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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ARN25699
0 ImagesCat. No.: HY-183584ARN25699 is a kinase inhibitor with an IC50 of 5.5 nM against GSK-3β, 2.2 nM against FYN-α, and 242.3 nM against DYRK1A, and it exhibits oral bioavailability. ARN25699 reduces hyperphosphorylation of tau protein and promotes microtubule bundle formation. ARN25699 has a broader kinome inhibitory profile and targets kinases associated with the pathogenic mechanisms linked to Alzheimer's disease. ARN25699 can be used in the research of Alzheimer's disease and related tauopathies.
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hAChE/hBuChE/GSK-3β-IN-1
0 ImagesCat. No.: HY-170417hAChE/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.
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GSK3-IN-10
0 ImagesCat. No.: HY-172198CAS No.: 844441-56-1GSK3-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.
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PJ17
0 ImagesCat. No.: HY-181811CAS No.: 2248983-31-3PJ17 is a potent dual-target inhibitor of AChE and GSK-3β, with IC50 values of 8.84 μM and 4.19 μM, respectively. PJ17 shows no significant neurotoxic effect in primary cerebellar granule neuron cultures. PJ17 serves as a template for the design of multitarget drugs. PJ17 can be used for the research of Alzheimer's disease.
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GSK-3β-IN-30
0 ImagesCat. No.: HY-187680GSK-3β-IN-30 is a glycogen synthase kinase-3β (GSK-3β) inhibitor. GSK-3β-IN-30 stabilizes its conformation in the binding pocket by occupying the ATP-binding cleft of GSK-3β, forming hydrogen bonds with Lys183 and Ser203, and establishing π-anion interactions with Asp181 and Asp200. GSK-3β-IN-30 can be used for the research of Alzheimer's disease.
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AJ-4
0 ImagesCat. No.: HY-184742AJ-4 is an orally active, blood-brain barrier-permeable GSK-3β/AChE inhibitor, with an IC50 of 4.7 nM against GSK-3β and 2.97 μM against AChE. AJ-4 increases the level of phosphorylated GSK-3β and reduces the expression of Amyloid-β and phosphorylated Tau. AJ-4 improves scopolamine-induced learning and memory impairment and alleviates hippocampal neuron damage in AD mice. AJ-4 can be used for the research of Alzheimer's disease.
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GSK-3β inhibitor 6
0 ImagesCat. No.: HY-143260CAS No.: 3033944-50-9GSK-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.
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GSK3β-IN-3
0 ImagesCat. No.: HY-W098905CAS No.: 301359-45-5GSK3β-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).
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CDK7-IN-20
0 ImagesCat. No.: HY-151878CAS No.: 3034210-97-1
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2B-(SP)
0 ImagesCat. No.: HY-P1114CAS No.: 186901-17-72B-(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.
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CHIR-98023
0 ImagesCat. No.: HY-126125CAS No.: 252916-76-0CHIR-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.
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MRT68921 hydrochloride
0 ImagesCat. No.: HY-100006BCAS No.: 2070014-87-6MRT68921 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.
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2B-(SP) TFA
0 ImagesCat. No.: HY-P1114A2B-(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.
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PAV-174
0 ImagesCat. No.: HY-180881PAV-174 is a potent antiviral agent that targets a host protein. PAV-174 prevents Herpes simplex virus (HSV-1) infection in cells (IC50 of 0.02 μM in Vero cells) and human brain organoids. PAV-174 inhibits oxidized macrophage migration inhibitory factor (oxMIF)-induced tau phosphorylation in vitro and in vivo independent of infection. PAV-174 reduces HSV-1-induced tau phosphorylation via the Akt/GSK3β signaling pathway. PAV-174 can be used for Alzheimer’s disease research.
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GSK3β-IN-4
0 ImagesCat. No.: HY-179723CAS No.: 3083425-61-7GSK3β-IN-4 is a selective, potent, orally active and brain-penetrant ATP-competitive GSK3β inhibitor with an IC50 of 0.37 nM. GSK3β-IN-4 shows an IC50 of 2.75 nM and SI of 7.4 for GSK3α. GSK3β-IN-4 reduces tau phosphorylation at Ser396 by inhibiting GSK3β and imoroves cognitive deficits in Alzheimer's disease models. GSK3β-IN-4 can be used for the research of Alzheimer's disease.
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GTGKT
0 ImagesCat. No.: HY-P11782CAS No.: 254732-11-1GTGKT is a CAGE inhibitor. GTGKT binds to CAGE and blocks the binding of CAGE to GSK3β. GTGKT alters the localization of CAGE and inhibits the binding of CAGE to the promoter sequence of Cyclin D1. GTGKT enhances the Apoptotic effect of anticancer agents. GTGKT reduces the expression of Cyclin D1. GTGKT decreases the tumorigenic potential of melanoma and hepatocellular carcinoma cells.
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Multi-kinase-IN-7
0 ImagesCat. No.: HY-178142Multi-kinase-IN-7 is a multikinase inhibitor with IC50s of 2.19, 2.95, 3.59 and 9.31 μM against EGFR, VEGFR2, TrKA and CDK2, respectively. Multi-kinase-IN-7 shows moderate and weaker activity against FAK, AKT1, GSK3β and CDK5 with IC50 values of 6.3, 9.2, 11.7 and 23.4 μM, respectively. Multi-kinase-IN-7 displays broad spectrum antiproliferative potential against NCI cancer cell lines. Multi-kinase-IN-7 induces cell cycle arrest, apoptosis and necrosis. Multi-kinase-IN-7 Inhibitor can be used for the study of breast cancer.
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GSK-3β inhibitor 7
0 ImagesCat. No.: HY-143261GSK-3β inhibitor 7 is a GSK-3β inhibitor with an IC50 value of 5.25 μM. GSK-3β inhibitor 7 is inserted into the ATP-binding binding pocket of GSK-3β and forms hydrogen-bond. GSK-3β inhibitor 7 shows high hepatocyte glucose uptake (83.5%), and can be used in the research of numerous diseases like diabetes, inflammation, cancer, Alzheimer's disease, and bipolar disorder.
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TC-G 24
0 ImagesCat. No.: HY-107529CAS No.: 1257256-44-2TC-G 24 (Compound 24) is a potent, selective glycogen synthase kinase-3β (GSK-3β) inhibitor with an IC50 of 17.1 nM. TC-G 24 can cross the BBB and can be used for studying many diseases such as type 2 diabetes mellitus, stroke, Alzheimer, and other related diseases.
