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

mTOR

Mammalian target of Rapamycin

mTOR

Related Products

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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.

mTOR Isoform Specific Products:

mTOR Isoform Comparison
Cat. No. Product Name Effect Purity Chemical Structure
  • HY-13610AR
    N1,N11-Diethylnorspermine tetrahydrochloride (Standard)
    		Inhibitor
    N1,N11-Diethylnorspermine (tetrahydrochloride) (Standard) is the analytical standard of N1,N11-Diethylnorspermine (tetrahydrochloride). This product is intended for research and analytical applications. N1, N11-Diethylnorspermine tetrahydrochloride (DENSPM tetrahydrochloride) is a potent anticancer agent. N1,N11-Diethylnorspermine tetrahydrochloride activates polyamine catabolism and downregulates mTOR protein. N1,N11-Diethylnorspermine tetrahydrochloride induces the release of cytochrome c from mitochondria, resulting in activation of caspase 3. N1,N11-Diethylnorspermine tetrahydrochloride kills glioblastoma multiforme (GBM) through induction of SSAT (spermidine/spermine N1-acetyltransferase) coupled with H2O2 production.
    N1,N11-Diethylnorspermine tetrahydrochloride (Standard)
  • HY-Y0396R
    N-Hydroxyphthalimide (Standard)
    		Inhibitor
    N-Hydroxyphthalimide (Standard) is the analytical standard of N-Hydroxyphthalimide (HY-Y0396). This product is intended for research and analytical applications. N-Hydroxyphthalimide is a blocking agent and catalyst. N-Hydroxyphthalimide promotes oxidation reactions by generating PINO free radicals and activating hydrogen atom transfer processes. N-Hydroxyphthalimide reduces the expression of anti-apoptotic proteins Survivin and Bcl-xL and activates caspase 9 and caspase 3. N-Hydroxyphthalimide induces Apoptosis. N-Hydroxyphthalimide inhibits the phosphorylation of mTOR (Ser2448, Ser2481) and Akt (Ser473). N-Hydroxyphthalimide has anticancer effects against breast and colon cancer.
    N-Hydroxyphthalimide (Standard)
  • 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-W781875
    Sirolimus isomer C
    Sirolimus isomer C is an impurity of Rapamycin (Sirolimus) (HY-10219).
    Sirolimus isomer C
  • HY-15174R
    Dactolisib Tosylate (Standard)
    		Inhibitor
    Dactolisib (Tosylate) (Standard) is the analytical standard of Dactolisib (Tosylate). This product is intended for research and analytical applications. Dactolisib Tosylate (BEZ235 Tosylate) is a dual PI3K and mTOR kinase inhibitor with IC50 values of 4, 75, 7, 5 nM for PI3Kα, β, γ, δ, respectively. Dactolisib Tosylate (BEZ235 Tosylate) inhibits mTORC1 and mTORC2.
    Dactolisib Tosylate (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-128932R
    Cefminox sodium (Standard)
    Cefminox (sodium) (MT-141) (Standard) is the analytical standard of Cefminox (sodium). This product is intended for research and analytical applications. Cefminox sodium is a semisynthetic cephamycin, which exhibits antibacterial activity. Cefminox sodium is a broad-spectrum, bactericidal cephalosporin antibiotic. Cefminox sodium also acts as a dual agonist of prostacyclin receptor (IP) and PPARγ. Cefminox sodium upregulates cAMP production and PTEN expression and inhibits Akt/mTOR signaling. Cefminox sodium also prevents pulmonary arterial hypertension in rat model.
    Cefminox sodium (Standard)
  • 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-13691R
    MKC-1 (Standard)
    		Inhibitor
    MKC-1 (Standard) is the analytical standard of MKC-1. This product is intended for research and analytical applications. MKC-1 (Ro-31-7453) is an orally active and potent cell cycle inhibitor with broad antitumor activity. MKC-1 inhibits the Akt/mTOR pathway. MKC-1 arrests cellular mitosis and induces cell apoptosis by binding to a number of different cellular proteins including tubulin and members of the importin β family.
    MKC-1 (Standard)
  • HY-W592871R
    10-Hydroxy-2-decenoic acid (Standard)
