled and randomized to vehicle control or GSK-3 inhibitor treatment groups. For glucose tolerance tests (GTTs), animals are fasted throughout the procedure with food removal early in the morning, 3 h before first prebleed (db/db mice), or the previous night, 16 h before the bleed (ZDF rats). When the time course of plasma glucose and insulin changes in fasting ZDF rats is measured, food is removed ∼16 h before test agent administration. The glucose challenges in the GTT are 1.35 g/kg i.p. (ipGTT) or 2 g/kg via oral gavage (oGTT). Test inhibitors are formulated as solutions in 20 mM citrate-buffered 15% Captisol or as fine suspensions in 0.5% carboxymethylcellulose[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
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CHIR-98014 Related Classifications

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  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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