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-111055
    BIP-135
    		Inhibitor 99.86%
    BIP-135 is a potent and selective ATP-competitive GSK-3 inhibitor, with IC50s of 16 nM and 21 nM for GSK-3α and GSK-3β, respectively. BIP 135 exhibits neuroprotective effect.
    BIP-135
  • HY-154852
    GSK-3 inhibitor 4
    		Inhibitor 98.77%
    GSK-3 inhibitor 4 is an orally active and brain-penetrant inhibitor of GSK-3, CDK2, and CDK5, with IC50 values of 0.56 nM (GSK-3β), 0.45 nM (GSK-3α), 0.47 μM, and 0.68 μM, respectively. GSK-3 inhibitor 4 effectively reduces the phosphorylation level of Tau protein. GSK-3 inhibitor 4 can be used in Alzheimer's disease (AD) studies.
    GSK-3 inhibitor 4
  • 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-147134
    GSK-3β inhibitor 10
    		Inhibitor 98.04%
    GSK-3β inhibitor 10 (compound 14a) is a highly potent GSK-3β inhibitor with an IC50 value of 80.5 nM. GSK-3β inhibitor 10 can be used for researching Alzheimer’s disease.
    GSK-3β inhibitor 10
  • HY-W035309
    5-Bromo-3-indoxylacetate
    		98.98%
    5-Bromo-3-indoxylacetate is an inhibitor of GSK-3 with pIC50=3.39.
    5-Bromo-3-indoxylacetate
  • HY-124607
    (R)-BRD3731
    		Inhibitor 98.22%
    (R)-BRD3731 is a GSK3 inhibitor extracted from patent US20160375006A1, compound example 273, has IC50s of 1.05 and 6.7 μM for GSK3β and GSK3α, respectively.
    (R)-BRD3731
  • HY-131177
    yGsy2p-IN-H23
    		Inhibitor 99.91%
    yGsy2p-IN-H23 is a potent and first-in-class inhibitor for yeast glycogen synthase 2 (yGsy2p) with an IC50 of 875 μM for human glycogen synthase 1 (hGYS1). yGsy2p-IN-H23 bounds within the uridine diphosphate glucose binding pocket of yGsy2p. yGsy2p-IN-H23 is used for the research of glycogen storage diseases (GSDs).
    yGsy2p-IN-H23
  • HY-N2492
    (E)-Methyl 4-coumarate
    		Inhibitor 99.87%
    (E)-Methyl 4-coumarate (Methyl 4-hydroxycinnamate) is a phenolic compound and derivative of Cinnamic acid (HY-N0610A). (E)-Methyl 4-coumarate can be found in several plants, such as the leaves of Allium cepa and Morinda citrifolia L. (E)-Methyl 4-coumarate, when combined with Carnosic acid (HY-N0644), induces Apoptosis. (E)-Methyl 4-coumarate inhibits GSK3β activity and modulates inflammatory cytokine levels (increasing IL-10 and decreasing IL-4). (E)-Methyl 4-coumarate combined with Carnosic acid exhibits anticancer effects against acute myeloid leukemia. (E)-Methyl 4-coumarate ameliorates Plasmodium berghei NK65 infection.
    (E)-Methyl 4-coumarate
  • HY-N6580
    Ginsenoside Rg4
    		Activator 99.94%
    Ginsenoside Rg4 is an orally active protopanaxatriol type ginsenoside. Ginsenoside Rg4 can activate PI3K, AKT and GSK-3β signaling. Ginsenoside Rg4 can inhibit ROS and inflammatory cytokine levels. Ginsenoside Rg4 can be used for the researches of inflammation, infection and metabolic disease, such as sepsis and lung inflammation.
    Ginsenoside Rg4
  • HY-148132
    GSK-3β inhibitor 11
    		Inhibitor 98.02%
    GSK-3β inhibitor 11 (compound 21) is a glycogen synthase kinase-3β (GSK-3β) inhibitor (IC50=10.02 μM). GSK-3β inhibitor 11 can be used in neurodegenerative disease research.
