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-13867A
    Bisindolylmaleimide I hydrochloride
    		98.44%
    Bisindolylmaleimide I (GF109203X) hydrochloride is a cell-permeable and reversible PKC inhibitor (IC50 of 20 nM, 17 nM, 16 nM, and 20 nM for PKCα, PKCβI, PKCβII, and PKCγ. Bisindolylmaleimide I hydrochloride is also a GSK-3 inhibitor.
    Bisindolylmaleimide I hydrochloride
  • HY-128879A
    VP3.15 dihydrobromide
    		Inhibitor 98.01%
    VP3.15 dihydrobromide 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 dihydrobromide has neuroprotective and neuroreparative activities, thus as potential combined anti-inflammatory and pro-remyelinating therapies for multiple sclerosis (MS).
    VP3.15 dihydrobromide
  • HY-137976
    Penehyclidine hydrochloride
    		Activator 99.2%
    Penehyclidine (Penequinine) hydrochloride, a anticholinergic agent, is a selective antagonist of M1 and M3 receptors. Penehyclidine hydrochloride activates NF-kβ in lung tissue and inhibits the release of inflammatory factors. Penehyclidine hydrochloride can alleviate the pulmonary inflammatory response in rats with chronic obstructive pulmonary disease (COPD) undergoing mechanical ventilation.
    Penehyclidine hydrochloride
  • HY-N0677
    Dehydroandrographolide succinate
    		99.88%
    Dehydroandrographolide succinate can be extracted from herbal medicine Andrographis paniculata (Burm f) Nees, is widely used in research for viral pneumonia and viral upper respiratory tract infections because of its immunostimulatory, anti-infective and anti-inflammatory effect. Dehydroandrographolide succinate exerts antithrombotic effect. Dehydroandrographolide succinate significantly inhibits the platelet aggregation rate (ED50 = 386.9 mg/kg) by decreasing TXB2 levels. Dehydroandrographolide succinate mitigates muscle astrophy via the Akt/GSK3β and MuRF-1 pathways.
    Dehydroandrographolide succinate
  • HY-107815
    CHIR 98024
    		Inhibitor 99.20%
    CHIR 98024 (Compound L) is a glycogen synthase kinase 3 (GSK3) inhibitor with an EC50 of 0.2566 μM.
    CHIR 98024
  • HY-117025A
    Manzamine A hydrochloride
    		Inhibitor 99.66%
    Manzamine A hydrochloride, 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 hydrochloride targets vacuolar ATPases and inhibits autophagy in pancreatic cancer cells. Manzamine A hydrochloride has antimalarial and anticancer activities. Manzamine A hydrochloride also shows potent activity against HSV-1.
    Manzamine A hydrochloride
  • HY-126144
    GSK-3β inhibitor 1
    		Inhibitor 98.04%
    GSK-3β inhibitor 1 (compound 3a) inhibits GSK-3β with an IC50 of 4.19 nM. GSK-3β inhibitor 1 demonstrates high antidiabetic efficacy in obese Streptozotocin (HY-13753)-treated rats.
    GSK-3β inhibitor 1
  • HY-117822
    BRD0209
    		Inhibitor 99.56%
    BRD0209 is a potent, selective and dual inhibitor of GSK3α/β inhibitor (GSK3α IC50 = 19 nM; GSK3β IC50 = 5 nM). BRD0209 is also a reversible ATP-competitive inhibitor with fast-off kinetics (Ki = 4.2 nM, respectively). BRD0209 is a tricyclic pyrazolotetrahydroquinolinone compound. BRD0209 has the potential for the research of mood disorder diseases.
    BRD0209
  • HY-137472
    SAR502250
    		Inhibitor 99.63%
    SAR502250 is a potent, selective, ATP competitive, orally active and brain-penetrant inhibitor of GSK3, with an IC50 of 12 nM for human GSK-3β. SAR502250 displays antidepressant-like activity. SAR502250 can be used for the research of Alzheimer’s disease (AD).
    SAR502250
  • HY-141480
    GSK-3β inhibitor 3
    		Inhibitor 99.22%
    GSK-3β inhibitor 3 is a potent, selective, irreversible and covalent inhibitor of Glycogen Synthase Kinase 3β (GSK-3β), with an IC50 of 6.6 μM. GSK-3β inhibitor 3 can be used for the research of acute promyelocytic leukemia.
