Torin 1

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Cat.No. 4247 - Torin 1 | C35H28F3N5O2 | CAS No. 1222998-36-8
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)
Datasheet
Citations (90)
Reviews (1)
Literature
Pathways

Biological Activity

Potent and selective mTOR inhibitor (IC50 = 2 - 10 nM for mTORC1 and mTORC2). Displays 200-fold selectivity for mTOR over DNA-PK, ATM and hVps34. Induces autophagy in HeLa cells.

Licensing Information

Sold under license from Whitehead Institute for Biomedical Research.

Technical Data

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

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 0.61 1 with gentle warming

Preparing Stock Solutions

The following data is based on the product molecular weight 607.62. Batch specific molecular weights may vary from batch to batch due to solvent 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

Certificate of Analysis / Product Datasheet
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References

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


If you know of a relevant reference for Torin 1, please let us know.

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Keywords: Torin 1, Torin 1 supplier, Torin1, mtor, mammalian, target, rapamycin, inhibitors, inhibits, potent, selective, mTOR, Autophagy, 4247, Tocris Bioscience

90 Citations for Torin 1

Citations are publications that use Tocris products. Selected citations for Torin 1 include:

Martina and Puertollano (2013) Rag GTPases mediate amino acid-dependent recruitment of TFEB and MITF to lysosomes. J Cell Biol 200 475 PMID: 23401004

Gammoh et al (2013) Interaction between FIP200 and ATG16L1 distinguishes ULK1 complex-dependent and -independent autophagy. Nat Struct Mol Biol 20 144 PMID: 23262492

Bachar-Wikstrom et al (2013) Stimulation of autophagy improves endoplasmic reticulum stress-induced diabetes. Diabetes 62 1227 PMID: 23274896

Kok et al (2013) Differential regulation of the expressions of the PGC-1α splice variants, lipins, and PPARα in heart compared to liver. J Lipid Res 54 1662 PMID: 23505321

Krajcovic et al (2013) mTOR regulates phagosome and entotic vacuole fission. Mol Biol Cell 24 3736 PMID: 24088573

Carnevale et al (2013) SYK regulates mTOR signaling in AML. Leukemia 27 2118 PMID: 23535559

Dai et al (2013) mTOR complex 2 phosphorylates IMP1 cotranslationally to promote IGF2 production and the proliferation of mouse embryonic fibroblasts. Genes Dev 27 301 PMID: 23388827

Narvajas et al (2013) Epigenetic regulation of autophagy by the methyltransferase G9a. Mol Cell Biol 33 3983 PMID: 23918802

Zhou et al (2013) Activation of lysosomal function in the course of autophagy via mTORC1 suppression and autophagosome-lysosome fusion. Cell Res 23 508 PMID: 23337583

Li et al (2013) Suppression of lysosome function induces autophagy via a feedback down-regulation of MTOR complex 1 (MTORC1) activity. J Biol Chem 288 35769 PMID: 24174532

Martina et al (2012) MTORC1 functions as a transcriptional regulator of autophagy by preventing nuclear transport of TFEB. Autophagy 8 903 PMID: 22576015

Fonseca et al (2012) Structure-activity analysis of niclosamide reveals potential role for cytoplasmic pH in control of mammalian target of rapamycin complex 1 (mTORC1) signaling. J Biol Chem 287 17530 PMID: 22474287

Pei et al (2017) The E3 ubiquitin ligase NEDD4 enhances killing of membrane-perturbing intracellular bacteria by promoting autophagy. Autophagy 13 2041 PMID: 29251248

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

Xia et al (2016) TDP-43 loss of function increases TFEB activity and blocks autophagosome-lysosome fusion. EMBO J 35 121 PMID: 26702100

Torgersen et al (2016) The anti-tumor drug 2-hydroxyoleic acid (Minerval) stimulates signaling and retrograde transport. Oncotarget 7 86871 PMID: 27894086

Liu (2016) Characterizing inactive ribosomes in translational profiling. Translation (Austin) 4 e1138018 PMID: 27335722

