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Submit ReviewTorin 1
Description: Potent and selective mTOR inhibitor
Chemical Name: 1-[4-[4-(1-Oxopropyl)-1-piperazinyl]-3-(trifluoromethyl)phenyl]-9-(3-quinolinyl)-benzo[h]-1,6-naphthyridin-2(1H)-one
Purity: ≥98% (HPLC)
Biological Activity for Torin 1
Torin 1 is a potent and selective ATP-competitive mTOR inhibitor (IC50 = 2 - 10 nM for mTORC1 and mTORC2). Torin 1 displays 200-fold selectivity for mTOR over DNA-PK, ATM and hVps34. In HeLa cells, Torin 1 induces autophagy. Torin 1 impairs cell growth and proliferation by suppression of the rapamycin-resistant functions of mTORC1. In human monocytes and myeloid dendritic cells, Torin 1 prevents decreases the anti-inflammatory potency of glucocorticoids. In the human endocrine cell line BON, Torin 1 increases neurotensin secretion and gene expression through MEK/ERK/c-Jun pathway activation.
Licensing Information
Sold under license from Whitehead Institute for Biomedical Research.
Technical Data for Torin 1
| M. Wt | 607.62 |
| Formula | C35H28F3N5O2 |
| Storage | Store at +4°C |
| Purity | ≥98% (HPLC) |
| CAS Number | 1222998-36-8 |
| PubChem ID | 49836027 |
| InChI Key | AKCRNFFTGXBONI-UHFFFAOYSA-N |
| Smiles | O=C(N5C6=CC(C(F)(F)F)=C(N7CCN(C(CC)=O)CC7)C=C6)C=CC2=C5C1=CC(C3=CN=C(C=CC=C4)C4=C3)=CC=C1N=C2 |
The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.
Tocris products are intended for laboratory research use only, unless stated otherwise.
Solubility Data for Torin 1
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 0.61 | 1 with gentle warming |
Preparing Stock Solutions for Torin 1
The following data is based on the product molecular weight 607.62. Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 0.01 mM | 164.58 mL | 822.88 mL | 1645.77 mL |
| 0.05 mM | 32.92 mL | 164.58 mL | 329.15 mL |
| 0.1 mM | 16.46 mL | 82.29 mL | 164.58 mL |
| 0.5 mM | 3.29 mL | 16.46 mL | 32.92 mL |
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Product Datasheets for Torin 1
References for Torin 1
References are publications that support the biological activity of the product.
Guertin and Sabatini (2009) The pharmacology of mTOR inhibition. Sci.Signal. 2 pe24 PMID: 19383975
Thoreen et al (2009) An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J.Biol.Chem. 284 8023 PMID: 19150980
Liu et al (2010) Discovery of 1-(4(-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo[h][1,6]naphthyridin-2(1H)-one as a highly potent, selective mammalian target of rapamycin (mTOR) inhibitor for the treatment of cancer. J.Med.Chem. 53 7146 PMID: 20860370
Peterson et al (2011) mTOR complex 1 regulates lipin 1 localization to control the SREBP pathway. Cell. 146 408 PMID: 21816276
Galluzzi et al (2017) Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles. Nat.Rev.Drug.Discov. PMID: 28529316
Weichhart et al (2011) Inhibition of mTOR blocks the anti-inflammatory effects of glucocorticoids in myeloid immune cells. Blood 117 4273 PMID: 21368289
Li et al (2011) mTORC1 inhibition increases neurotensin secretion and gene expression through activation of the MEK/ERK/c-Jun pathway in the human endocrine cell line BON. Am.J.Physiol.Cell Physiol. 301 C213 PMID: 21508335
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Keywords: Torin 1, Torin 1 supplier, Torin1, mtor, mammalian, target, rapamycin, inhibitors, inhibits, potent, selective, autophagy, mTOR, Autophagy, 4247, Tocris Bioscience
249 Citations for Torin 1
Citations are publications that use Tocris products. Selected citations for Torin 1 include:
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Christopher J et al (2020) BCR-Induced Ca2+ Signals Dynamically Tune Survival, Metabolic Reprogramming, and Proliferation of Naive B Cells. Cell Rep 31 107474 PMID: 32294437
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Vladimir et al (2020) De novo phosphatidylcholine synthesis is required for autophagosome membrane formation and maintenance during autophagy. Autophagy 16 1044-1060 PMID: 31517566
