GSK-3α
GSK-3α is a serine/threonine kinase within the GSK-3 family, whose activity is negatively regulated by serine phosphorylation and positively controlled by tyrosine phosphorylation[1]. Mechanistically, GSK-3 regulates glycogen synthase, glucose metabolism, energy homeostasis, gene expression, cellular architecture, apoptosis, epithelial barrier proteins, and dendritic-cell inflammatory activation[2][3][4]. In disease models, Gsk3a−/− mice developed progressive cardiomyocyte hypertrophy and contractile dysfunction, and the heart failed to respond effectively to hemodynamic stress[5]. Compared with GSK-3β, GSK-3α showed distinct regulation of CRE- and NF-κB-dependent transactivation, neuronal survival responses, and sperm fertilization, supporting non-redundant isoform biology[1][6][7]. For experimental applications, small-molecule GSK-3 inhibitors and GSK-3α siRNA help test barrier integrity, neuroprotection, β-adrenergic responsiveness, and isoform-specific transcriptional control[1][3][5][6].
References:
- [1]. Liang MH, et al. Differential roles of glycogen synthase kinase-3 isoforms in the regulation of transcriptional activation. J Biol Chem. 2006 Oct 13;281(41):30479-84. [Content Brief]
- [2]. Wang L, et al. Glycogen synthesis and beyond, a comprehensive review of GSK3 as a key regulator of metabolic pathways and a therapeutic target for treating metabolic diseases. Med Res Rev. 2022 Mar;42(2):946-982. [Content Brief]
- [3]. Severson EA, et al. Glycogen Synthase Kinase 3 (GSK-3) influences epithelial barrier function by regulating occludin, claudin-1 and E-cadherin expression. Biochem Biophys Res Commun. 2010 Jul 2;397(3):592-7. [Content Brief]
- [4]. Rodionova E, et al. GSK-3 mediates differentiation and activation of proinflammatory dendritic cells. Blood. 2007 Feb 15;109(4):1584-92. [Content Brief]
- [5]. Zhou J, et al. GSK-3alpha directly regulates beta-adrenergic signaling and the response of the heart to hemodynamic stress in mice. J Clin Invest. 2010 Jul;120(7):2280-91. [Content Brief]
- [6]. Liang MH, et al. Regulation and function of glycogen synthase kinase-3 isoforms in neuronal survival. J Biol Chem. 2007 Feb 9;282(6):3904-17. [Content Brief]
- [7]. Dey S, et al. Roles of glycogen synthase kinase 3 alpha and calcineurin in regulating the ability of sperm to fertilize eggs. FASEB J. 2020 Jan;34(1):1247-1269. [Content Brief]
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GSK-3α Related Products (49)
Related Products (49)
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Recombinant Proteins (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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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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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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GSK-3α/β-IN-1
0 ImagesCat. No.: HY-172586CAS No.: 1574354-24-7GSK-3α/β-IN-1 is GSK-3α/β inhibitor with IC50 s of 0.265 μM and 0.255 μM for GSK-3α and GSK-3β, respectively. GSK-3α/β-IN-1 also inhibits PKA with an IC50 of 0.188 μM. GSK-3α/β-IN-1 potently inhibits cell viability of three Glioblastoma (GBM) cell lines (IC50 : 3-6 μM, 72 h) with no toxicity to human astrocytes and good metabolic stability. GSK-3α/β-IN-1 has potential CNS activity in all-human blood-brain barrier (BBB) model of GBM.
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BI-5521
0 ImagesCat. No.: HY-171881CAS No.: 864686-48-6BI-5521 is an orally active GSK-3 inhibitor with an IC50 of 1.1 nM against GSK-3β. BI-5521 targets the two GSK-3 isoforms with similar potency and exhibits potent inhibitory activity against DYRK1A. By modulating GSK-3 activity, BI-5521 inhibits tumor proliferation and cancer cell growth, exerts cytotoxic effects, and reduces cancer cell viability. It shows consistent chemosensitivity across all subtypes of rhabdomyosarcoma, produces synergistic growth inhibitory effects when combined with SOS1 inhibitors, reduces oral glucose levels, regulates the myofibroblast differentiation pathway, decreases the nuclear localization of YAP/SMAD2/3, and lowers the positive rate of α-SMA in fibroblasts without affecting the apoptosis of CD4+ T cells. BI-5521 can be used in the research of non-small cell lung cancer, pleomorphic rhabdomyosarcoma, type 2 diabetes, pancreatic ductal adenocarcinoma, Alzheimer's disease, bipolar disorder, and metabolic dysfunction-associated steatotic liver disease.
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JNK3 inhibitor-9
0 ImagesCat. No.: HY-168859JNK3 inhibitor-9 (Compound 24a) is a potent, selective and BBB-permeable JNK3 inhibitor with an IC50 value of 12 nM. JNK3 inhibitor-9 also potently inhibits GSK3α/β (IC50s: 14 and 35 nM, respectively) involved in Tau phosphorylation. JNK3 inhibitor-9 reduces c-Jun and APP phosphorylation. JNK3 inhibitor-9 protects neurons from Aβ1-42 toxicity.
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GCN2/GSK3α-IN-1
0 ImagesCat. No.: HY-208758CAS No.: 1627180-54-4GCN2/GSK3α-IN-1 is a GCN2 and GSK3α inhibitor with an IC50 of less than 1 μM for both targets. GCN2/GSK3α-IN-1 can be used in cancer research.
