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-155705
    BMP agonist 1
    		Inhibitor
    BMP agonist 1 (compound 2 b) is a small-molecule agonist of bone morphogenic protein (BMP). BMP induces C2C12 cell differentiation with BMP and highly depends on active BMP signaling. BMP agonist 1 inhibits GSK3β, increases β-catenin signaling and synergistically regulates Id2and Id3 expression. BMP agonist 1 is used in diseases and defects of the skeleton research.
    BMP agonist 1
  • HY-N8423R
    α-Amyrin (Standard)
    		Activator
    α-Amyrin (Standard) is the analytical standard of α-Amyrin. This product is intended for research and analytical applications. α-Amyrin is a pentacyclic triterpenoid compound with oral activity. α-Amyrin activates the ERK and GSK-3β signaling pathways. α-Amyrin can be used in the study of metabolic syndrome induced by high fructose diet and cognitive dysfunction caused by low cholinergic neurotransmission.
    α-Amyrin (Standard)
  • HY-162913
    GSK-3β inhibitor 20
    		Inhibitor
    GSK-3β inhibitor 20 (compound 3A) is an potent inhibitor of GSK-3β with an IC50 value of 74.4 nM.
    GSK-3β inhibitor 20
  • HY-N11576
    Secalonic acid D
    		Activator
    Secalonic acid D is a toxic compound against tumor cells. Secalonic acid D can be isolated from the metabolites of Aspergillus aculeatus. Secalonic acid D activates GSK3-β, and degrades β-catenin. Thus, Secalonic acid D down-regulates c-Myc expression, arrests cell cycle at G1 phase, induces cell apoptosis.
    Secalonic acid D
  • HY-117194
    18BIOder
    		Inhibitor
    18BIOder is a neuroprotective GSK-3β inhibitor, highly selectively inhibiting HIV-1.
    18BIOder
  • HY-168857
    GSK-3β inhibitor 24
    		Inhibitor
    GSK-3β inhibitor 24 (Compound 41) is a potent GSK-3β inhibitor with an IC50 of 0.22 nM. GSK-3β inhibitor 24 increases GSK-3β phosphorylation at Ser9 site dose-dependently. GSK-3β inhibitor 24 inhibits the hyperphosphorylation of tau protein by decreasing the p-tau-Ser396 abundance. GSK-3β inhibitor 24 up-regulates β-catenin and neurogenesis-related markers (GAP43 and MAP-2). GSK-3β inhibitor 24 demonstrates remarkable anti-Alzheimer's disease (AD) effects.
    GSK-3β inhibitor 24
  • HY-111931
    Indirubin-3'-monoxime-5-sulphonic acid
    		Inhibitor
    Indirubin-3'-monoxime-5-sulphonic acid is a potent and selective inhibitor of CDK1, CDK5, and GSK-3β with IC50s of 5 nM, 7 nM, and 80 nM, respectively.
    Indirubin-3'-monoxime-5-sulphonic acid
  • HY-162722
    GSK-3 inhibitor 6
    		Inhibitor
    GSK-3 inhibitor 6 (2) is a CNS penetrated GSK-3 inhibitor, with IC50 values of 29 nM and 24 nM for GSK-3α and GSK-3β, respectively.
    GSK-3 inhibitor 6
  • HY-P1173
    L803-mts
    		Inhibitor 98.65%
    L803-mts (Myristoylated L 803) is a selective and substrate-competitive GSK-3 peptide inhibitor (IC50: 40 μM). L803-mts also reduces Aβ deposits and ameliorates cognitive deficits in 5XFAD mice. L803-mts shows antidepressive effect in the forced swimming test.
    L803-mts
  • HY-156032
    PIMPC
    		Inhibitor
    PIMPC is a compound with antioxidant and metal-chelating properties. PIMPC is a novel inhibitor of glycogen synthase kinase 3 (GSK-3). PIMPC has potential anti-Alzheimer's disease effect.
