Temsirolimus

別名：NSC 683864,CCI-779

製品コード：S1044 純度：99.96%

Temsirolimus is a specific mTOR inhibitor with IC50 of 1.76 μM in a cell-free assay. Temsirolimus induces autophagy and apoptosis.

CAS No. 162635-04-3

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 29500	国内在庫あり
10mg	JPY 22000	国内在庫あり
50mg	JPY 55500	国内在庫あり
200mg	JPY 130500	国内在庫あり
1g	JPY 448500	国内在庫なし(納期7~10日)

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Temsirolimus関連製品

関連ターゲット	mTORC1 mTORC2	もっと見る
関連製品	Rapamycin AZD8055 Torin 1 Ridaforolimus (Deforolimus, MK-8669) Sapanisertib (MLN0128) Torkinib (PP242) Vistusertib (AZD2014) MHY1485 KU-0063794 Torin 2 OSI-027 WYE-354 WYE-125132 (WYE-132) 3BDO Palomid 529 (P529) Zotarolimus (ABT-578) Salidroside GDC-0349 WAY-600 Onatasertib (CC 223) XL388 WYE-687	もっと見る
関連化合物ライブラリー	Kinase Inhibitor Library PI3K/Akt Inhibitor Library Apoptosis Compound Library Cell Cycle compound library NF-κB Signaling Compound Library	もっと見る

シグナル伝達経路

mTORシグナル伝達経路

mTOR阻害剤の選択性比較

阻害剤	Citation	Src	Lck	Fyn	Lyn	Yes	Fgr	その他
Saracatinib (AZD0530)	299	++++	++++	+++	+++		+++	EGFR (L861Q),c-YES,EGFR (L858R)
Pelitinib (EKB-569)	11	+						EGFR,MEK/ERK,ErbB2
Resveratrol	70	+						SIRT2,SIRT1,Quinone reductase 2
NVP-BHG712	15	+						EphB4,C-Raf,c-Abl
ENMD-2076	9	++	++	++		++		FLT3,RET,Aurora A
PRT062607 (P505-15) HCl	49	++	+		++	++	++	Syk,MLK1,PYK2
PP2	121		++++	+++
PP121	5	+++						PDGFR,Hck,VEGFR2
PP1	26		+++	+++				Kit,EGFR
CH6953755	0					++++
TL02-59	0						++++
1-Naphthyl PP1 hydrochloride	0	+		+				c-Abl,CDK2,CAMKII
Masitinib mesylate	0				+			FAK,FGFR3,human recombinant c-Kit
1-NM-PP1	1	+++		++++				CDK2-as1,CAMKII-as1,c-Abl-as2
HPK1-IN-2	0		+					Flt3,HPK1
XL228	0	+++			++++			ABL T315I,IGF-1R,Aurora A
DGY-06-116	0	++++
Elzovantinib (TPX-0022)	0	++++						MET,CSF1R
eCF506	1	++++
RK 24466	2		++++
1-Naphthyl PP1(1-NA-PP1)	1	+		+				PKD3,PKD2,PKD1
AMG-47a	0		+
Src Inhibitor 1	4	++	++
KX1-004	0	+
Myristic Acid	1	+
7-Hydroxy-4-chromone	0	+
UM-164	1	++++						p38β,p38α
Repotrectinib (TPX-0005)	11	+++						Trk receptor,ROS1,WT ALK
CCT196969	2	++	+++					CRAF,V600E-BRAF,BRAF
ON123300	3			+++				CDK4/CyclinD1,ARK5,RET
SU6656	30	+		++	++	+++
WH-4-023	25	+++	++++
Doramapimod (BIRB 796)	125			✔				c-RAF,JNK2,p38α
TPX-0046	0	✔
Dehydroabietic acid	0	✔						TAK1,Syk
Ginkgolic acid C17:1	0	✔						SHP-1,PTEN,STAT3
AD80	7	✔						S6 Kinase,Raf,RET V804M
Quercetin	46	✔						Sirtuin,PKC,PI3Kγ

1. "+" indicates inhibitory effect. Increased inhibition is marked by a higher "+" designation. 2. "✔" indicates inhibitory effect, but without specific value.

