Torin 2

製品コードS2817 バッチS281702

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C24H15F3N4O
分子量 432.4 CAS No. 1223001-51-1
Solubility (25°C)* 体外 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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.
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]

プロトコル(参考用のみ)

キナーゼアッセイ 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.
細胞アッセイ 細胞株 MZ-CRC-1 and TT cells
濃度 50 nM
反応時間 3 days or 5 days
実験の流れ

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.
動物実験 動物モデル male Swiss albino mice
投薬量 20 mg/kg
投与方法 Intravenous or oral

カスタマーフィードバック

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]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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
CIC-mediated modulation of MAPK signaling opposes receptor tyrosine kinase inhibitor response in kinase-addicted sarcoma [ Cancer Res, 2022, canres.1397.2021] PubMed: 35074756

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人間や獣医の診断であるか治療的な使用のためにでない。

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