受注:045-509-1970 |
技術サポート:[email protected] 平日9:00〜18:00 1営業日以内にご連絡を差し上げます |
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) |
|
||||||
* <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. |
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] |
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 |
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]
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 |
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。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。