Everolimus

別名：RAD001,SDZ-RAD

製品コード：S1120 純度：99.78%

エベロリムス (Everolimus (RAD001, SDZ-RAD)) は FKBP12 に結合することで形成した複合体により mTOR を阻害します。Cell-free assay における IC50 は1.6 ～ 2.4 ｎM です。エベロリムスは アポトーシス (apoptosis) と オートファジー (autophagy) を誘発することによりがん細胞の増殖を阻害します。

CAS No. 159351-69-6

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 33000	国内在庫あり
10mg	JPY 22000	国内在庫あり
25mg	JPY 41500	国内在庫あり
100mg	JPY 100500	国内在庫あり
1g	JPY 220500	国内在庫あり

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（729）

製品安全説明書

現在のバッチを見る：純度： 99.78%

99.78

Everolimus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

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
A549	Autophagy assay	5 uM	6 h	Induction of autophagy in human A549 cells assessed as increase in conversion of LC3-1 to LC3-2 at 5 uM after 6 hrs by Western blot analysis	26176165
A549	Function Assay	5 uM	3 to 24 h	Inhibition of mTOR phosphorylation at ser2448 in human A549 cells at 5 uM after 3 to 24 hrs by Western blot analysis	26176165
A549	Function Assay	5 uM	3 to 24 h	Inhibition of mTOR in human A549 cells assessed as downregulation of p70S6K phosphorylation at thr389 at 5 uM after 3 to 24 hrs by Western blot analysis	26176165
OVCAR3	Cytotoxic Assay		72 h	IC50=16 μM	24445311
DU145	Cytotoxic Assay		72 h	IC50=8 μM	24445311
SK-HEP1	Cytotoxic Assay		72 h	IC50=12 μM	24445311
CAKI1	Cytotoxic Assay		72 h	IC50=14 μM	24445311
HT29	Cytotoxic Assay		72 h	IC50=15 μM	24445311
HCT116	Cytotoxic Assay		72 h	IC50=12 μM	24445311
ColoR	Cytotoxic Assay		72 h	IC50=8.7 μM	24445311
Colo205	Cytotoxic Assay		72 h	IC50=20 μM	24445311
SQ20B	Cytotoxic Assay		72 h	IC50=5.5 μM	24445311
HOP62	Cytotoxic Assay		72 h	IC50=19 μM	24445311
Colo205	Function Assay		24 h	Inhibits mTORC1 in human COLO205 cells assessed as reduction of S6 phosphorylation at 0.1 to 8 uM	24836070
Colo205	Function Assay		24 h	Inhibits mTORC1 in human COLO205 cells assessed as reduction of 4-EBP1 phosphorylation at 0.1 to 8 uM	24836070
SK-HEP1	Function Assay		24 h	Inhibits mTORC1 in human SK-HEP1 cells assessed as reduction of S6 phosphorylation at 0.1 to 8 uM	24836070
SK-HEP1	Function Assay		24 h	Inhibits mTORC1 in human SK-HEP1 cells assessed as reduction of 4-EBP1 phosphorylation at 0.1 to 8 uM	24836070
Sf9	Function Assay		15 to 20 mins	Inhibition of human BSEP overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-taurocholate in presence of ATP measured after 15 to 20 mins by membrane vesicle transport assay, IC50 = 2 μM.	23956101
Sf9	Function Assay		20 mins	Inhibition of human MRP2 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay, IC50 = 11.3 μM.	23956101
他の多くの細胞株試験データをご覧になる場合はこちらをクリックして下さい

生物活性

製品説明

Targets

FKBP12 ^[1] (Cell-free assay)	mTOR (FKBP12) ^[1] (Cell-free assay)
1.6-2.4 nM	1.6 nM-2.4 nM

In Vitro
In vitro	Everolimus exhibits the immunosuppressive activity which is comparable to that of rapamycin. Everolimus competes with immobilized FK 506 for binding to biotinylated FKBP12 and shows the inhibitory effect on a two-way MLR performed with spleen cells from BALB/c and CBA mice with IC50 of 0.12-1.8 nM. ^[1] Everolimus also shows antiangiogenic/vascular effects in VEGF-induced HUVEC proliferation with IC50 of 0.12 nM and bFGF-induced HUVEC proliferation with IC50 of 0.8 nM, respectively. ^[2] A recent study shows that Everolimus shows a dose-dependent inhibitory effects on both the total cells and the stem cells from the BT474 cell line and the primary breast cancer cells with IC50 of 156 nM in total cells of primary breast cancer cells and 71 nM in total cells of BT474 cells. In addition, combination treatment with Everolimus and trastuzumab produces the significantly increased inhibition on the growth of cancer stem cells with the inhibition rate increased by more than 50 %. ^[3]
Kinase Assay	FKBP12 binding assay & Mixed lymphocyte reaction (MLR)
Kinase Assay	FKBP12 binding assay: Binding to the FK 506 binding protein (FKBP12) is indirectly assessed by means of an ELISA-type competition assay. FK 506 is included in each individual experiment as a standard, and the inhibitory activity is expressed as relative IC50 compared to FK 506 (rIC50 = IC50 Everolimus/IC50 FK 506). Mixed lymphocyte reaction (MLR): The immunosuppressive activities of RAP and its derivatives are assessed in a two-way MLR, using spleen cells of BALB/c and CBA mice. RAP is included in each individual experiment as a standard, and the inhibitory activity is expressed as relative IC50 compared to RAP (rIC50 = IC50 Everolimus/IC50 RAP).
細胞実験	細胞株	BT474 cell line and the primary breast cancer cells
	濃度	0.001-10 μM
	反応時間	24 hours
	実験の流れ	The 3-(4-5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye reduction assay (MTT assay) is used to compare the effects of Everolimus or trastuzumab on total breast cancer cells and breast CSCs. The total cells and the stem cells from the BT474 cell line and the primary breast cancer cells are respectively seeded into 96-well plates with different concentrations of the drugs, with five wells for each concentration, and the cells are cultured at 37 °C with 5 % CO₂ in an incubator for 24 hours. The concentrations of Everolimus are 1 nM, 10 nM, 100 nM, 1 μM and 10 μM, and the concentrations of trastuzumab are 0.5 μg/mL, 1 μg/mL, 10 μg/mL, 50 μg/mL, and 100 μg/mL. The combinatorial inhibitory effect of Everolimus and Trastuzumab on the in vitro growth of breast CSCs is examined by MTT assay as well using 10 μg/mL trastuzumab in combination of increasing concentrations of everolimus (1 nM, 10 nM, 100 nM and 1 μM). After drug treatment for 24 hours, 20 μL MTT [5 mg/mL in phosphate buffered saline (PBS)] is added to each well, and the cells are incubated at 37 °C with 5 % CO₂ and saturated humidity for 4 hours. Following the subsequent removal of the supernatant, 150 μL dimethyl sulfoxide (DMSO) is added to each well, and the cells are vortexed for 10 minutes. The light absorbance (OD value) is measured for each well using an ELISA reader. Each experiment is repeated in triplicate, and dose–response curves are plotted. The probit software of the statistical software package SPSS 17.0 for Windows is used to calculate the inhibitory concentration (IC50) of Everolimus.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	Mcl-1 / p-ERK / S6K1(T389) pS6RP cleaved caspase-3		27351224
	Growth inhibition assay	Cell counts IC50 Cell proliferation		27127803
	Immunofluorescence	TERT		27127803

