Temsirolimus (CCI-779, NSC 683864)
Licensed by Pfizer Catalog No.S1044
Molecular Weight(MW): 1030.29
Temsirolimus (CCI-779, NSC 683864) is a specific mTOR inhibitor with IC50 of 1.76 μM in a cell-free assay.
Cited by 18 Publications
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mTOR inhibitors attenuate ganetespib-driven elevation of HSPs in multiple tumor cell types. A375 melanoma cells were treated with vehicle, ganetespib (25 nmol/L), BEZ235 (500 nmol/L), or temsirolimus (500 nmol/L), either alone or in combination, for 24 hours. The levels of HSP90α, HSP70, HSP27, and GAPDH were determined by immunoblotting.
Mol Cancer Res 2014 12, 703-13. Temsirolimus (CCI-779, NSC 683864) purchased from Selleck.
SCID mice with PC-9/Vec or PC-9/HGF tumors were administered as described in Figure. Four hours after final administration of erlotinib, tumors were harvested, and tumor cell angiogenesis (CD31) were determined by immunohistochemistry.
PLoS One 2013 8, e62104. Temsirolimus (CCI-779, NSC 683864) purchased from Selleck.
SCID mice with PC-9/Vec or PC-9/HGF tumors were administered 25 mg/kg erlotinib once daily for 4 days or 50 mg/kg temsirolimus once from day 8. Four hours after final erlotinib administration, tumors were harvested, and the relative levels of proteins in the tumor lysates were determined by western blotting.
PLoS One 2013 8, e62104. Temsirolimus (CCI-779, NSC 683864) purchased from Selleck.
Purity & Quality Control
Choose Selective mTOR Inhibitors
|Description||Temsirolimus (CCI-779, NSC 683864) is a specific mTOR inhibitor with IC50 of 1.76 μM in a cell-free assay.|
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.  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.  Temsirolimus (100 ng/mL) potently inhibits proliferation and induces apoptosis in primary human lymphoblastic leukemia (ALL) cells. 
|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  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%.  Inhibition of mTOR by Temsirolimus improves performance on four different behavioral tasks and decreases aggregate formation in a mouse model of Huntington disease.  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. |
In vitro assay of mTOR catalytic activity: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.
-  Shor B, et al. Cancer Res, 2008, 68(8), 2934-2943.
-  Wu L, et al. Cancer Res, 2005, 65(7), 2825-2831.
-  Teachey DT, et al. Blood, 2006, 107(3), 1149-1155.
|In vitro||Ethanol||75 mg/mL (72.79 mM)|
|DMSO||67 mg/mL (65.03 mM)|
|In vivo||Add solvents individually and in order:
30% PEG400+0.5% Tween80+5% propylene glycol
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Clinical Trial Information
|NCT Number||Recruitment||Conditions||Sponsor/Collaborators||Start Date||Phases|
|NCT01182883||Withdrawn||Brain Stem Neoplasms|Glioma|Pinealoma||National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC)||July 28, 2010||Phase 1|
|NCT02908035||Not yet recruiting||Chronic Limb Ischemia||Mercator MedSystems, Inc.||January 2017||Phase 2|
|NCT02567435||Suspended||Alveolar Rhabdomyosarcoma|Botryoid-Type Embryonal Rhabdomyosarcoma|Embryonal Rhabdomyosarcoma|Rhabdomyosarcoma|Sclerosing Rhabdomyosarcoma|Spindle Cell Rhabdomyosarcoma|Untreated Childhood Rhabdomyosarcoma||National Cancer Institute (NCI)||May 2016||Phase 3|
|NCT02693535||Recruiting||Lymphoma, Non-Hodgkin|Multiple Myeloma|Advanced Solid Tumors||American Society of Clinical Oncology|AstraZeneca|Bayer|Bristol-Myers Squibb|Eli Lilly and Company|Genentech, Inc.|Merck Sharp & Dohme Corp.|Pfizer||March 2016||Phase 2|
|NCT02560012||Recruiting||Carcinoma, Renal Cell||The University of Texas Health Science Center, Houston||December 2015||Phase 2|
|NCT02420613||Recruiting||Diffuse Intrinsic Pontine Glioma||M.D. Anderson Cancer Center||October 2015||Phase 1|
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