Torin 2

Catalog No.S2817 Batch:S281704

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Technical Data

Formula

C24H15F3N4O
Molecular Weight 432.4 CAS No. 1223001-51-1
Solubility (25°C)* In vitro DMSO 30 mg/mL (69.38 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 68 publications

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
Nuciferine protects against high-fat diet-induced hepatic steatosis and insulin resistance via activating TFEB-mediated autophagy-lysosomal pathway [ Acta Pharm Sin B, 2022, 12(6):2869-2886] PubMed: 35755273

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SHIPPING AND STORAGE
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