| Field | Specification |
|---|---|
| Target | |
| CAS no. | |
| Applications | |
| Molecular weight | |
| Molecular formula | C24H15F3N4O |
| Purity | |
| Activity | |
| SMILES | |
| Form | Solid |
| Storage | |
| Shipping | |
| Catalog no. (Mfr.) | |
| Main SKU |
Compound Overview
Torin 2 is an mTOR inhibitor with an EC50 of 0.25 nM for cellular mTOR activity, showing 800-fold selectivity over PI3K (EC50 200 nM). It also inhibits DNA-PK with an IC50 of 0.5 nM in a cell-free assay and can suppress both mTORC1 and mTORC2. It is supplied as a white to light yellow solid (C24H15F3N4O, MW 432.40) at 99.65% purity.
Physical & Chemical Properties
| CAS Number | 1223001-51-1 |
|---|---|
| Molecular Formula | C24H15F3N4O |
| Molecular Weight | 432.40 g/mol |
| Purity | 99.65% |
| Appearance | Solid |
| Color | White to light yellow |
| SMILES | O=C1N(C2=C(C=C1)C=NC3=CC=C(C=C32)C4=CC=C(N=C4)N)C5=CC=CC(C(F)(F)F)=C5 |
| Target | mTOR, mTORC1, mTORC2, DNA-PK, p110γ, PI3K-C2β, PI3K-C2α, hVps34, PI3K, PI4Kβ |
| Signaling Pathway | PI3K/Akt/mTOR; Cell Cycle/DNA Damage; Autophagy; Apoptosis |
| Bioactivity Class | Autophagy |
| Solubility | In Vitro: DMSO: 15.62 mg/mL (36.12 mM; Requires sonication; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO) |
| Storage | Powder: -20°C, 3 years; 4°C, 2 years. In solvent: -80°C, 1 year; -20°C, 6 months. |
| Shipping | Room temperature in continental US; may vary elsewhere. |
Biological Activity
IC50 & Target
[1][4]
|
mTOR 2.81 nM (IC50) |
mTOR 0.25 nM (EC50, Cell Assay) |
DNA-PK 0.5 nM (IC50) |
p110γ 5.67 nM (IC50) |
PI3K-C2β 24.5 nM (IC50) |
PI3K-C2α 28.1 nM (IC50) |
hVps34 8.58 nM (IC50) |
PI3K 200 nM (EC50, Cell Assay) |
PI4Kβ 18.3 nM (IC50) |
Literature Cited
Sources cited in this description and in the In Vitro & In Vivo Data tab. Peer-reviewed publications that used this product are listed under References.
[4]. Wang X, et al. mTORC signaling in hematopoiesis. Int J Hematol. 2016 May;103(5):510-8.
Safety
For Research Use Only. Not for use in diagnostic or therapeutic procedures, and not for human or veterinary use. Handle in accordance with the Safety Data Sheet and your institution's chemical hygiene plan.
In Vitro
| Solvent | Solubility | Notes |
|---|---|---|
| DMSO | 15.62 mg/mL (36.12 mM) | requires sonication; use freshly opened DMSO (absorbed moisture lowers solubility) |
Aliquot the stock solution and store it at -80°C (up to 1 year) or -20°C (up to 6 months); avoid repeated freeze-thaw cycles.
In Vivo
Choose the formulation that suits the animal model and route of administration; percentages are volume ratios of the final working solution. Start from a clear DMSO stock (see In Vitro above), add the co-solvents one at a time in the order listed, mixing after each addition, and prepare the working solution fresh on the day of dosing. If precipitation or phase separation occurs, gentle warming or sonication can help.
Protocol 1
| Composition | 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline |
|---|---|
| Result | ≥ 1.56 mg/mL (3.61 mM); clear solution |
| How to prepare | Gives a clear solution at ≥ 1.56 mg/mL (saturation not determined). For 1 mL of working solution: add 100 μL DMSO stock (15.6 mg/mL) to 400 μL PEG300; then 50 μL Tween-80; then 450 μL saline to bring the volume to 1 mL. Saline: dissolve 0.9 g sodium chloride in ddH2O and make up to 100 mL. |
Direct preparation of the working solution
These formulations are prepared directly, without a DMSO stock; use them promptly after preparation.
Protocol 2
| Composition | 10% 1-Methyl-2-pyrrolidinone + 90% PEG300 |
|---|---|
| Result | ≥ 2 mg/mL (4.63 mM); clear solution |
Data provided by the manufacturer.
In Vitro
Torin 2 is further profiled against a panel of lipid kinases, with IC50s of 2.81 nM for mTOR, 0.5 nM for DNA-pK, 5.67 nM for p110γ, 8.58 nM for hVPS34, 18.3 nM for PI4Kβ, 24.5 nM for PI3K-C2β and 28.1 nM for PI3K-C2α. In cells, Torin 2 (Torin2) has an EC50 of 250 pM for inhibiting mTOR, with 800-fold selectivity in cells over PI3K and most other protein kinases[1]. Torin 2 (Torin2) shows potent biochemical and cellular activity against the PIKK family kinases ATM (EC50 28 nM), ATR (EC50 35 nM), and DNA-PK (EC50 118 nM). Akt T308, which is a direct PDK1 substrate and an indirect PI3K substrate, is potently inhibited by Torin 2, with an EC50 below 10 nM[2]. Torin-2 can suppress mTORC1 as well as mTORC2[4].
