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-11012
    TDZD-8 Inhibitor 99.81%
    TDZD-8 是 GSK-3β 的抑制剂，IC50 为 2 μM；TDZD-8 对 Cdk-1/cyclin?B，CK-II，PKA 和 PKC 的作用较弱，IC50 值均 >100 μM。
    TDZD-8
  • HY-13076
    CHIR-98014 Inhibitor ≥98.0%
    CHIR-98014 是一种有效的，细胞通透的 GSK-3 抑制剂，可抑制 GSK-3α 和 GSK-3β 的活性，IC50 值分别为 0.65 和 0.58 nM；CHIR-98014 对 cdc2 和 erk2 的作用较弱。
    CHIR-98014
  • HY-15761
    AZD2858 Inhibitor 98.42%
    AZD2858 是一种有效的，可口服的 GSK-3 抑制剂，可以抑制 GSK-3α 和 GSK-3β 的活性，IC50 值分别为 0.9 和 5 nM，可用于骨折愈合的研究。
    AZD2858
  • HY-113914
    9-ING-41 Inhibitor 98.83%
    9-ING-41 (Elraglusib) 是一种基于马来酰亚胺的 ATP 竞争性和选择性的糖原合酶激酶-3β (GSK-3β) 抑制剂，IC50 为 0.71 μM。9-ING-41 显著导致癌细胞的细胞周期停滞，自噬和凋亡。9-ING-41 具有抗癌活性，并具有增强化疗活性分子抗肿瘤作用的潜力。
    9-ING-41
  • HY-W094474
    Lithium chloride hydrate

    氯化锂 水合物

    		Inhibitor
    Lithium chloride hydrate 是一种具有口服活性的情绪稳定剂，是一种有效的病毒抑制剂和免疫调节剂。Lithium chloride hydrate 通过抑制 GSK3β 和促进神经发生而具有抗抑郁活性。Lithium chloride hydrate 可减轻认知功能障碍和急性躁狂和抑郁症状。Lithium chloride hydrate 可用于病毒感染和阿尔茨海默病的研究。
    Lithium chloride hydrate
  • HY-10014
    R547 Inhibitor 99.57%
    R547 是一种高效、选择性的，口服有效的 ATP 竞争性的 CDK 抑制剂，对 CDK1/cyclin B、 CDK2/cyclin E 和 CDK4/cyclin D1 作用的 Ki 值分别为 2 nM、3 nM、1 nM。
    R547
  • HY-100207
    CP21R7 Inhibitor 99.63%
    CP21R7 是一种有效的 GSK-3β 抑制剂，IC50 值为 1.8 nM；CP21R7 同时可抑制 PKCα，IC50 值为 1900 nM。
    CP21R7
  • HY-15438
    SB 415286 Inhibitor 99.57%
    SB 415286 是一种有效的 GSK-3α 抑制剂，IC50 值为 77.5 nM，Ki 值为 30.75 nM；SB 415286 对人 GSK-3α 和 GSK-3β 的抑制效果相同。
    SB 415286
  • HY-15449
    Kaempferide