Mao et al (2016) IL-15 activates mTOR and primes stress-activated gene expression leading to prolonged antitumor capacity of NK cells. Blood 128 1475 PMID: 27465917

Zhang et al (2014) Development of a novel method for quantification of autophagic protein degradation by AHA labeling. PLoS Genet 10 901 PMID: 24675368

Sharma et al (2014) Japanese encephalitis virus replication is negatively regulated by autophagy and occurs on LC3-I- and EDEM1-containing membranes. Arthritis Rheumatol 10 1637 PMID: 25046112

Bernard et al (2014) Autophagy fosters myofibroblast differentiation through MTORC2 activation and downstream upregulation of CTGF. Cell Cycle 10 2193 PMID: 25495560

Li et al (2014) Rapamycin-insensitive up-regulation of adipocyte phospholipase A2 in tuberous sclerosis and lymphangioleiomyomatosis. J Exp Med 9 e104809 PMID: 25347447

Liang et al (2014) Regulation of YAP by mTOR and autophagy reveals a therapeutic target of tuberous sclerosis complex. J Exp Med 211 2249 PMID: 25288394

Li et al (2014) Estradiol and mTORC2 cooperate to enhance prostaglandin biosynthesis and tumorigenesis in TSC2-deficient LAM cells. BMC Biochem 211 15 PMID: 24395886

Zullo et al (2014) Mammalian target of Rapamycin inhibition and mycobacterial survival are uncoupled in murine macrophages. Proc Natl Acad Sci U S A 15 4 PMID: 24528777

Kimura et al (2016) Polarization of M2 macrophages requires Lamtor1 that integrates cytokine and amino-acid signals Nature Communications 7 13130 PMID: 27731330

Pema et al (2016) mTORC1-mediated inhibition of polycystin-1 expression drives renal cyst formation in tuberous sclerosis complex. Mol Biol Cell 7 10786 PMID: 26931735

Saric et al (2016) mTOR controls lysosome tubulation and antigen presentation in macrophages and dendritic cells. Autophagy 27 321 PMID: 26582390

Hao et al (2016) An evolutionarily conserved mechanism for cAMP elicited axonal regeneration involves direct activation of the dual leucine zipper kinase DLK. Proc Natl Acad Sci U S A 5 PMID: 27268300

Chen et al (2016) Trehalose, sucrose and raffinose are novel activators of autophagy in human keratinocytes through an mTOR-independent pathway. PLoS One 6 28423 PMID: 27328819

Ma et al (2016) The Loss of Lam2 and Npr2-Npr3 Diminishes the Vacuolar Localization of Gtr1-Gtr2 and Disinhibits TORC1 Activity in Fission Yeast. PLoS One 11 e0156239 PMID: 27227887

Zhang et al (2016) A Founder Mutation in VPS11 Causes an Autosomal Recessive Leukoencephalopathy Linked to Autophagic Defects. Cell Rep 12 e1005848 PMID: 27120463

Martina et al (2014) The nutrient-responsive transcription factor TFE3 promotes autophagy, lysosomal biogenesis, and clearance of cellular debris. Sci Signal 7 ra9 PMID: 24448649

Fournier et al (2013) Inactivation of the mTORC1-eukaryotic translation initiation factor 4E pathway alters stress granule formation. Mol Cell Biol 33 2285 PMID: 23547259

Francipane and Lagasse (2013) Selective targeting of human colon cancer stem-like cells by the mTOR inhibitor Torin-1. Oncotarget 4 1948 PMID: 24185040

Morita et al (2013) mTORC1 controls mitochondrial activity and biogenesis through 4E-BP-dependent translational regulation. Cell Metab 18 698 PMID: 24206664

Taguchi et al (2012) Keap1 degradation by autophagy for the maintenance of redox homeostasis. J Exp Bot 109 13561 PMID: 22872865

Kobayashi et al (2016) Involvement of PARK2-Mediated Mitophagy in Idiopathic Pulmonary Fibrosis Pathogenesis. J Immunol 197 504 PMID: 27279371

