2. Signaling Pathways
  3. PI3K/Akt/mTOR
    Stem Cell/Wnt
  4. GSK-3

GSK-3

Glycogen synthase kinase-3; Glycogen synthase kinase 3

GSK-3

Related Products

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Glycogen synthase kinase 3 (GSK-3) is a multifunctional serine/threonine kinase consisting of two isoforms, alpha and beta. It is a highly conserved negative regulator of receptor tyrosine kinase, cytokine, and Wnt signaling pathways. Stimulation of these pathways inhibits GSK-3 to modulate diverse downstream effectors that include transcription factors, nutrient sensors, glycogen synthesis, mitochondrial function, circadian rhythm, and cell fate. GSK-3 also regulates alternative splicing in response to T-cell receptor activation, and recent phosphoproteomic studies have revealed that multiple splicing factors and regulators of RNA biosynthesis are phosphorylated in a GSK-3-dependent manner.

The malfunction or aberrant activity of GSK-3 leads to several of disorders, such as Alzheimer's disease (AD) and other neurodegenerative pathologies, and other type of diseases as diabetes, cardiovascular disorders and cancer. GSK-3 is also related to innate immune response against pathogens, which makes GSK-3 an excellent target for therapeutic intervention.

GSK-3 Isoform Specific Products:

GSK-3 Isoform Comparison
Cat. No. Product Name Effect Purity Chemical Structure
  • HY-10182
    Laduviglusib
    		Inhibitor 99.76%
    Laduviglusib (CHIR-99021) is a potent, selective and orally active GSK-3α/β inhibitor with IC50s of 10 nM and 6.7 nM. Laduviglusib shows >500-fold selectivity for GSK-3 over CDC2, ERK2 and other protein kinases. Laduviglusib is also a potent Wnt/β-catenin signaling pathway activator. Laduviglusib enhances mouse and human embryonic stem cells self-renewal. Laduviglusib induces autophagy.
    Laduviglusib
  • HY-12012
    SB 216763
    		Inhibitor 99.82%
    SB 216763 is potent, selective and ATP-competitive GSK-3 inhibitor with IC50s of 34.3 nM for both GSK-3α and GSK-3β.
    SB 216763
  • HY-13867
    Bisindolylmaleimide I
    		Inhibitor 98.66%
    Bisindolylmaleimide I (GF109203X) is a cell-permeable and reversible PKC inhibitor (IC50 of 20 nM, 17 nM, 16 nM, and 20 nM for PKCα, PKCβI, PKCβII, and PKCγ. Bisindolylmaleimide I is also a GSK-3 inhibitor.
    Bisindolylmaleimide I
  • HY-16294
    LY2090314
    		Inhibitor 99.78%
    LY2090314 is a potent inhibitor of glycogen synthase kinase-3 (GSK-3) with IC50 values of 1.5 nM and 0.9 nM for GSK-3α and GSK-3β, respectively.
    LY2090314
  • HY-10182A
    Laduviglusib monohydrochloride
    		Inhibitor 99.93%
    Laduviglusib (CHIR-99021) monohydrochloride is a potent and selective GSK-3α/β inhibitor with IC50s of 10 nM and 6.7 nM. Laduviglusib monohydrochloride shows >500-fold selectivity for GSK-3 over CDC2, ERK2 and other protein kinases. Laduviglusib monohydrochloride is also a potent Wnt/β-catenin signaling pathway activator. Laduviglusib monohydrochloride enhances mouse and human embryonic stem cells self-renewal. Laduviglusib monohydrochloride induces autophagy.
    Laduviglusib monohydrochloride
  • HY-10182R
    Laduviglusib (Standard)
    		Inhibitor
    Laduviglusib (Standard) is the analytical standard of Laduviglusib. Laduviglusib (CHIR-99021) is a potent, selective and orally active GSK-3α/β inhibitor with IC50s of 10 nM and 6.7 nM. Laduviglusib shows >500-fold selectivity for GSK-3 over CDC2, ERK2 and other protein kinases. Laduviglusib is also a potent Wnt/β-catenin signaling pathway activator. Laduviglusib enhances mouse and human embryonic stem cells self-renewal. Laduviglusib induces autophagy.
    Laduviglusib (Standard)
  • HY-112388
    GSK-3b Inhibitor XI
    		Inhibitor 99.10%
    GSK3β inhibitor XI is a potent inhibitor of glycogen synthase kinase 3β (GSK3β; Ki=25 nM). It is selective for GSK3β over a panel of 79 kinases at a concentration of 10 μM. GSK3β inhibitor XI inhibits GSK3β in HEK293 cells (EC50=32 nM).
    GSK-3b Inhibitor XI
  • HY-162675
    COB-187
    		Inhibitor
    COB-187 is a potent, ATP-competitive and selective inhibitor of GSK-3β. COB-187 inhibits GSK-3 through a reversible and Cysteine (Cys)-199-dependent mechanism. COB-187 inhibits LPS induced cytokine production and SARS-CoV-2 spike protein-induced CXCL10 production.
