CHIR-98014

Catalog No.S2745 Synonyms: CT98014

CHIR-98014 Chemical Structure

Molecular Weight(MW): 486.31

CHIR-98014 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.

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4 Customer Reviews

  • Western blotting (D) in U937 cells following 16-hour exposure to BEZ235/ABT-737 (0.5 μmol/L each) in the presence or absence of BIO, MeBIO, or CHIR-98014 (2 μmol/L each).

    Cancer Res, 2013, 73(4):1340-51.. CHIR-98014 purchased from Selleck.

    Differentiation of hESCs along the vascular. (B) FACS analysis showing the percentage of cells expressing CD34, PDGFRa, and KDR after 4 days of differentiation using our differentiation protocol in H9 hESC line. Similarly, an analysis was provided for the H1 hESC line using the same protocol but with CHIR98014 as the GSKi.

    Stem Cells Dev 2013 22, 1893-90. CHIR-98014 purchased from Selleck.

  •  

    T (Brachyury) and b-catenin expression in hESCs after GSKi treatment. (C) Immunofluorescence analysis of OCT4 and brachyury in hESCs after 24 h of GSKi treatment. Top row: H1-hESCs treated with basal media alone without any GSKi, middle row: H9 hESCs treated with CHIR99021, bottom row: H1-hESCs treated with 2 mM CHIR98014. (D) 20 · magnification of bcatenin expression in H1-hESCs after 24 h of GSKi treatment. Top row: hESCs treated with basal media alone without any
    GSKi, middle row: hESCs treated with CHIR99021, bottom row: hESCs treated with CHIR98014. All scale bars represent 200 mm.

    Stem Cells Dev 2013 22, 1893-90. CHIR-98014 purchased from Selleck.

    T (Brachyury) and b-catenin expression in hESCs after GSKi treatment. (B) Comparison of transcription profiles for T and CXCR4 in hESCs treated using CHIR99021 at 5mM and a different GSKi, CHIR98014 at 2mM. Although gene expression levels were different, the transcription profiles for both genes were approximately similar for both GSKis with T upregulating and peaking at day 1, while CXCR4 begins up-regulating at day 2.

    Stem Cells Dev 2013 22, 1893-90. CHIR-98014 purchased from Selleck.

Purity & Quality Control

Choose Selective GSK-3 Inhibitors

Biological Activity

Description CHIR-98014 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

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]

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]

Protocol

Kinase Assay:

[1]

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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.
Cell Research:

[1]

+ Expand
  • Cell lines: CHO-IR cells
  • Concentrations: 0.01-10 μM
  • Incubation Time: 30 min
  • Method:

    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.


    (Only for Reference)
Animal Research:

[1]

+ Expand
  • Animal Models: db/db mice with 8-9 weeks
  • Formulation: 15% Captisol/citrate vehicle
  • Dosages: 30 mg/kg
  • Administration: Subcutaneously
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 8 mg/mL warmed (16.45 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents individually and in order:
5% DMSO+corn oil
2mg/mL

* 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.

Chemical Information

Molecular Weight 486.31
Formula

C20H17Cl2N9O2

CAS No. 252935-94-7
Storage powder
Synonyms CT98014

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID