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]
-
GSK-3α Related Products (49)
Related Products (49)
-
Recombinant Proteins (1)
-
PF-04802367
0 ImagesSynonyms: PF-367PF-04802367 (PF-367) is a highly selective GSK-3 inhibitor with an IC50 of 2.1 nM based on a recombinant human GSK-3β enzyme assay and 1.1 nM based on ADP-Glo assay. PF-04802367 shows desirable central nervous system (CNS) properties and potency. PF-04802367 is equally effective at inhibition of the two known GSK-3 isoforms (GSK-3α and GSK-3β) with IC50 values of 10.0 and 9.0 nM in mobility shift assays, respectively.
-
A 1070722
0 ImagesA 1070722 is a potent and selective glycogen synthase kinase 3 (GSK-3) inhibitor, with a Ki of 0.6 nM for both GSK-3α and GSK-3β. A 1070722 can penetrate the blood-brain barrier (BBB) and accumulates in brain regions, thus potential for PET radiotracer for the quantification of GSK-3 in brain. A 1070722 decreases spontaneous locomotion.
-
BRD3731
0 ImagesBRD3731 is a selective GSK3β inhibitor, with IC50s of 15 nM and 215 nM for GSK3β and GSK3α, respectively. BRD3731 is potentail for the research of post-traumatic stress disorder (PTSD), psychiatric disorder, diabetes, and neurodegenerative disorders.
-
PPA24
0 ImagesPPA24 is a PP2A activator with a KD of 8.465 μM for PP2ACα. PPA24 induces cancer cell death via apoptosis. PP2ACα induces ROS generation and decreases the level of c-Myc expression. PPA24 can be used to study colorectal cancer (CRC), Folinic acid (HY-17556), 5-Fluorouracil (HY-90006), and Oxaliplatin (HY-17371) (FOLFOX)-resistant CRC, and melanoma cancer.
-
Benarthin
0 ImagesCat. No.: HY-117738CAS No.: 143651-45-0Benarthin is an orally active Pyroglutamyl peptidase inhibitor, THY1 inhibitor (with a Kd value of 5.13e-08 M) and competitive PGP-1 inhibitor (Ki = 1.2 µM). Benarthin is isolated from the culture broth of Streptomyces xanthophaeus MJ244-SF1. Benarthin disrupts the THY1-SFRP1 interaction, inhibits the activation of the GSK3α/β-β-catenin pathway, and reduces the upregulation of FASLG. Benarthin attenuates urothelial anoikis and reduces cell Apoptosis. Benarthin possesses iron-chelating activity. Benarthin maintains urothelial barrier integrity and blocks the pathological cascade of renal interstitial fibroblasts induced by HAP stimulation. Benarthin can be used in studies related to kidney stones.
-
GSK-3 inhibitor 3
0 ImagesGSK-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-3β inhibitor 23
0 ImagesCat. No.: HY-170491Purity: 99.88%GSK-3β inhibitor 23 (Compound 11726169) is the inhibitor for glycogen synthase kinase-3, that inhibits GSK-3β and GSK-3α with IC50 of 12.1 nM and 18.8 nM. GSK-3β inhibitor 23 exhibits antiviral activity against HIV 1. GSK-3β inhibitor 23 exhibits good metabolic stablility in mouse/human liver microsomes and plasma, but poor Caco-2 permeability (which predicts low oral bioavailability).
-
(E/Z)-BIO-acetoxime
0 ImagesSynonyms: GSK-3 Inhibitor X(E/Z)-BIO-acetoxime (GSK-3 Inhibitor X) is a potent and selective GSK-3α/β inhibitor, with an IC50 of 10 nM. (E/Z)-BIO-acetoxime shows more than 200-flod selectivity over CDK5/p25, CDK2/cyclin A and CDK1/cyclin B (IC50=2.4, 4.3, 63 μM).
-
GSK-3 inhibitor 4
0 ImagesGSK-3 inhibitor 4 is an orally active and brain-penetrant inhibitor of GSK-3, CDK2, and CDK5, with IC50 values of 0.56 nM (GSK-3β), 0.45 nM (GSK-3α), 0.47 μM, and 0.68 μM, respectively. GSK-3 inhibitor 4 effectively reduces the phosphorylation level of Tau protein. GSK-3 inhibitor 4 can be used in Alzheimer's disease (AD) studies.
-
GSK-3β inhibitor 13
0 ImagesGSK-3β inhibitor 13 (compound 47) is an orally active and potent GSK-3β inhibitor with blood-brain permeability. GSK-3β inhibitor 13 inhibits GSK-3β and GSK-3α with IC50s of 0.73 nM and 0.35 nM, respectively. GSK-3β inhibitor 13 significantly decreases the phosphorylation of tau (IC50=58 nM), which leads the formation of the neurofibrillary tangles associated with Alzheimer's disease.
-
(R)-BRD3731
0 Images(R)-BRD3731 is a GSK3 inhibitor extracted from patent US20160375006A1, compound example 273, has IC50s of 1.05 and 6.7 μM for GSK3β and GSK3α, respectively.
-
CDK8-IN-12
0 ImagesCDK8-IN-12 is an orally active, potent CDK8 inhibitor with a Ki of 14 nM. CDK8-IN-12 has off-target kinase inhibition on GSK-3α, GSK-3β, PCK-θ with Kis of 13 nM, 4 nM, 109 nM, respectively. CDK8-IN-12 shows potent anti-proliferative effects selectively on MV4-11 cell. CDK8-IN-12 is an anti-cancer agent.
-
GS87
0 ImagesGS87 is a highly specific and potent GSK3 inhibitor with IC50s of 415nM and 521nM for GSK3α and GSK3β, respectively. GS87 induces differentiation of acute myeloid leukemia (AML) cell lines by effectively activating GSK3-dependent signaling components including MAPK signaling. GS87 modulates key GSK3 target proteins involved in cell proliferation and differentiation more effectively than Lithium and SB415285 (SB). GS87 has the potential for acting as a differentiation agent for non-promyelocytic AML research.
-
ES-072
0 ImagesES-072 is an orally effective selective EGFR mutant (EGFR-T790M) inhibitor. ES-072 activates GSK3α by inhibiting EGFR-T790M activity, which promotes phosphorylation of PD-L1 at Ser279 and Ser283. The phosphorylated PD-L1 recruits the E3 ubiquitin ligase ARIH1, leading to ubiquitination and proteasomal degradation of PD-L1. This mechanism not only reduces cancer cell growth but also enhances anti-tumor immune response by lowering PD-L1 levels. ES-072 can be used to inhibit proliferation in non-small cell lung cancer (NSCLC) cells.
-
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.
-
CDK5-IN-4
0 ImagesCat. No.: HY-161595CAS No.: 1212711-91-5
-
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.
