Torin 2
Modify Date: 2024-01-03 13:57:03
Torin 2 structure
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Common Name | Torin 2 | ||
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| CAS Number | 1223001-51-1 | Molecular Weight | 432.397 | |
| Density | 1.4±0.1 g/cm3 | Boiling Point | 623.7±55.0 °C at 760 mmHg | |
| Molecular Formula | C24H15F3N4O | Melting Point | N/A | |
| MSDS | USA | Flash Point | 331.0±31.5 °C | |
Use of Torin 2Torin 2 is an mTOR inhibitor with EC50 of 0.25 nM for inhibiting cellular mTOR activity, and exhibits 800-fold selectivity over PI3K (EC50: 200 nM). Torin 2 also inhibits DNA-PK with an IC50 of 0.5 nM in the cell free assay. Torin 2 can suppress both mTORC1 and mTORC2. |
| Name | 9-(6-aminopyridin-3-yl)-1-[3-(trifluoromethyl)phenyl]benzo[h][1,6]naphthyridin-2-one |
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| Synonym | More Synonyms |
| Description | Torin 2 is an mTOR inhibitor with EC50 of 0.25 nM for inhibiting cellular mTOR activity, and exhibits 800-fold selectivity over PI3K (EC50: 200 nM). Torin 2 also inhibits DNA-PK with an IC50 of 0.5 nM in the cell free assay. Torin 2 can suppress both mTORC1 and mTORC2. |
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| Related Catalog | |
| Target |
mTOR:2.81 nM (IC50) mTOR:0.25 nM (EC50, Cell Assay) mTORC1 mTORC2 DNA-PK:0.5 nM (IC50) PI3K-C2α:28.1 nM (IC50) PI3K-C2β:24.5 nM (IC50) p110γ:5.67 nM (IC50) hVps34:8.58 nM (IC50) ΡΙ4Κβ:18.3 nM (IC50) Autophagy PI3K:200 nM (EC50, Cell Assay) |
| In Vitro | Torin 2 is subject to further profiling against a panel of lipid kinases with IC50s of 2.81 nM, 0.5 nM, 5.67 nM, 8.58 nM, 18.3 nM, 24.5 nM and 28.1 nM for mTOR, DNA-pK, p110γ, hVPS34, PI4Kβ, PI3K-C2β and PI3K-C2α, respectively. Torin 2 (Torin2) possesses a 250 pM EC50 for inhibiting mTOR in cells while maintaining 800-fold cellular selectivity relative to inhibition of PI3K and most other protein kinases[1]. Torin 2 (Torin2) exhibits potent biochemical and cellular activity against PIKK family kinases including ATM (EC50 28 nM), ATR (EC50 35 nM) and DNA-PK (EC50 118 nM). Torin 2 potently inhibits T308 of Akt, a direct substrate of PDK1 and an indirect substrate of PI3Ks, with an EC50 of less than 10 nM[2]. Torin-2 can suppress bothmTORC1 and mTORC2[4]. |
| In Vivo | Torin 2 (Torin2) exhibits good bioavailability and exposure and can maintain strong inhibition of mTOR activity in lung and liver to at least six hours after a single dose of 20 mg/kg. Torin 2 is easier to produce on scale and exhibits improved pharmacokinetic properties which should enable it use in vivo experiments[1]. Torin 2 (Torin2) strongly suppresses pS6K(T389) and p4EBP1(T37/46) and partly suppresses pAkt(T308). Treatment of mice with AZD6244 at 25 mg/kg results in a profound inhibition of pERK. Combined administration of Torin 2 (40 mg/kg) and AZD6244 (25 mg/kg) demonstrates strong inhibition of all pharmacodynamics markers[2]. Treatment with Torin 2 (Torin2) and Rapamycin induces IL-6 secretion by astrocytes and may contribute to the reduction of mechanical hypersensitivity after SCI. Torin1 and Torin 2 treatment increases IL-6 mRNA, suggesting that the PI3K-mTOR pathway is a negative regulator of IL-6 expression in astrocytes. Importantly, Torin 2 treatment does not show any cell toxicity, as no signs of cell death are observed by TUNEL assay or by detection of cleaved-caspase 3 by western blotting[3]. |
| Cell Assay | HCT116 cells are treated with 100 nM Torin 2 or AZD8055 for 1 hour before they are thoroughly washed out by 3×PBS and 1×DMEM medium. Then cells are incubated in DMEM medium for indicated time before they are lysed and collected using M-PER. Protein concentrations are measured and equal amount of proteins are loaded. Experiments are repeated three times and one set of results[2]. |
| Animal Admin | Mice[1] Six-week old male C57BL/6 mice are fasted overnight prior to Torin 2 treatment. The mice are treated with vehicle (for 10 h) or Torin 2 (20 mg/kg for 6h) via oral gavage and then re-fed 1 h prior to sacrifice (CO2 asphyxiation). Liver and lung are collected and frozen on dry ice. 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). The concentration of clear lysate is measured using the Bradford assay and samples are subsequently normalized by protein content and analyzed by SDS-PAGE and immunoblotting. Rats[3] Female rats (220 g) are group-housed 4 animals per cage, and kept on a 12-hour light/dark cycle with food and water ad libitum. Spinal cord injury is done with the Keck Center for Neurosciences impactor using a 10 g weight dropped from a height of 25 mm onto the dorsal surface of the exposed spinal cord. After recording BBB scores, withdrawal thresholds evoked by touch stimulus, and body weights for the first week post-injury, animals are divided into 5 treatment groups: naïve (N=4), sham (N=6), vehicle (N=6), Torin 2 (N=6), and Torin 2+Rapamycin (N=8). Torin 2 alone (4 mg/kg) or in combination with Rapamycin (1.5 mg/kg) is administered orally by gavage once a day starting at day 15 after injury and ending at day 29. In sham operated rats only the laminectomy is performed. |
| References |
[4]. Wang X, et al. mTORC signaling in hematopoiesis. Int J Hematol. 2016 May;103(5):510-8. |
| Density | 1.4±0.1 g/cm3 |
|---|---|
| Boiling Point | 623.7±55.0 °C at 760 mmHg |
| Molecular Formula | C24H15F3N4O |
| Molecular Weight | 432.397 |
| Flash Point | 331.0±31.5 °C |
| Exact Mass | 432.119781 |
| PSA | 73.80000 |
| LogP | 4.20 |
| Vapour Pressure | 0.0±1.8 mmHg at 25°C |
| Index of Refraction | 1.676 |
| Hazard Codes | Xi |
|---|---|
| RIDADR | NONH for all modes of transport |
| Torin 2 |
| Benzo[h][1,6]naphthyridin-2(1H)-one, 9-(6-amino-3-pyridinyl)-1-[3-(trifluoromethyl)phenyl]- |
| HMS3265O06 |
| HMS3265O05 |
| cc-275 |
| 9-(6-Amino-3-pyridinyl)-1-[3-(trifluoromethyl)phenyl]benzo[h][1,6]naphthyridin-2(1H)-one |
| 9-(6-Amino-3-pyridinyl)-1-[3-(trifluoromethyl)phenyl]benzo[h]-1,6-naphthyridin-2(1H)-one |
| Torin2 |