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 Related Products (55):

Cat. No. Product Name Effect Purity
  • HY-10219
    Rapamycin Inhibitor 99.39%
    Rapamycin is a specific mTOR inhibitor with IC50 of 0.1 nM.
  • HY-10218
    Everolimus Inhibitor 98.79%
    Everolimus is a targeted, highly specific agent with an IC50 for binding to isolated FKBP-12, or FKBP-12 complexed to mTOR of 5 to 6 nM, and no significant activity against other protein kinases.
  • HY-13328
    INK-128 Inhibitor 99.06%
    INK-128 is a potent and selective mTOR inhibitor with IC50 of 1 nM, > 200-fold less potent to class I PI3K isoforms, superior in blocking mTORC1/2 and sensitive to pro-invasion genes.
  • HY-13003
    Torin 1 Inhibitor 99.16%
    Torin 1 is a potent inhibitor of mTOR with an IC50 of 3 nM. Torin 1 inhibits both mTORC1/2 complexes with IC50 values between 2 and 10 nM.
  • HY-B0795
    MHY1485 Activator 99.05%
    MHY1485 is a mTOR activator, which also is an inhibitor of autophagy. MHY1485 increases mTORC1, but decreases mTORC2 signaling in mast cells following FcεRI cross-linking.
  • HY-N4315
    Pomiferin Inhibitor
    Pomiferin, a flavonoid from the fruits of Maclura pomifera, acts as an potential inhibitor of HDAC, with an IC50 of 1.05 μM, and also potently inhibits mTOR (IC50, 6.2 µM).
  • HY-107363
    FT-1518 Inhibitor
    FT-1518 is a new generation selective, potent and oral bioavailable mTORC1 and mTORC2 inhibitor, and exhibits antitumor activity.
  • HY-107365
    PQR-530 Inhibitor
    PQR-530 is a potent, oral and brain-penetrant dual pan-PI3K/mTORC1/2 inhibitor, exhibiting antitumor activity.
  • HY-10422
    AZD-8055 Inhibitor 98.60%
    AZD-8055 is a novel ATP-competitive inhibitor of mTOR kinase activity, with an IC50 of 0.8 nM. AZD-8055 inhibits both mTORC1 and mTORC2.
  • HY-50673
    BEZ235 Inhibitor 98.83%
    BEZ235 is a dual pan-class I PI3K and mTOR kinase inhibitor with IC50 of 4 nM/5 nM/7 nM/75 nM, and 20.7 nM for p110α/p110γ/p110δ/p110β and mTOR, respectively. BEZ235 inhibits mTORC1 and mTORC2.
  • HY-15247
    AZD2014 Inhibitor 98.80%
    AZD2014 is an ATP competitive mTOR inhibitor with IC50 of 2.81 nM. AZD2014 inhibits both mTORC1 and mTORC2 complexes.
  • HY-10474
    PP 242 Inhibitor
    PP 242 is the first selective and ATP competitive mTOR inhibitor with an IC50 of 8 nM. PP242 inhibits both mTORC1 and mTORC2 with IC50s of 30 nM and 58 nM, respectively.
  • HY-12513
    LY3023414 Inhibitor 99.70%
    LY3023414 potently and selectively inhibits class I PI3K isoforms, DNA-PK, and mTORC1/2 with IC50s of 6.07 nM, 77.6 nM, 38 nM, 23.8 nM, 4.24 nM and 165 nM for PI3Kα, PI3Kβ, PI3Kδ, PI3Kγ, DNA-PK and mTOR, respectively. LY3023414 potently inhibits mTORC1/2 at low nanomolar concentrations.
  • HY-50910
    Temsirolimus Inhibitor 99.25%
    Temsirolimus is an inhibitor of mTOR with IC50 value of 1.76 μM.
  • HY-10297
    GSK2126458 Inhibitor 99.31%
    GSK2126458 is a highly selective and potent inhibitor of PI3K with Ki of 0.019 nM/0.13 nM/0.024 nM/0.06 nM and 0.18 nM/0.3 nM for p110α/β/δ/γ, mTORC1/2, respectively.
  • HY-13002
    Torin 2 Inhibitor 99.89%
    Torin 2 is an mTOR inhibitor with EC50 of 0.25 nM for inhibiting cellular mTOR activity, and exhibits 800-fold selectivity over PI3K (EC50: 200 nM). Torin 2 also inhibits DNA-PK with an IC50 of 0.5 nM in the cell free assay. Torin 2 can suppress both mTORC1 and mTORC2.
  • HY-15177
    PF-04691502 Inhibitor 99.49%
    PF-04691502 is a potent and selective inhibitor of PI3K and mTOR kinases with antitumor activity. PF-04691502 inhibits human and mouse PI3Kα with Ki of 1.8 and 1.2 nM, respectively, human PI3K isoforms β, δ, and γ with Ki of 2.1, 1.6, and 1.9 nM, respectively, and human mTOR with Ki of 16 nM.
  • HY-50908
    Deforolimus Inhibitor 98.46%
    Deforolimus (AP23573; MK-8669) is a potent and selective mTOR inhibitor; inhibits S6 phosphorylation with an IC50 of 0.2 nM in HT-1080 cells.
  • HY-N0109
    Salidroside Activator 98.46%
    Salidroside is a prolyl endopeptidase Inhibitor. Salidroside alleviates cachexia symptoms in mouse models of cancer cachexia via activating mTOR signalling.
  • HY-10115A
    PI-103 Hydrochloride Inhibitor 99.78%
    PI-103 Hydrochloride is a potent PI3K and mTOR inhibitor with IC50s of 8 nM, 88 nM, 48 nM, 150 nM, 20 nM, and 83 nM for p110α, p110β, p110δ, p110γ, mTORC1, and mTORC2. PI-103 also inhibits DNA-PK with an IC50 of 2 nM.
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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