Torin 2

Catalog No.S2817

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.

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Torin 2 Chemical Structure

Torin 2 Chemical Structure
Molecular Weight: 432.4

Validation & Quality Control

2 customer reviews :

Quality Control & MSDS

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Product Information

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  • Research Area
  • Combination Therapy
    Combination Therapy

Product Description

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.
Targets mTOR [1]
(p53−/− MEFs)
ATM [5]
(PC3 cells)
ATR [5]
(PC3 cells)
DNA-PK [5]
(PC3 cells)
IC50 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]
Features

Protocol(Only for 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
Formulation first dissolve at 25 mg/mL in 100% N-methyl-2-pyrrolidone and then dilute 1:4 with sterile 50% PEG400 prior to injection
Dosages 25 mg/kg
Administration Intravenous or oral

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Liu Q, et al. J Med Chem, 2011, 54(5), 1473-1480.

[2] Settembre C, et al. EMBO J, 2012, 31(5), 1095-1108.

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Chemical Information

Download Torin 2 SDF
Molecular Weight (MW) 432.4
Formula

C24H15F3N4O

CAS No. 1223001-51-1
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms N/A
Solubility (25°C) * In vitro DMSO 20 mg/mL (46.25 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo 30% PEG400+0.5% Tween80+5% propylene glycol 30 mg/mL
* <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.
Chemical Name Benzo[h]-1,6-naphthyridin-2(1H)-one, 9-(6-amino-3-pyridinyl)-1-[3-(trifluoromethyl)phenyl]-

Customer Product Validation(2)


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Rating
Source FEBS J 2014 281(16), 3591-608. Torin 2 purchased from Selleck
Method Western blotting
Cell Lines U2OS cells
Concentrations 0.1 uM
Incubation Time 1 h
Results In order to determine whether PKB phosphorylation in the presence of glucosamine requires the same upstream kinases as in the presence of glucose, it assessed PKB phosphorylation in the presence of the mTOR kinase inhibitor Torin 2. Torin 2 completely blocked PKB Ser473 phosphorylation with little effect on PKB Thr308 phosphorylation in cells maintained in either glucose or glucosamine.

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Rating
Source Torin 2 purchased from Selleck
Method ELISA
Cell Lines Bone marrow derived macrophages
Concentrations 10 nM
Incubation Time 1 h
Results

Tech Support

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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