    山奈素

    		Activator 99.35%
    Kaempferide 是具有口服活性的可以从 Hippophae rhamnoides L 中分离得到的黄酮醇。Kaempferide 有抗癌、抗炎症、抗氧化、抗糖尿病、抗肥胖、抗高血压和神经保护等活性。Kaempferide 可以诱导细胞凋亡 (apoptosis)。Kaempferide 通过抗氧化来促进成骨，可以用于骨质疏松的研究。
    Kaempferide
  • HY-19807
    Indirubin-3'-monoxime Inhibitor 99.89%
    Indirubin-3'-monoxime 是一种有效的 GSK-3β 抑制剂，对 5-Lipoxygenase 的抑制作用较弱，IC50 值分别为 22 nM 和 7.8-10 µM；Indirubin-3'-monoxime 同时对 CDK5/p25 和 CDK1/cyclin B 也有较强作用，IC50 值分别为 100 和 180 nM。
    Indirubin-3'-monoxime
  • HY-10182G
    Laduviglusib (GMP) Inhibitor
    Laduviglusib (CHIR-99021) (GMP) 是 GMP 级别的 Laduviglusib (HY-10182)。GMP 级别的小分子可用做细胞疗法中的辅助试剂。Laduviglusib 是一种有效的，选择性的，具有口服活性的 GSK-3α/β 抑制剂。
    Laduviglusib (GMP)
  • HY-15504
    RGB-286638 Inhibitor 99.84%
    RGB-286638 是一种有效的 CDK 抑制剂，抑制 cyclin T1-CDK9，cyclin B1-CDK1，cyclin E-CDK2，cyclin D1-CDK4，cyclin E-CDK3 和 p35-CDK5 活性，IC50 分别为 1，2，3，4，5 和 5 nM；同时可抑制 GSK-3β，TAK1，Jak2 和 MEK1，IC50 值分别为 3，5，50，和 54 nM。
    RGB-286638
  • HY-12524
    Bikinin Inhibitor 99.96%
    Bikinin 是一种非甾体类的，植物性 GSK-3/Shaggy-like kinases 的 ATP 竞争性抑制剂，可激活 BR 信号通路。
    Bikinin
  • HY-131447
    KY19382 Inhibitor ≥98.0%
    KY19382 是一种有效的和具有口服活性的 CXXC5-DVL 和 GSK3β 的双重抑制剂，IC50 值分别为 19 和 10 nM。KY19382 通过对 CXXC5-DVL 相互作用和 GSK3β 活性的抑制作用激活 Wnt/β-catenin 信号传导。KY19382 可用于高脂饮食 (HFD) 诱发的代谢性疾病的研究。
    KY19382
  • HY-116830
    BRD0705 Inhibitor 99.80%
    BRD0705 是一种有效的，具有旁系选择性和口服活性的 GSK3α 抑制剂，IC50 为 66 nM，Kd 为 4.8 μM。 BRD0705 与 GSK3β (IC50 为 515 nM) 相比，对 GSK3α 的选择性更高 (8 倍)。BRD0705 可用于急性髓细胞性白血病的研究。
    BRD0705
  • HY-145669
    DIF-3 Activator 98.07%
    DIF-3 通过激活 GSK-3β 促进cyclin D1 和 c-Myc 的降解，从而降低 cyclin D1 和 c-Myc 的表达水平。DIF-3 抑制 DLD-1 细胞中的 Wnt/β-catenin 信号通路相关蛋白。DIF-3通过诱导 cyclin D1 降解和抑制 cyclin D1 mRNA 表达对人宫颈癌细胞系HeLa发挥强大的抗增殖作用。
    DIF-3
  • HY-124607B
    BRD3731 Inhibitor 98.21%
    BRD3731 是一种选择性的 GSK3β 抑制剂，抑制 GSK3β 和 GSK3α 的 IC50 值分别为 15 nM 和 215 nM。BRD3731 有潜力用于创伤后应激障碍 (PTSD) 精神障碍、糖尿病和神经退行性障碍的研究。
    BRD3731
  • HY-111379
    EHT 5372 Inhibitor 98.12%
    EHT 5372 是一种高效和选择性的 DYRK's 家族激酶抑制剂，对 DYRK1A，DYRK1B，DYRK2，DYRK3，CLK1，CLK2，CLK4，GSK-3α，和 GSK-3β 的 IC50 值分别为 0.22，0.28，10.8，93.2，22.8，88.8，59.0，7.44 和 221 nM。
    EHT 5372
  • HY-153089
    GSK3-IN-3 Inhibitor 98.80%
    GSK3-IN-3 是一种线粒体自噬 (mitophagy) 诱导剂，可诱导帕金依赖性线粒体自噬。GSK3-IN-3 也是一种 GSK-3 抑制剂，IC50 值为 3.01 μM。 GSK3-IN-3 具有非 ATP 和非底物竞争性，对 6-OHDA 有神经保护作用。
    GSK3-IN-3
  • 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
目录号 产品名 / 同用名 种属 表达系统
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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