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-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-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-114903
    (E/Z)-BIO-acetoxime
    		Inhibitor 99.0%
    (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-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-134622
    GSK-3/CDK5/CDK2-IN-1
    		Inhibitor 98.10%
    GSK-3/CDK5/CDK2-IN-1, an imidazole derivative, is an inhibitor of cdk5, cdk2, and GSK-3 extracted from patent WO2002010141A1, example 9a. GSK-3/CDK5/CDK2-IN-1 can be used for the research of cancer, and neurodegenerative diseases.
    GSK-3/CDK5/CDK2-IN-1
  • 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-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-134557
    GS87
    		Inhibitor 99.81%
    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-149054
    GSK-3β inhibitor 13
    		Inhibitor 99.74%
    GSK-3β inhibitor 13 (compound 47) is an orally active and potent GSK-3β inhibitor with blood-brain permeability. GSK-3β inhibitor 13 inhibits GSK-3β and GSK-3α with IC50s of 0.73 nM and 0.35 nM, respectively. GSK-3β inhibitor 13 significantly decreases the phosphorylation of tau (IC50=58 nM), which leads the formation of the neurofibrillary tangles associated with Alzheimer's disease.
    GSK-3β inhibitor 13
  • HY-164476
    ES-072
    		Activator 98.05%
    ES-072 is an orally effective selective EGFR mutant (EGFR-T790M) inhibitor. ES-072 activates GSK3α by inhibiting EGFR-T790M activity, which promotes phosphorylation of PD-L1 at Ser279 and Ser283. The phosphorylated PD-L1 recruits the E3 ubiquitin ligase ARIH1, leading to ubiquitination and proteasomal degradation of PD-L1. This mechanism not only reduces cancer cell growth but also enhances anti-tumor immune response by lowering PD-L1 levels. ES-072 can be used to inhibit proliferation in non-small cell lung cancer (NSCLC) cells.
    ES-072
  • HY-W014901S
    Bisphenol F-13C6
    		Activator 98.32%
    Bisphenol F-13C6 is the 13C labeled Bisphenol F (HY-W014901). Bisphenol F is an orally active endocrine disruptor. Bisphenol F promotes ROS generation, upregulates p-AKT/p-GSK3β, and induces Apoptosis. Bisphenol F interferes with glucose metabolism, affects neurodevelopment and reproductive function. Bisphenol F reduces social novelty preference in mouse offspring. Bisphenol F can be used in bone, blood, and fat-related studies. Bisphenol F is used as a substitute for Bisphenol A (HY-18260).
    Bisphenol F-<sup>13</sup>C<sub>6</sub>
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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