1. PI3K/Akt/mTOR
  2. PI3K

PI3K

PI3K (Phosphoinositide 3-kinase), via phosphorylation of the inositol lipid phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), forms the second messenger molecule phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P3) which recruits and activates pleckstrin homology domain containing proteins, leading to downstream signalling events crucial for proliferation, survival and migration. Class I PI3K enzymes consist of four distinct catalytic isoforms, PI3Kα, PI3Kβ, PI3Kδ and PI3Kγ.

There are three major classes of PI3K enzymes, being class IA widely associated to cancer. Class IA PI3K are heterodimeric lipid kinases composed of a catalytic subunit (p110α, p110β, or p110δ; encoded by PIK3CA, PIK3CB, and PIK3CD genes, respectively) and a regulatory subunit (p85).

The PI3K pathway plays an important role in many biological processes, including cell cycle progression, cell growth, survival, actin rearrangement and migration, and intracellular vesicular transport.

View PI3K Pathway Map

PI3K Isoform Specific Products:

  • PI3Kα

  • PI3Kβ

  • PI3Kγ

  • PI3Kδ

  • PI3KC2α

  • PI3KC2β

  • PI3KC2γ

  • Vps34

  • PI3K

PI3K 相关产品 (103):

Cat. No. Product Name Effect Purity
  • HY-19312
    3-Methyladenine Inhibitor 99.84%
    3-Methyladenine 是一种有效的 autophagyPI3K 的抑制剂,能够通过抑制 PI3K 的活性,来阻断自噬,对 Vps34 和 PI3Kγ 的 IC50 值分别为 25 μM 和 60 μM。
  • HY-10108
    LY294002 Inhibitor 99.95%
    LY294002 是一种广谱 PI3K 抑制剂,抑制 PI3Kα/PI3Kδ/PI3KβIC50 分别为 0.5/0.57/0.97 μM,也抑制 CK2IC50 为 98 nM。
  • HY-10197
    Wortmannin Inhibitor 99.65%
    Wortmannin 是一种多靶点抑制剂,抑制 PI3K 和 MLCK 活性,IC50 分别为 3 nM 和 200 nM。并有效抑制 DNA-PK 和 ATM,IC50 分别为 16 nM 和 150 nM。Wortmannin 也是 Polo 样激酶 (Plk) 的有效抑制剂。
  • HY-15244
    BYL-719 Inhibitor 99.90%
    BYL-719 是一种有效的选择性 PI3Kα 抑制剂,IC50 为 5 nM。
  • HY-70063
    NVP-BKM120 Inhibitor 99.68%
    NVP-BKM120 是一种 pan-class I PI3K 抑制剂,作用于 p110α/p110β/p110δ/p110γIC50 分别为 52 nM/166 nM/116 nM/262 nM。
  • HY-111383
    LX2343 Inhibitor 99.86%
    LX2343 是一种 BACE1 酶抑制剂,IC50 值为 11.43±0.36 μM。LX2343 是一种非 ATP 竞争性的 PI3K 抑制剂,IC50 为 15.99±3.23 μM。LX2343 刺激自噬促进 清除。
  • HY-109068
    Parsaclisib Inhibitor
    Parsaclisib 是一种有效的,选择性的 PI3Kδ 抑制剂,在 1 mM ATP 条件下,IC50 值为 1 nM,对其选择性是对 PI3Kα,PI3Kβ,PI3Kγ 及其他 57 种激酶的约 20000 倍。
  • HY-111510
    IPI-3063 Inhibitor 98.80%
    IPI-3063 是一种有效的选择性 PI3K p110δ 抑制剂,IC50 为 2.5±1.2 nM。
  • HY-100716
    IPI549 Inhibitor 99.34%
    IPI549 是一种有效的选择性 PI3Kγ 抑制剂,IC50 为 16 nM。
  • HY-13026
    CAL-101 Inhibitor 99.98%
    CAL-101 是一种有效的选择性的 p110δ 抑制剂,IC50 为 2.5 nM,比作用于其他I类 PI3K 酶 (抑制 p110αp110βp110γ; IC50 分别为 820,565 和 89 nM) 选择性高 40 到 300 倍。
  • HY-50673
    BEZ235 Inhibitor 98.83%
    BEZ235 是一种双重的 pan-class I PI3KmTOR 抑制剂,作用于 p110α/γ/δ/βmTORIC50 分别为 4 nM/5 nM/7 nM/75 nM 和 20.7 nM。BEZ235 抑制 mTORC1mTORC2
  • HY-12481
    SAR405 Inhibitor 99.94%
    SAR405 是一种 PIK3C3/Vps34 抑制剂,IC50 为 1.2 nM。SAR405 是自噬机制的近端抑制剂。
  • HY-15346
    BAY 80-6946 Inhibitor 98.91%
    BAY 80-6946 是一种 ATP竞争性的选择性 I 型 PI3 激酶抑制剂,作用于 PI3KαPI3KδPI3KβPI3KγIC50 分别为 0.5,0.7,3.7 和 6.4 nM,作用于 mTOR,IC50为 45 nM。
  • HY-18085
    Quercetin Inhibitor >98.0%
    Quercetin 是一种天然黄酮类化合物,能够刺激 SIRT1,同时为 PI3K 的抑制剂,作用于 PI3K γ, PI3K δ 和 PI3K β, IC50 分别为 2.4±0.6 μM, 3.0±0.0 μM 和 5.4±0.3 μM。
  • HY-50094
    GDC-0941 Inhibitor 99.52%
    GDC-0941 是一种有效的 PI3Kα/δ 抑制剂,IC50 值为 3 nM;对 p110β 和 p110γ具有适度的选择性。
  • HY-12513
    LY3023414 Inhibitor 99.70%
    LY3023414 有效且选择性地抑制 PI3KαPI3KβPI3KδPI3KγDNA-PK,和 mTORIC50 分别为 6.07 nM,77.6 nM,38 nM,23.8 nM,4.24 nM,和 165 nM。在低纳摩尔浓度下,LY3023414 有效抑制 mTORC1/2
  • HY-12279
    TGR-1202 Inhibitor 98.55%
    TGR-1202 是一种新颖的 PI3Kδ 抑制剂,IC50EC50 值分别为 22.2 nM 和 24.3 nM;TGR-1202 同时可抑制 CK1εEC50 值为 6.0 μM。
  • HY-10297
    GSK2126458 Inhibitor 99.31%
    GSK2126458 是一种高选择性,有效的PI3K抑制剂,抑制 p110α/β/δ/γ,mTORC1/2 的活性,Ki 值分别为 0.019 nM/0.13 nM/0.024 nM/0.06 nM 和 0.18 nM/0.3 nM。
  • HY-N1412
    1,3-Dicaffeoylquinic acid Activator 99.82%
    1,3-Dicaffeoylquinic acid 是咖啡酰奎宁酸衍生物,能够激活PI3K/Akt
  • HY-15177
    PF-04691502 Inhibitor 99.49%
    PF-04691502 是一种有效的选择性的 PI3KmTOR 抑制剂。PF-04691502 抑制人和鼠 PI3Kα,Ki 分别为 1.8 和 1.2 nM,抑制人 PI3K 亚型 β,δ 和 γ,Ki 分别为 2.1,1.6 和 1.9 nM,抑制人 mTOR,Ki 为 16 nM。
pi3k-map.png

