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

mTOR

Mammalian target of Rapamycin

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 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.

Cat. No. Product Name Effect Purity Chemical Structure
  • HY-N15267
    Ovalitenone
    Inhibitor
    Ovalitenone is a flavonoid compound that can be isolated from the plant Millettia peguensis. It shows no cytotoxic effects on lung cancer H460 and A549 cells, but it significantly inhibits anchorage-independent growth, CSC-like phenotypes, colony formation, and the migration and invasion capabilities of cancer cells. Ovalitenone can significantly reduce the levels of N-cadherin, snail, and slug, while increasing E-cadherin, thus inhibiting the EMT pathway. Additionally, Ovalitenone suppresses the signaling pathways regulated by focal adhesion kinase (FAK), ATP-dependent tyrosine kinase (AKT), mammalian target of rapamycin (mTOR), and cell division cycle 42 (Cdc42).
    Ovalitenone
  • HY-N0022R
    Isoacteoside (Standard)
    Inhibitor
    Isoacteoside (Standard) is the analytical standard of Isoacteoside. This product is intended for research and analytical applications. Isoacteoside is a natural product that can significantly inhibit the formation of glycation end products. Isoacteoside Standard regulates the AKT/PI3K/m-TOR/NF-κB signaling pathway, induces apoptosis in OVCAR-3 cell. Isoacteoside Standard exhibits antitumor, anti-inflammatory, anti-obesity and neuroprotective activities.
    Isoacteoside (Standard)
  • HY-162025
    mTOR inhibitor-17
    Inhibitor
    mTOR inhibitor-17 (Compound 9e) is a selective inhibitor for mTOR. mTOR inhibitor-10 inhibits mTOR and PI3K-α, with IC50 of 0.68 and 1359 nM. mTOR inhibitor-10 inhibits proliferation of LNCaP with IC50 of 40 nM.
    mTOR inhibitor-17
  • HY-155475
    mTORC1-IN-2
    Inhibitor
    mTORC1-IN-2 (compound H3) is a NO donor compound that alleviates vasodilation and attenuates myocardial hypoxic injury. mTORC1-IN-2 upregulates TSC2-P expression and inhibits mTORC1 expression.
    mTORC1-IN-2
  • HY-W779800
    D-α-Hydroxyglutaric acid-13C5 disodium
    Inhibitor
    D-α-Hydroxyglutaric acid-13C5 disodium is the 13C-labeled D-α-Hydroxyglutaric acid (HY-113038). Radioactive isotopes labeled compounds can be used in metabolic analysis, allowing the movement of individual atoms to be precisely tracked and quantified.
    D-α-Hydroxyglutaric acid-<sup>13</sup>C<sub>5</sub> disodium
  • HY-164662
    mTOR inhibitor-24
    Inhibitor
    mTOR inhibitor-24 (comounp 9d) is a mTOR inhibitor, with IC50s of 0.34 nM (mTOR) and 324 nM (PI3K-α) respectively. mTOR inhibitor-24 inhibtis LNCaP cell proliferation (IC50: 180 nM).
    mTOR inhibitor-24
  • HY-117923
    PF-06465603
    Inhibitor
    PF-06465603 is a highly potent and selective ATP-competitive kinase inhibitor and a class 1 PI3K and mTOR inhibitor. PF-06465603 is a metabolite of PF-04691502 with a terminal carboxylic acid structure.
    PF-06465603
  • HY-171229
    1-Acetyl-DHAP
    Substrate
    1-Acetyl-DHA (Compound 7) is a substrate of the phosphotriesterase homology protein (PHP) and can be hydrolyzed by PHP with a kcat/km value of 100 M-1s-1. The level of 1-Acetyl-DHA is regulated by mTORC1 and is negatively correlated with the nuclear acetate level. 1-Acetyl-DHA plays an important role in cellular metabolism and the regulation of histone acetylation.
    1-Acetyl-DHAP
  • HY-112903A
    YW3-56 hydrochloride
    Inhibitor
    YW3-56 (hydrochloride) is a PAD inhibitor. YW3-56 (hydrochloride) activates p53 target genes. YW3-56 (hydrochloride) activates ATF and blocks autophagy flux. YW3-56 induces ER stress through the PERK-eIF2α-ATF4 signaling cascade and inhibits the mTOR signaling. YW3-56 (hydrochloride) inhibits triple-negative breast cancer.
    YW3-56 hydrochloride
  • HY-100542R
    D-α-Hydroxyglutaric acid disodium (Standard)
    Inhibitor
