1. PI3K/Akt/mTOR
  2. mTOR

mTOR

mTOR (mammalian target of Rapamycin) is a protein that in humans is encoded by the mTOR gene. mTOR is a serine/threonine protein kinase that regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, and transcription. mTOR belongs to the phosphatidylinositol 3-kinase-related kinase protein family. mTOR integrates the input from upstream pathways, including insulin, growth factors and amino acids. mTOR also senses cellular nutrient, oxygen, and energy levels. The mTOR pathway is dysregulated in human diseases, such as diabetes, obesity, depression, and certain cancers. Rapamycin inhibits mTOR by associating with its intracellular receptor FKBP12. The FKBP12-rapamycin complex binds directly to the FKBP12-Rapamycin Binding (FRB) domain of mTOR, inhibiting its activity.

View mTOR Pathway Map

mTOR Isoform Specific Products:

  • mTOR

  • mTORC1

  • mTORC2

mTOR 相关产品 (55):

Cat. No. Product Name Effect Purity
  • HY-10219
    Rapamycin Inhibitor 99.39%
    Rapamycin 是一种特异性的 mTOR 抑制剂,IC50 为 0.1 nM。
  • HY-10218
    Everolimus Inhibitor 98.79%
    Everolimus 是一种高特异性的靶向试剂,使离体的 FKBP-12,或 FKBP-12 复合体结合到 mTORIC50 为 5 到 6 nM。
  • HY-13328
    INK-128 Inhibitor 99.06%
    INK-128 是一种有效的,选择性的 mTOR 抑制剂,IC50 值为 1 nM,对 PI3K 亚型也有作用。INK-128 抑制 mTORC1/2
  • HY-13003
    Torin 1 Inhibitor 99.16%
    Torin 1 是一种有效的 mTOR 抑制剂,IC50 为 3 nM。Torin 1 抑制 mTORC1/2 复合物,IC50 值在 2 和 10 nM 之间。
  • HY-B0795
    MHY1485 Activator 99.05%
    MHY1485 是一种 mTOR 激活剂,也是一种自噬 (autophagy) 抑制剂。MHY1485 增强 mTORC1,但在肥大细胞膜上随着 FcεRI 交联后降低 mTORC2 信号传导。
  • HY-N4315
    Pomiferin Inhibitor
    Pomiferin 是从 Maclura pomifera 的果实中得到的黄酮类化合物,为 HDACmTOR 的抑制剂,IC50 值分别为 1.05 μM 和 6.2 µM。
  • HY-107365
    PQR-530 Inhibitor
    PQR-530 是一种有效,可口服,可透过血脑屏障的,广谱的 PI3K/mTORC1/2 双重抑制剂,具有抗肿瘤活性。
  • HY-107363
    FT-1518 Inhibitor
    FT-1518 是一种选择性的,可口服的,有效的新一代 mTORC1mTORC2 抑制剂,具有抗肿瘤的活性。
  • HY-10422
    AZD-8055 Inhibitor 98.60%
    AZD-8055 是一种ATP竞争性的 mTOR 抑制剂,IC50 为 0.8 nM。AZD-8055 抑制 mTORC1mTORC2
  • 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-15247
    AZD2014 Inhibitor 98.80%
    AZD2014 是一种ATP竞争性的 mTOR 抑制剂,IC50 为 2.81 nM。AZD2014 抑制 mTORC1mTORC2 复合物。
  • HY-10474
    PP 242 Inhibitor
    PP 242 是第一个选择性的ATP竞争性的 mTOR 抑制剂,IC50 为 8 nM。PP242 抑制 mTORC1mTORC2IC50 分别为 30 nM 和 58 nM。
  • 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-50910
    Temsirolimus Inhibitor 99.25%
    Temsirolimus 是一种 mTOR 抑制剂,IC50 值为 1.76 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-13002
    Torin 2 Inhibitor 99.89%
    Torin 2 是一种 mTOR 抑制剂,抑制细胞内 mTOR 活性,EC50 为 0.25 nM,比作用于 PI3K (EC50: 200 nM) 选择性高 800 倍。体外酶实验中,Torin 2 还抑制 DNA-PKIC50 为 0.5 nM。Torin 2 抑制 mTORC1mTORC2
  • 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。
  • HY-50908
    Deforolimus Inhibitor 98.46%
    Deforolimus (AP23573; MK-8669) 是一种有效和选择性 mTOR 抑制剂,在 HT-1080 细胞中抑制 S6 磷酸化的 IC50 值为 0.2 nM。
  • HY-N0109
    Salidroside Activator 98.46%
    Salidroside 是一种脯氨酰内肽酶 (prolyl endopeptidase) 抑制剂。Salidroside 可通过激活 mTOR 信号缓解肿瘤恶病质小鼠模型中的恶病质症状。
  • HY-50710
    KU-0063794 Inhibitor 99.23%
    KU-0063794 是一种有效的,特异性的 mTOR 抑制剂,能够抑制 mTORC1mTORC2IC50 值均约为 10 nM;对 PI3Ks 无作用。
mtor-map.png