    GSK-3β inhibitor 11
  • HY-148561
    CDK8-IN-12
    		Inhibitor 99.74%
    CDK8-IN-12 is an orally active, potent CDK8 inhibitor with a Ki of 14 nM. CDK8-IN-12 has off-target kinase inhibition on GSK-3α, GSK-3β, PCK-θ with Kis of 13 nM, 4 nM, 109 nM, respectively. CDK8-IN-12 shows potent anti-proliferative effects selectively on MV4-11 cell. CDK8-IN-12 is an anti-cancer agent.
    CDK8-IN-12
  • HY-161618
    MJ04
    		Inhibitor 98.08%
    MJ04 is a selective inhibitor for Janus Kinase 3 (JAK 3) with an IC50 of 2.03 nM. MJ04 inhibits T cell differentation and inhibits the proinfammatory cytokines in Lipopolysaccharides (HY-D1056)‑induced macrophages. MJ04 exhibits good pharmacokinetic characters in mice, promotes hair growth in DHT-induced androgenetic alopecia (AGA) in athymic mice model, without significant toxicity (LD50 >2 g/kg).
    MJ04
  • HY-148329
    GSK3-IN-2
    		Inhibitor 99.87%
    GSK3-IN-2 (compound 8) is a potent GSK3 inhibitor.
    GSK3-IN-2
  • HY-N1121
    Triptonodiol
    		Inhibitor 98.0%
    Triptonodiol can be isolated from Trypterygium wilfordii. Triptonodiol has anti-inflammatory and anti-cancer activity. Triptonodiol inhibits the biological activity of GSK.
    Triptonodiol
  • HY-117025
    Manzamine A
    		Inhibitor 98.2%
    Manzamine A, an orally active beta-carboline alkaloid, inhibits specifically GSK-3β and CDK-5 with IC50s of 10.2 μM and 1.5 μM, respectively. Manzamine A targets vacuolar ATPases and inhibits autophagy in pancreatic cancer cells. Manzamine A has antimalarial and anticancer activities. Manzamine A also shows potent activity against HSV-1.
    Manzamine A
  • HY-P1113A
    Phospho-Glycogen Synthase Peptide-2(substrate) TFA
    		99.75%
    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) TFA
  • HY-116830B
    BRD5648
    		99.94%
    BRD5648 ((R)-BRD0705) is a negative control 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).
    BRD5648
  • HY-126771
    Chrysomycin A
    		Inhibitor 98.0%
    Chrysomycin A (Chr-A), an antibiotic, can be obtained from Streptomyces. Chrysomycin A exhibits antitumor and anti-tuberculous and MRSA activities. As for glioblastoma, Chrysomycin A inhibits the proliferation, migration, and invasion of cancer cells through the Akt/GSK-3β/β-catenin signaling pathway.
    Chrysomycin A
  • HY-B0320AR
    Cromolyn disodium (Standard)
    		Inhibitor
    Cromolyn disodium (Standard) (Cromoglycate disodium (Standard)) is the analytical standard of Cromolyn disodium (HY-B0320A). This product is intended for research and analytical applications. Cromolyn (Cromoglycate) disodium is an orally active GSK-3β inhibitor with an IC50 of 2.0 μM. Cromolyn disodium is also a mast cell stabilizer that can inhibit the release of mediators from mast cells, regulate reflex bronchoconstriction, and reduce non-specific bronchial hyperreactivity, and Cromolyn disodium can be used in the research of bronchial asthma. In addition, Cromolyn disodium has multiple activities such as anti-inflammatory, anti-allergic, anti-histamine, anti-cancer, and neuroprotective effects.
    Cromolyn disodium (Standard)
  • HY-B0712R
    Ceftriaxone (Standard)
    		Inhibitor
    Ceftriaxone (Standard) is the analytical standard of Ceftriaxone. This product is intended for research and analytical applications. Ceftriaxone (Ro 13-9904 free acid) 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 is a covalent inhibitor of GSK3β with IC50 value of 0.78 μM. Ceftriaxone is an inhibitor of Aurora B. Ceftriaxone has anti-inflammatory, antitumor and antioxidant activities. Ceftriaxone can be used in the study of bacterial infections and meningitis[1][2][3][4][5][6][7].
    Ceftriaxone (Standard)
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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