Reagentia en instrumenten voor immunologie, celbiologie en moleculaire biologie.

Torin 2 [1223001-51-1]

Afdrukken

Referentie HY-13002-10mg

Formaat : 10mg

Merk : MedChemExpress

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Description

Torin 2 is an mTOR inhibitor with EC₅₀ of 0.25 nM for inhibiting cellular mTOR activity, and exhibits 800-fold selectivity over PI3K (EC₅₀: 200 nM). Torin 2 also inhibits DNA-PK with an IC₅₀ of 0.5 nM in the cell free assay. Torin 2 can suppress both mTORC1 and mTORC2.

IC₅₀ & Target^[1]^[4]

mTOR

2.81 nM (IC₅₀)

mTOR

0.25 nM (EC₅₀, Cell Assay)

mTORC1

mTORC2

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)

ΡΙ4Κβ

18.3 nM (IC₅₀)

Autophagy

Cellular Effect

Cell Line	Type	Value	Description	References
HCT-116	GI₅₀	32.19 nM Compound: Torin2	Growth inhibition of human HCT116 cells measured after 72 hrs by Celltiter-Glo assay Growth inhibition of human HCT116 cells measured after 72 hrs by Celltiter-Glo assay	[PMID: 32911078]
HeLa	GI₅₀	97.95 nM Compound: Torin2	Growth inhibition of human HeLa cells measured after 72 hrs by Celltiter-Glo assay Growth inhibition of human HeLa cells measured after 72 hrs by Celltiter-Glo assay	[PMID: 32911078]
HeLa	IC₅₀	< 10 nM Compound: 15	Inhibition of N-terminally FLAG-tagged mTORC2 (unknown origin) expressed in human HeLa cells using S6K1 or Akt1 as substrate after 20 mins by immunoblotting assay Inhibition of N-terminally FLAG-tagged mTORC2 (unknown origin) expressed in human HeLa cells using S6K1 or Akt1 as substrate after 20 mins by immunoblotting assay	[PMID: 29211480]
MOLM-13	IC₅₀	< 1 nM Compound: Torin2	Antiproliferative activity against human MOLM13 cells by Cell-Titer Glo assay Antiproliferative activity against human MOLM13 cells by Cell-Titer Glo assay	[PMID: 30370766]
MOLM-14	IC₅₀	< 1 nM Compound: Torin2	Antiproliferative activity against human MOLM14 cells by Cell-Titer Glo assay Antiproliferative activity against human MOLM14 cells by Cell-Titer Glo assay	[PMID: 30370766]
MV4-11	IC₅₀	< 1 nM Compound: Torin2	Antiproliferative activity against human MV4-11 cells by Cell-Titer Glo assay Antiproliferative activity against human MV4-11 cells by Cell-Titer Glo assay	[PMID: 30370766]
PC-3	EC₅₀	200 nM Compound: 3, Torin2	Inhibition of PI3Kalpha in human PC3 cells expressing Akt1 S473D mutant assessed as phosphorylation of Akt Thr308 by immunoblotting Inhibition of PI3Kalpha in human PC3 cells expressing Akt1 S473D mutant assessed as phosphorylation of Akt Thr308 by immunoblotting	[PMID: 21322566]
RD	CC₅₀	0.04 μM Compound: 1	Cytotoxicity against human RD cells incubated for 4 days by CellTiter-Glo luminescence assay Cytotoxicity against human RD cells incubated for 4 days by CellTiter-Glo luminescence assay	[PMID: 31082764]

In Vitro

Torin 2 is subject to further profiling against a panel of lipid kinases with IC₅₀s of 2.81 nM, 0.5 nM, 5.67 nM, 8.58 nM, 18.3 nM, 24.5 nM and 28.1 nM for mTOR, DNA-pK, p110γ, hVPS34, PI4Kβ, PI3K-C2β and PI3K-C2α, respectively. Torin 2 (Torin2) possesses a 250 pM EC₅₀ for inhibiting mTOR in cells while maintaining 800-fold cellular selectivity relative to inhibition of PI3K and most other protein kinases^[1]. Torin 2 (Torin2) exhibits potent biochemical and cellular activity against PIKK family kinases including ATM (EC₅₀ 28 nM), ATR (EC₅₀ 35 nM) and DNA-PK (EC₅₀ 118 nM). Torin 2 potently inhibits T308 of Akt, a direct substrate of PDK1 and an indirect substrate of PI3Ks, with an EC₅₀ of less than 10 nM^[2]. Torin-2 can suppress both mTORC1 and mTORC2^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

Torin 2 exhibits good bioavailability and exposure and can maintain strong inhibition of mTOR activity in lung and liver to at least six hours after a single dose of 20 mg/kg. Torin 2 is easier to produce on scale and exhibits improved pharmacokinetic properties which should enable it use in vivo experiments^[1]. Torin 2 strongly suppresses pS6K(T389) and p4EBP1(T37/46) and partly suppresses pAkt(T308). Treatment of mice with AZD6244 at 25 mg/kg results in a profound inhibition of pERK. Combined administration of Torin 2 (40 mg/kg) and AZD6244 (25 mg/kg) demonstrates strong inhibition of all pharmacodynamics markers^[2]. Treatment with Torin 2 and Rapamycin induces IL-6 secretion by astrocytes and may contribute to the reduction of mechanical hypersensitivity after SCI. Torin1 and Torin 2 treatment increases IL-6 mRNA, suggesting that the PI3K-mTOR pathway is a negative regulator of IL-6 expression in astrocytes. Importantly, Torin 2 treatment does not show any cell toxicity, as no signs of cell death are observed by TUNEL assay or by detection of cleaved-caspase 3 by western blotting^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Masse moléculaire

432.40

Formule

C₂₄H₁₅F₃N₄O

CAS No.

1223001-51-1

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

Livraison

Room temperature in continental US; may vary elsewhere.

Stockage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	1 year
	-20°C	6 months

Solvant et solubilité

In Vitro:

DMSO : 15.62 mg/mL (36.12 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.3127 mL	11.5634 mL	23.1267 mL
5 mM	0.4625 mL	2.3127 mL	4.6253 mL
10 mM	0.2313 mL	1.1563 mL	2.3127 mL

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 1.56 mg/mL (3.61 mM); Clear solution

This protocol yields a clear solution of ≥ 1.56 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (15.6 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.

For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.