2. Signaling Pathways
  3. PI3K/Akt/mTOR
    Stem Cell/Wnt
  4. GSK-3

GSK-3 (糖原合成酶激酶3)

Glycogen synthase kinase-3; Glycogen synthase kinase 3

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 亚型特异性产品:

GSK-3 Isoform Comparison
Cat. No. Product Name Effect Purity Chemical Structure
  • HY-137472
    SAR502250 Inhibitor 99.63%
    SAR502250 是一种有效的，选择性的，ATP竞争性，具有口服活性和可透过血脑屏障的 GSK3 抑制剂，对人 GSK-3β 的 IC50 值为 12 nM。SAR502250 显示出抗抑郁样活性。SAR502250 可用于研究阿尔茨海默症 (AD)。
    SAR502250
  • HY-15356
    BIO-acetoxime Inhibitor ≥98.0%
    BIO-acetoxime (BIA) 是一种有效、选择性的 GSK-3 抑制剂，对 GSK-3α/β 的 IC50 值均为 10 nM；BIO-acetoxime 具有抗惊厥和抗感染作用。
    BIO-acetoxime
  • HY-107531
    A 1070722 Inhibitor 99.95%
    A 1070722 是一个高效、选择性的糖原合成酶激酶 3 (GSK-3) 抑制剂，对 GSK-3α 和 GSK-3β 作用的 Ki 为 0.6 nM。A 1070722 能穿透血脑屏障并在脑区积聚，具有作为定量测定脑部 GSK-3 的 PET 放射性跟踪剂的潜力。
    A 1070722
  • HY-130795
    GSK-3β inhibitor 2 Inhibitor
    GSK-3β inhibitor 2 (Compound 3) 是一种有效，选择性和口服活性的 GSK-3β 抑制剂，IC50 为 1.1 nM。GSK-3β inhibitor 2 可以穿越血脑屏障。GSK-3β inhibitor 2 有用于阿尔茨海默氏病的潜力。
    GSK-3β inhibitor 2
  • HY-139324
    Cu(II)GTSM Inhibitor
    Cu(II)GTSM 是一种细胞通透性铜复合物，可显著抑制 GSK3β。Cu(II)GTSM 抑制 Amyloid-β 寡聚体 (AβOs)，降低 tau 磷酸化。Cu(II)GTSM 也降低了 Amyloid-β 三聚体的丰度。Cu(II)GTSM 可以被作为一种潜在的抗癌和抗菌剂。
    Cu(II)GTSM
  • HY-122026
    PF-04802367 Inhibitor 98.84%
    PF-04802367 (PF-367) 是一种高选择性 GSK-3 抑制剂，对 GSK-3β 酶的 IC50 为 2.1 nM。PF-04802367 具有理想的中枢神经系统 (CNS) 特性和效力。PF-04802367 抑制两种 GSK-3 亚型（GSK-3α 和 GSK-3β）效果差不多， IC50 值分别为 10.0 和 9.0 nM。
    PF-04802367
  • HY-103647
    K00546 Inhibitor 98.08%
    K00546 是一种有效的 CDK1 和 CDK2 抑制剂，对 CDK1/cyclin B 和 CDK2/cyclin A 的 IC50 分别为 0.6 nM 和 0.5 nM。K00546 也是一种有效的 CDC2 样激酶 1 (CLK1) 和 CLK3 抑制剂，IC50 分别为 8.9 nM 和 29.2 nM。
    K00546
  • HY-13973A
    GSK-3 inhibitor 1 Inhibitor 99.89%
    GSK-3 inhibitor 1 (化合物 core 3) 是一种 GSK-3 抑制剂。GSK-3 inhibitor 1 能诱导干细胞/祖细胞自我更新 (如诱导干/祖细胞增殖，同时在子代细胞中维持分化成组织细胞的能力)。
    GSK-3 inhibitor 1
  • HY-B0712
    Ceftriaxone

    头孢曲松

    		Inhibitor 98.19%
    Ceftriaxone (Ro 13-9904 free acid) 是一种广谱 β-内酰胺类三代头孢菌素类抗生素，对多种革兰氏阴性菌和阳性菌有良好的抗菌活性。Ceftriaxone 是 GSK3β 的共价抑制剂，IC50 值为 0.78 mM。Ceftriaxone 是 Aurora B 的抑制剂。Ceftriaxone 具有抗炎、抗肿瘤和抗氧化活性。Ceftriaxone 可用于治疗细菌性感染和脑膜炎的研究。
    Ceftriaxone
  • HY-108359
    Alsterpaullone Inhibitor 98.38%
    Alsterpaullone (9-Nitropaullone) 是一种高效的 CDK 抑制剂，作用于 CDK1/cyclin B、CDK2/cyclin A、CDK2/cyclin E 和 CDK5/p35 的 IC50 值分别为 35 nM、15 nM、200 nM 和 40 nM。Alsterpaullone 是 ATP 竞争性的 GSK-3alpha/GSK-3beta 抑制剂，且作用的 IC50 值都为 4 nM。Alsterpaullone 具有抗肿瘤活性，有用于神经退行性和增生性疾病研究的潜力。Alsterpaullon 诱导白血病细胞凋亡 (apoptosis)。
    Alsterpaullone
  • HY-N8423
    α-Amyrin