    GSK-3β inhibitor 3
  • HY-149845
    PROTAC GSK-3β Degrader-1
    		Degrader 99.05%
    PROTAC GSK-3β Degrader-1 (compound 1) is a degrader targets GSK-3β degradation with an IC50 value of 833 nM. PROTAC GSK-3β Degrader-1 contains SB-216763 (a GSK-3β inhibitor), a PEG linker and a CRBN (E3 ligase liand). PROTAC GSK-3β Degrader-1 reduces the neurotoxicity induced by Aβ25-35 peptide and CuSO4. PROTAC GSK-3β Degrader-1 can be used to research in Alzheimer's disease.
    PROTAC GSK-3β Degrader-1
  • HY-134393B
    6-Me-ATP (trisodium) solution (100mM)
    		Chemical 99.89%
    6-Me-ATP (N6-Methyl-ATP) trisodium solution (100mM) is a N6-modified ATP derivative. 6-Me-ATP trisodium shows excellent binding affinity to GSK3, serving as the phosphate group donor for GSK3β-catalyzed phosphorylation of its substrate peptide.
    6-Me-ATP (trisodium) solution (100mM)
  • HY-126066
    (-)-Syringaresinol
    		Inhibitor 99.95%
    (-)-Syringaresinol is an orally active isomer of syringaresinol (HY-N8307) found in Annona Montana. (-)-Syringaresinol exhibits antioxidant, anti-inflammatory, and anticancer activities. (-)-Syringaresinol can alleviate ulcerative colitis via the PI3K-Akt/MAPK/Wnt signaling pathway. (-)-Syringaresinol inhibits HL-60 cell proliferation by arresting the G1 phase and inducing apoptosis. (-)-Syringaresinol inhibits LPS (HY-D1056)-induced microglial activation by downregulating the NF-κB p65 signaling pathway and its interaction with ERβ, exerting anti-neuroinflammatory effects.
    (-)-Syringaresinol
  • HY-164907
    GSK-3β inhibitor 22
    		Inhibitor 99.38%
    GSK-3β inhibitor 22 (compound 20o) is a GSK-3β inhibitor with an IC50 of 3.1 nM. GSK-3β inhibitor 22 has the potential of the study of Alzheimer's disease.
    GSK-3β inhibitor 22
  • HY-122665
    HTH-01-091
    		Inhibitor 98.64%
    HTH-01-091 is a potent and selective maternal embryonic leucine zipper kinase (MELK) inhibitor, with an IC50 of 10.5 nM. HTH-01-091 also inhibits PIM1/2/3, RIPK2, DYRK3, smMLCK and CLK2. HTH-01-091 can be uesd for breast cancer research.
    HTH-01-091
  • HY-126144A
    (E/Z)-GSK-3β inhibitor 1
    		Inhibitor 99.03%
    (E/Z)-GSK-3β inhibitor 1 is a racemic compound of (E)-GSK-3β inhibitor 1 and (Z)-GSK-3β inhibitor 1 isomers. GSK-3β inhibitor 1 (compound 3a) is a glycogen synthase kinase 3β (GSK-3β) inhibitor and demonstrates high antidiabetic efficacy, with an IC50 of 4.9 nM.
    (E/Z)-GSK-3β inhibitor 1
  • HY-112392
    GSK-3 Inhibitor XIII
    		Inhibitor 98.79%
    GSK-3 Inhibitor XIII is a potent and ATP-competitive GSK-3 inhibitor with a Ki of 24 nM.
    GSK-3 Inhibitor XIII
  • HY-N3181
    Nodosin
    		Inhibitor 98.44%
    Nodosin is an orally active diterpenoid compound that can be isolated from Isodon serra. Nodosin can inhibit the proliferation and induce cell cycle arrest and apoptosis of tumor cells. Nodosin can also inhibit oxidative stress, inflammatory responses, and ferroptosis. Nodosin has anti-inflammatory and anti-tumor activities.
    Nodosin
  • HY-172118
    CDKL5/GSK3-IN-1
    		Inhibitor 98.72%
    CDKL5/GSK3-IN-1 (Compound 2) is a potent and selectivity chemical probe for CDKL5/GSK3.CDKL5/GSK3-IN-1 has potent inhibition of CDKL5 and GSK3α/β, with IC50 values of 4.6, 24 and 9.5 nM for CDKL5, GSK3β and GSK3α, respectively, in the NanoBRET assay. CDKL5/GSK3-IN-1 can be used for the research of CNS diseases.
    CDKL5/GSK3-IN-1
  • HY-W969907
    GSK3-IN-7
    		99.35%
    GSK3a-IN-38 is a groundbreaking small molecule that effectively inhibits GSK-3a activity.
    GSK3-IN-7
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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