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-111065
    OXA-01
    		Inhibitor
    OXA-01 is a potent mTORC1 and mTORC2 inhibitor, with IC50 values of 29 nM and 7 nM, respectively.
    OXA-01
  • HY-W130610R
    Stearamide (Standard)
    		Activator
    Ginsenoside C-K (Standard) is the analytical standard of Ginsenoside C-K. This product is intended for research and analytical applications. Ginsenoside C-K, a bacterial metabolite of G-Rb1, exhibits anti-inflammatory effects by reducing iNOS and COX-2. Ginsenoside C-K exhibits an inhibition against the activity of CYP2C9 and CYP2A6 in human liver microsomes with IC50s of 32.0±3.6 μM and 63.6±4.2 μM, respectively.
    Stearamide (Standard)
  • HY-147284
    PI3K-IN-37
    		Inhibitor 99.0%
    PI3K-IN-37 (Example 84.1) is a PI3K α/β/δ inhibitor with IC50s of 6, 8, 4 nM, respectively. PI3K-IN-37 can also inhibit mTOR (IC50=4 nM).
    PI3K-IN-37
  • HY-10620
    PI3K-IN-22
    		Inhibitor 99.50%
    PI3K-IN-22 is a PI3Kα/mTOR dual kinase inhibitor. PI3K-IN-22 has IC50s of 0.9, 0.6 nM for PI3Kα and mTOR, respectively. PI3K-IN-22 can be used for the research of cancer.
    PI3K-IN-22
  • HY-123849
    SN32976
    		Inhibitor 99.49%
    SN32976 is a potent and selective class I PI3K and mTOR inhibitor with IC50s of 15.1 nM, 461 nM, 110 nM, 134 nM and 194 nM for PI3Kα, PI3Kβ, PI3Kγ, PI3Kδ and mTOR, respectively. SN32976 shows high selectivity among other 442 kinases. SN32976 shows anticancer effects.
    SN32976
  • HY-15271A
    WYE-687 dihydrochloride
    		Inhibitor ≥98.0%
    WYE-687 dihydrochloride is an ATP-competitive mTOR inhibitor with an IC50 of 7 nM. WYE-687 dihydrochloride concurrently inhibits activation of mTORC1 and mTORC2. WYE-687 also inhibits PI3Kα and PI3Kγ with IC50s of 81 nM and 3.11 μM, respectively.
    WYE-687 dihydrochloride
  • HY-141805
    MHY-1685
    		Inhibitor 99.84%
    MHY-1685, a novel mammalian target of rapamycin (mTOR) inhibitor, provides opportunities to improve hCSC-based myocardial regeneration.
    MHY-1685
  • HY-153120A
    PI3K/mTOR Inhibitor-13 sodium
    		Inhibitor 98.13%
    PI3K/mTOR Inhibitor-13 sodium is an orally active dual inhibitor of phosphoinositol 3-kinase (PI3K) and mTOR kinase. PI3K/mTOR Inhibitor-13 sodium has potential applications in sexual diseases, solid tumor and idiopathic pulmonary fibrosis (IPF).
    PI3K/mTOR Inhibitor-13 sodium
  • HY-N6651
    Isocryptotanshinone
    		Inhibitor ≥98.0%
    Isocryptotanshinone is a dual STAT3 and PTP1B (IC50 = 56.1 μM) inhibitor. Isocryptotanshinone inhibits STAT3 by binding to the STAT3 SH2 domain to block phosphorylation and nuclear translocation[1][2]. Isocryptotanshinone exerts its anti-proliferative effect via the induction of cell cycle arrest, apoptosis, and pro-death autophagy, through the regulation of STAT3, AKT/mTOR and MAPK signaling pathways[1][3][4]. Isocryptotanshinone suppresses the xenograft gastric cancer (GC) tumor growth in BALB/c nude mice. Isocryptotanshinone can be used for cancer research, such as lung cancer, breast cancer and GC[1][3][4].
    Isocryptotanshinone
  • HY-156027
    SIRT6-IN-3
    		Inhibitor 98.19%
    SIRT6-IN-3 (compound 8a) is a selective inhibitor of SIRT6 (IC50=7.49 μM). SIRT6-IN-3 inhibits pancreatic ductal adenocarcinoma (PDAC) cells proliferation and induces apoptosis. SIRT6-IN-3 increases the sensitivity of cancer cells to gemcitabine (HY-17026) via blocking the DNA damage repair pathway. SIRT6-IN-3 is used in pancreatic cancer research.