    D-α-Hydroxyglutaric acid (disodium) (Standard) is the analytical standard of D-α-Hydroxyglutaric acid (disodium). This product is intended for research and analytical applications. D-α-Hydroxyglutaric acid disodium (Disodium (R)-2-hydroxyglutarate) is the principal metabolite accumulating in neurometabolic disease D-2-hydroxyglutaric aciduria. D-α-Hydroxyglutaric acid disodium is a weak competitive antagonist of α-ketoglutarate (α-KG) and inhibits multiple α-KG-dependent dioxygenases with a Ki of 10.87 mM. D-α-Hydroxyglutaric acid disodium increases reactive oxygen species (ROS) production. D-α-Hydroxyglutaric acid disodium binds and inhibits ATP synthase and inhibits mTOR signaling[1][2][3][4][5].
    D-α-Hydroxyglutaric acid disodium (Standard)
  • HY-10115R
    PI-103 (Standard)
    Inhibitor
    PI-103 (Standard) is the analytical standard of PI-103. This product is intended for research and analytical applications. PI-103 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. PI-103 induces autophagy[1][2][3][4].
    PI-103 (Standard)
  • HY-162024
    mTOR inhibitor-16
    Inhibitor
    mTOR inhibitor-16 (Compound 9f) is a selective inhibitor for mTOR. mTOR inhibitor-10 inhibits mTOR and PI3K-α, with IC50 of 1.25 and 82 nM. mTOR inhibitor-10 inhibits proliferation of LNCaP with IC50 of 140 nM.
    mTOR inhibitor-16
  • HY-164385
    NSC126405
    Inhibitor
    NSC126405 is a mTOR-DEPTOR inhibitor that binds to DEPTOR, prevents mTOR-DEPTOR binding and induces multiple myeloma (MM) cytotoxicity. NSC126405 can be utilized in cancer research.
    NSC126405
  • HY-50673A
    Dactolisib hydrochloride
    Inhibitor
    Dactolisib (BEZ235) hydrochloride is an orally active, dual pan-class I PI3K and mTOR inhibitor for p110α/γ/δ/β and mTOR with IC50 of 4 nM/5 nM/7 nM/75 nM and 20.7 nM, respectively. Dactolisib hydrochloride (BEZ235) inhibits mTORC1 and mTORC2.
    Dactolisib hydrochloride
  • HY-N0914R
    Ajugol (Standard)
    Inhibitor
    Ajugol (Standard) is the analytical standard of Ajugol (HY-N0914). This product is intended for research and analytical applications. Ajugol is an orally active iridoid glycoside found in the traditional Chinese medicine Leonurus japonicus. Ajugol is an autophagy activator. Ajugol activates TFEB-mediated autophagy and lysosomal biogenesis. Ajugol also has anti-inflammatory effects. Ajugol has great potential in the research of asthma, non-alcoholic fatty liver disease (NAFLD), and osteoarthritis.
    Ajugol (Standard)
  • HY-W419331
    Methionyl-methionine
    Activator
    Methionylmethionine (Met-Met) significantly promotes α-s1 casein (αS1-CN) expression in the mammary explants by enhancing intracellular substrate availability and activating JAK2-STAT5 and mTOR-mediated signaling pathways.
    Methionyl-methionine
  • HY-W654330
    Pyraclostrobin-d6
    Pyraclostrobin-d6 is deuterium-labeled Pyraclostrobin (HY-N6626).
    Pyraclostrobin-d<sub>6</sub>
  • HY-116191
    WJD008
    Inhibitor
    WJD008 is a potent dual phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor with antiproliferative and anticlonogenic activity in tumor cells and transformed cells with PIK3CA mutant. WJD008 inhibits kinase activity of PI3K α and mTOR and abrogates insulin-like growth factor-I-activated PI3K-Akt-mTOR signaling cascade. WJD008 is promising for research of cancers.
    WJD008
  • HY-10218S1
    Everolimus-13C2,d4
    Inhibitor
    Everolimus-13C2,d4 (RAD001-13C2,d4) is 13C labeled Everolimus. Everolimus (RAD001) is a Rapamycin (HY-10219) derivative and a potent, selective and orally active mTOR1 inhibitor. Everolimus binds to FKBP-12 to generate an immunosuppressive complex. Everolimus inhibits tumor cells proliferation and induces cell apoptosis and autophagy. Everolimus has potent immunosuppressive and anticancer activities.
    Everolimus-<sup>13</sup>C<sub>2</sub>,d<sub>4</sub>
  • HY-169960
    2DII
    Inhibitor
    2DII is a potent and selective mTORC2 inhibitor. 2DII selectively binds mSin1 PH domain and decreases the expression of AKT1 phosphorylation.
    2DII
Cat. No. Product Name / Synonyms Application Reactivity

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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