Erbil et al (2016) RACK1 Is an Interaction Partner of ATG5 and a Novel Regulator of Autophagy. J Biol Chem 291 16753 PMID: 27325703

Pastore et al (2016) TFEB and TFE3 cooperate in the regulation of the innate immune response in activated macrophages. Autophagy 12 1240 PMID: 27171064

Bouche et al (2016) Drosophila Mitf regulates the V-ATPase and the lysosomal-autophagic pathway. Autophagy 12 484 PMID: 26761346

Fernández et al (2016) Iron overload causes endolysosomal deficits modulated by NAADP-regulated 2-pore channels and RAB7A. Autophagy 12 1487 PMID: 27383256

Li et al (2016) A novel Rab10-EHBP1-EHD2 complex essential for the autophagic engulfment of lipid droplets. Sci Adv 2 e1601470 PMID: 28028537

Bayraktar et al (2016) IBMPFD Disease-Causing Mutant VCP/p97 Proteins Are Targets of Autophagic-Lysosomal Degradation. PLoS One 11 e0164864 PMID: 27768726

Puente et al (2016) Nutrient-regulated Phosphorylation of ATG13 Inhibits Starvation-induced Autophagy. J Biol Chem 291 6026 PMID: 26801615

Contreras et al (2016) Neuronal gene repression in Niemann-Pick type C models is mediated by the c-Abl/HDAC2 signaling pathway. Biochim Biophys Acta 1859 269 PMID: 26603102

Holler et al (2016) Trehalose upregulates progranulin expression in human and mouse models of GRN haploinsufficiency: a novel therapeutic lead to treat frontotemporal dementia. Mol Neurodegener 11 46 PMID: 27341800

Gandin et al (2016) mTORC1 and CK2 coordinate ternary and eIF4F complex assembly. Nat Commun 7 11127 PMID: 27040916

Jennewein et al (2016) Diagnostic and clinical relevance of the autophago-lysosomal network in human gliomas. Oncotarget 7 20016 PMID: 26956048

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

Lee et al (2015) Reinstating aberrant mTORC1 activity in Huntington's disease mice improves disease phenotypes. Neuron 85 303 PMID: 25556834

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

Xu et al (2013) Live imaging and single-cell analysis reveal differential dynamics of autophagy and apoptosis. Autophagy 9 1418 PMID: 23748697

Montané and Menand (2013) ATP-competitive mTOR kinase inhibitors delay plant growth by triggering early differentiation of meristematic cells but no developmental patterning change. Nat Commun 64 4361 PMID: 23963679

Esen et al (2013) WNT-LRP5 signaling induces Warburg effect through mTORC2 activation during osteoblast differentiation. Cell Metab 17 745 PMID: 23623748

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 insulin-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

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

Zaccara et al (2014) p53-directed translational control can shape and expand the universe of p53 target genes. Cell Death Differ PMID: 24926617

Su et al (2014) An invertebrate Warburg effect: a shrimp virus achieves successful replication by altering the host metabolome via the PI3K-Akt-mTOR pathway. PLoS Pathog 10 e1004196 PMID: 24945378

Yamamoto et al (2014) Fertilization-induced autophagy in mouse embryos is independent of mTORC1. Biol Reprod 91 7 PMID: 24855105

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

Sobol et al (2015) Amyloid precursor protein (APP) affects global protein synthesis in dividing human cells. J Cell Physiol 230 1064 PMID: 25283437

Sinha et al (2017) Loss of ULK1 increases RPS6KB1-NCOR1 repression of NR1H/LXR-mediated Scd1 transcription and augments lipotoxicity in hepatic cells. Autophagy 13 169 PMID: 27846372

Yuan et al (2017) Tenovin-6 impairs autophagy by inhibiting autophagic flux. Cell Death Dis 8 e2608 PMID: 28182004


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Reviews for Torin 1

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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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Pathways for Torin 1

mTOR

mTOR Signaling Pathway

mTOR is a serine/threonine kinase that nucleates at multiprotein complexes mTORC1 and mTORC2. Signaling by these complexes regulates cell growth, proliferation and survival.