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受注：045-509-1970 |
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化学情報
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Synonyms | NSC 683864,CCI-779 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
| 化学式 | C56H87NO16 |
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| 分子量 | 1030.29 | CAS No. | 162635-04-3 | |
| Solubility (25°C)* | 体外 | Ethanol | 100 mg/mL (97.06 mM) | |
| DMSO | 86 mg/mL (83.47 mM) | |||
| Water | Insoluble | |||
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* <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. |
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溶剤液（一定の濃度）を調合する
生物活性
| 製品説明 | Temsirolimus is a specific mTOR inhibitor with IC50 of 1.76 μM in a cell-free assay. Temsirolimus induces autophagy and apoptosis. |
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| in vitro | In the absence of FKBP12, Temsirolimus potently inhibits mTOR kinase activity with IC50 of 1.76 μM, similar to that of rapamycin with IC50 of 1.74 μM. Temsirolimus treatment at nanomolar concentrations (10 nM to <5 μM) displays a modest and selective antiproliferative activity via FKBP12-dependent mechanism, but can completely inhibit the proliferation of a broad panel of tumor cells at low micromolar concentrations (5-15 μM), involving FKBP12-independent suppression of mTOR signaling. Temsirolimus treatment at micromolar but not nanomolar concentrations (20 μM) causes a marked decline in global protein synthesis and disassembly of polyribosomes, accompanied by rapid increase in the phosphorylation of translation elongation factor eEF2 and the translation initiation factor eIF2A. [1] Temsirolimus inhibits the phosphorylation of ribosomal protein S6, more potently in PTEN-positive DU145 cells than in PTEN-negative PC-3 cells, and inhibits cell growth and clonogenic survival of both cells in a concentration-dependent manner. [2] Temsirolimus (100 ng/mL) potently inhibits proliferation and induces apoptosis in primary human lymphoblastic leukemia (ALL) cells. [3] |
| in vivo | In the NOD/SCID xenograft models with human ALL, Temsirolimus treatment at 10 mg/kg/day produces a decrease in peripheral blood blasts and in splenomegaly [3] Administration of Temsirolimus (20 mg/kg i.p. 5 days/week) significantly delays the growth of DAOY xenografts by 160% after 1 week and 240% after 2 weeks, compared with controls. Single high-dose of Temsirolimus (100 mg/kg i.p) treatment induces 37% regression of tumor volume within 1 week. Temsirolimus treatment for 2 weeks also delays the growth of rapamycin-resistant U251 xenografts by 148%. [4] Inhibition of mTOR by Temsirolimus improves performance on four different behavioral tasks and decreases aggregate formation in a mouse model of Huntington disease. [5] Administration of Temsirolimus induces significant dose-dependent, antitumor responses against subcutaneous growth of 8226, OPM-2, and U266 xenografts with ED50 of 20 mg/kg and 2 mg/kg for 8226 and OPM-2, respectively, which are associated with inhibited proliferation and angiogenesis, induction of apoptosis, and reduction in tumor cell size. [6] |
プロトコル(参考用のみ)
| キナーゼアッセイ | In vitro assay of mTOR catalytic activity | |
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| The Flag-tagged wild-type human mTOR (Flag-mTOR) DNA constructs are transiently transfected into HEK293 cells. Protein extraction and purification of Flag-mTOR are carried out 48 hours later. In vitro kinase assays of purified Flag-mTOR in the presence of various concentrations of Temsirolimus without FKBP12 are performed in 96-well plate and detected by dissociation-enhanced lanthanide fluorescent immunoassay (DELFIA) using His6-S6K1 as the substrate. Enzymes is first diluted in kinase assay buffer (10 mM Hepes (pH 7.4), 50 mM NaCl, 50 mM β-glycerophosphate, 10 mM MnCl2, 0.5 mM DTT, 0.25 μM microcystin