| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
Torin 1, a tricyclic benzonaphthyridinone analog, is a novel, potent and selective mTORC1/2 (mammalian target of rapamycin complex1/2) inhibitor with potential anticancer activity. It is 1000-fold more selective for mTOR over PI3K and inhibits mTORC1/2 with IC50 values of 2 nM/10 nM in cell-free assays.
| Targets |
mTORC1 (IC50 = 2-10 nM); mTORC2 (IC50 = 2-10 nM); mTOR (IC50 = 3 nM); DNA-PK (IC50 = 1 μM); PI3K-α (IC50 = 1.8 μM); ATM (IC50 = 0.6 μM); hVps34 (IC50 = 3 μM); Autophagy
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| ln Vitro |
Torin1 (250 nM) completely inhibits proliferation and causes a G1/S cell cycle arrest, and decreases cell size to a greater degree than 50 nM rapamycin in wild-type MEFs[1]. With the exception of DNA-PK, Torin1 is very selective in comparison to other PIKK family kinases, having a selectivity of more than 800 fold between mTOR and PI3Kis[2].
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| ln Vivo |
In a dose-dependent manner, Deforolimus administration has significant antitumor effects in mice bearing PC-3 (prostate), HCT-116 (colon), MCF7 (breast), PANC-1 (pancreas), or A549 (lung) xenografts. In addition, Deforolimus inhibits mTOR signaling in the SK-LMS-1 xenograft model, which is linked to tumor growth inhibition. [1]
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| Enzyme Assay |
Using vesicular stomatitis virus G-pseudotyped MSCV retrovirus, HEK-293T cell lines that express Raptor with an N-terminal FLAG tag are produced in order to produce soluble mTORC1. HeLa cells that express Protor-1 with an N-terminal FLAG tag are created specifically for mTORC2. In order to purify both complexes, cells are lysed in a solution containing 50 mM HEPES, pH 7.4, 10 mM sodium pyrophosphate, 10 mM sodium β-glycerophosphate, 100 mM NaCl, 2 mM EDTA, and 0.3% CHAPS. Microcentrifugation at 13,000 rpm for 10 minutes is used to separate the insoluble fraction after 30 minutes of cell lysing at 4 °C. After one hour of FLAG-M2 monoclonal antibody-agarose incubation, the supernatants are washed four times in lysis buffer and once in lysis buffer with a final sodium chloride concentration of 0.5 mol/L. In 50 mM HEPES, pH 7.4, 100 mM NaCl, 100 g/mL 3 FLAG peptide is used to elute purified mTORC1. Eluate can be aliquoted and kept at -80°C in storage. With 150 ng of inactive S6K1 or Akt1 as substrates, kinase assays are carried out for 20 min at 30°C in a final volume of 20 μL containing the kinase buffer (25 mM HEPES, pH 7.4, 50 mM KCl, 10 mM MgCl2, 500 M ATP). Adding 80 μL of sample buffer and boiling the mixture for 5 minutes stops the reaction. After that, SDS-PAGE and immunoblotting are used to analyze the samples.
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| Cell Assay |
On Day 0, 96-well plates are seeded with 500 cells per well and grown overnight. The proper compounds are applied to the cells on Day 1 and the cells are then examined on Days 3-5. 50 L of CellTiter-Glo reagent is added to each well of the plates before they are mixed on an orbital shaker for 12 minutes. Plates are then incubated for 60 min at room temperature before being subjected to the analysis. On a common plate luminometer, luminescence is measured.
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| Animal Protocol |
Torin 1 powder is first dissolved in 100% N-methyl-2-pyrrolidone at a concentration of 25 mg/mL for pharmacodynamic experiments, and then diluted 1:4 with sterile 50% PEG400 before injection. The night before receiving medication, male C57BL/6 mice aged six weeks are fasted. The mice are administered either vehicle (for 10 hours) or 26 (20 mg/kg for 2, 6, or 10 hours) by IP injection, and they are then given food again 1 hour before being sacrificed (by CO2 asphyxiation). A collection of tissues is placed on dry ice and frozen. The frozen tissue is thawed on ice and lysed by sonication in tissue lysis buffer (50 mM HEPES, pH 7.4, 40 mM NaCl, 2 mM EDTA, 1.5 mM sodium orthovanadate, 50 mM sodium fluoride, 10 mM sodium pyrophosphate, 10 mM sodium β-glycerophosphate, 0.1% SDS, 1.0% sodium deoxycholate and 1.0% Triton, supplemented with protease inhibitor cocktail tablets). Using the Bradford assay, the amount of clear lysate is determined. After samples are normalized for protein content and subjected to SDS-PAGE and immunoblotting analysis, the results are reported.