    10-Hydroxy-2-decenoic acid (Standard) is an analytical standard for 10-Hydroxy-2-decenoic acid (HY-W592871). This product is intended for research and analytical applications.10-Hydroxy-2-decenoic acid (10-HDA) is an orally active unsaturated medium-chain fatty acid with various physiological activities. 10-Hydroxy-2-decenoic acid induces ROS-mediated apoptosis in A549 cells. 10-Hydroxy-2-decenoic acid inhibits VEGF-induced angiogenesis in human venous endothelial cells. 10-Hydroxy-2-decenoic acid alleviates non-alcoholic fatty liver disease (NAFLD) by activating the AMPK-α signaling pathway. 10-Hydroxy-2-decenoic acid protects against bone loss by inhibiting NF-κB signaling downstream of FFAR4. 10-Hydroxy-2-decenoic acid is an antibiotic against many bacteria and fungi, such as Neurospora sitophila, molds and Staphylococcus aureus. 10-Hydroxy-2-decenoic acid has longevity-promoting effects in C. elegans. 10-Hydroxy-2-decenoic acid prevents osteoarthritis by targeting aspartyl β hydroxylase and inhibiting chondrocyte senescence.
    10-Hydroxy-2-decenoic acid (Standard)
  • 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-164384
    DFX117
    		Inhibitor
    DFX117 is a selective, orally active inhibitor for PI3Kα and c-Met tyrosine kinase. DFX117 inhibits PI3K/Akt/mTOR pathway, inhibits the proliferation of NCI-H1975, NCI-H1993, and HCC827 with IC50s 0.02-0.08 µM. DFX117 arrests cell cycle at G0/G1 phase, induces apoptosis in A549 and NCI-H1975. DFX117 exhibits antitumor efficacy in mice.
    DFX117
  • HY-162023
    mTOR inhibitor-10
    		Inhibitor
    mTOR inhibitor-10 (Compound 9c) is a selective inhibitor for mTOR. mTOR inhibitor-10 inhibits mTOR and PI3K-α, with IC50 of 0.7 and 825 nM. mTOR inhibitor-10 inhibits proliferation of LNCaP with IC50 of 87 nM.
    mTOR inhibitor-10
  • HY-N4247R
    Kuwanon G (Standard)
    		Inhibitor
    Kuwanon G (Standard) is the analytical standard of Kuwanon G (HY-N4247). This product is intended for research and analytical applications. Kuwanon G is a flavonoid compound and an antagonist of the bombesin receptor. Kuwanon G has multiple activities such as bactericidal, anti-tumor, anti-inflammatory, antioxidant, anti-atherosclerotic, and neuroprotective effects. Kuwanon G exhibits strong antibacterial activity against oral pathogens, especially cariogenic bacteria and periodontal pathogens. Kuwanon G can induce apoptosis and inhibit proliferation, migration, and invasion of tumor cells. Kuwanon G can be used in the research of diseases such as gastric cancer and atherosclerosis.
    Kuwanon G (Standard)
  • HY-N0787R
    Cryptochlorogenic acid (Standard)
    		Inhibitor
    Cryptochlorogenic acid (Standard) is the analytical standard of Cryptochlorogenic acid. This product is intended for research and analytical applications. Cryptochlorogenic acid is a natural product.
    Cryptochlorogenic acid (Standard)
  • HY-13246R
    Apitolisib (Standard)
    		Inhibitor
    Apitolisib (Standard) is the analytical standard of Apitolisib. This product is intended for research and analytical applications. Apitolisib (GDC-0980; GNE 390; RG 7422) is a selective, potent, orally bioavailable Class I PI3 kinase and mTOR kinase (TORC1/2) inhibitor with IC50s of 5 nM/27 nM/7 nM/14 nM for PI3Kα/PI3Kβ/PI3Kδ/PI3Kγ, and with a Ki of 17 nM for mTOR.
    Apitolisib (Standard)
  • HY-10115AR
    PI-103 Hydrochloride (Standard)
    		Inhibitor
    PI-103 (Hydrochloride) (Standard) is the analytical standard of PI-103 (Hydrochloride). This product is intended for research and analytical applications. PI-103 Hydrochloride is a dual 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 Hydrochloride also inhibits DNA-PK with an IC50 of 2 nM. PI-103 Hydrochloride induces autophagy.
    PI-103 Hydrochloride (Standard)
  • HY-14581R
    Palomid 529 (Standard)
    		Inhibitor
    Palomid 529 (Standard) is the analytical standard of Palomid 529. This product is intended for research and analytical applications. Palomid 529 is a potent inhibitor of mTORC1 and mTORC2 complexes.
    Palomid 529 (Standard)
Cat. No. Product Name / Synonyms Application Reactivity
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Download mTOR Signaling Pathway Map.

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.

mTOR Isoform Comparison

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