Phosphatidylinositol 3 kinases (PI3Ks) are a family of lipid kinases that integrate signals from growth factors, cytokines and other environmental cues, translating them into intracellular signals that regulate multiple signaling pathways. These pathways control many physiological functions and cellular processes, which include cell proliferation, growth, survival, motility and metabolism[1]

 

In the absence of activating signals, p85 interacts with p110 and inhibits p110 kinase activity. Following receptor tyrosine kinase (RTK) or G protein-coupled receptor (GPCR) activation, class I PI3Ks are recruited to the plasma membrane, where p85 inhibition of p110 is relieved and p110 phosphorylates PIP2 to generate PIP3. The activated insulin receptor recruits intracellular adaptor protein IRS1. Phosphorylation of IRS proteins on tyrosine residues by the insulin receptor initiates the recruitment and activation of PI3K. PIP3 acts as a second messenger which promotes the phosphorylation of Akt at Thr308 by PDK-1. RTK activation can also trigger Ras-Raf-MEK-ERK pathway. Activated Akt, ERK and RSK phosphorylate TSC2 at multiple sites to inhibit TSC1-TSC2-TBC1D7, which is the TSC complex that acts as a GTPase-activating protein (GAP) for the small GTPase RHEB. During inhibition of the TSC complex, GTP-loaded RHEB binds the mTOR catalytic domain to activate mTORC1. Glycogen synthase kinase 3β (GSK-3β) activates the TSC complex by phosphorylating TSC2 at Ser1379 and Ser1383. Phosphorylation of these two residues requires priming by AMPK-dependent phosphorylation of Ser1387. Wnt signaling inhibits GSK-3β and the TSC complex, and thus activates mTORC1. mTORC2 is activated by Wnt in a manner dependent on the small GTPase RAC1. Akt activation contributes to diverse cellular activities which include cell survival, growth, proliferation, angiogenesis, metabolism, and migration. Important downstream targets of Akt are GSK-3, FOXOs, BAD, AS160, eNOS, and mTOR. mTORC1 negatively regulates autophagy through multiple inputs, including inhibitory phosphorylation of ULK1, and promotes protein synthesis through activation of the translation initiation promoter S6K and through inhibition of the inhibitory mRNA cap binding 4E-BP1[1][2][3].

 

PI3Kδ is a heterodimeric enzyme, typically composed of a p85α regulatory subunit and a p110δ catalytic subunit. In T cells, the TCR, the costimulatory receptor ICOS and the IL-2R can activate PI3Kδ. In B cells, PI3Kδ is activated upon crosslinking of the B cell receptor (BCR). The BCR co-opts the co-receptor CD19 or the adaptor B cell associated protein (BCAP), both of which have YXXM motifs to which the p85α SH2 domains can bind. In lumphocytes, BTK and ITK contribute to the activation of PLCγ and promotes the generation of DAG and the influx of Ca2+, which in turn activate PKC and the CARMA1-, BCL 10- and MALT1 containing (CBM) complex. The resulting NF-κB inhibitor kinase (IKK) activation leads to the phosphorylation and the degradation of IκB, and to the nuclear accumulation of the p50-p65 NF-κB heterodimer. MyD88 is an adapter protein that mediates signal transduction for most TLRs and leads to activation of PI3K[4].

 

Reference:

[1]. Thorpe LM, et al. PI3K in cancer: divergent roles of isoforms, modes of activation and therapeutic targeting.Nat Rev Cancer. 2015 Jan;15(1):7-24. 
[2]. Vanhaesebroeck B, et al. PI3K signalling: the path to discovery and understanding.Nat Rev Mol Cell Biol. 2012 Feb 23;13(3):195-203. 
[3]. Fruman DA, et al. The PI3K Pathway in Human Disease.Cell. 2017 Aug 10;170(4):605-635.
[4]. Lucas CL, et al. PI3Kδ and primary immunodeficiencies.Nat Rev Immunol. 2016 Nov;16(11):702-714. 

Isoform Specific Products

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