    α-香树脂醇

    		Activator 99.94%
    α-Amyrin 是一种具有口服活性的五环三萜类化合物。α-Amyrin 可激活 ERK 和 GSK-3β 信号通路。α-Amyrin 可应用于高果糖饮食诱导的代谢综合征和低胆碱能神经传递所致的认知功能障碍的研究。
    α-Amyrin
  • HY-129492
    GNF4877 Inhibitor 99.32%
    GNF4877是 DYRK1A 和 GSK3β 的有效抑制剂，IC50 值分别为 6 nM 和 16 nM，可导致 NFATc 核输出受阻并增加 β 细胞增殖 (对小鼠 β (R7T1) 细胞的 EC50 值为 0.66 μM)。
    GNF4877
  • HY-117025A
    Manzamine A hydrochloride Inhibitor 99.66%
    Manzamine A hydrochloride 是一种具有口服活性的 β-carboline 生物碱，抑制 GSK-3β 和 CDK-5 的 IC50 值为 10.2 μM 和 1.5 μM。Manzamine A hydrochloride 靶向胰腺癌细胞的 vacuolar ATPases 并抑制自噬 (autophagy)。Manzamine A hydrochloride 具有抗疟和抗癌活性。Manzamine A hydrochloride 对 HSV-1 具有较强的活性。
    Manzamine A hydrochloride
  • HY-126144
    GSK-3β inhibitor 1 Inhibitor 98.04%
    GSK-3β inhibitor 1 (compound 3a) 是糖原合成酶激酶 3β (GSK-3β)的抑制剂，可用于糖尿病的研究，其对 GSK-3β 的 IC50 值为 4.9 nM。
    GSK-3β inhibitor 1
  • HY-103221
    MeBIO Inhibitor ≥98.0%
    MeBIO 是一种有效的 AhR 激动剂，其 IC50 分别为 44 μM (GSK-3) 和 55 μM (CDK1/cyclin b). MeBIO 对 GSK-3β 不起作用。
    MeBIO
  • HY-154851
    GSK-3 inhibitor 3 Inhibitor 98.72%
    GSK-3 inhibitor 3 是 GSK-3 的选择性、具有口服活性和脑渗透性的抑制剂，对 GSK-3α 和 GSK-3β 的 IC50s 分别为 0.35 nM 和 0.25 nM。在三重转基因小鼠阿尔茨海默病模型中，GSK-3 inhibitor 3 降低 Tau 蛋白 (tau protein) S396 磷酸化水平，IC50为 10 nM。GSK-3 inhibitor 3 可用于神经系统疾病研究。
    GSK-3 inhibitor 3
  • HY-108264
    TCS 21311 Inhibitor 99.18%
    TCS 21311 (NIBR3049) 是一种有效的高选择性 JAK3 抑制剂，其 IC50 为 8 nM，它的选择性是 JAK1，JAK2 和 TYK2 的100倍以上。TCS 21311 (NIBR3049) 抑制 PKCα，PKCθ 和 GSK3β，IC50 值分别为 13、68 和 3 nM。
    TCS 21311
  • HY-134575
    C24:1-Ceramide ≥99.0%
    C24:1-神经酰胺是最丰富的天然存在的神经酰胺之一。神经酰胺调节许多不同的生物活动，例如细胞凋亡 (apoptosis)、细胞分化、平滑肌细胞增殖和线粒体呼吸链的抑制。
    C24:1-Ceramide
  • HY-121035
    7BIO Inhibitor ≥98.0%
    7BIO (7-Bromoindirubin-3-Oxime) 是靛玉红的衍生物。7BIO (7-Bromoindirubin-3-Oxime) 对细胞周期蛋白依赖性激酶5 (CDK5) 和糖原合酶激酶-3β (GSK3β) 具有抑制作用。7BIO (7-Bromoindirubin-3-Oxime) 抑制 Aβ 寡聚体诱导的神经炎症、突触损伤、tau 过度磷酸化、星形胶质细胞和小胶质细胞的活化，并减轻 Aβ 寡聚体诱导的小鼠认知障碍[1]。
    7BIO
  • HY-112392
    GSK-3 Inhibitor XIII Inhibitor 98.61%
    GSK-3 Inhibitor XIII 是一种有效的 ATP 竞争性 GSK-3 抑制剂，Ki 为 24 nM。
    GSK-3 Inhibitor XIII
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目录号 产品名 / 同用名 应用 反应物种
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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

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