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-15356
    BIO-acetoxime
    		Inhibitor ≥98.0%
    BIO-acetoxime (BIA) is a potent and selective GSK-3 inhibitor, with IC50s of both 10 nM for GSK-3α/β. BIO-acetoxime has anticonvulsant and anti-infection activity.
    BIO-acetoxime
  • HY-103647
    K00546
    		Inhibitor 98.08%
    K00546 is a potent CDK1 and CDK2 inhibitor with IC50s of 0.6 nM and 0.5 nM for CDK1/cyclin B and CDK2/cyclin A, respectively. K00546 is also a potent CDC2-like kinase 1 (CLK1) and CLK3 inhibitor with IC50s of 8.9 nM and 29.2 nM, respectively.
    K00546
  • HY-N0721
    Neoandrographolide
    		Inhibitor 99.65%
    Neoandrographolide is a diterpenoid compound isolated from Andrographis paniculata. Neoandrographolide inhibits osteoclasts differentiation and bone resorption through inhibition of MAPK/NF-κB/PI3K/AKT/GSK3β/PPAR/CAMK signaling pathway. Neoandrographolide inhibits apoptosis in rat embryonic ventricular cardiomyocytes. Neoandrographolide inhibits iNOS and the generation of ROS, activates eNOS, exhibiting anti-inflammatory and hypolipidemic activity.
    Neoandrographolide
  • HY-N6866
    Gomisin N
    		Inhibitor 99.94%
    Gomisin N is an orally active lignan compound. Gomisin N can be isolated from Schisandra chinensis. Gomisin N induces Apoptosis in a variety of cells. Gomisin N activates AMPK, Akt, MAPK/ERK, Nrf2, caspase-3 and PARP-1. Gomisin N inhibits GSK3β, nitric oxide (NO), and proinflammatory cytokines (IL-1β, IL-6, TNF-α). Gomisin N has anti-inflammatory, antioxidant, anti-obesity, anti-diabetic, and anti-melanogenesis activities. Gomisin N has anti-tumor activity against cervical cancer and liver cancer. Gomisin N improves Alzheimer's disease.
    Gomisin N
  • HY-139254
    Indirubin-3′-oxime
    		Inhibitor 99.10%
    Indirubin-3′-oxime (IDR3O), a synthetic derivative of indirubin, is a potent inhibitor of cyclin-dependent kinases (CDKs) and glycogen synthase kinase 3β (GSK3β). Indirubin-3′-oxime directly inhibits the activity of all three isoforms of JNK (JNK1, JNK2, and JNK3), with IC50s of 0.8 μM, 1.4 μM, and 1.0 μM, respectively. Indirubin-3′-oxime can enhance height growth via activation of Wnt/β-catenin signaling in chondrocytes.
    Indirubin-3′-oxime
  • 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-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-154851
    GSK-3 inhibitor 3
    		Inhibitor 98.72%
    GSK-3 inhibitor 3 is a selective, orally active and brain-penetrant inhibitor of GSK-3, with IC50s of 0.35 nM and 0.25 nM for GSK-3α and GSK-3β, respectively. GSK-3 inhibitor 3 lowers levels of tau protein phosphorylation at S396 in a triple-transgenic mouse Alzheimer’s disease model, with IC50 of 10 nM. GSK-3 inhibitor 3 can be used for neurological disease research.
    GSK-3 inhibitor 3
  • HY-107815
    CHIR 98024
    		Inhibitor 98.08%
    CHIR 98024 (Compound L) is a glycogen synthase kinase 3 (GSK3) inhibitor with an EC50 of 0.2566 μM.
    CHIR 98024
  • 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-B1014
    Acenocoumarol
    		Activator 99.87%
    Acenocoumarol is an anticoagulant that functions as a Vitamin K antagonist. Acenocoumarol inhibits MAPK/ERK/JNK signaling pathway, reduces the nuclear translocation of NF-κB p65, activates Akt/GSK3β signaling pathway. Acenocoumarol induces apoptosis in cell A549, arrests cell cycle at S phase.
    Acenocoumarol
  • HY-B1619
    Cromolyn
    		Inhibitor 99.91%
    Cromolyn is a mast cell stabilizer. Cromolyn has the potential for the research of bronchial asthma, allergic rhinitis, and certain allergic eye conditions such as vernal conjunctivitis, keratitis, and keratoconjunctivitis.
    Cromolyn
  • HY-15504A
    RGB-286638 free base
    		Inhibitor 98.07%
    RGB-286638 is a CDK inhibitor that inhibits the kinase activity of cyclin T1-CDK9, cyclin B1-CDK1, cyclin E-CDK2, cyclin D1-CDK4, cyclin E-CDK3, and p35-CDK5 with IC50s of 1, 2, 3, 4, 5 and 5 nM, respectively; also inhibits GSK-3β, TAK1, Jak2 and MEK1, with IC50s of 3, 5, 50, and 54 nM.
    RGB-286638 free base
  • HY-144290
    ARN25068
    		Inhibitor 99.66%
    ARN25068 is a sub-micromolar inhibitor of the three protein kinases, GSK-3β, FYN and DYRK1A to tackle tau hyperphosphorylation.
    ARN25068
  • 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-10182R
    Laduviglusib (Standard)
    		Inhibitor
    Laduviglusib (Standard) is the analytical standard of Laduviglusib. Laduviglusib (CHIR-99021) is a potent, selective and orally active GSK-3α/β inhibitor with IC50s of 10 nM and 6.7 nM. Laduviglusib shows >500-fold selectivity for GSK-3 over CDC2, ERK2 and other protein kinases. Laduviglusib is also a potent Wnt/β-catenin signaling pathway activator. Laduviglusib enhances mouse and human embryonic stem cells self-renewal. Laduviglusib induces autophagy.
    Laduviglusib (Standard)
  • HY-112809
    GSK2646264
    		Inhibitor 98.39%
    GSK2646264 (Compound 44) is a potent and selective spleen tyrosine kinase (SYK) inhibitor with a pIC50 of 7.1. GSK2646264 also inhibits other kinases with pIC50 values of 5.4, 5.4, 5.3, 5, 4.5, <4.6 and <4.3 against LCK, LRRK2, GSK3β, JAK2, VEGFR2, Aurora B and Aurora A, respectively. GSK2646264 is penetrable into the epidermis and dermis of the skin.
    GSK2646264
  • HY-13867A
    Bisindolylmaleimide I hydrochloride
    		99.18%
    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-13973A
    GSK-3 inhibitor 1
    		Inhibitor 99.89%
    GSK-3 inhibitor 1 (compound core 3) is a GSK-3 inhibitor that induces stem/progenitor cell self-renewal (e.g. induces stem/progenitor cell proliferation while maintaining the ability to differentiate into tissue cells in the progeny).
    GSK-3 inhibitor 1
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.