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Temsirolimus (Torisel) Licensed by Pfizer

Temsirolimus (CCI-779, Torisel) is a specific mTOR inhibitor with IC50 of 1.76 μM.

Catalog No.S1044

1 Reviews 4 Product Citations

: Tel: +1-832-582-8158[email protected]

Temsirolimus (Torisel) Chemical Structure
Molecular Weight: 1030.29

Validation & Quality Control

Product Citations(4)

Autophagy, 2011, 7(2), 176-187

Tuberc Respir Dis (Seoul), 2012, 72(4), 343-351

Mol Genet Metab, 2010, 100(4), 309-315

Hum Pathol, 2012, 43(12):2197-206

Customer Reviews(1) in vivo invitation

Quality Control & MSDS

Related Compound Libraries

Temsirolimus (Torisel) is available in the following compound libraries:

Cambridge Cancer Compound Library(96-well) Chemical Library (96-well) Chemotherapeutic Agent Library (96-well) FDA Approved Drug Library (96-well) Inhibitor Library (96-well) Kinase Inhibitor Library (96-well) Pfizer Licensed Library

Product Information

Compare mTOR Inhibitors

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Research Area

Cat.No.	Product Name	Solubility (25°C)
S1039	Rapamycin (Sirolimus)	<1 mg/mL	20 mg/mL	4 mg/mL
S1120	Everolimus (RAD001)	<1 mg/mL	30 mg/mL	7 mg/mL
S1009	BEZ235 (NVP-BEZ235)	<1 mg/mL	1 mg/mL	<1 mg/mL
S1555	AZD8055	2 mg/mL	93 mg/mL	15 mg/mL
S1038	PI-103	<1 mg/mL	24 mg/mL	<1 mg/mL
S2811	INK 128 (MLN0128)	<1 mg/mL	62 mg/mL	2 mg/mL
S2218	PP242	<1 mg/mL	62 mg/mL	18 mg/mL
S2827	Torin 1	<1 mg/mL	2 mg/mL	<1 mg/mL
S1022	Deforolimus (Ridaforolimus)	<1 mg/mL	198 mg/mL	<1 mg/mL
S1044	Temsirolimus (Torisel)	1 mg/mL	75 mg/mL	75 mg/mL
S1226	Ku-0063794	<1 mg/mL	16 mg/mL	<1 mg/mL
S1523	XL765 (SAR245409)	<1 mg/mL	15 mg/mL	<1 mg/mL
S2658	GSK2126458	<1 mg/mL	101 mg/mL	<1 mg/mL
S2624	OSI-027	<1 mg/mL	18 mg/mL	<1 mg/mL
S2743	PF-04691502	<1 mg/mL	14 mg/mL	<1 mg/mL
S2783	AZD2014	<1 mg/mL	38 mg/mL	<1 mg/mL
S2628	PF-05212384 (PKI-587)	<1 mg/mL	2 mg/mL	<1 mg/mL
S2696	GDC-0980 (RG7422)	<1 mg/mL	20 mg/mL	<1 mg/mL
S1266	WYE-354	<1 mg/mL	99 mg/mL	<1 mg/mL
S1360	GSK1059615	<1 mg/mL	2 mg/mL	<1 mg/mL
S2661	WYE-125132	<1 mg/mL	104 mg/mL	<1 mg/mL
S2668	WYE-687	<1 mg/mL	0.5 mg/mL	<1 mg/mL
S2699	CH5132799	<1 mg/mL	12 mg/mL	<1 mg/mL
S2817	Torin 2	<1 mg/mL	22 mg/mL	<1 mg/mL
S2238	Palomid 529	<1 mg/mL	81 mg/mL	<1 mg/mL
S2622	PP-121	<1 mg/mL	64 mg/mL	2 mg/mL
S2749	NVP-BGT226	<1 mg/mL	30 mg/mL	<1 mg/mL
S2689	WAY-600	<1 mg/mL	22 mg/mL	2 mg/mL

Combination Therapy

Dr. Antonino Maria Sparta demonstrates a breakthrough in leukemia research by utilizing two inhibitors produced by Selleck Chemicals.