Cell Data

Cell Lines	Assay Type	Incubation Time	活性情報	PMID
A498	Cytotoxicity assay	6 days	Cytotoxicity against human A498 cells assessed as inhibition of cell viability after 6 days by MTT assay, IC50 = 0.5 μM.	23360104
A498	Cytotoxicity assay	72 hrs	Cytotoxicity against human A498 cells after 72 hrs by MTT assay, IC50 = 0.35 μM.	25124114
human LNCAP cells	Proliferation assay	3 days	Antiproliferative activity against human LNCAP cells after 3 days by MTS assay, IC50=0.5 nM	21438579
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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.

Targets

mTOR ^[1]
(Cell-free assay)

1.76 μM

In Vitro
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]
Kinase Assay	In vitro assay of mTOR catalytic activity
Kinase Assay	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.
細胞実験	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.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	p-rS6 / rS6 / p-AKT /AKT p-mTOR / mTOR / p-S6 / S6 / p-4E-BP1 / 4E-BP1		22039466
	Immunofluorescence	NRF2		22848625
	Growth inhibition assay	Cell viability Cell growth (HGC-3 cells)		22039466

In Vivo
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]
動物実験	動物モデル	Female athymic nude mice injected s.c. with DAOY, or U251 cells
	投与量	20 mg/kg
	投与経路	Injection daily 5 times per week

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT05773326	Recruiting	High Grade Glioma\|Glioma\|Glioma Malignant\|Glioblastoma	Nader Sanai\|Barrow Neurological Institute\|Ivy Brain Tumor Center\|St. Joseph''s Hospital and Medical Center Phoenix	May 15 2023	Early Phase 1
NCT01653067	Unknown status	Diffuse Large B-Cell Lymphoma	Mathias Witzens-Harig\|Johannes Gutenberg University Mainz\|Technical University of Munich\|Ludwig-Maximilians - University of Munich\|University Hospital Ulm\|University Hospital Erlangen\|Charite University Berlin Germany\|University Hospital Freiburg\|Johann Wolfgang Goethe University Hospital\|University Hospital Heidelberg	September 2012	Phase 2
NCT02093598	Completed	Carcinoma Endometrioid\|mTOR Protein	MedSIR	May 2012	Phase 2

参考
[1] Shor B, et al. Cancer Res, 2008, 68(8), 2934-2943. [2] Wu L, et al. Cancer Res, 2005, 65(7), 2825-2831. [3] Teachey DT, et al. Blood, 2006, 107(3), 1149-1155. [4] Geoerger B, et al. Cancer Res, 2001, 61(4), 1527-1532. [5] Ravikumar B, et al. Nat Genet, 2004, 36(6), 585-595. [6] Frost P, et al. Blood, 2004, 104(13), 4181-4187. + 展開

参考

+ 展開

化学情報

分子量	1030.29	化学式	C₅₆H₈₇NO₁₆
CAS No.	162635-04-3	SDF	Download Temsirolimus SDFをダウンロードする
Smiles	CC1CCC2CC(C(=CC=CC=CC(CC(C(=O)C(C(C(=CC(C(=O)CC(OC(=O)C3CCCCN3C(=O)C(=O)C1(O2)O)C(C)CC4CCC(C(C4)OC)OC(=O)C(C)(CO)CO)C)C)O)OC)C)C)C)OC
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	１ケ月-20°Cin solvent

In vitro
Batch:

DMSO : 100 mg/mL ( (97.06 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Ethanol : 100 mg/mL

Water : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

Clear solution

5% DMSO 1 95% Corn oil

0.7mg/ml (0.68mM)

Taking the 1 mL working solution as an example, add 50 μL of 14 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

Clear solution

5%DMSO 1 40%PEG300 Click to order 2 5%Tween 80 Click to order 3 50%ddH2O

1.65mg/ml (1.60mM)

Taking the 1 mL working solution as an example, add 50 μL of 33 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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