The mammalian target of rapamycin (mTOR) signaling pathway integrates both intracellular and extracellular signals and serves as a central regulator of cell metabolism, growth, proliferation and survival[1]. mTOR is the catalytic subunit of two distinct complexes called mTORC1 and mTORC2. mTORC1 comprises DEPTOR, PRAS40, RAPTOR, mLST8, mTOR, whereas mTORC2 comprises DEPTOR, mLST8, PROTOR, RICTOR, mSIN1, mTOR[2]. Rapamycin binds to FKBP12 and inhibits mTORC1 by disrupting the interaction between mTOR and RAPTOR. mTORC1 negatively regulates autophagy through multiple inputs, including inhibitory phosphorylation of ULK1 and TFEB. mTORC1 promotes protein synthesis through activation of the translation initiation promoter S6K and through inhibition of the inhibitory mRNA cap binding 4E-BP1, and regulates glycolysis through HIF-1α. It promotes de novo lipid synthesis through the SREBP transcription factors. mTORC2 inhibits FOXO1,3 through SGK and Akt, which can lead to increased longevity. The complex also regulates actin cytoskeleton assembly through PKC and Rho kinase[3]

 

Growth factors: Growth factors can signal to mTORC1 through both PI3K-Akt and Ras-Raf-MEK-ERK axis. For example, ERK and RSK phosphorylate TSC2, and inhibit it.

 

Insulin Receptor: The activated insulin receptor recruits intracellular adaptor protein IRS1. Phosphorylation of these 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 and triggers the Akt-dependent multisite phosphorylation of TSC2. TSC is a heterotrimeric complex comprised of TSC1, TSC2, and TBC1D7, and functions as a GTPase activating protein (GAP) for the small GTPase Rheb, which directly binds and activates mTORC1. mTORC2 primarily functions as an effector of insulin/PI3K signaling. 

 

Wnt: The Wnt pathway activates mTORC1. Glycogen synthase kinase 3β (GSK-3β) acts as a negative regulator of mTORC1 by phosphorylating TSC2. mTORC2 is activated by Wnt in a manner dependent on the small GTPase RAC1[4].

 

Amino acids: mTORC1 senses both lysosomal and cytosolic amino acids through distinct mechanisms. Amino acids induce the movement of mTORC1 to lysosomal membranes, where the Rag proteins reside. A complex named Ragulator, interact with the Rag GTPases, recruits them to lysosomes through a mechanism dependent on the lysosomal v-ATPase, and is essential for mTORC1 activation. In turn, lysosomal recruitment enables mTORC1 to interact with GTP-bound RHEB, the end point of growth factor. Cytosolic leucine and arginine signal to mTORC1 through a distinct pathway comprised of the GATOR1 and GATOR2 complexes.    

 

Stresses: mTORC1 responds to intracellular and environmental stresses that are incompatible with growth such as low ATP levels, hypoxia, or DNA damage. A reduction in cellular energy charge, for example during glucose deprivation, activates the stress responsive metabolic regulator AMPK, which inhibits mTORC1 both indirectly, through phosphorylation and activation of TSC2, as well as directly through the phosphorylation of RAPTOR. Sestrin1/2 are two transcriptional targets of p53 that are implicated in the DNA damage response, and they potently activate AMPK, thus mediating the p53-dependent suppression of mTOR activity upon DNA damage. During hypoxia, mitochondrial respiration is impaired, leading to low ATP levels and activation of AMPK. Hypoxia also affects mTORC1 in AMPK-independent ways by inducing the expression of REDD1, the protein products of which then suppress mTORC1 by promoting the assembly of TSC1-TSC2[2].

 

Reference:

[1]. Laplante M, et al.mTOR signaling at a glance.J Cell Sci. 2009 Oct 15;122(Pt 20):3589-94. 
[2]. Zoncu R, et al. mTOR: from growth signal integration to cancer, diabetes and ageing.Nat Rev Mol Cell Biol. 2011 Jan;12(1):21-35. 
[3]. Johnson SC, et al. mTOR is a key modulator of ageing and age-related disease.Nature. 2013 Jan 17;493(7432):338-45.
[4]. Shimobayashi M, et al. Making new contacts: the mTOR network in metabolism and signalling crosstalk.Nat Rev Mol Cell Biol. 2014 Mar;15(3):155-62.

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