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

mTOR

Mammalian target of Rapamycin

mTOR

Related Products

PDF 2.11 MB

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-13847
    GNE-555
    		Inhibitor
    GNE-555 is a selective, metabolically stable mTOR inhibitor (Ki=1.5 nM) that also has good oral bioavailability. GNE-555 exhibits antiproliferative activity on PC3 and MCF-7 cells and can be used in cancer research.
    GNE-555
  • HY-B0627A
    Metformin (glycinate)
    		Inhibitor
    Metformin (1,1-Dimethylbiguanide) glycinate inhibits the mitochondrial respiratory chain in the liver, leading to AMPK activation and enhancing insulin sensitivity, and can be used in the study of type 2 diabetes. Metformin glycinate exerts central glucose-lowering effects by inhibiting Ras-related protein 1 (Rap1) in SF1 hypothalamic neurons. Metformin glycinate also inhibits liver oxidative stress, nitrosative stress, inflammation, and apoptosis caused by liver ischemia/reperfusion injury. In addition, Metformin glycinate regulates the expression of autophagy-related proteins by activating AMPK and inhibiting the mTOR signaling pathway, thereby inducing tumor cell autophagy and inhibiting the growth of renal cell carcinoma in vitro and in vivo.
    Metformin (glycinate)
  • HY-181710
    LASSBio-2337
    		Inhibitor
    LASSBio-2337 is a dual pan-PI3K/mTOR inhibitor with an mTOR IC50 of 5.8 μM.LASSBio-2337 functionally modulates mTOR and all PI3K isoforms.LASSBio-2337 acts as a cytotoxic agent in leukemia cells, including multidrug-resistant populations.LASSBio-2337 spares nontumor human peripheral blood mononuclear cells.LASSBio-2337 displays moderate PAMPA-GIT permeability.LASSBio-2337 shows low metabolic stability in rat liver microsomes.LASSBio-2337 is aqueous insoluble.LASSBio-2337 can be used for the research of acute lymphoblastic leukemia, chronic myelogenous leukemia, breast cancer.
    LASSBio-2337
  • HY-177092
    AGF347
    		Inhibitor
    AGF347 is a potent and multi-targeted antifolate that targets serine hydroxymethyltransferase (SHMT)2 in the mitochondria and SHMT1 in the cytosol, and inhibits de novo purine biosynthesis. AGF347 induces apoptosis, inhibits mTOR signaling, decreases GSH pools, and increases ROS. AGF347 inhibits proliferation of Cisplatin (HY-17394) sensitive and resistant epithelial ovarian cancer (EOC) cells. AGF347 exhibits antitumor efficacy in SKOV3 EOC xenograft mouse models. AGF347 can be used for ovarian cancer research.
    AGF347
  • HY-119831
    Rohitukine
    		Inhibitor
    Rohitukine is an orally active CDK9/T1 inhibitor with an IC50 of 0.3 μM. Rohitukine blocks ATP binding sites of CDK2/A and CDK9/T1, suppresses PPARγ, AKT, mTOR, C/EBPα, SREBP-2, and NF-κB signaling, and increases hepatic LXRα expression. Rohitukine induces S-phase cell cycle arrest, ROS generation, apoptosis, and exhibits anti-inflammatory activity. Rohitukine can be used for the research of leukemia, pancreatic cancer, prostate cancer, breast cancer, CNS cancer, ovarian cancer, lung cancer, dyslipidemia, inflammatory diseases, inflammatory bowel disease, and arthritis.
    Rohitukine
  • HY-128027
    eCF309
    		Inhibitor 98.2%
    eCF309 is a potent and highly selective mTOR inhibitor with an IC50 of 15 nM. eCF309 displays higher selectivity over PI3Ks. eCF309 can be used for the study of breast cancer and prostate cancer.
    eCF309
  • HY-Y0106R
    2,6-Dihydroxyacetophenone (Standard)
