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-100618R
    Hispidin (Standard)
    Hispidin (Standard) is the analytical standard of Hispidin. This product is intended for research and analytical applications. Hispidin, a PKC inhibitor and a phenolic compound can be found in Phellinus linteus, has been shown to possess strong anti-oxidant, anti-cancer, anti-diabetic, and anti-dementia properties[1][2][3][4][5][6][7].
    Hispidin (Standard)
  • HY-169670
    Protein kinase inhibitor 13
    		Inhibitor
    Protein kinase inhibitor 13 (Compound I-90) is the inhibitor for protein kinase that exhibits inhibitory effects on kinases such as PIM-1, CDK-2, GSK-3 and SRC.
    Protein kinase inhibitor 13
  • HY-N4247R
    Kuwanon G (Standard)
    		Inhibitor
    Kuwanon G (Standard) is the analytical standard of Kuwanon G (HY-N4247). This product is intended for research and analytical applications. Kuwanon G is a flavonoid compound and an antagonist of the bombesin receptor. Kuwanon G has multiple activities such as bactericidal, anti-tumor, anti-inflammatory, antioxidant, anti-atherosclerotic, and neuroprotective effects. Kuwanon G exhibits strong antibacterial activity against oral pathogens, especially cariogenic bacteria and periodontal pathogens. Kuwanon G can induce apoptosis and inhibit proliferation, migration, and invasion of tumor cells. Kuwanon G can be used in the research of diseases such as gastric cancer and atherosclerosis.
    Kuwanon G (Standard)
  • HY-169606
    GSK-3β inhibitor 25
    		Inhibitor
    GSK-3β inhibitor 25 (Compound 6h) exhibits a weak inhibitory activity against GSK-3β wih an IC50>100 μM.
    GSK-3β inhibitor 25
  • HY-10512R
    AR-A014418 (Standard)
    		Inhibitor
    AR-A014418 (Standard) is the analytical standard of AR-A014418. This product is intended for research and analytical applications. AR-A014418 is a potent, selective and ATP-competitive GSK3β inhibitor (IC50=104 nM; Ki=38 nM).
    AR-A014418 (Standard)
  • HY-124068
    LQB-118
    		Modulator
    LQB-118 is an orally active compound derived from sandalwood. LQB-118 can inhibit the migration of glioblastoma cells and induce cell death. LQB-118 can suppress the migration and invasion of prostate cancer cells by regulating the AKT/GSK3β pathway and the expression of the MMP-9/reck genes. LQB-118 can also inhibit yeast polysaccharide-induced inflammation both in vivo and in vitro. Additionally, LQB-118 selectively induces ROS-triggered and mitochondrial-dependent apoptosis in Leishmania amazonensis. LQB-118 can be used in studies related to inflammation, infections, and cancer diseases.
    LQB-118
  • HY-169602
    GSK-3β inhibitor 26
    		Inhibitor
    GSK-3β inhibitor 26 (Compound D14) is a GSK-3β inhibitor with an IC50 of 18.23 μM. GSK-3β inhibitor 26 can be used in the research of cancer, inflammation and neurodegenerative diseases.
    GSK-3β inhibitor 26
  • HY-10182AR
    Laduviglusib monohydrochloride (Standard)
    		Inhibitor
    Laduviglusib (monohydrochloride) (Standard) is the analytical standard of Laduviglusib (monohydrochloride). This product is intended for research and analytical applications. 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 (Standard)
  • HY-111260
    R547 mesylate
    		Inhibitor
    R547 mesylate is a potent, selective and orally active ATP-competitive CDK inhibitor, with Kis of 2 nM, 3 nM and 1 nM for CDK1/cyclin B, CDK2/cyclin E and CDK4/cyclin D1, respectively.
    R547 mesylate
  • HY-136679
    TD114-2
    		Inhibitor
    TD114-2 (cmpound 29) is a potent and highly selective inhibitor of glycogen synthase kinase-3β (GSK-3β) (IC50=48 nM). TD114-2 is associated with the hydrogen bond formation of arginine 141 (ARG141) specific to GSK-3β, an amino acid that is often a negatively charged residue in other kinases, which determines the high selectivity of GSK-3β. TD114-2 can be used in the study of diabetes, neurodegenerative diseases and other diseases associated with GSK-3β.
    TD114-2
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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