CHIR-99021

Reagent Authentication Certificate:

Chemical Probes Portal CHIR-99021.pdf

Protein target name:

GSK3A, GSK3B

Mechanism of action:

ATP-competitive inhibitor

Recommended Concentration for use in cells:

10 nM - 1 uM

Probe Availability

Tocris (1782235-14-6)

Abcam (252917-06-9)

MedChem Express (252917-06-9)

Cayman (252917-06-9)

Probe Information

Target and Probe Information

Target Details

Target class:

Protein kinase

Subclass:

CMGC

HUGO ID:

HGNC:4616 HGNC:4617

Entrez gene ID:

2931 2932

UNIPROT ID:

P49840 P49841

Probe Details

Chemical Probes Portal ID:

CPP35

Probe alias:

CT-99021, GSK-3 Inhibitor XVI

PubChem CID:

9956119

ChEMBL ID:

CHEMBL412142

SMILES string:

CC1=CN=C(N1)C2=CN=C(N=C2C3=C(C=C(C=C3)Cl)Cl)NCCNC4=NC=C(C=C4)C#N

InChi Key:

AQGNHMOJWBZFQQ-UHFFFAOYSA-N

PAINs evaluation:

PAINs free

Physico-chemical properties

Solubility - preferred solvent:

DMSO

Solubility - concentration:

100 mg/mL

Storage Recommendations

Storage (dry powder):

Shelf stable

Storage (solution):

-20 oC

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

GSK3A 6.7 nM, GSK3B 10 nM

Off target activity

Potency assay (off target):

CHIR-99021 is 5,000-10,000-fold selective for GSK kinases over 20 other protein kinases

Probe Selectivity in Vitro:

CHIR-99021 KD > 4 uM for 22 pharmacologically relevant receptors CHIR-99021 Ki > 8 uM for 23 non-kinase enzymes

In cell validation

On target activity in cells

Potency in cells:

EC50

763 nM

Potency assay (cells):

In CHO-IR and primary rat hepatocytes, CHIR-99021 activated glycogen synthase

Primary Reference

Reference (doi):

10.2337/diabetes.52.3.588

Reference (PMID):

12606497

External Resources

Available data:

GDSC1 GDSC1

Endorsed probe

The Chemical Probes Portal endorses this compound as chemical probe for use in cells.

SAB Rating

Rating for use in Cells

3 review(s)

Rating for use in Model Organisms

3 review(s)

SAB Members

SAB Comments

This is a selective glycogen synthase kinase-3 alpha and beta inhibitor with potent in vitro activity.

It's been shown to inhibit the Wnt/beta-catenin pathway in several studies. This probe reduced hyperglycemia in a test for glucose tolerance and improved insulin sensitivity in mice (db/db) and rats, where it also reduced postprandial glucose levels (subcutaneous or oral, 16-48 mg/kg). In fasted hyperglycemic ZDF rats, CHIR-99021 significantly reduced fasting plasma glucose levels (single oral delivery at 30 mg/kg).

Jun 12 2016 - 3:57am

This molecule is a potent and highly selective inhibitor of glycogen synthase kinase 3 (GSK-3) (IC50 6.7 GSK-3β; 10 nM GSK-3α) with >500-fold selectivity over closely related kinases and >800-fold selectivity against 45 additional enzymes and receptors. Activity demonstrated in isolated tissue preparations and po in rat models (10-30 mg/kg) and s/c. Whilst it is suitable for probe use based on these data, other probes are available which may be superior. In particular, ML320 (http://www.ncbi.nlm.nih.gov/books/NBK133436/) claims a similar GSK-3 profile with improved kinome selectivity and microsomal stability, although no rodent model data were available.

Jun 30 2016 - 3:55am

This is an appropriate molecule to consider for in vitro and in vivo studies, with data supporting its mechanism of action at GSK3, at downstream pathway points and in disease models in rats. One note of caution: although the selectivity data reported so far are encouraging, the compound has only been evaluated against 20 kinases, 23 enzymes and 22 receptors. Many other molecules have been reported as GSK3a/b inhbitors - many are of poor quality - but newer tools with more complete characterization are available and should be considered.

Sep 8 2016 - 4:09pm

CHIR-99021

Probe Availability

Probe Information

Target Details

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

Primary Reference

External Resources

Supporting Organizations

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CHIR-99021

Probe Availability

Probe Information

Target Details

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

Primary Reference

External Resources

Supporting Organizations

Interested in supporting the portal?