    COB-187
  • HY-12302
    Kenpaullone
    		Inhibitor 98.20%
    Kenpaullone is a potent inhibitor of CDK1/cyclin B and GSK-3β, with IC50s of 0.4 μM and 23 nM, and also inhibits CDK2/cyclin A, CDK2/cyclin E, and CDK5/p25 with IC50s of 0.68 μM, 7.5 μM, 0.85 μM, respectively. Kenpaullone, a small molecule inhibitor of KLF4, reduces self-renewal of breast cancer stem cells and cell motility in vitro.
    Kenpaullone
  • HY-10590
    TWS119
    		Inhibitor 99.20%
    TWS119 is a specific inhibitor of GSK-3β, with an IC50 of 30 nM, and activates the wnt/β-catenin pathway.
    TWS119
  • HY-10580
    GSK 3 Inhibitor IX
    		Inhibitor 99.74%
    GSK 3 Inhibitor IX (6-Bromoindirubin-3'-oxime; BIO) is a potent, selective, reversible and ATP-competitive inhibitor of GSK-3α/β and CDK1-cyclinB complex with IC50s of 5 nM/320 nM/80 nM for (GSK-3α/β)/CDK1/CDK5, respectively.
    GSK 3 Inhibitor IX
  • HY-10182B
    Laduviglusib trihydrochloride
    		Inhibitor 99.35%
    Laduviglusib (CHIR-99021) trihydrochloride is a potent and selective GSK-3α/β inhibitor with IC50s of 10 nM and 6.7 nM. Laduviglusib trihydrochloride shows >500-fold selectivity for GSK-3 over CDC2, ERK2 and other protein kinases. Laduviglusib trihydrochloride is also a potent Wnt/β-catenin signaling pathway activator. Laduviglusib trihydrochloride enhances mouse and human embryonic stem cells self-renewal. Laduviglusib trihydrochloride induces autophagy.
    Laduviglusib trihydrochloride
  • HY-14872
    Tideglusib
    		Inhibitor 99.79%
    Tideglusib (NP031112) is an irreversible GSK-3 inhibitor with IC50s of 5 nM and 60 nM for GSK-3βWT (1 h preincubation) and GSK-3βC199A (1 h preincubation), respectively.
    Tideglusib
  • HY-B0712B
    Ceftriaxone sodium salt
    		Inhibitor 99.25%
    Ceftriaxone sodium salt (Ro 13-9904) is a broad spectrum β-lactam third-generation cephalosporin antibiotic, which has good antibacterial activity against a variety of gram-negative and positive bacteria. Ceftriaxone sodium salt is a covalent inhibitor of GSK3β with IC50 value of 0.78 μM. Ceftriaxone sodium salt is an inhibitor of Aurora B. Ceftriaxone sodium salt has anti-inflammatory, antitumor and antioxidant activities. Ceftriaxone sodium salt can be used in the study of bacterial infections and meningitis.
    Ceftriaxone sodium salt
  • HY-10512
    AR-A014418
    		Inhibitor 99.14%
    AR-A014418 is a potent, selective and ATP-competitive GSK3β inhibitor (IC50=104 nM; Ki=38 nM).
    AR-A014418
  • HY-124719
    hSMG-1 inhibitor 11j
    		Inhibitor 99.82%
    hSMG-1 inhibitor 11j, a pyrimidine derivative, is a potent and selective inhibitor of hSMG-1, with an IC50 of 0.11 nM. hSMG-1 inhibitor 11j exhibits >455-fold selectivity for hSMG-1 over mTOR (IC50=50 nM), PI3Kα/γ (IC50=92/60 nM) and CDK1/CDK2 (IC50=32/7.1 μM). hSMG-1 inhibitor 11j can be used for the research of cancer.
    hSMG-1 inhibitor 11j
  • HY-B0320A
    Cromolyn sodium
    		Inhibitor 99.93%
    Cromolyn sodium (Disodium Cromoglycate; FPL-670) is an antiallergic agent. Cromolyn sodium is a GSK-3β inhibitor with an IC50 of 2.0 μM.
    Cromolyn sodium
  • HY-137894A
    Tagtociclib hydrate
    		Inhibitor 99.95%
    PF-07104091 hydrate is a potent and selective CDK2/cyclin E1 and GSK3β inhibitor, with Kis of 1.16 and 537.81 nM, respectively. PF-07104091 hydrate has anti-tumor activity for cyclin E1-amplified cancers. (patent WO2020157652A2).
    Tagtociclib hydrate
  • HY-12292
    IM-12
    		Inhibitor 99.61%
    IM-12 is an inhibitor of GSK-3β, with an IC50 of 53 nM, and also enhances Wnt signalling.
    IM-12
  • HY-113914
    9-ING-41
    		Inhibitor 99.13%
    9-ING-41 (Elraglusib) is a maleimide-based ATP-competitive and selective glycogen synthase kinase-3β (GSK-3β) inhibitor with an IC50 of 0.71 μM. 9-ING-41 significantly leads to cell cycle arrest, autophagy and apoptosis in cancer cells. 9-ING-41 has anticancer activity and has the potential for enhancing the antitumor effects of chemotherapeutic agents.
    9-ING-41
Cat. No. Product Name / Synonyms Species Source
Cat. No. Product Name / Synonyms Application Reactivity
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Download GSK-3 Signaling Pathway Map.