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| References |
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| Additional Infomation |
Torin 1 is a member of the class of pyridoquinolines that is 9-(quinolin-3-yl)benzo[h][1,6]naphthyridin-2-one bearing an additional 4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl substituent at position 1. It is a potent inhibitor of mTOR and exhibits anti-cancer properties. It has a role as a mTOR inhibitor and an antineoplastic agent. It is a N-acylpiperazine, a N-arylpiperazine, an organofluorine compound, a pyridoquinoline and a member of quinolines.
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| Molecular Formula |
C35H28F3N5O2
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|---|---|
| Molecular Weight |
607.6243
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| Exact Mass |
607.219
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| Elemental Analysis |
C, 69.18; H, 4.64; F, 9.38; N, 11.53; O, 5.27
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| CAS # |
1222998-36-8
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| Related CAS # |
1222998-36-8
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| PubChem CID |
49836027
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
817.2±65.0 °C at 760 mmHg
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| Flash Point |
448.0±34.3 °C
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| Vapour Pressure |
0.0±2.9 mmHg at 25°C
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| Index of Refraction |
1.663
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| LogP |
5.26
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
45
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| Complexity |
1110
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC(C1C([H])=C(C([H])=C([H])C=1N1C([H])([H])C([H])([H])N(C(C([H])([H])C([H])([H])[H])=O)C([H])([H])C1([H])[H])N1C(C([H])=C([H])C2=C([H])N=C3C([H])=C([H])C(C4C([H])=NC5=C([H])C([H])=C([H])C([H])=C5C=4[H])=C([H])C3=C12)=O)(F)F
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| InChi Key |
AKCRNFFTGXBONI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C35H28F3N5O2/c1-2-32(44)42-15-13-41(14-16-42)31-11-9-26(19-28(31)35(36,37)38)43-33(45)12-8-24-20-40-30-10-7-22(18-27(30)34(24)43)25-17-23-5-3-4-6-29(23)39-21-25/h3-12,17-21H,2,13-16H2,1H3
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| Chemical Name |
1-[4-(4-propanoylpiperazin-1-yl)-3-(trifluoromethyl)phenyl]-9-quinolin-3-ylbenzo[h][1,6]naphthyridin-2-one
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| Synonyms |
Torin-1; Torin1; Torin 1
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~2 mg/mL (~3.3 mM)
Water: <1 mg/mL Ethanol: <1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.25 mg/mL (0.41 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 0.25 mg/mL (0.41 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: 0.05 mg/mL (0.08 mM) in 1% DMSO 99% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Solubility in Formulation 4: 30% PEG 400+0.5% Tween80+5% Propylene glycol: 30mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6458 mL | 8.2288 mL | 16.4577 mL | |
| 5 mM | 0.3292 mL | 1.6458 mL | 3.2915 mL | |
| 10 mM | 0.1646 mL | 0.8229 mL | 1.6458 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05343611 | Recruiting | Dietary Supplement: HPP Choko Dietary Supplement: HPP/VE Choko |
Dementia Malnutrition |
Massimo Venturelli, PhD | May 1, 2022 |
mTORC1 regulation of 4E-BP1 phosphorylation and binding to eIF-4E reveals rapamycin-resistant functions.J Biol Chem.2009 Mar 20;284(12):8023-32.
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Torin1 is a potent and selective mTOR inhibitor.J Biol Chem.2009 Mar 20;284(12):8023-32. |
Torin1 inhibits mTORC1-dependent processes that are resistant to rapamycin.J Biol Chem.2009 Mar 20;284(12):8023-32. |
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