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Temsirolimus

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Chemical Structure| 162635-04-3 同义名 : 西罗莫司脂化物 ;CCI-779;Torisel;US brand name: Torisel.;Torisel®
CAS号 : 162635-04-3
货号 : A642622
分子式 : C56H87NO16
纯度 : 99%
分子量 : 1030.287
MDL号 : MFCD00934421
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(101.91 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

无水乙醇: 200 mg/mL(194.12 mM)，配合低频超声助溶，注意：无水乙醇开封后，易挥发，也会吸收空气中的水分，导致溶解能力下降，请避免使用开封较久的乙醇
动物实验配方：

2% DMSO+30% PEG 300 +2% Tween 80+water 7 mg/mL

生物活性
靶点

  • mTOR

    mTOR, IC50:1.76 μM
描述 mTOR is a serine-threonine kinase that interacts with several proteins to form two distinct complexes, mTORC1 and mTORC2, which show different sensitivities to rapamycin[3]. Temsirolimus (CCI-779, NSC 683864) is a specific mTOR inhibitor with IC50 of 1.76 μM in a cell-free assay. 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[7]. 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]. 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%[5]. In a phase 2 study, 25 mg temsirolimus was intravenously (IV) conducted once per week and the VEGF-A monoclonal antibody bevacizumab 10 mg/kg IV once every 2 weeks in 58 patients with differentiated PNETs and progressive disease by RECIST, results showed response rate (RR) was 41% (23 of 56 patients). PFS at 6 months was 79% (44 of 56). Median PFS was 13.2 months (95%CI,11.2to16.6).Median overall survival was 34 months (95% CI, 27.1 to not reached). For evaluable patients, the most common grade 3 to 4 adverse events attributed to therapy were hypertension (21%), fatigue (16%), lymphopenia (14%), and hyperglycemia (14%), suggesting substantial activity and reasonable tolerability of this drug[6].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
human 697 cell Growth inhibition assay Inhibition of human 697 cell growth in a cell viability assay, IC50=1.7 nM SANGER
human A2780 cell Growth inhibition assay Inhibition of human A2780 cell growth in a cell viability assay, IC50=5.88 nM SANGER
human A3-KAW cell Growth inhibition assay Inhibition of human A3-KAW cell growth in a cell viability assay, IC50=10.43 nM SANGER
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT03629847 Neuroendocrine Tumors Phase 1 Phase 2 Recruiting December 2018 Saudi Arabia ... 展开 >> Oncology Centre, King Faisal Specialist Hospital & Research Center Recruiting Riyadh, Saudi Arabia, 11211 Contact: Ali Aljubran, MD    966-1-4647272 ext 32084    ajubran@kfshrc.edu.sa    Contact: Lani Cabangon, RN    966-1-4647272 ext 32089    lcabangon06@kfshrc.edu.sa    Sub-Investigator: Hussein Raef          Sub-Investigator: Nora Alkahtani, MD          Sub-Investigator: Shouki Bazarbashi, MD          Sub-Investigator: Ahmed Alzahrani, MD          Sub-Investigator: Mohamed Alsubayel, MD          Sub-Investigator: Monther Kabbani, MD          Sub-Investigator: Hamad Albahli, MD          Sub-Investigator: Hadeel Almana, MD 收起 <<
NCT01184326 Solid Tumor K... 展开 >>idney Cancer 收起 << Phase 1 Completed - United States, Massachusetts ... 展开 >> Beth Israel Deaconess Medical Center Boston, Massachusetts, United States, 02115 Dana-Farber Cancer Institute Boston, Massachusetts, United States, 02115 收起 <<
NCT01184326 - Completed - -
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

0.97mL

0.19mL

0.10mL

4.85mL

0.97mL

0.49mL

9.71mL

1.94mL

0.97mL
参考文献

[1]2018:5896786. doi: 10.1155/2018/5896786.

[2]Wu L. Effects of the mammalian target of rapamycin inhibitor CCI-779 used alone or with chemotherapy on human prostate cancer cells and xenografts. Cancer Res. 2005 Apr 1;65(7):2825-31. doi: 10.1158/0008-5472.CAN-04-3137.

[3]Agostini D. New Insights into the Role of Exercise in Inhibiting mTOR Signaling in Triple-Negative Breast Cancer. Oxid Med Cell Longev. 2018 Sep 30;2018:5896786. doi: 10.1155/2018/5896786.

[4]33(14):1551-6. doi: 10.1200/JCO.2014.56.2082. Epub 2014 Dec 8.

[5]Geoerger B. Antitumor activity of the rapamycin analog CCI-779 in human primitive neuroectodermal tumor/medulloblastoma models as single agent and in combination chemotherapy. Cancer Res. 2001 Feb 15;61(4):1527-32.