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-114903
    (E/Z)-BIO-acetoxime
    		Inhibitor
    (E/Z)-BIO-acetoxime (GSK-3 Inhibitor X) is a potent and selective GSK-3α/β inhibitor, with an IC50 of 10 nM. (E/Z)-BIO-acetoxime shows more than 200-flod selectivity over CDK5/p25, CDK2/cyclin A and CDK1/cyclin B (IC50=2.4, 4.3, 63 μM).
    (E/Z)-BIO-acetoxime
  • HY-161618
    MJ04
    		Inhibitor
    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-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
    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
    		98.02%
    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 (sodium) (Standard)
    		Inhibitor
    Cromolyn (sodium) (Standard) is the analytical standard of Cromolyn (sodium). This product is intended for research and analytical applications. Cromolyn sodium (Disodium Cromoglycate; FPL-670) is an antiallergic agent. Cromolyn sodium is a GSK-3β inhibitor with an IC50 of 2.0 μM.
    Cromolyn (sodium) (Standard)
  • HY-122665A
    HTH-01-091 TFA
    		Inhibitor 99.48%
    HTH-01-091 TFA is a potent and selective maternal embryonic leucine zipper kinase (MELK) inhibitor, with an IC50 of 10.5 nM. HTH-01-091 TFA also inhibits PIM1/2/3, RIPK2, DYRK3, smMLCK and CLK2. HTH-01-091 TFA can be uesd for breast cancer research.
    HTH-01-091 TFA
  • 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-W969907
    GSK3-IN-7
    		99.35%
    GSK3a-IN-38 is a groundbreaking small molecule that effectively inhibits GSK-3a activity.
    GSK3-IN-7
  • 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-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
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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