In Vivo
Torin 2 shows good bioavailability and exposure, and it keeps mTOR activity strongly inhibited in lung and liver for at least six hours after a single 20 mg/kg dose. Torin 2 is also easier to produce at scale and has improved pharmacokinetic properties, which should allow its use in in vivo experiments[1]. pS6K(T389) and p4EBP1(T37/46) are strongly suppressed by Torin 2, and pAkt(T308) is partly suppressed. In mice, AZD6244 at 25 mg/kg results in profound inhibition of pERK. The combination of Torin 2 (40 mg/kg) and AZD6244 (25 mg/kg) strongly inhibits all pharmacodynamics markers[2]. Torin 2 together with Rapamycin induces IL-6 secretion by astrocytes, which may contribute to reduced mechanical hypersensitivity after SCI. IL-6 mRNA is increased by treatment with Torin1 and Torin 2, suggesting that the PI3K-mTOR pathway negatively regulates IL-6 expression in astrocytes. Importantly, Torin 2 shows no cell toxicity: neither TUNEL assay nor western blot detection of cleaved-caspase 3 reveals signs of cell death[3].
Data provided by the manufacturer. Numbered citations refer to the Literature Cited list in the product description.
Cell Assay[2]
Treat HCT116 cells with 100 nM Torin 2 or AZD8055 for 1 hour, then wash out thoroughly with 3×PBS and 1×DMEM medium. Incubate the cells in DMEM medium for the indicated time, then lyse and collect them using M-PER. Measure protein concentrations and load equal amounts of protein. Repeat the experiment three times and present one set of results[2].
Animal Administration[1][3]
Mice[1] Fast six-week-old male C57BL/6 mice overnight before Torin 2 treatment. Give vehicle (for 10 h) or Torin 2 (20 mg/kg for 6h) by oral gavage, and re-feed the mice 1 h before sacrifice (CO2 asphyxiation). Collect liver and lung and freeze on dry ice. Thaw the frozen tissue on ice and lyse 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; 1.0% Triton; plus protease inhibitor cocktail tablets). Measure the concentration of the clear lysate by Bradford assay, normalize samples by protein content, and analyze by SDS-PAGE and immunoblotting. Rats[3] House female rats (220 g) 4 animals per cage on a 12-hour light/dark cycle with food and water ad libitum. Induce spinal cord injury with the Keck Center for Neurosciences impactor, dropping a 10 g weight from a 25 mm height onto the dorsal surface of the exposed spinal cord. Record BBB scores, touch-evoked withdrawal thresholds, and body weights during the first week post-injury, then divide the animals into 5 treatment groups: naïve (N=4), sham (N=6), vehicle (N=6), Torin 2 (N=6), and Torin 2+Rapamycin (N=8). Administer Torin 2 alone (4 mg/kg) or in combination with Rapamycin (1.5 mg/kg) orally by gavage once a day, starting at day 15 after injury and ending at day 29. In sham operated rats, perform the laminectomy only.
Data provided by the manufacturer. Numbered citations refer to the Literature Cited list in the product description.
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A fast-acting lipid checkpoint in G1 prevents mitotic defects. Nat Commun 2024 Mar 18;15(1):2441. PMID: 38499565
Altered immune and metabolic molecular pathways drive islet cell dysfunction in human type 1 diabetes. J Clin Invest 2025 Sep 30:e195267. PMID: 41026524
Autophagic sequestration of SQSTM1 disrupts the aggresome formation of ubiquitinated proteins during proteasome inhibition. Cell Death Dis 2022 Jul 15;13(7):615. PMID: 35840557
Pharmacological Targeting of Vacuolar H+-ATPase via Subunit V1G Combats Multidrug-Resistant Cancer. Cell Chem Biol 2020 Nov 19;27(11):1359-1370.e8. PMID: 32649904
Torin2 Exploits Replication and Checkpoint Vulnerabilities to Cause Death of PI3K-Activated Triple-Negative Breast Cancer Cells. Cell Syst 2020 Jan 22;10(1):66-81.e11. PMID: 31812693
USP21 deubiquitinase elevates macropinocytosis to enable oncogenic KRAS bypass in pancreatic cancer. Genes Dev 2021 Oct 1;35(19-20):1327-1332. PMID: 34531315
Interleukins 15 and 18 synergistically prime the antitumor function of natural killer cells through noncanonical activation of mTORC1. Sci Signal 2025 Sep 16;18(904):eadq8778. PMID: 40956875
mTORC1/2 and Protein Translation Regulate Levels of CHK1 and the Sensitivity to CHK1 Inhibitors in Ewing Sarcoma Cells. Mol Cancer Ther 2018 Dec;17(12):2676-2688.
The UPR regulator IRE1 promotes balanced organ development by restricting TOR-dependent control of cellular differentiation in Arabidopsis. Plant J 2022 Mar;109(5):1229-1248. PMID: 34902186
CC-223, NSC781406, and BGT226 Exerts a Cytotoxic Effect Against Pancreatic Cancer Cells via mTOR Signaling. Front Pharmacol 2020 Nov 11:11:580407. PMID: 33343350