In Vivo
In Vivo	Everolimus (0.1 to 10 mg/kg) dose-dependently inhibits growth of the primary (ear) and lymph node metastases of B16/BL6 melanoma, with decreased total number of vessels and reduced mature vessels. ^[2] In a xenograft animal model of BT474 stem cells, Everolimus shows significant reductions in mean tumor sizes (590.6 mm³), compared to the control group with a tumor size of 698 mm³. Furthermore, combination treatment with Everolimus and trastuzumab significantly decreases the xenograft tumor size (410.8 mm³) more than Everolimus treatment alone. ^[3]
動物実験	動物モデル	Cultured BT474 stem cells are injected beneath the left breast pad of BALB/c nude mice.
	投与量	≤2 mg/kg
	投与経路	Administered via p.o.

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT05843253	Not yet recruiting	High Grade Glioma\|Diffuse Intrinsic Pontine Glioma\|Anaplastic Astrocytoma\|Glioblastoma\|Glioblastoma Multiforme\|Diffuse Midline Glioma H3 K27M-Mutant\|Metastatic Brain Tumor\|WHO Grade III Glioma\|WHO Grade IV Glioma	Nationwide Children''s Hospital\|Novartis	May 30 2024	Phase 2
NCT05501769	Active not recruiting	Breast Cancer	Arvinas Estrogen Receptor Inc.\|Pfizer\|Arvinas Inc.	September 8 2022	Phase 1
NCT05476939	Recruiting	Diffuse Intrinsic Pontine Glioma\|Diffuse Midline Glioma H3 K27M-Mutant	Gustave Roussy Cancer Campus Grand Paris\|Chimerix\|Innovative Therapies For Children with Cancer Consortium	September 29 2022	Phase 3
NCT05293964	Recruiting	Breast Cancer	Jiangsu Simcere Pharmaceutical Co. Ltd.	May 18 2022	Phase 1

参考
[1] Sedrani R, et al. Transplant Proc, 1998, 30(5), 2192-2194. [2] Lane HA, et al. Clin Cancer Res, 2009, 15(5), 1612-1622. [3] Zhu Y, et al. Tumour Biol. 2012 Apr 11. Doi: 10.1007/s13277-012-0383-6. [4] Boulay A, et al. Clin Cancer Res, 2005, 11(14), 5319-5328. [5] Cejka D, et al. Cancer Biol Ther, 2008, 7(9), 1377-1385. + 展開

参考

+ 展開

化学情報

分子量	958.22	化学式	C₅₃H₈₃NO₁₄
CAS No.	159351-69-6	SDF	Download Everolimus 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)OCCO)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个月-20°Cin solvent

In vitro
Batch:

DMSO : 100 mg/mL ( (104.36 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

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。

技術サポート

ストックの作り方、阻害剤の保管方法、細胞実験や動物実験の際に注意すべき点など、製品を取扱う時に問い合わせが多かった質問に対しては取扱説明書でお答えしています。

Handling Instructions

他に質問がある場合は、お気軽にお問い合わせください。

* 必須

* 大学・企業名 大学・企業名を記入してください

* 名前 名前を記入してください

* 電子メール 電子メール・アドレスを記入してください 有効なメールアドレスを入力してください

電話番号

* 内容 お問い合わせ内容をご入力ください

よくある質問（FAQ）

質問1:
For the in vivo work, I know the drug needs to be dissolved in 30% propylene glycol (dilution in water) and 5%Tween 80. Would the final solution be a clear liquid or a turbid suspension?

回答
Our S1120 Everolimus (RAD001) in 30% Propylene glycol+5% Tween 80+ddH2O at 5mg/ml is a clear solution. And for oral gavage, there is another common vehicle, 1% CMC Na. Everolimus can be dissolved in it at 30mg/ml as a suspension.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):