Torin 2

製品コードS2817 バッチS281704

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
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Torin 2は、p53−/− MEFs細胞株においてIC50が0.25 nMである強力かつ選択的なmTOR阻害剤であり、PI3Kと比較して800倍高いmTOR選択性と改善された薬物動態特性を有しています。PC3細胞株において、ATM/ATR/DNA-PKをそれぞれEC50が28 nM/35 nM/118 nMで阻害します。Torin 2は細胞生存率を低下させ、オートファジーとアポトーシスを誘導します。
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. This compound inhibits mTORC1, thus activates TFEB by promoting its nuclear translocation with EC50 of 1.666 mM. This chemical (< 50 nM) causes a significant reduction in viability of both MZ-CRC-1 and TT cells. It (100 nM) exerts a significant reduction of migration of both MZ-CRC-1 and TT cells.

in vivo

Torin 2 exhibits >95% pharmacodynamic response and half-time of 11.7 min in the mouse liver microsome stability study. This compound 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. This chemical (20mg/kg) ablates MYCN tumors with reduction in MYCN protein levels and induction of apoptosis in Th-MYCN mice.

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

参考

  • https://pubmed.ncbi.nlm.nih.gov/21322566/
  • https://pubmed.ncbi.nlm.nih.gov/22343943/
  • https://pubmed.ncbi.nlm.nih.gov/22753663/
  • https://pubmed.ncbi.nlm.nih.gov/22789543/
  • https://pubmed.ncbi.nlm.nih.gov/23436801/

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]

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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
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長期の保管のために-20°Cの下で製品を保ってください。

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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