Torin 2

For research use only.

Catalog No.S2817

46 publications

Torin 2 Chemical Structure

CAS No. 1223001-51-1

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.

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Selleck's Torin 2 has been cited by 46 publications

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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]
Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human PC3 cells NIP0eVVHfW6ldHnvckBie3OjeR?= NYX0TZd3UW6qaXLpeIlwdiCxZjDQTVNM[WyyaHGgbY4hcHWvYX6gVGM{KGOnbHzzJIV5eHKnc4PpcochSWu2MTDTOFc{TCCvdYThcpQh[XO|ZYPz[YQh[XNicHjvd5Bpd3K7bHH0bY9vKG:oIFHreEBVcHJ|MEigZpkhcW2vdX7vZoxwfHSrbnesJGVEPTB;MD6yJO69VQ>? NX;6c4c4OjF|MkK1OlY>

... Click to View More Cell Line Experimental Data
Assay
Methods Test Index PMID
Western blot
p-S6K / S6K / p-AKT / AKT / IRS1 / p-4EBP1 / 4EBP1 / p-GSK3; 

PubMed: 23436801     


Torin2 is a potent mTOR inhibitor in HCT-116 cells

p-Chk1 / Chk1 / p-Chk2 / Chk2 / p-DNA-PK ; 

PubMed: 23436801     


Torin2 inhibits ATR (UV radiation), ATM and DNA-PK (ionizing radiation) strongly.

23436801
Immunofluorescence
LC3B ; 

PubMed: 23436801     


Hela cells were treated with indicated concentrations of Torin2 for 3 days stained with antibody specific for LC3B and DAPI. 

23436801
Growth inhibition assay
Cell viability; 

PubMed: 24434750     


Concentration–response curves of Torin 2, Torin 1 and WWH030 against gametocytes measured in the high throughout viability assay. Torin 1 was much weaker in potency compared to Torin 2.

24434750
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

Kinase Assay:

[1]
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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 Research:

[3]
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  • 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.


    (Only for Reference)
Animal Research:

[1]
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  • Animal Models: male Swiss albino mice
  • Dosages: 20 mg/kg
  • Administration: Intravenous or oral
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 20 mg/mL (46.25 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
5%DMSO+40%PEG300+5%Tween80+50%ddH2O
For best results, use promptly after mixing. 		1.5 mg/mL

* 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.

Chemical Information

Molecular Weight 432.4
Formula

C24H15F3N4O
CAS No. 1223001-51-1
Storage powder
in solvent
Synonyms N/A
Smiles C1=CC(=CC(=C1)N2C(=O)C=CC3=CN=C4C=CC(=CC4=C32)C5=CN=C(C=C5)N)C(F)(F)F

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID