GSK-3β
Glycogen synthase kinase-3β (GSK-3β) is a constitutively active serine/threonine kinase that regulates numerous cellular substrates and functions as a central signaling node in metabolism, development, and cell fate control[1]. Mechanistically, GSK-3β participates in multiple signaling pathways, including Wnt/β-catenin, PI3K/Akt, Notch, and NF-κB networks, where its phosphorylation-dependent activity influences transcriptional regulation, cellular differentiation, and stress responses[2][3]. Through these pathway interactions, GSK-3β contributes to the control of glucose metabolism and broader cardiometabolic homeostasis, while dysregulated GSK-3β signaling has been linked to pathological remodeling and disease progression in diverse experimental models[4][1]. In neurological disease models, GSK-3β has been associated with hyperphosphorylated tau pathology and neuronal dysfunction, supporting its relevance as a target for mechanistic studies of neurodegeneration[3]. Compared with the closely related isoform GSK-3α, GSK-3β exhibits both overlapping and isoform-specific biological functions, and genome-wide as well as genetic studies demonstrate distinct downstream targets and physiological roles for the two kinases[4][5][6]. This isoform divergence is particularly important for experimental design because GSK-3α and GSK-3β can exert different or even opposing effects in specific biological contexts[4]. For experimental applications, small-molecule GSK-3 inhibitors remain widely used research tools; however, many available compounds lack isoform selectivity, emphasizing the need for isoform-specific pharmacological and genetic approaches when investigating GSK-3β-dependent mechanisms[6][5].
References:
- [1]. Beurel E, et al. Glycogen synthase kinase-3 (GSK3): regulation, actions, and diseases. Pharmacol Ther. 2015 Apr;148:114-31. [Content Brief]
- [2]. Espinosa L, et al. Phosphorylation by glycogen synthase kinase-3 beta down-regulates Notch activity, a link for Notch and Wnt pathways. J Biol Chem. 2003 Aug 22;278(34):32227-35. [Content Brief]
- [3]. Kaidanovich-Beilin O, et al. GSK-3: Functional Insights from Cell Biology and Animal Models. Front Mol Neurosci. 2011 Nov 16;4:40. doi: 10.3389/fnmol.2011.00040. PMID: 22110425; PMCID: PMC3217193. [Content Brief]
- [4]. Umbarkar P, et al. GSK-3 at the heart of cardiometabolic diseases: Isoform-specific targeting is critical to therapeutic benefit. Biochim Biophys Acta Mol Basis Dis. 2023 Aug;1869(6):166724. doi: 10.1016/j.bbadis.2023.166724. Epub 2023 Apr 23. PMID: 37094727; PMCID: PMC10247467. [Content Brief]
- [5]. Lee HC, et al. Glycogen synthase kinase 3 alpha and 3 beta have distinct functions during cardiogenesis of zebrafish embryo. BMC Dev Biol. 2007 Aug 3;7:93. [Content Brief]
- [6]. Chen X, et al. A Chemical-Genetic Approach Reveals the Distinct Roles of GSK3α and GSK3β in Regulating Embryonic Stem Cell Fate. Dev Cell. 2017 Dec 4;43(5):563-576.e4. doi: 10.1016/j.devcel.2017.11.007. PMID: 29207259; PMCID: PMC5851779. [Content Brief]
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GSK-3β Related Products (186)
Related Products (186)
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Recombinant Proteins (5)
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Antibodies (4)
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Lignarenone B
0 ImagesCat. No.: HY-116125CAS No.: 125010-17-5Lignarenone B is a phenyl conjugated trienone. Lignarenone B can be isolated from the Mediterranean bullomorph Scaphander lignarius. Lignarenone B can inhibit the activity of GSK3β. Lignarenone B can be used in the research of Alzheimer's disease.
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ChE/GSK-3β-IN-1
0 ImagesCat. No.: HY-179496ChE/GSK-3β-IN-1 (compound 18o) is a potent dual ChE/GSK-3β inhibitor. ChE/GSK-3β-IN-1 exhibits dual inhibition of AChE (IC50 = 1.7 μM), butyrylcholinesterase (BChE) (IC50 = 5.3 μM), and GSK-3β (IC50 = 5.7 μM). ChE/GSK-3β-IN-1 inhibits Aβ1-42 self-aggregation. ChE/GSK-3β-IN-1 can be used for Alzheimer’s disease (AD) research.