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Mason et al (2018) Lifespan extension without fertility reduction following dietary addition of the autophagy activator Torin1 in Drosophila melanogaster. PLoS One 13 e0190105 PMID: 29329306
Tol et al (2018) HEPES activates a MiT/TFE-dependent lysosomal-autophagic gene network in cultured cells: A call for caution. Autophagy 14 437 PMID: 29455584
Georgilis et al (2018) PTBP1-Mediated Alternative Splicing Regulates the Inflammatory Secretome and the Pro-tumorigenic Effects of Senescent Cells. Cancer Cell 34 85 PMID: 29990503
Napolitano et al (2018) mTOR-dependent phosphorylation controls TFEB nuclear export. Nat Commun 9 3312 PMID: 30120233
Barutcu et al (2018) Role of the MAPK/cJun NH2-terminal kinase signaling pathway in starvation-induced autophagy. Autophagy 14 1586 PMID: 29950132
Kim et al (2018) Carbon monoxide-induced TFEB nuclear translocation enhances mitophagy/mitochondrial biogenesis in hepatocytes and ameliorates inflammatory liver injury. Cell Death Dis 9 1060 PMID: 30333475
Shi et al (2018) Amino acids stimulate the endosome-to-Golgi trafficking through Ragulator and small GTPase Arl5. Nat Commun 9 4987 PMID: 30478271
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Gubbiotti et al (2018) Metabolic reprogramming of murine cardiomyocytes during autophagy requires the extracellular nutrient sensor decorin. J Biol Chem 293 16940 PMID: 30049794
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Guerroue et al (2017) Autophagosomal Content Profiling Reveals an LC3C-Dependent Piecemeal Mitophagy Pathway. Mol Cell 68 786 PMID: 29149599
Sobol et al (2017) Deubiquitinase OTUD6B Isoforms Are Important Regulators of Growth and Proliferation. Mol Cancer Res 15 117 PMID: 27864334
Nguyen et al (2017) DGAT1-Dependent Lipid Droplet Biogenesis Protects Mitochondrial Function during Starvation-Induced Autophagy. Dev Cell 42 9 PMID: 28697336
Cooper et al (2017) TBK1 Provides Context-Selective Support of the Activated AKT/mTOR Pathway in Lung Cancer. Cancer Res 77 5077 PMID: 28716898
Hong et al (2017) PtdIns3P controls mTORC1 signaling through lysosomal positioning. J Cell Biol 216 4217 PMID: 29030394
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Schwartz et al (2017) Tim-3 is a Marker of Plasmacytoid Dendritic Cell Dysfunction during HIV Infection and Is Associated with the Recruitment of IRF7 and p85 into Lysosomes and with the Submembrane Displacement of TLR9. J Immunol 198 3181 PMID: 28264968
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Gupta et al (2017) PARK2 Depletion Connects Energy and Oxidative Stress to PI3K/Akt Activation via PTEN S-Nitrosylation. Mol Cell 65 999 PMID: 28306514
Sciarretta et al (2015) mTORC2 regulates cardiac response to stress by inhibiting MST1. Elife 11 125 PMID: 25843706
Shi et al (2015) Hedgehog signaling activates a positive feedback mechanism involving Ins-like growth factors to induce osteoblast differentiation. Front Behav Neurosci 112 4678 PMID: 25825734
Speranza et al (2015) Activation of 5-HT7 receptor stimulates neurite elongation through mTOR, Cdc42 and actin filaments dynamics. Nat Chem Biol 9 62 PMID: 25814944
Thorne et al (2015) GSK-3 modulates cellular responses to a broad spectrum of kinase inhibitors. Mol Biol Cell 11 58 PMID: 25402767
Toops et al (2015) Cholesterol-mediated activation of acid sphingomyelinase disrupts autophagy in the retinal pigment epithelium. J Exp Med 26 41640 PMID: 25378587
Yang et al (2015) PDK1 orchestrates early NK cell development through induction of E4BP4 expression and maintenance of IL-15 responsiveness. J Clin Invest 212 253 PMID: 25624444
Dasgupta et al (2015) Coactivator SRC-2-dependent metabolic reprogramming mediates prostate cancer survival and metastasis. Sci Signal 125 1174 PMID: 25664849