LR, and 100 μg/mL BSA). To each well, 12 μL of the diluted enzyme is mixed briefly with 0.5 μL Temsirolimus. The kinase reaction is initiated by adding 12.5 μL kinase assay buffer containing ATP and His6-S6K to give a final reaction volume of 25 μL containing 800 ng/mL FLAG-mTOR, 100 μM ATP, and 1.25 μM His6-S6K. The reaction plate is incubated for 2 hours (linear at 1-6 hours) at room temperature with gentle shaking and then terminated by adding 25 μL Stop buffer (20 mM Hepes (pH 7.4), 20 mM EDTA, and 20 mM EGTA). The DELFIA detection of the phosphorylated (Thr-389) His6-S6K is performed at room temperature using a monoclonal anti-P(T389)-p70S6K antibody labeled with Europium-N1-ITC (Eu) (10.4 Eu per antibody). 45 μL of the terminated kinase reaction mixture is transferred to a MaxiSorp plate containing 55 μL PBS. The His6-S6K is allowed to attach for 2 hours after which the wells are aspirated and washed once with PBS. 100 μL of DELFIA buffer with 40 ng/mL Eu-P(T389)-S6K antibody is added. The antibody binding is continued for 1 hour with gentle agitation. The wells are then aspirated and washed four times with PBS containing 0.05% Tween 20 (PBST). 100 μL of DELFIA Enhancement solution is added to each well and the plates are read in a PerkinElmer Victor model plate reader. | ||
| 細胞アッセイ | 細胞株 | A549, H157, H460, H446, HCT116, HT29, SW480, DLD1, Caco2, LNCap, DU145, MDA468, MDA231, HEK293, and PC3-MM2 |
| 濃度 | Dissolved in DMSO, final concentrations ~20 μM | |
| 反応時間 | 72 hours | |
| 実験の流れ | Cells are exposed to various concentrations of Temsirolimus for 72 hours. After treatment, viable cell densities are determined by MTS dye conversion using CellTiter AQ assay kit. |
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| 動物実験 | 動物モデル | Female athymic nude mice injected s.c. with DAOY, or U251 cells |
| 投薬量 | 20 mg/kg | |
| 投与方法 | Injection daily 5 times per week | |
参考
カスタマーフィードバック
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Data from [Data independently produced by Mol Cancer Res, 2014, 12, 703-13]
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Data from [Data independently produced by PLoS One, 2013, 8, e62104]
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Data from [Data independently produced by PLoS One, 2013, 8, e62104]
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：
| Single-Molecule-Based, Label-Free Monitoring of Molecular Glue Efficacies for Promoting Protein-Protein Interactions Using YaxAB Nanopores [ ACS Nano, 2024, 18(45):31451-31465] | PubMed: 39482865 |
| The mTOR pathway controls phosphorylation of BRAF at T401 [ Cell Commun Signal, 2024, 22(1):428] | PubMed: 39223665 |
| Enzymatic depletion of circulating glutamine is immunosuppressive in cancers [ iScience, 2024, 27(6):109817] | PubMed: 38770139 |
| The combination of breast cancer PDO and mini-PDX platform for drug screening and individualized treatment [ J Cell Mol Med, 2024, 28(9):e18374] | PubMed: 38722288 |
| Long-term statins administration exacerbates diabetic nephropathy via ectopic fat deposition in diabetic mice [ Nat Commun, 2023, 14(1):390] | PubMed: 36693830 |
| Unbiased evaluation of rapamycin's specificity as an mTOR inhibitor [ Aging Cell, 2023, 22(8):e13888] | PubMed: 37222020 |
| Unbiased evaluation of rapamycin's specificity as an mTOR inhibitor [ Aging Cell, 2023, e13888.] | PubMed: 37222020 |
| A cisplatin conjugate with tumor cell specificity exhibits antitumor effects in renal cancer models [ BMC Cancer, 2023, 23(1):499] | PubMed: 37268911 |
| A cisplatin conjugate with tumor cell specificity exhibits antitumor effects in renal cancer models [ BMC Cancer, 2023, 23(1):499] | PubMed: 37268911 |
| Therapeutic Efficacy of Temsirolimus in a Patient-derived Model of Metastatic Fibrolamellar Hepatocellular Carcinoma [ In Vivo, 2023, 37(5):1940-1950] | PubMed: 37652480 |
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。