Torin 2

Catalog No.S2817 Batch:S281705

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Technical Data

Formula

C24H15F3N4O
Molecular Weight 432.4 CAS No. 1223001-51-1
Solubility (25°C)* In vitro DMSO 41 mg/mL (94.81 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 2 is a potent and selective mTOR inhibitor with IC50 of 0.25 nM in p53−/− MEFs cell line; 800-fold greater selectivity for mTOR than PI3K and improved pharmacokinetic properties. Inhibition of ATM/ATR/DNA-PK with EC50 of 28 nM/35 nM/118 nM,in PC3 cell lines respectively. Torin 2 decreases cell viability and induces autophagy and apoptosis.
Targets
mTOR [1]
(p53−/− MEFs)		 ATM [5]
(PC3 cells)		 ATR [5]
(PC3 cells)		 DNA-PK [5]
(PC3 cells)
0.25 nM 28 nM(EC50) 35 nM(EC50) 118 nM(EC50)
In vitro

Torin 2 has the same binding mode as PI3Kγ, V882 serves as a hinge binding point and in the inner hydrophobic pocket Y867, D841 and D964 provide three more hydrogen bonds with aminopyridine side chain analogous to Y2225, D2195 and D2357 of mTOR. [1] Torin 2 inhibits mTORC1, thus activates TFEB by promoting its nuclear translocation with EC50 of 1.666 mM. [2] Torin 2(< 50 nM) causes a significant reduction in viability of both MZ-CRC-1 and TT cells. Torin 2 (100 nM) exerts a significant reduction of migration of both MZ-CRC-1 and TT cells. [3]
In vivo

Torin 2 exhibits >95% pharmacodynamic response and half-time of 11.7 min in the mouse liver microsome stability study. Torin 2 exhibits the best bioavailability (51%), short half-life (0.72 hours) and low clearance(19.6 mL/min/kg) in male Swiss albino mice following intravenous and oral administration. [1] Torin 2(20mg/kg) ablates MYCN tumors with reduction in MYCN protein levels and induction of apoptosis in Th-MYCN mice. [4]

Protocol (from reference)

Kinase Assay:

[1]
  • mTOR and PI3K Cellular Assays

    Cellular IC50 values for mTOR are determined using p53−/− MEFs. Cells are treated with vehicle or increasing concentrations of Torin 2 for 1 h and then lyse. Phosphorylation of S6K1 Thr-389 is monitored by immunoblotting using a phospho-specific antibody. Meanwhile, cellular IC50 values for PI3Ka are determined based on phosphorylation of Akt Thr-308 in p53−/−/mLST8−/− MEFs or human PC3 cells expressing the S473D mutant of Akt1.
Cell Assay:

[3]
  • Cell lines

    MZ-CRC-1 and TT cells

  • Concentrations

    50 nM

  • Incubation Time

    3 days or 5 days

  • Method

    For viability, MZ-CRC-1 and TT cells are seeded in quadruplicate in 96-well plates (1.0×104 cells per well) in culture media with 2.5% and 4% FBS, respectively. After 24 hours, cells are treated with Torin 2. At the indicated time point, cells are incubated for 3 hours with 10 μL of CellTiter96 AQueous One solution in 100 μL of culture media and absorbance is measured at 490 nm.
Animal Study:

[1]
  • Animal Models

    male Swiss albino mice

  • Dosages

    20 mg/kg

  • Administration

    Intravenous or oral

Customer Product Validation

Data from [Data independently produced by FEBS J, 2014, 281(16), 3591-608]

,

Data from [Data independently produced by , , Arterioscler Thromb Vasc Biol, 2018, doi:10.1161/ATVBAHA.118.311321]

Data from [Data independently produced by , , Oncotarget, 2016, 7(48):79842-79853]

Selleck's Torin 2 has been cited by 69 publications

Androgen receptor monomers and dimers regulate opposing biological processes in prostate cancer cells [ Nat Commun, 2024, 15(1):7675] PubMed: 39227594
Endothelial Mechanistic Target of Rapamycin Activation with Different Strains of R. rickettsii: Possible Role in Rickettsial Pathogenesis [ Microorganisms, 2024, 12(2)296] PubMed: 38399700
Analysis of ATG4C function in vivo [ Autophagy, 2023, 19(11):2912-2933] PubMed: 37459465
Analysis of ATG4C function in vivo [ Autophagy, 2023, 19(11):2912-2933] PubMed: 37459465
Continuous sensing of nutrients and growth factors by the mTORC1-TFEB axis [ Elife, 2023, 12e74903] PubMed: 37698461
Sequential Treatment with Temozolomide Plus Naturally Derived AT101 as an Alternative Therapeutic Strategy: Insights into Chemoresistance Mechanisms of Surviving Glioblastoma Cells [ Int J Mol Sci, 2023, 24(10)9075] PubMed: 37240419
Myc controls NK cell development, IL-15-driven expansion, and translational machinery [ Life Sci Alliance, 2023, 6(7)e202302069] PubMed: 37105715
Dephosphorylation of 4EBP1/2 Induces Prenatal Neural Stem Cell Quiescence [ bioRxiv, 2023, 2023.02.14.528513] PubMed: 36824760
Characterization of the autophagy-modulating natural compound prodigiosin for the elimination of therapy-resistant tumor cells [ DNB, 2023, ] PubMed: none
Pyruvate Facilitates FACT-Mediated γH2AX Loading to Chromatin and Promotes the Radiation Resistance of Glioblastoma [ Adv Sci (Weinh), 2022, 10.1002/advs.202104055] PubMed: 35048565

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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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