Glycogen synthase kinase 3 (GSK-3) is a multifunctional serine/threonine kinase found in all eukaryotes. GSK-3 is one of the few signaling mediators that play central roles in a diverse range of signaling pathways, including those activated by Wnt, PI3K, growth factors, cytokines, and ligands for G protein-coupled receptors. The PI3K pathway is known for regulating metabolism, cell growth, and cell survival. The PI3K activity is stimulated by diverse oncogenes and growth factor receptors. PI3K-mediated production of PIP3 leads to the activation of Akt. The activation of Akt leads to the phosphorylation of GSK-3, which is active in resting cells, but is inactivated by the phosphorylation. The GSK-3 has been linked to the regulation of an assembly of transcription factors, including β-catenin, NF-κB, c-Jun, CREB, and STAT. Thus, the altered activity of GSK-3 causes various effects on cytokine expression. 

 

In the absence of Wnt signaling, β-catenin is phosphorylated by CK1 and GSK-3. This phosphorylation leads to recognition by β-TrCP, leading to the ubiquitylation of β-catenin and degradation by the proteasome. Upon binding of a lipid-modified Wnt protein to the receptor complex, a signaling cascade is initiated. LRP is phosphorylated by CK1/CK2 and GSK-3, and Axin is recruited to the plasma membrane. The kinases in the β-catenin destruction complex are inactivated and β-catenin translocates to the nucleus to form an active transcription factor complex with TCF, leading to transcription of a large set of target genes.

 

Some endogenous growth factors could bind to and activate the tyrosine kinase receptor. This facilitates the recruitment of other proteins (SHC, SOS), which results in the activation of the ERK-MAPK cascade and the inhibition of GSK-3. GSK-3 exerts many cellular effects: it regulates cytoskeletal proteins, and is important in determining cell survival/cell death. GSK-3 has also been identified as a target for the actions of lithium. GSK-3 can inhibit glycogen synthase, the enzyme that catalyzes the transfer of glucose from UDPG to glycogen[1][2].

 

Reference:

[1]. Brenner D, et al. Regulation of tumour necrosis factor signalling: live or let die.Nat Rev Immunol. 2015 Jun;15(6):362-74. 
[2]. Conrad M, et al. Regulated necrosis: disease relevance and therapeutic opportunities.Nat Rev Drug Discov. 2016 May;15(5):348-66. 

GSK-3 Isoform Comparison

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