Chung et al (2015) The mTORC1/4E-BP pathway coordinates hemoglobin production with L-leucine availability. Mol Cancer Res 8 ra34 PMID: 25872869
Dey-Guha et al (2015) A mechanism for asymmetric cell division resulting in proliferative asynchronicity. Autophagy 13 223 PMID: 25582703
Matsuzawa et al (2015) TNFAIP3 promotes survival of CD4 T cells by restricting MTOR and promoting autophagy. Sci Rep 11 1052 PMID: 26043155
Ito et al (2015) PARK2-mediated mitophagy is involved in regulation of HBEC senescence in COPD pathogenesis. Nature 11 547 PMID: 25714760
Rebsamen et al (2015) SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1. Autophagy 519 477 PMID: 25561175
Figueroa et al (2015) Autophagy activation and protection from mitochondrial dysfunction in human chondrocytes. Autophagy 67 966 PMID: 25605458
Saqcena et al (2015) Apoptotic effects of high-dose rapamycin occur in S-phase of the cell cycle. Autophagy 14 2285 PMID: 25945415
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Valvezan et al (2014) Oncogenic mutations in adenomatous polyposis coli (Apc) activate mechanistic target of rapamycin complex 1 (mTORC1) in mice and zebrafish. Dis Model Mech 7 63 PMID: 24092877
Sahani et al (2014) Expression of the autophagy substrate SQSTM1/p62 is restored during prolonged starvation depending on transcriptional upregulation and autophagy-derived amino acids. Autophagy 10 431 PMID: 24394643
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Hatanaka et al (2014) Palmitate induces mRNA translation and increases ER protein load in islet β-cells via activation of the mammalian target of rapamycin pathway. Diabetes 63 3404 PMID: 24834975
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Juan et al (2021) Genistein Activates Transcription Factor EB and Corrects Niemann-Pick C Phenotype. Int J Mol Sci 22 PMID: 33921734
Hanna et al (2021) A high-throughput screening identifies ZNF418 as a novel regulator of the ubiquitin-proteasome system and autophagy-lysosomal pathway. Autophagy 17 3124-3139 PMID: 33249983
Koji L et al (2021) NEK9 regulates primary cilia formation by acting as a selective autophagy adaptor for MYH9/myosin IIA. Nat Commun 12 3292 PMID: 34078910
David C et al (2021) Glucose starvation induces autophagy via ULK1-mediated activation of PIKfyve in an AMPK-dependent manner. Dev Cell 56 1961-1975.e5 PMID: 34107300
John M et al (2021) The mTORC1-mediated activation of ATF4 promotes protein and glutathione synthesis downstream of growth signals. Elife 10 PMID: 33646118
Konstantinos et al (2021) Cdk5 and GSK3β inhibit fast endophilin-mediated endocytosis. Nat Commun 12 2424 PMID: 33893293
Sami J et al (2021) Development of a specific live-cell assay for native autophagic flux. J Biol Chem 297 101003 PMID: 34303705
Andrew et al (2021) Patient-specific iPSCs carrying an SFTPC mutation reveal the intrinsic alveolar epithelial dysfunction at the inception of interstitial lung disease. Cell Rep 36 109636 PMID: 34469722
Neysan et al (2021) Genotoxic stress in constitutive trisomies induces autophagy and the innate immune response via the cGAS-STING pathway. Commun Biol 4 831 PMID: 34215848
Shuang et al (2021) Loss of SNORA73 reprograms cellular metabolism and protects against steatohepatitis. Nat Commun 12 5214 PMID: 34471131
An-Dao et al (2021) mTORC1 promotes TOP mRNA translation through site-specific phosphorylation of LARP1. Nucleic Acids Res 49 3461-3489 PMID: 33398329
Mathilde et al (2021) Atg7 deficiency in microglia drives an altered transcriptomic profile associated with an impaired neuroinflammatory response. Mol Brain 14 87 PMID: 34082793
Selim et al (2021) Comparing mTOR inhibitor Rapamycin with Torin-2 within the RIST molecular-targeted regimen in neuroblastoma cells. Int J Med Sci 18 137-149 PMID: 33390782
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Päivi et al (2021) FTLD Patient-Derived Fibroblasts Show Defective Mitochondrial Function and Accumulation of p62. Mol Neurobiol 58 5438-5458 PMID: 34328616