    		Inhibitor
    2,6-Dihydroxyacetophenone (Standard) is the analytical standard of 2,6-Dihydroxyacetophenone (HY-Y0106). This product is intended for research and analytical applications. 2,6-Dihydroxyacetophenone, a polyphenolic derivative of Acetophenone (HY-Y0989), is an orally active mTOR inhibitor. 2,6-Dihydroxyacetophenone shows antioxidant activity. 2,6-Dihydroxyacetophenone inhibits cell growth and proliferation in CRC cells. 2,6-Dihydroxyacetophenone arrests at G0/G1 phase of cell cycle, induces apoptosis and suppresses cell migration in CRC cells. 2,6-Dihydroxyacetophenone inhibits xanthine oxidase (XOD) with an IC50 of 1.24 mM. 2,6-dihydroxyacetophenone improves uric acid metabolism in hyperuricemia mice, reduces plasma cholesterol in hypercholesterolemic rats, and inhibits lipid accumulation in HFD-induced obese mice. 2,6-Dihydroxyacetophenone can be used for the study of colorectal cancer (CRC), hyperuricemia and hypercholesterolemia.
    2,6-Dihydroxyacetophenone (Standard)
  • HY-141701
    mTOR/HDAC-IN-1
    		Inhibitor
    mTOR/HDAC-IN-1 (Compound 50) is a selective mTOR and HDAC dual inhibitor with IC50 values of 0.49 and 0.91 nM against mTOR and HDAC1, respectively. mTOR/HDAC-IN-1 can be studied as an anti-cancer agent.
    mTOR/HDAC-IN-1
  • HY-172964
    KIM-161
    		Inhibitor
    KIM-161 is a PIK3CA inhibitor. KIM-161 has significant antiproliferative activity with IC50 values of 1.428 and 1.562 µM against PI3KCA mutant breast cancer MCF7 and T47D cells, respectively. KIM-161 induces apoptosis and cell cycle arrest by inhibiting the PI3K/AKT/mTOR signaling pathway and inducing ROS production. KIM-161 can be used to study breast cancer and its PI3KCA mutant subtypes.
    KIM-161
  • HY-141476
    PI3K/mTOR Inhibitor-3
    		Inhibitor
    PI3K/mTOR Inhibitor-3 (compound 12), an imidazoline, is a potent PI3K and mTOR dual inhibitor. PI3K/mTOR Inhibitor-3 has anti-cancer activity.
    PI3K/mTOR Inhibitor-3
  • HY-144295
    PI3Kα-IN-5
    		Inhibitor
    PI3Kα-IN-5 (compound 6 ab) is a potent PI3Kα/mTOR inhibitor, with an IC50 of 0.7 nM and 3.3 nM, respectively. PI3Kα-IN-5 can be used for the research of colorectal cancer.
    PI3Kα-IN-5
  • HY-179623
    PI3Kα-IN-29
    		Inhibitor
    PI3Kα-IN-29 is a potent, orally active and selective PI3Kα with an IC50 of 2.5 nM. PI3Kα-IN-29 exhibits >400-fold selectivity over PI3Kβ/δ/γ/mTOR. PI3Kα-IN-29 selectively degrades the H1047R mutant p110α protein and inhibits PI3Kα kinase activity. PI3Kα-IN-29 suppresses PI3K/AKT/mTOR signaling, induces G1 arrest, and inhibits migration. PI3Kα-IN-29 inhibits tumor growth in a T47 mouse model. PI3Kα-IN-29 can be used for the research of breast cancer.
    PI3Kα-IN-29
  • HY-168609
    CRI9
    		Inhibitor
    CRI9 inhibits the c-MET/PI3K/Akt/mTOR pathway, suppressing the growth of liver cancer cells. CRI9 shows strong cytotoxicity against HCC cells, inducing apoptosis.
    CRI9
  • HY-154957
    mTOR inhibitor-11
    		Inhibitor
    mTOR inhibitor-11 (Compound 9) is a brain-penetrant mTOR inhibitor (IC50: 21 nM for pS6). mTOR inhibitor-11 also inhibits pCHK1 and PDE4D with IC50s of 17.2 and 17.0 μM. mTOR inhibitor-11 can be used for research of CNS disease.
    mTOR inhibitor-11
  • HY-N2217R
    Rotundic acid (Standard)
    		Inhibitor