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IM-12 (GMP)
0 ImagesCat. No.: HY-12292GCAS No.: 1129669-05-1IM-12 GMP is IM-12 (HY-12292) produced by using GMP guidelines. GMP small molecules works appropriately as an auxiliary reagent for cell therapy manufacture. IM-12 is an orally active anti-inflammatory agent that targets and inhibits the NF-κB and STAT3 signaling pathways. IM-12 activates the Wnt signaling pathway and promotes the nuclear translocation of β-catenin by inhibiting GSK3β, while also blocking the tyrosine kinase activity of p210BCR/ABL. IM-12 reduces the levels of IL-6, IL-17, NO, prostaglandin E2, iNOS and COX-2, and induces ER stress, Ca2+ release, autophagy and apoptosis. IM-12 is heat-sensitive and does not induce autophagy in IM-resistant p210BCR/ABLT315I mutant cells. IM-12 is also a component of the 5iLA medium used for naive pluripotent stem cell research. IM-12 has been applied in studies related to carrageenan (HY-125474)-induced hind paw edema, TNBS-induced colitis, and acute and chronic myeloid leukemia.
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Anticancer agent 357
0 ImagesCat. No.: HY-187517Anticancer agent 357 is an orally active HER2 inhibitor. Anticancer agent 357 reduces the phosphorylation levels of HER2, AKT and GSK-3β, and downregulates the expression of β-catenin. Anticancer agent 357 inhibits the proliferation and migration of colon cancer cells with high HER2 expression, and suppresses tumor growth in xenograft models. Anticancer agent 357 can be used in colorectal cancer-related research.
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SF-9-2
0 ImagesCat. No.: HY-175236CAS No.: 3053768-78-5SF-9-2 is a PD-L1/PD-1 binding inhibitor (IC50 = 24.9 nM). SF-9-2 inhibits epithelial-mesenchymal transition, migration, invasion, and proliferation of SK-N-SH cells, and also induces apoptosis and cell cycle arrest. SF-9-2 blocks PD-L1-induced SK-N-SH cell growth through the MAPK signaling pathway. SF-9-2 restores GSK-3β activity and enhances PD-L1 degradation through the ubiquitin-proteasome pathway. SF-9-2 inhibits tumor growth in the SK-N-SH NOG mouse model without significant toxicity. SF-9-2 also acts as an immune checkpoint inhibitor, blocking PD-L1 to restore T cell function. SF-9-2 can be used in neuroblastoma research.
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BiS3
0 ImagesCat. No.: HY-P11927BiS3 is a selective hyperbivalent macrocyclic peptide GSK3β inhibitor, with a Kd of 0.28 nM and an IC50 of 4.8 nM against GSK3β. BiS3 is applicable to studies related to GSK3β signaling and colorectal cancer.
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Degalactotigonin
0 ImagesCat. No.: HY-N9684CAS No.: 39941-51-0Degalactotigonin is a saponin-selective inhibitor targeting the EGFR, GSK3β and Hedgehog/Gli1 pathways and can be isolated from Solanum nigrum (Solanum nigrum). Degalactotigonin inhibits EGFR phosphorylation and the downstream Akt/ERK signaling pathway, and at the same time inhibits the Hedgehog/Gli1 pathway through GSK3β inactivation, thereby inducing cancer cell apoptosis, arresting the cell cycle, and inhibiting migration and invasion. Degalactotigonin can be used in targeted research on malignant tumors such as pancreatic cancer and osteosarcoma.
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AKI-062a
0 ImagesCat. No.: HY-181584CAS No.: 1093303-07-1
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Aloisine A
0 ImagesCat. No.: HY-112363CAS No.: 496864-16-5Synonyms: RP107Aloisine 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.
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ARN25657
0 ImagesCat. No.: HY-176287ARN25657 is a dual-acting D3R/GSK-3β modulator. ARN25657 has both partial D3R agonist activity (EC50 = 15.2 nM, Ki =1.5 nM) and potent GSK-3β inhibitor activity (IC50 = 19.3 nM). ARN25657 exhibits excellent GSK-3β selectivity over FYN, PKA, and CDK5/p35. ARN25657 inhibits P-glycoprotein (P-gP)-mediated acetoxymethyl calcein efflux and improves in vitro ADME properties while maintaining a balanced dual-target profile. ARN25657 is useful for studying bipolar disorder and related neuropsychiatric disorders.