Product Description

Biological Activity Protocol Chemical Information Customer Reviews Product Citations Tech Support & FAQs

Biological Activity

Description	Temsirolimus (CCI-779, Torisel) is a specific mTOR inhibitor with IC50 of 1.76 μM.
Targets	mTOR
IC50	1.76 μM ^[1]
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]
Clinical Trials	A Phase IV study of two different doses of Temsirolimus in patients with mantle cell lymphoma is currently ongoing.
Features

Protocol(Only for Reference)

Kinase Assay:
^[1]

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.

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.

Cell Assay:
^[1]

Cell lines	A549, H157, H460, H446, HCT116, HT29, SW480, DLD1, Caco2, LNCap, DU145, MDA468, MDA231, HEK293, and PC3-MM2
Concentrations	Dissolved in DMSO, final concentrations ~20 μM
Incubation Time	72 hours
Method	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.

Animal Study:
^[4]

Animal Models	Female athymic nude mice injected s.c. with DAOY, or U251 cells
Formulation	Prepared in 100% EtOH as a 50 mg/mL stock solution, and diluted in 5% Tween 80 and 5% polyethylene glycol 400
Dosages	20 mg/kg
Administration	Injection daily 5 times per week

References

Chemical Information

Download Temsirolimus (Torisel) SDF

Molecular Weight (MW)	1030.29
Formula	C₅₆H₈₇NO₁₆
CAS No.	162635-04-3, 343261-52-9, 1034922-90-1
Synonyms	CCI-779

Solubility (25°C) DMSO 75 mg/mL Water 1 mg/mL Ethanol 75 mg/mL
Storage	2 years -20°CPowder
	2 weeks4°Cin DMSO
	6 months-80°Cin DMSO

Chemical Name	Rapamycin, 42-[3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate]

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Research Area

Customer Reviews (1)

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Rating

Source

Dr. Zhang of Tianjin Medical University. Temsirolimus (Torisel) purchased from Selleck

Method

Western blotting

Cell Lines

Breast cancer cells

Concentrations

0-5 nM

Incubation Time

24 h

Results

Temsirolimus treatment resulted in a reduction of mTOR phosphorylation in Breast cancer cells.

Product Citations (4)

Caffeine induces apoptosis by enhancement of autophagy via PI3K/Akt/mTOR/p70S6K inhibition. [Saiki S, et al. Autophagy 2011;7(2), 176-187]
PubMed: 21081844
Dual Inhibition of PI3K/Akt/mTOR Pathway and Role of Autophagy in Non-Small Cell Lung Cancer Cells. [Jeong EH, et al. Tuberc Respir Dis (Seoul) 2012;72(4), 343-351]
PubMed: 23227075
Inhibition of glycogen biosynthesis via mTORC1 suppression as an adjunct therapy for Pompe disease. [Ashe KM, et al. Mol Genet Metab 2010;100(4), 309-315]
PubMed: 20554235

Clinicopathologic and biological analysis of PIK3CA mutation in ovarian clear cell carcinoma. [Rahman M, et al. Hum Pathol 2012;43(12):2197-206]
PubMed: 22705003

Tech Support & FAQs

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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PI3K/Akt/mTOR Pathway Products

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Temsirolimus (Torisel) + Mitoxantrone	Low doses of Temsirolimus (5 mg/kg or 10 mg/kg, 3 days per week for 3 weeks) given between courses of Mitoxantrone (1.5 mg/kg) or docetaxe (10 mg/kg) treatment potently increases the growth delay of PC-3 tumors. ^[2]
Temsirolimus (Torisel) + Cisplatin	Administration of Temsirolimus (20 mg/kg i.p., 5 days/week for 2 weeks) in combination with Cisplatin (5 mg/kg i.p., day 1) induces 1.3 times greater growth inhibition of DAOY xenografts than cisplatin treatment alone. ^[4]

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