1. Signaling Pathways
  2. PI3K/Akt/mTOR
  3. 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

  • PI3KC3

PI3K 相关产品 (113):

Cat. No. Product Name Effect Purity
  • HY-19312
    3-Methyladenine Inhibitor 99.84%
    3-Methyladenine是 PI3K 的抑制剂。它通过抑制class III PI3K广泛作为自噬 (autophagy) 的抑制剂使用。
  • HY-10108
    LY294002 Inhibitor 99.95%
    LY294002 是一种广谱 PI3K 抑制剂,抑制 PI3Kα, PI3KδPI3KβIC50 分别为 0.5, 0.57, 0.97 μM。LY294002 也可抑制 CK2 的活性,IC50 为 98 nM。
  • HY-10197
    Wortmannin Inhibitor 99.85%
    Wortmannin 是一种多靶点抑制剂。Wortmannin 抑制 PI3KMLCKDNA-PKATMATRPolo-like kinase 3 (Plk3),IC50 分别为 3 nM,200 nM,16 nM,150 nM,1.8 μM 和 48 nM。
  • HY-15244
    Alpelisib Inhibitor 99.90%
    Alpelisib (BYL-719) 是有效,选择性的 PI3Kα 抑制剂,IC50 为5 nM。
  • HY-70063
    Buparlisib Inhibitor 99.90%
    Buparlisib (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-15837
    SAR-260301 Inhibitor 99.74%
    SAR-260301 是一种选择性 PI3Kβ 抑制剂,IC50 为 23 nM。
  • HY-13334A
    BGT226 Inhibitor
    BGT226 (NVP-BGT226) 是一种 PI3K (针对 PI3KαPI3KβPI3KγIC50分别是4 nM,63 nM,38 nM ) /mTOR 双抑制剂,对人头颈癌细胞具有较强的生长抑制活性。
  • HY-111508
    PI3K/mTOR Inhibitor-2 Inhibitor
    PI3K/mTOR Inhibitor-2 是一种有效的双重 pan-PI3K/mTOR 抑制剂,抑制 PI3Kα/PI3Kβ/PI3Kδ/PI3KγIC50 值为 3.4/34/16/1 nM,mTORIC50 值为 4.7 nM。抗肿瘤活性。
  • HY-15346
    Copanlisib Inhibitor 98.91%
    Copanlisib (BAY 80-6946) 是一种 ATP竞争,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。
  • 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
    Idelalisib Inhibitor 99.98%
    Idelalisib (CAL-101) 是一种高选择性和有效的 p110δ 抑制剂,IC50为2.5 nM,比p110δ和其他PI3K class I酶的选择性高40 到 300。
  • HY-18085
    Quercetin Inhibitor >98.0%
    Quercetin是一种天然黄酮类化合物,可激活或抑制许多蛋白质的活性。 槲皮素可激活SIRT1,也可抑制 PI3K,抑制PI3K γ,PI3K δ,PI3K β的 IC50 分别为2.4 μM, 3.0 μM, 5.4 μM。
  • HY-50673
    Dactolisib Inhibitor 99.13%
    Dactolisib (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。Dactolisib (BEZ235) 抑制 mTORC1mTORC2
  • HY-50094
    Pictilisib Inhibitor 99.62%
    Pictilisib (GDC-0941) 是有效的 PI3Kα/δ 抑制剂,IC50为 3 nM;对110β (11倍) 和 p110γ (25倍) 具有适度的选择性。
  • HY-12481
    SAR405 Inhibitor 99.94%
    SAR405是 PIK3C3/Vps34 的抑制剂,IC50为1.2 nM。SAR405可防止自噬并与肿瘤细胞中的MTOR抑制作用协同。
  • HY-P0175
    740 Y-P Activator
    740 Y-P (PDGFR 740Y-P) 是有效,可渗透细胞的 PI3K 活化物。
  • HY-12513
    LY3023414 Inhibitor 99.77%
    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-13522
    Fimepinostat Inhibitor 99.95%
    Fimepinostat (CUDC-907) 有效抑制 I 型 PI3K 及 I 和 II 型 HDAC 酶,作用于 PI3Kα/PI3Kβ/PI3Kδ 和 HDAC1/HDAC2/HDAC3/HDAC10 ,IC50 分别为 19/54/39 nM 和 1.7/5.0/1.8/2.8 nM。
  • HY-101562
    GDC-0077 Inhibitor 99.07%
    GDC-0077是具有潜在抗肿瘤活性的有口服的PI3K抑制剂。 来自专利WO 2017001645 A1,结构式I。
  • HY-17044
    Duvelisib Inhibitor 99.91%
    Duvelisib 是一种选择性 p100δ 抑制剂,作用于 p110δ, p110γ, p110β 和 p110α,IC50 分别为 2.5 nM,27.4 nM,85 nM 和 1602 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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