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-10096
    TCS2002
    		Inhibitor 99.8%
    TCS2002 (Compound 9b) is a highly selective, orally bioavailable and potent GSK-3β inhibitor with the IC50 of 35 nM. TCS2002 shows good pharmacokinetic profiles including favorable BBB penetration. TCS2002 can be used for the research of Alzheimer’s disease.
    TCS2002
  • HY-10182C
    Laduviglusib dihydrochloride
    		Inhibitor
    Laduviglusib;CHIR 99021;CHIR99021;CHIR-99021;CT99021;CT 99021;CT-99021
    Laduviglusib dihydrochloride
  • HY-128879
    VP3.15
    		Inhibitor
    VP3.15 is a potent, orally bioavailable and CNS-penetrant dual phosphodiesterase (PDE)7- glycogen synthase kinase (GSK)3 inhibitor, with IC50s of 1.59 μM and 0.88 μM for PDE7 and GSK-3, respectively. VP3.15 has neuroprotective and neuroreparative activities, thus as potential combined anti-inflammatory and pro-remyelinating therapies for multiple sclerosis (MS).
    VP3.15
  • HY-169632
    GSK3β-IN-1
    		Inhibitor
    GSK3β-IN-1 (compound 1) is a glycogen synthase kinase-3β (GSK-3β) inhibitor (IC50=65 nM), which can be used in the study of Alzheimer's disease.
    GSK3β-IN-1
  • HY-155366
    hAChE-IN-6
    		Inhibitor
    hAChE-IN-6 (compound 51) is a brain penetrant AChE inhibitor with an IC50 of 0.16 μM. hAChE-IN-6 also inhibits hBuChE and GSK3β with IC50 values of 0.69 μM and 0.26 μM, respectively. hAChE-IN-6 inhibits tau protein and Aβ1-42 self-aggregation, and can be used for Alzheimer's disease (AD) research.
    hAChE-IN-6
  • HY-153011
    ROCK-IN-5
    		Inhibitor ≥98.0%
    ROCK-IN-5 (compound I-B-37) is a potent inhibitor of ROCK, ERK, GSK, and AGC protein kinases. ROCK-IN-5 has the potential for proliferative, cardiac and neurodegenerative diseases research.
    ROCK-IN-5
  • HY-155025
    Antitrypanosomal agent 14
    		Inhibitor
    Antitrypanosomal agent 14 (Compound 1) is a T. brucei inhibitor (EC50: 0.47 μM). Antitrypanosomal agent 14 inhibits TbGSK3 with an IC50 of 12 μM. Antitrypanosomal agent 14 can be used for the research of Human African trypanosomiasis.
    Antitrypanosomal agent 14
  • HY-170491
    GSK-3β inhibitor 23
    		Inhibitor
    GSK-3β inhibitor 23 (Compound 11726169) is the inhibitor for glycogen synthase kinase-3, that inhibits GSK-3β and GSK-3α with IC50 of 12.1 nM and 18.8 nM. GSK-3β inhibitor 23 exhibits antiviral activity against HIV 1. GSK-3β inhibitor 23 exhibits good metabolic stablility in mouse/human liver microsomes and plasma, but poor Caco-2 permeability (which predicts low oral bioavailability).
    GSK-3β inhibitor 23
  • HY-112363
    Aloisine A
    		Inhibitor
    Aloisine A (RP107) is a a potent cyclin-dependent kinase (CDK) inhibitor with IC50s of 0.15 μM, 0.12 μM, 0.4 μM, 0.16 μM for CDK1/cyclin B, CDK2/cyclin A, CDK2/cyclin E, CDK5/p35, respectively. Aloisine A ininhibits GSK-3α (IC50=0.5 μM) and GSK-3β (IC50=1.5 μM). Aloisine A stimulates wild-type CFTR and mutated CFTR, with submicromolar affinity by a cAMP-independent mechanism. Aloisine A has the potential for CFTR-related diseases, including cystic fibrosis research.
    Aloisine A
  • HY-161595
    CDK5-IN-4
    		Inhibitor
    CDK5-IN-4 (compound 4) is a potent multikinase type-II inhibitor targeting CDK5, with an IC50 of 9.8 μM. CDK5-IN-4 also inhibits GSK-3α, GSK-3β, CDK9, and CDK2, with IC50 values of 0.98, 4.00, 1.76, and 6.24 μM, respectively. CDK5-IN-4 can be used for glioblastoma research.