Mario et al (2021) Increased fidelity of protein synthesis extends lifespan. Cell Metab 33 2288-2300.e12 PMID: 34525330
John M et al (2021) Hepatic mTORC1 signaling activates ATF4 as part of its metabolic response to feeding and insulin. Mol Metab 53 101309 PMID: 34303878
Markus et al (2021) p38 regulates the tumor suppressor PDCD4 via the TSC-mTORC1 pathway. Cell Stress 5 176-182 PMID: 34917890
Qiong et al (2021) Activation of mTORC1 at late endosomes misdirects T cell fate decision in older individuals. Sci Immunol 6 PMID: 34145066
Michael et al (2021) Amino acids and mechanistic target of rapamycin regulate the fate of live engulfed cells. FASEB J 35 e21909 PMID: 34547144
Jun et al (2021) Impaired TRIM16-Mediated Lysophagy in Chronic Obstructive Pulmonary Disease Pathogenesis. J Immunol 207 65-76 PMID: 34135057
Guido et al (2021) Oleate-induced aggregation of LC3 at the trans-Golgi network is linked to a protein trafficking blockade. Cell Death Differ 28 1733-1752 PMID: 33335289
Joshua D et al (2021) mTORC1 promotes cell growth via m6A-dependent mRNA degradation. Mol Cell 81 2064-2075.e8 PMID: 33756105
John M et al (2021) mTORC1 stimulates cell growth through SAM synthesis and m6A mRNA-dependent control of protein synthesis. Mol Cell 81 2076-2093.e9 PMID: 33756106
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Hans-Uwe et al (2021) Evidence for Lysosomal Dysfunction within the Epidermis in Psoriasis and Atopic Dermatitis. J Invest Dermatol 141 2838-2848.e4 PMID: 34090855
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Roberto et al (2021) NPC1-mTORC1 Signaling Couples Cholesterol Sensing to Organelle Homeostasis and Is a Targetable Pathway in Niemann-Pick Type C. Dev Cell 56 260-276.e7 PMID: 33308480
Paul F et al (2021) Rheb mediates neuronal-activity-induced mitochondrial energetics through mTORC1-independent PDH activation. Dev Cell 56 811-825.e6 PMID: 33725483
Sica et al (2019) Lethal Poisoning of Cancer Cells by Respiratory Chain Inhibition plus Dimethyl α-Ketoglutarate. Cell Rep 27 820 PMID: 30995479
Neubert et al (2019) HIF1A and NFAT5 coordinate Na+-boosted antibacterial defense via enhanced autophagy and autolysosomal targeting. Autophagy 1 PMID: 30982460
Ji et al (2019) Type 2 diabetes is associated with suppression of autophagy and lipid accumulation in β-cells. J Cell Mol Med 23 2890 PMID: 30710421
Li et al (2017) mTORC1 Phosphorylates Acetyltransferase p300 to Regulate Autophagy and Lipogenesis. Mol Cell 68 323-335.e6 PMID: 29033323
Jun et al (2017) m6A Facilitates eIF4F-Independent mRNA Translation. Mol Cell 68 504-514.e7 PMID: 29107534
Yong Ha et al (2017) mTORC1-Mediated Inhibition of 4EBP1 Is Essential for Hedgehog Signaling-Driven Translation and Medulloblastoma. Dev Cell 43 673-688.e5 PMID: 29103956
Heidi M et al (2017) mTOR Controls Mitochondrial Dynamics and Cell Survival via MTFP1. Mol Cell 67 922-935.e5 PMID: 28918902
Mark S et al (2017) Primary fibroblasts from CSPα mutation carriers recapitulate hallmarks of the adult onset neuronal ceroid lipofuscinosis. Sci Rep 7 6332 PMID: 28740222
Lei et al (2017) SYK kinase mediates brown fat differentiation and activation. Nat Commun 8 2115 PMID: 29235464
Michael S et al (2017) Influenza virus differentially activates mTORC1 and mTORC2 signaling to maximize late stage replication. PLoS Pathog 13 e1006635 PMID: 28953980
Qingsong et al (2017) Nonradioactive quantification of autophagic protein degradation with L-azidohomoalanine labeling. Nat Protoc 12 279-288 PMID: 28079880
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Yuan et al (2017) Tenovin-6 impairs autophagy by inhibiting autophagic flux. Cell Death Dis 8 e2608 PMID: 28182004
Ma et al (2015) Tor Signaling Regulates Transcription of Amino Acid Permeases through a GATA Transcription Factor Gaf1 in Fission Yeast. PLoS One 10 e0144677 PMID: 26689777
