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-150537
    AChE/GSK-3β-IN-1
    		Inhibitor
    AChE/GSK-3β-IN-1 (compound GT15) is a potent, dual AChE/GSK-3β inhibitor with IC50 values of 1.2, 149.8 and 22.4 nM for hAChE , hBChE and hGSK-3β, respectively. AChE/GSK-3β-IN-1 penetrates the blood-brain barrier (BBB). AChE/GSK-3β-IN-1 has high kinase selectivity profiles for the CMGC kinase family. AChE/GSK-3β-IN-1 occupies the ATP binding site of DYRK1A. AChE/GSK-3β-IN-1 inhibits ROS expression and reduces oxidative stress. AChE/GSK-3β-IN-1 can be used for Alzheimer’s disease research.
    AChE/GSK-3β-IN-1
  • HY-143261
    GSK-3β inhibitor 7
    		Inhibitor
    GSK-3β inhibitor 7 is a GSK-3β inhibitor with an IC50 value of 5.25 μM. GSK-3β inhibitor 7 is inserted into the ATP-binding binding pocket of GSK-3β and forms hydrogen-bond. GSK-3β inhibitor 7 shows high hepatocyte glucose uptake (83.5%), and can be used in the research of numerous diseases like diabetes, inflammation, cancer, Alzheimer's disease, and bipolar disorder.
    GSK-3β inhibitor 7
  • HY-116830A
    (Rac)-BRD0705
    		Inhibitor
    (Rac)-BRD0705 is a less active racemate of BRD0705. BRD0705 is a potent, paralog selective and orally active GSK3α inhibitor with an IC50 of 66 nM and a Kd of 4.8 μM. BRD0705 displays increased selectivity for GSK3α (8-fold) versus GSK3β (IC50 of 515 nM). BRD0705 can be used for acute myeloid leukemia (AML).
    (Rac)-BRD0705
  • HY-107529
    TC-G 24
    		Inhibitor
    TC-G 24 (Compound 24) is a potent, selective glycogen synthase kinase-3β (GSK-3β) inhibitor with an IC50 of 17.1 nM. TC-G 24 can cross the BBB and can be used for studying many diseases such as type 2 diabetes mellitus, stroke, Alzheimer, and other related diseases.
    TC-G 24
  • HY-141685
    3-Methylthienyl-carbonyl-JNJ-7706621
    		Inhibitor
    3-Methylthienyl-carbonyl-JNJ-7706621 is a potent and selective inhibitor of cyclin-dependent kinase (CDK), with IC50s of 6.4 nM and 2 nM for CDK1/cyclin B and CDK2/cyclin A, respectively. 3-Methylthienyl-carbonyl-JNJ-7706621 also shows potent inhibition of GSK-3 (IC50=0.041 μM) and modest potency against CDK4, VEGF-R2, and FGF-R2 (IC50=0.11, 0.13, 0.22 μM, respectively). 3-Methylthienyl-carbonyl-JNJ-7706621 can be used for the research of cancer.
    3-Methylthienyl-carbonyl-JNJ-7706621
  • HY-P10605
    GSK3β-peptide
    GSK3β-peptide is a substrate mimetic peptide of glycogen synthase kinase 3-β (GSK3-β) that can bind to the active site of GSK3-β and mimic the behavior of a real substrate. GSK3β-peptide can be used to develop substrate mimetic inhibitors of Akt as potential anticancer drugs.
    GSK3β-peptide
  • HY-W844558
    Protein kinase inhibitor 11
    		Inhibitor 98.28%
    Protein kinase inhibitor 11 (Compound I-96) is a protein kinase inhibitor that can inhibit the activity of PIM-1, CDK-2, GSK-3, and SRC. Protein kinase inhibitor 11 holds promise for research in cancer, immune disorders, and neurodegenerative diseases.
    Protein kinase inhibitor 11
  • HY-149542
    GSK-3β inhibitor 15
    		Inhibitor
    GSK-3β inhibitor 15 (Compound 54) is a GSK-3β inhibitor (IC50: 3.4 nM). GSK-3β inhibitor 15 inhibits Aβ1-42-induced GSK-3β and tau protein phosphorylation. GSK-3β inhibitor 15 inhibits LPS-induced iNOS expression. GSK-3β inhibitor 15 has neuroprotective effects on Aβ1-42-induced neurotoxicity. GSK-3β inhibitor 15 can be used for research of Alzheimer’s disease (AD).