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Erlotinib-13C6 hydrochloride
0 ImagesCat. No.: HY-12008S1CAS No.: 1210610-07-3Synonyms: CP-358774-13C6 hydrochloride; NSC 718781-13C6 hydrochloride; OSI-774-13C6 hydrochlorideErlotinib-13C6 hydrochloride (CP-358774-13C6 hydrochloride) is the 13C-labeled Erlotinib Hydrochloride (HY-12008). Erlotinib (CP-358774) Hydrochloride is a selective, orally active EGFR tyrosine kinase inhibitor. Erlotinib Hydrochloride also acts as a substrate and inhibitor of OATP2B1, with an IC50 of approximately 0.079 μM for inhibiting OATP2B1-mediated uptake of estrone 3-sulfate. Erlotinib Hydrochloride blocks EGFR phosphorylation, downstream signal transduction, as well as the growth and proliferation of cancer cells. Erlotinib Hydrochloride inhibits MMP-10-mediated renal injury, fibrotic lesions, the ERK1/2, GSK-3β and β-catenin signaling pathways, as well as the deposition of fibronectin, α-SMA, collagen and renal injury markers. Erlotinib Hydrochloride is metabolized via CYP3A to produce the active metabolite OSI-420. Erlotinib Hydrochloride can be used in research related to non-small cell lung cancer, gastric cancer, papillary renal cell carcinoma, EGFR inhibitor resistance and renal fibrosis.
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CDK5-IN-4
0 ImagesCat. No.: HY-161595CAS No.: 1212711-91-5
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AChE/BACE1/GSK3β-IN-1
0 ImagesCat. No.: HY-151260CAS No.: 2866066-81-9AChE/BACE1/GSK3β-IN-1 is an orally active triple inhibitor of AChE/BACE1/GSK3β. AChE/BACE1/GSK3β-IN-1 has effective inhibitory activity against AChE, BACE1 and GSK3β with IC50 values of 1.0 μM, 20 μM and 15 μM, respectively. AChE/BACE1/GSK3β-IN-1 has good blood-brain barrier penetrability, suitable bioavailability. AChE/BACE1/GSK3β-IN-1 can be used for the research of Alzheimer's disease (AD).
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ZLWH-23
0 ImagesCat. No.: HY-144316CAS No.: 2765251-12-3
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GSK-3β inhibitor 12
0 ImagesGSK-3β inhibitor 12 (Compound 15) is a GSK-3β inhibitor. GSK-3β inhibitor 12 is applicable to the research of Alzheimer's disease.
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GSK-3β/HDAC-IN-1
0 ImagesCat. No.: HY-161667GSK-3β/HDAC-IN-1 (Compd 4) is a brain-penetrant and first in class dual non-ATP-competitive Glycogen Synthase Kinase 3β/Histone Deacetylases (GSK-3β/HDACs) Inhibitor with IC50s of 0.142, 0.03 and 0.045 μM against GSK-3β, HDAC2 and HDAC6, respectively. GSK-3β/HDAC-IN-1 can be used for Alzheimer’s disease research.
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GSK-3β/CK-1δ-IN-1
0 ImagesCat. No.: HY-173494GSK-3β/CK-1δ-IN-1 (8d) is a dual and blood-brain barrier penetrated GSK-3β / CK-1δ inhibitor, with IC50 values of 0.77 μM for GSK-3β and 0.57 μM for CK-1δ, respectively. GSK-3β/CK-1δ-IN-1 (8d) can be used in the research for neuroblastoma.
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BRD1172
0 ImagesCat. No.: HY-120917CAS No.: 1597438-86-2Synonyms: ML320BRD1172 (ML320) is a selectivity GSK3β inhibitor with an IC50 of 24 nM for GSK3β over CDK5. BRD1172 significantly inhibits GSK3β-mediated Tau phosphorylation in SH-SY5Y cells, and relieves negative regulation by GSK3β on β-catenin degradation and TCF/LEF promoter activities. BRD1172 can be used for Alzheimer’s disease, cardiac hypertrophy and cancers research.