Moon et al (2015) mTORC1-Induced HK1-Dependent Glycolysis Regulates NLRP3 Inflammasome Activation. Cell Rep 12 102 PMID: 26119735
Fonseca et al (2015) La-related Protein 1 (LARP1) Represses Terminal Oligopyrimidine (TOP) mRNA Translation Downstream of mTOR Complex 1 (mTORC1). J Biol Chem 290 15996 PMID: 25940091
Gubbiotti et al (2015) Decorin is an autophagy-inducible proteoglycan and is required for proper in vivo autophagy. Matrix Biol 48 14 PMID: 26344480
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Torres-Ayuso et al (2015) Diacylglycerol kinase-ζ regulates mTORC1 and lipogenic metabolism in cancer cells through SREBP-1. Oncogenesis 4 e164 PMID: 26302180
Fields et al (2015) HIV-1 Tat alters neuronal autophagy by modulating autophagosome fusion to the lysosome: implications for HIV-associated neurocognitive disorders. J Neurosci 35 1921 PMID: 25653352
Avey et al (2015) Phosphoproteomic Analysis of KSHV-Infected Cells Reveals Roles of ORF45-Activated RSK during Lytic Replication. PLoS Pathog 11 e1004993 PMID: 26133373
Newton et al (2015) Pharmacological inhibition of lysosomes activates the MTORC1 signaling pathway in chondrocytes in an autophagy-independent manner. Autophagy 11 1594 PMID: 26259639
Wong et al (2015) Regulation of autophagy by coordinated action of mTORC1 and protein phosphatase 2A. Nat Commun 6 8048 PMID: 26310906
Sagnier et al (2015) Autophagy restricts HIV-1 infection by selectively degrading Tat in CD4+ T lymphocytes. J Virol 89 615 PMID: 25339774
Ma et al (2015) Regulation of the transcription factor EB-PGC1α axis by beclin-1 controls mitochondrial quality and cardiomyocyte death under stress. Mol Cell Biol 35 956 PMID: 25561470
Jung et al (2015) Amino Acid-Dependent mTORC1 Regulation by the Lysosomal Membrane Protein SLC38A9. Mol Cell Biol 35 2479 PMID: 25963655
Grassi et al (2015) Autophagy regulates hepatocyte identity and epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions promoting Snail degradation. Cell Death Dis 6 e1880 PMID: 26355343
Askvig and Watt (2015) The MAPK and PI3K pathways mediate CNTF-induced neuronal survival and process outgrowth in hypothalamic organotypic cultures. J Cell Commun Signal 9 217 PMID: 25698661
Pyo et al (2018) ULK1 O-GlcNAcylation Is Crucial for Activating VPS34 via ATG14L during Autophagy Initiation. Cell Rep 25 2878 PMID: 30517873
Matsui et al (2018) Autophagosomal YKT6 is required for fusion with lysosomes independently of syntaxin 17. J Cell Biol 217 2633 PMID: 29789439
Cosima T et al (2018) The pro-oxidant adaptor p66SHC promotes B cell mitophagy by disrupting mitochondrial integrity and recruiting LC3-II. Autophagy 14 2117-2138 PMID: 30109811
Nikolai et al (2018) The Long-lived Protein Degradation Assay: an Efficient Method for Quantitative Determination of the Autophagic Flux of Endogenous Proteins in Adherent Cell Lines. Bio Protoc 8 e2836 PMID: 34286043
Yasuo et al (2018) Cancer Cells Co-opt the Neuronal Redox-Sensing Channel TRPA1 to Promote Oxidative-Stress Tolerance. Cancer Cell 33 985-1003.e7 PMID: 29805077
Xin et al (2018) mTORC1 Promotes Metabolic Reprogramming by the Suppression of GSK3-Dependent Foxk1 Phosphorylation. Mol Cell 70 949-960.e4 PMID: 29861159
Peter et al (2018) Translational and HIF-1α-Dependent Metabolic Reprogramming Underpin Metabolic Plasticity and Responses to Kinase Inhibitors and Biguanides. Cell Metab 28 817-832.e8 PMID: 30244971
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We got expected effect on cells.
By
Anonymous on 04/03/2020
Assay Type: In Vitro
Species: Mouse
Cell Line/Tissue: Primary pancreatic ductal epithelial cells
0.076–500 nM Torin
inhibition of Torin in acute brain slices.
By
Anonymous on 01/10/2018
Assay Type: Ex Vivo
Species: Mouse
Cell Line/Tissue: acute brain slices
We used Torin-1 to inhibit torin signalling, we got the expected effect on metabolic changes in acute brain slices
30 minute pre-incubation on acute slices
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