    GSK-3β inhibitor 15
  • HY-163748
    GSK-3β inhibitor 17
    		Inhibitor
    GSK-3β inhibitor 17 (compound 5 n) is a potent GSK-3β inhibitor. GSK-3β inhibitor 17 decreases cisplatin (HY-17394) induced p-p65, KIM-1 protein and mRNA expression. GSK-3β inhibitor 17 decreases cisplatin induced TNF-α, IL-1β, IL-6 and MCP-1 mRNA expression. GSK-3β inhibitor 17 shows anti-inflammation effect and has the potential for the research of acute kidney injury.
    GSK-3β inhibitor 17
  • HY-107528
    FRATtide
    		Inhibitor
    FRATtide is a peptide derived from the GSK-3 binding protein that inhibits the phosphorylation of Axin and β-catenin. FRATtide inhibits GSK-3 binding to Axin.
    FRATtide
  • HY-P1113
    Phospho-Glycogen Synthase Peptide-2(substrate)
    Phospho-Glycogen Synthase Peptide-2 (substrate) is peptide substrate for glycogen synthase kinase-3 (GSK-3) and can be used for affinity purification of protein-serine kinases.
    Phospho-Glycogen Synthase Peptide-2(substrate)
  • HY-155365
    hAChE-IN-5
    		Inhibitor
    hAChE-IN-5 (compound 49) is a potent hAChE and hBuChE inhibitor with IC50 values of 0.17 μM and 0.17 μM, respectively. hAChE-IN-5 shows potent GSK3β inhibition with an IC50 value of 0.21 μM. hAChE-IN-5 is used as tau protein aggregation and Aβ1-42 self-aggregation inhibitor. hAChE-IN-5 can bind virtually with the PAS affecting Aβ aggregation, thus preventing Aβ-dependent neurotoxicity. hAChE-IN-5 can penetrate BBB and has the potential for multi-targeted anti-Alzheimer's agents research.
    hAChE-IN-5
  • HY-151962
    JNK3 inhibitor-5
    		Inhibitor
    JNK3 inhibitor-5 (Compound 22b) is a potent and selective JNK3 inhibitor with an IC50 of 0.379 nM. JNK3 inhibitor-5 effectively protects the neuronal cells against amyloid beta-induced apoptosis. JNK3 inhibitor-5 has a high cell permeability and is predicted as BBB permeable.
    JNK3 inhibitor-5
  • 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-174272
    GSK-3β inhibitor 27
    		Inhibitor
    GSK-3β inhibitor 27 (Compound 1c) is a reversible and competitive GSK-3β inhibitor with an IC50 value of 2.2 μM. GSK-3β inhibitor 27 inhibits tau hyperphosphorylation, reduces Aβ protein aggregation and possesses metal chelation and neuroprotective potential. GSK-3β inhibitor 27 is promising for research of neurodegenerative diseases (such as Alzheimer’s disease).
    GSK-3β inhibitor 27
  • HY-N8423R
    α-Amyrin (Standard)
    		Activator
    α-Amyrin (Standard) is a pentacyclic triterpenoid compound with oral activity. α-Amyrin (Standard) activates the ERK and GSK-3β signaling pathways. α-Amyrin (Standard) can inhibit cancer cells proliferation and induce apoptosis. α-Amyrin (Standard) shows anti-bacterial and anti-inflammation activity. α-Amyrin (Standard) can reduce blood glucose level. α-Amyrin (Standard) can be used for the researches of cancer, infection, inflammation, metabolic disease and neurological disease, such as breast cancer, Streptococcus oralis infection, skin inflammation and diabetes.
    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-165341
    SCR1693
    		Inhibitor
    SCR1693 is a selective, reversible, orally active and noncompetitive inhibitor of AChE (IC50 = 0.68 μM) as well as a calcium channel blocker. SCR1693 reduces tau phosphorylation levels, and inhibits the generation and release of Aβ. SCR1693 restores insulin signaling and improves cognitive deficits. SCR1693 can be used for the study of Alzheimer's disease, especially which complicated with type 2 diabetes mellitus.
    SCR1693
  • 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-172586
    GSK-3α/β-IN-1
    		Inhibitor
    GSK-3α/β-IN-1 is GSK-3α/β inhibitor with IC50 s of 0.265 μM and 0.255 μM for GSK-3α and GSK-3β, respectively. GSK-3α/β-IN-1 also inhibits PKA with an IC50 of 0.188 μM. GSK-3α/β-IN-1 potently inhibits cell viability of three Glioblastoma (GBM) cell lines (IC50 : 3-6 μM, 72 h) with no toxicity to human astrocytes and good metabolic stability. GSK-3α/β-IN-1 has potential CNS activity in all-human blood-brain barrier (BBB) model of GBM.
    GSK-3α/β-IN-1
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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