Torin 1

製品コードS2827 バッチS282704

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C35H28F3N5O2
分子量 607.62 CAS No. 1222998-36-8
Solubility (25°C)* 体外 DMSO 1 mg/mL warmed with 50ºC water bath (1.64 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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.
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]

プロトコル(参考用のみ)

キナーゼアッセイ 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.
細胞アッセイ 細胞株 MEFs
濃度 ~250 nM
反応時間 4 days
実験の流れ 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.
動物実験 動物モデル U87MG xenograft model
投薬量 20 mg/kg
投与方法 Administered via i.p. once daily

カスタマーフィードバック

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]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Akt enhances the vulnerability of cancer cells to VCP/p97 inhibition-mediated paraptosis [ Cell Death Dis, 2024, 15(1):48] PubMed: 38218922
MTOR Suppresses Cigarette Smoke-Induced Airway Inflammation and MMP12 Expression in Macrophage in Chronic Obstructive Pulmonary Disease [ Int J Chron Obstruct Pulmon Dis, 2024, 19:269-279] PubMed: 38288346
Lysosomes mediate the mitochondrial UPR via mTORC1-dependent ATF4 phosphorylation [ Cell Discov, 2023, 9(1):92] PubMed: 37679337
Lysosomes mediate the mitochondrial UPR via mTORC1-dependent ATF4 phosphorylation [ Cell Discov, 2023, 9(1):92] PubMed: 37679337
PD-1 instructs a tumor-suppressive metabolic program that restricts glycolysis and restrains AP-1 activity in T cell lymphoma [ Nat Cancer, 2023, 4(10):1508-1525] PubMed: 37723306
Analysis of ATG4C function in vivo [ Autophagy, 2023, 19(11):2912-2933] PubMed: 37459465
Direct regulation of FNIP1 and FNIP2 by MEF2 sustains MTORC1 activation and tumor progression in pancreatic cancer [ Autophagy, 2023, 1-20.] PubMed: 37772772
Analysis of ATG4C function in vivo [ Autophagy, 2023, 19(11):2912-2933] PubMed: 37459465
SARS-CoV-2 ORF7a blocked autophagy flux by intervening in the fusion between autophagosome and lysosome to promote viral infection and pathogenesis [ J Med Virol, 2023, 10.1002/jmv.29200] PubMed: 37916857
NCoR1 controls Mycobacterium tuberculosis growth in myeloid cells by regulating the AMPK-mTOR-TFEB axis [ PLoS Biol, 2023, 21(8):e3002231] PubMed: 37590294

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人間や獣医の診断であるか治療的な使用のためにでない。

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