    Rotundic acid (Standard) is the analytical standard of Rotundic acid (HY-N2217). This product is intended for research and analytical applications. Rotundic acid is an orally effective triterpenoid with a Kd value of 51.3 µM for PTP1B. Rotundic acid downregulates the AKT/mTOR pro-survival pathway and modulates the MAPK pathway. Rotundic acid induces cell cycle S-phase arrest, DNA damage and apoptosis; it inhibits migration, invasion, angiogenesis and proliferation of cancer cells. Rotundic acid improves leptin sensitivity, regulates gut microbiota and reduces cellular senescence. Rotundic acid can be used in research related to hepatocellular carcinoma, obesity, aging, acute lung injury and type 2 diabetes.
    Rotundic acid (Standard)
  • HY-155376
    mTOR inhibitor-14
    		Inhibitor
    mTOR inhibitor-14 (compound 14c) is a potent mTOR inhibitor. mTOR inhibitor-14 also shows minimal CYP2C8 inhibition. mTOR inhibitor-14 can inhibit tumor growth.
    mTOR inhibitor-14
  • HY-17654
    BIEGi-1
    		Inhibitor
    BIEGi-1 is an EGFR inhibitor. BIEGi-1 effectively disrupts the EGFR-Rheb interaction in cells. BIEGi-1 robustly inhibits EGFR kinase activity (reduces p-Y1068-EGFR) as well as mTORC1 activation (reduces p-T389-S6K1) in EGFR-mutant cells. BIEGi-1 shows strong antiproliferative effects on EGFR-mutant PC9 and HCC827 cells with IC50 values of 17 nM and 20 nM, respectively. BIEGi-1 can be used for the study of cancers harboring EGFR mutations, such as non-small cell lung cancer (NSCLC).
    BIEGi-1
  • HY-173141
    mTOR inhibitor-26
    		Inhibitor
    mTOR inhibitor-26 (Compound HPT-11) is an inhibitor of mTOR with an IC50 of 0.7 nM. It effectively inhibits the proliferation of AML cell lines Molm-13 and MV-4-11. mTOR inhibitor-26 exhibits antitumor activity and favorable metabolic stability, making it a promising candidate for cancer research.
    mTOR inhibitor-26
  • HY-13610
    N1,N11-Diethylnorspermine
    		Inhibitor
    N1,N11-Diethylnorspermine is a synthetic analog of the naturally occurring polyamine spermine, can induce polyamine depletion and inhibit tumor cell growth. N1,N11-Diethylnorspermine activates polyamine catabolism and downregulates mTOR protein. N1,N11-Diethylnorspermine 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
  • HY-N0390G
    L-Glutamine (GMP)
    		Inhibitor
    L-Glutamine GMP is L-Glutamine (HY-N0390) produced by using GMP guidelines. GMP small molecules works appropriately as an auxiliary reagent for cell therapy manufacture. L-Glutamine is an orally active nutritional agent and cellular metabolism regulator. L-Glutamine is taken up in a Na+-dependent manner and targets multiple key molecules including glutaminase, mTORC1, NF-κB, STAT-3 and HIF-1α. L-Glutamine enhances glutaminolytic catabolism, drives the conversion of glutamate to α-ketoglutarate, thereby regulating gene expression, integrating metabolic signals, mediating glutamine flux and maintaining redox homeostasis. L-Glutamine also promotes cell proliferation, osteogenic differentiation and fracture healing, exerts neuroprotective and cardioprotective effects, and inhibits osteoarthritis. L-Glutamine can be applied to research related to osteoporosis, osteoarthritis, ischemic stroke and acute cantharidin-induced cardiotoxicity.
    L-Glutamine (GMP)
Cat. No. Product Name / Synonyms Application Reactivity
All Rights Reserved.
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

Your Search Returned No Results.

Sorry. There is currently no product that acts on isoform together.

Please try each isoform separately.