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

PDF 1.37 MB

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-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-penetrable 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
  • HY-RS05864
    Gsk3a Rat Pre-designed siRNA Set A
    		Inhibitor

    Gsk3a Rat Pre-designed siRNA Set A contains three designed siRNAs for Gsk3a gene (Rat), as well as a negative control, a positive control, and a FAM-labeled negative control.
    Gsk3a Rat Pre-designed siRNA Set A
  • HY-134393
    6-Me-ATP
    		Chemical
    6-Me-ATP (N6-Methyl-ATP) is a N6-modified ATP derivative. 6-Me-ATP shows excellent binding affinity to GSK3, serving as the phosphate group donor for GSK3β-catalyzed phosphorylation of its substrate peptide.
    6-Me-ATP
  • HY-W773779
    GSK3-IN-9
    		Inhibitor
    GSK3-IN-9 (Compound 0713) is a selective glycogen synthase kinase 3 (GSK3) inhibitor. GSK3-IN-9 Fragile X syndrome, attention deficit hyperactivity disorder (ADHD), childhood seizure, intellectual disability, diabetes, acute myeloid leukemia (AML), autism, and psychiatric disorder.
    GSK3-IN-9
  • HY-RS05862
    GSK3A Human Pre-designed siRNA Set A
    		Inhibitor

    GSK3A Human Pre-designed siRNA Set A contains three designed siRNAs for GSK3A gene (Human), as well as a negative control, a positive control, and a FAM-labeled negative control.
    GSK3A Human Pre-designed siRNA Set A
  • HY-168079
    GSK-3β inhibitor 21
    		Inhibitor
    GSK-3β inhibitor 21 (compound 44) is an ATP-competitive GSK-3β inhibitor (IC50=6.06 μM) with anti-amyloid aggregation and tau phosphorylation inhibitory activities. GSK-3β inhibitor 21 can be used in the study of Alzheimer's disease.
    GSK-3β inhibitor 21
  • HY-143260
    GSK-3β inhibitor 6
    		Inhibitor
    GSK-3β inhibitor 6 is a potent GSK-3β inhibitor with an IC50 value of 24.4 μM. GSK-3β inhibitor 6 shows high hepatocyte glucose uptake (38%). GSK-3β inhibitor 6 can be used in the research of numerous diseases like diabetes, inflammation, cancer, Alzheimer's disease, and bipolar disorder.
    GSK-3β inhibitor 6
  • HY-RS05863
    Gsk3a Mouse Pre-designed siRNA Set A
    		Inhibitor

    Gsk3a Mouse Pre-designed siRNA Set A contains three designed siRNAs for Gsk3a gene (Mouse), as well as a negative control, a positive control, and a FAM-labeled negative control.
    Gsk3a Mouse Pre-designed siRNA Set A
  • HY-155989
    GSK3-IN-4
    		Inhibitor
    GSK3-IN-4 (compound 0715) is a potent GSK3 inhibitor. GSK3-IN-4 can be used for psychiatric disorder research.
    GSK3-IN-4
  • HY-W098905
    GSK3β-IN-3
    		Inhibitor
    GSK3β-IN-3 is an ATP-competitive GSK-3β inhibitor (IC50 = 0.90 μM). GSK3β-IN-3 can reduce the phosphorylation level of tau protein in the BR5706 strain and reduce the deposition of Aβ aggregates in the CL2006 strain, and can be used to research Alzheimer's disease (AD).
    GSK3β-IN-3
  • HY-B0712S1
    Ceftriaxone-13C2,d3 triethylammonium salt
    		Inhibitor
    Ceftriaxone-13C2,d3 triethylammonium salt is 13C and deuterated labeled Ceftriaxone (HY-B0712). 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 mM. 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.
    Ceftriaxone-<sup>13</sup>C<sub>2</sub>,d<sub>3</sub> triethylammonium salt
  • HY-161458
    GSK-3β inhibitor 16
    		Inhibitor
    GSK-3β inhibitor 16 (compound 7c) is a GSK-3β inhibitor with the IC50 of 4.68 nM. GSK-3β inhibitor 16 decreases Tau hyperphosphorylated aggregate and alleviates cognitive impairments in the Scopolamin (HY-N0296)-induced model in mice.
    GSK-3β inhibitor 16
  • HY-151878
    CDK7-IN-20
    		Inhibitor
    CDK7-IN-20 is a potent, selective and irreversible CDK7 (CDK) inhibitor with an IC50 value of 4 nM. CDK7-IN-20 displays >206-fold selectivity for CDK7 over CDK1, CDK2, CDK3, CDK5, CDK6, CDK9 and CDK12 . CDK7-IN-20 has the potential for autosomal dominant polycystic kidney disease (ADPKD) research.
    CDK7-IN-20
  • HY-P1114
    2B-(SP)
    2B-(SP) is a eIF2B-based substrate for glycogen synthase kinase-3 (GSK-3). 2B-(SP) is readily phosphorylated by both the α and β isoforms of GSK-3.
    2B-(SP)
  • HY-126125
    CHIR-98023
    		Inhibitor
    CHIR-98023 is a potent, selective and reversible inhibitor of GSK3, with IC50s of 10 nM and 6.7 nM for GSK3α and GSK3β, respectively. CHIR-98023 can improve insulin action and glucose metabolism.
    CHIR-98023
  • HY-100006B
    MRT68921 hydrochloride
    		Inhibitor
    MRT68921 hydrochloride is a potent NUAK1/ULK1 dual inhibitor. MRT68921 hydrochloride inhibits ULK1 and ULK2 with IC50 values of 2.9 nM and 1.1 nM, respectively. MRT68921 hydrochloride can block cells autophagy and kill tumor cells by breaking the balance of oxidative stress signals. MRT68921 hydrochloride can inhibit cell proliferation and induce ROS production and apoptosis. MRT68921 hydrochloride can be used for the research of cancer, such as breast cancer.
    MRT68921 hydrochloride
  • HY-P1114A
    2B-(SP) (TFA)
    2B-(SP) TFA is a eIF2B-based substrate for glycogen synthase kinase-3 (GSK-3). 2B-(SP) TFA is readily phosphorylated by both the α and β isoforms of GSK-3.
    2B-(SP) (TFA)
  • HY-161751
    MJ34
    		Inhibitor
    MJ34 is a potent inhibitor of GSK-3β and GSK-3α, with the IC50s of 15.4 nM and 31.5 nM, respectively. MJ34 plays an important role in cancer research
    MJ34
Cat. No. Product Name / Synonyms Species Source
Cat. No. Product Name / Synonyms Application Reactivity
All Rights Reserved.
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

Your Search Returned No Results.

Sorry. There is currently no product that acts on isoform together.

Please try each isoform separately.