    PIMPC
  • HY-B0712R
    Ceftriaxone (Standard)
    		Inhibitor
    Ceftriaxone (Standard)
  • HY-112336
    Aloisine RP106
    		Inhibitor
    Aloisine RP106 (compound 38) is a potent inhibitor of Cdk1/cyclin B, Cdk5/p25, and GSK3 with IC50s of 0.70µM, 1.5µM, 0.92 µM, respectively.
    Aloisine RP106
  • HY-111932
    Indirubin-5-sulfonate
    		Inhibitor
    Indirubin-5-sulfonate is a cyclin-dependent kinase (CDK) inhibitor, with IC50 values of 55 nM, 35 nM, 150 nM, 300 nM and 65 nM for CDK1/cyclin B, CDK2/cyclin A, CDK2/cyclin E, CDK4/cyclin D1, and CDK5/p35, respectively. Indirubin-5-sulfonate also shows inhibitory activity against GSK-3β.
    Indirubin-5-sulfonate
  • HY-151575
    PfGSK3/PfPK6-IN-2
    		Inhibitor
    PfGSK3/PfPK6-IN-2 is a potent dual PfGSK3/PfPK6 (Plasmodium falciparum GSK3/PK6) inhibitor (IC50: 172 nM and 11 nM respectively). PfGSK3/PfPK6-IN-2 can be used in the research of Malaria.
    PfGSK3/PfPK6-IN-2
  • HY-153760
    GSK-3β inhibitor 14
    		Inhibitor 99.92%
    GSK-3β inhibitor 14 (Compound 6i), benzothiazepinone derivative, is a weak GSK-3β inhibitor (IC50 >100 μM).
    GSK-3β inhibitor 14
  • HY-144826
    ZDWX-25
    		Inhibitor
    ZDWX-25 is a highly potent GSK-3β and DYRK1A dual inhibitor with an IC50 value of 71 nM for GSK-3β. ZDWX-25 possesses significant cytotoxic activities against SH-SY5Y and HL-7702 cells. ZDWX-25 can be used for researching alzheimer's disease.
    ZDWX-25
  • HY-134557
    GS87
    		Inhibitor
    GS87 is a highly specific and potent GSK3 inhibitor with IC50s of 415nM and 521nM for GSK3α and GSK3β, respectively. GS87 induces differentiation of acute myeloid leukemia (AML) cell lines by effectively activating GSK3-dependent signaling components including MAPK signaling. GS87 modulates key GSK3 target proteins involved in cell proliferation and differentiation more effectively than Lithium and SB415285 (SB). GS87 has the potential for acting as a differentiation agent for non-promyelocytic AML research.
    GS87
  • HY-162638
    GSK-3β inhibitor 18
    		Inhibitor
    GSK-3β inhibitor 18 (compound 2) is a potent inhibitor of GSK-3β, with the IC50 of 0.0021 μM.
    GSK-3β inhibitor 18
  • HY-P3713
    Presenilin 1 (349-361)
    Presenilin 1 (349-361) is an active petide, and synthetic peptides representing amino acids 349–361 can be phosphorylated by glycogen synthase kinase-3β(GSK3β) in vitro. Presenilin 1 (349-361) can be used for the research of various diseases.
    Presenilin 1 (349-361)
  • HY-168859
    JNK3 inhibitor-9
    		Inhibitor
    JNK3 inhibitor-9 (Compound 24a) is a potent, selective and BBB-permeable JNK3 inhibitor with an IC50 value of 12 nM. JNK3 inhibitor-9 also potently inhibits GSK3α/β (IC50s: 14 and 35 nM, respectively) involved in Tau phosphorylation. JNK3 inhibitor-9 reduces c-Jun and APP phosphorylation. JNK3 inhibitor-9 protects neurons from Aβ1-42 toxicity.
    JNK3 inhibitor-9
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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