    SIRT6-IN-3
  • HY-N3628
    Coronarin A
    		Inhibitor ≥98.0%
    Coronarin A is an orally active natural compound that inhibits mTORC1 and S6K1 to increase IRS1 activity. Coronarin A shows anti-inflammatory activity and can also be used for type 2 diabetes mellitus research.
    Coronarin A
  • HY-109633
    PI3K-IN-18
    		Inhibitor 99.0%
    PI3K-IN-18 (Compound 1) is a PI3K inhibitor, and can also effectively inhibit the homologous enzymemTOR. The IC50 values of PI3K-IN-18 for mTOR and PI3K-α were 49 nM and 41 nM, respectively.
    PI3K-IN-18
  • HY-N5136
    25(R,S)-Ruscogenin
    		Inhibitor 99.83%
    Ruscogenin suppresses HCC metastasis by reducing the expression of MMP-2, MMP-9, uPA, VEGF and HIF-1α via regulating the PI3K/Akt/mTOR signaling pathway. And Ruscogenin alleviates LPS-induced pulmonary endothelial cell apoptosis by su
    25(R,S)-Ruscogenin
  • HY-130687A
    Psicose
    		Activator
    Psicose is a natural and low-calorie sweetener. Psicose can activate the PI3K/Akt/mTOR pathway to promote muscle synthesis. Psicose can upregulate IGF-1 and downregulate Myostatin. Psicose regulates mitochondrial function by increasing G6P activity. Psicose enhances antioxidant enzyme activity and reduces oxidative stress markers. Psicose reduces plasma triglycerides and total cholesterol. Psicose can improve muscle fiber size and reduce fibrosis. Psicose can be used for research on sarcopenia.
    Psicose
  • HY-P3072
    Mastoparan 17
    		Control 98.15%
    Mastoparan 17 is a tetradecapeptide. Mastoparan 17 is an inactive analogue of Mastoparan (HY-P0246) .
    Mastoparan 17
  • HY-N0486S12
    L-Leucine-d2
    		Activator 99.0%
    L-Leucine-d2 is the deuterium labeled L-Leucine. L-Leucine is an essential branched-chain amino acid (BCAA), which activates the mTOR signaling pathway.
    L-Leucine-d<sub>2</sub>
  • HY-N2423
    Sinigrin hydrate
    		Inhibitor 99.92%
    Sinigrin (Allyl-glucosinolate) hydrate is an orally active glucosinolate found in cruciferous plants. Sinigrin hydrate possesses multiple activities such as anti-cancer, antibacterial, antifungal, anti-inflammatory, antioxidant, and inhibition of fat synthesis. Sinigrin hydrate can be used in the research of tumors, inflammatory, and metabolic diseases.
    Sinigrin hydrate
  • HY-N6841
    Rhodiolin
    		Inhibitor
    Rhodiolin, a flavonoid, is an orally active glucose 6-phosphate isomerase (GPI) inhibitor. Rhodiolin inhibits papillary thyroid cancer (PTC) by targeting glycolysis enzyme glucose 6-phosphate isomerase GPI and suppressing PI3K/AKT/mTOR phosphorylation and induce apoptosis. Rhodiolin as a NS2B-NS3 protease inhibitor can disrupt dengue viral replication. Rhodiolin is also a potential candidate for developing anticancer strategies inhibiting CK1ε kinase. Rhodiolin can be used for the study of anti-tumor and anti-viral .
    Rhodiolin
  • HY-RS08810
    MTOR Human Pre-designed siRNA Set A
    		Inhibitor

    MTOR Human Pre-designed siRNA Set A contains three designed siRNAs for MTOR gene (Human), as well as a negative control, a positive control, and a FAM-labeled negative control.
    MTOR Human Pre-designed siRNA Set A
  • HY-N1244
    Sarmentosin
    		Inhibitor
    Sarmentosin is an activator of Nrf2. Sarmentosin inhibits mTOR signaling and induces autophagy-dependent apoptosis in human HCC cells.
    Sarmentosin
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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