    CDK5-IN-4
  • HY-173005
    JZ19
    		Inhibitor
    JZ19 reduces the LDH and ROS levels, and exhibits antioxidant activity against oxygen-glucose deprivation (OGD)-induced cardiomyocyte injury. JZ19 reverses Isoproterenol (HY-B0468)-induced cardiomyocyte hypertrophy and apoptosis through PI3K-AKT-GSK3β signaling pathway. JZ19 alleviates Isoproterenol (HY-B0468)-induced heart failure in mouse models.
    JZ19
  • HY-151260
    AChE/BACE1/GSK3β-IN-1
    		Inhibitor
    AChE/BACE1/GSK3β-IN-1 is an orally active triple inhibitor of AChE/BACE1/GSK3β. AChE/BACE1/GSK3β-IN-1 has effective inhibitory activity against AChE, BACE1 and GSK3β with IC50 values of 1.0 μM, 20 μM and 15 μM, respectively. AChE/BACE1/GSK3β-IN-1 has good blood-brain barrier penetrability, suitable bioavailability. AChE/BACE1/GSK3β-IN-1 can be used for the research of Alzheimer's disease (AD).
    AChE/BACE1/GSK3β-IN-1
  • HY-169024
    GSK-3β inhibitor 19
    		Inhibitor
    GSK-3β inhibitor 19 (compound 36) is a GSK-3β inhibitor, with IC50 of 70 nM. GSK-3β inhibitor 19 can be used in anti-inflammatory and Alzheimer's disease related research.
    GSK-3β inhibitor 19
  • HY-144316
    ZLWH-23
    		Inhibitor
    ZLWH-23 is a selective AChE inhibitor (IC50=0.27 μM) with GSK-3β inhibitory property (IC50=6.78 μM). ZLWH-23 possesses selectivity for AChE over BChE (IC50=20.82 μM) and for GSK-3β over multi-kinases. ZLWH-23 has the potential for the research of Alzheimer's disease.
    ZLWH-23
  • HY-148133
    GSK-3β inhibitor 12
    		Inhibitor 99.81%
    GSK-3β inhibitor 12 (compound 15) is an inhibitor of GSK-3β. GSK-3β inhibitor 12 inhibits 49.11% and 37.11% activity of 25 μM and 50 μM GSK-3β, respectively. GSK-3β inhibitor 12 can be used for the research of neurodegenerative diseases.
    GSK-3β inhibitor 12
  • HY-161667
    GSK-3β/HDAC-IN-1
    		Inhibitor
    GSK-3β/HDAC-IN-1 (Compd 4) is a brain-penetrant and first in class dual non-ATP-competitive Glycogen Synthase Kinase 3β/Histone Deacetylases (GSK-3β/HDACs) Inhibitor with IC50s of 0.142, 0.03 and 0.045 μM against GSK-3β, HDAC2 and HDAC6, respectively. GSK-3β/HDAC-IN-1 can be used for Alzheimer’s disease research.
    GSK-3β/HDAC-IN-1
  • HY-10512S
    AR-A014418-d3
    		Inhibitor
    AR-A014418-d3 is the deuterium labeled AR-A014418. AR-A014418 is a potent, selective, and ATP-competitive GSK3β inhibitor (IC50=104 nM; Ki=38 nM)[1].
    AR-A014418-d<sub>3</sub>
  • HY-107530
    3F8
    		Inhibitor
    3F8 is a potent and selective GSK-3β inhibitor that could be useful as new reagent and potential therapeutic candidate for GSK3 related diseases.
    3F8
  • HY-170417
    hAChE/hBuChE/GSK-3β-IN-1
    		Inhibitor
    hAChE/hBuChE/GSK-3β-IN-1 (Compound 6c) is a BBB-penatrable and multi-target anti-Alzheimer's disease compound. hAChE/hBuChE/GSK-3β-IN-1 is the inhibitors of hAChE (IC50: 28.88 nM), hBuChE (IC50: 131.90 nM) and GSK-3β (IC50: 51.42 nM). hAChE/hBuChE/GSK-3β-IN-1 is the tau and Aβ protein aggregation inhibitors.
    hAChE/hBuChE/GSK-3β-IN-1
  • HY-172198
    GSK3-IN-10
    		Inhibitor
    GSK3-IN-10 (Compound 4) is a multi-target inhibitor, that mainly targets GSK3α and GSK3β with IC50 of 1.0 nM and 2.0 nM. GSK3-IN-10 inhibits the activation of β-catenin, promotes the neuronal survival, and exhibits a protective effect against endoplasmic reticulum stress.
    GSK3-IN-10
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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