Torin 1

Catalog No.S2827 Batch:S282703

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Technical Data

Formula

C35H28F3N5O2
Molecular Weight 607.62 CAS No. 1222998-36-8
Solubility (25°C)* In vitro DMSO 2 mg/mL (3.29 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description Torin 1 is a potent inhibitor of mTORC1/2 with IC50 of 2 nM/10 nM in cell-free assays; exhibits 1000-fold selectivity for mTOR than PI3K.
Targets
mTORC1 [1]
(Cell-free assay)		 mTOR [2]
(Cell-free assay)		 DNA-PK [2]
(Cell-free assay)		 mTORC2 [1]
(Cell-free assay)		 p110γ [2]
(Cell-free assay)		 View More
2 nM 4.32 nM 6.34 nM 10 nM 171 nM
In vitro Torin1 inhibits phosphorylation of mTORC1 and mTORC2 substrates in cells at concentrations of 2 and 10 nM, respectively. Moreover, Torin1 exhibits 1000-fold selectivity for mTOR over PI3K (EC50 = 1800 nM) and exhibits 100-fold binding selectivity relative to 450 other protein kinases. [1] [2] Torin1 causes cell cycle arrest through a rapamycin-resistant mechanism that is also independent of mTORC2. Torin1 disrupts mTORC1-dependent phenotypes more completely than rapamycin. Rapamycin-resistant functions of mTORC1 are required for cap-dependent translation. [1] In a recent study, it is reported Torin1 increases neurotensin secretion and gene expression through activation of the MEK/ERK/c-Jun pathway in the human endocrine cell line BON. [3]
In vivo Torin1 is efficacious at a dose of 20 mg/kg in a U87MG xenograft model and demonstrates good pharmacodynamic inhibition of downstream effectors of mTOR in tumor and peripheral tissues. [2]

Protocol (from reference)

Kinase Assay:[1]
  • mTORC1 and mTORC2 in Vitro Kinase Assays

    To produce soluble mTORC1, HEK-293T cell lines that stably express N-terminally FLAG-tagged Raptor are generated using vesicular stomatitis virus G-pseudotyped MSCV retrovirus. For mTORC2, similar HeLa cells that stably express N-terminally FLAG-tagged Protor-1 are generated. Both complexes are purified by lysing cells in 50 mm HEPES, pH 7.4, 10 mm sodium pyrophosphate, 10 mm sodium β-glycerophosphate, 100 mm NaCl, 2 mm EDTA, 0.3% CHAPS. Cells are lysed at 4 °C for 30 min, and the insoluble fraction is removed by microcentrifugation at 13,000 rpm for 10 min. Supernatants are incubated with FLAG-M2 monoclonal antibody-agarose for 1 h and then washed three times with lysis buffer and once with lysis buffer containing a final concentration of 0.5 M NaCl. Purified mTORC1 is eluted with 100 μg/mL 3×FLAG peptide in 50 mm HEPES, pH 7.4, 100 mm NaCl. Eluate can be aliquoted and stored at -80 °C. Substrates S6K1 and Akt1 are purified. Kinase assays are performed for 20 min at 30 °C in a final volume of 20 μL consisting of the kinase buffer (25 mm HEPES, pH 7.4, 50 mm KCl, 10 mm MgCl2, 500 μm ATP) and 150 ng of inactive S6K1 or Akt1 as substrates. Reactions are stopped by the addition of 80 μL of sample buffer and boiled for 5 min. Samples are subsequently analyzed by SDS-PAGE and immunoblotting.
Cell Assay:[1]
  • Cell lines

    MEFs

  • Concentrations

    ~250 nM

  • Incubation Time

    4 days

  • Method

    Cell viability is assessed with the CellTiter-Glo Luminescent Cell Viability Assay. On Day 0, 96-well plates are seeded with 500 cells per well and grown overnight. On Day 1, cells are treated with the appropriate compounds and subsequently analyzed on Days 3-5. For analysis, plates are incubated for 60 min at room temperature; 50 μL of CellTiter-Glo reagent is added to each well, and plates are mixed on an orbital shaker for 12 min. Luminescence is quantified on a standard plate luminometer.

Animal Study:[2]
  • Animal Models

    U87MG xenograft model

  • Dosages

    20 mg/kg

  • Administration

    Administered via i.p. once daily

Customer Product Validation

Data from [Data independently produced by Am J Pathol, 2014, 184(1), 214-29]

Data from [Data independently produced by Mol Cell Biol, 2014, 34(24), 4474-84]

Data from [Data independently produced by Biochem Biophys Res Commun, 2014, 10.1016/j.bbrc.2014.05.047]

Data independently produced by , , Lim Hsiu Kim, Lina from National University of Singapore

Selleck's Torin 1 has been cited by 253 publications

mTORC1 restricts TFE3 activity by auto-regulating its presence on lysosomes [ Mol Cell, 2024, S1097-2765(24)00832-3] PubMed: 39486419
Nucleolar stress caused by arginine-rich peptides triggers a ribosomopathy and accelerates aging in mice [ Mol Cell, 2024, 84(8):1527-1540.e7] PubMed: 38521064
LARP1 binds ribosomes and TOP mRNAs in repressed complexes [ EMBO J, 2024, ] PubMed: 39533057
Akt enhances the vulnerability of cancer cells to VCP/p97 inhibition-mediated paraptosis [ Cell Death Dis, 2024, 15(1):48] PubMed: 38218922
Macrophage NRF1 promotes mitochondrial protein turnover via the ubiquitin proteasome system to limit mitochondrial stress and inflammation [ Cell Rep, 2024, 43(10):114780] PubMed: 39325625
The mTOR pathway controls phosphorylation of BRAF at T401 [ Cell Commun Signal, 2024, 22(1):428] PubMed: 39223665
The mevalonate pathway contributes to breast primary tumorigenesis and lung metastasis [ Mol Oncol, 2024, 10.1002/1878-0261.13716] PubMed: 39119789
Inhibition of PIKfyve Leads to Lysosomal Disorders via Dysregulation of mTOR Signaling [ Cells, 2024, 13(11)953] PubMed: 38891085
SUMOylated Golgin45 associates with PML-NB to transcriptionally regulate lipid metabolism genes during heat shock stress [ Commun Biol, 2024, 7(1):532] PubMed: 38710927
Necrosulfonamide causes oxidation of PCM1 and impairs ciliogenesis and autophagy [ iScience, 2024, 27(4):109580] PubMed: 38600973

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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