Tanespimycin (17-AAG)

別名：CP127374, NSC-330507, KOS 953

製品コード：S1141 純度：99.92%

Tanespimycin (17-AAG, CP127374, NSC-330507, KOS 953) is a potent HSP90 inhibitor with IC50 of 5 nM in a cell-free assay, having a 100-fold higher binding affinity for HSP90 derived from tumour cells than HSP90 from normal cells. Tanespimycin (17-AAG) induces apoptosis, necrosis, autophagy and mitophagy. Phase 3.

CAS No. 75747-14-7

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 29500	国内在庫あり
5mg	JPY 22000	国内在庫あり
25mg	JPY 44500	国内在庫あり
100mg	JPY 119500	国内在庫あり
1g	JPY 557800	国内在庫なし(納期7~10日)

代表番号: 045-509-1970\|電子メール：sales@selleck.co.jp よく尋ねられる質問

文献中Selleckの製品使用例（142）

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製品安全説明書

現在のバッチを見る：純度： 99.92%

99.92

Tanespimycin (17-AAG)関連製品

関連ターゲット	HSP40 HSP70 HSP90 HSP105 HSF1	もっと見る
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関連化合物ライブラリー	Kinase Inhibitor Library Angiogenesis Related compound Library TGF-beta/Smad compound library Cytoskeletal Signaling Pathway Compound Library Anti-Cardiovascular Disease Compound Library	もっと見る

シグナル伝達経路

HSP (HSP90)シグナル伝達経路

HSP (HSP90)阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	活性情報	PMID
C2BBe1	Growth Inhibition Assay	IC50=0.2219 μM	SANGER
TE-9	Growth Inhibition Assay	IC50=0.21786 μM	SANGER
MFE-280	Growth Inhibition Assay	IC50=0.21298 μM	SANGER
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生物活性

製品説明

特性

Displays very low toxicity toward normal cells.

Targets

HSP90 ^[1]
(Cell-free assay)

5 nM

In Vitro
In vitro	17-AAG, an analog of geldanamycin, exhibits greater than 100 times higher binding affinity for Hsp90 derived from HER-2-overexpressing cancer cells (BT474, N87, SKOV3 and SKBR3) or BT474 breast carcinoma cells with IC50 values of 5-6 nM. ^[1] 17-AAG causes the degradation of HER2, HER3, Akt, and both mutant and wild-type androgen receptor (AR), leading to the RB-dependent G1 growth arrest of prostate cancer cells such as LNCaP, LAPC-4, DU-145, and PC-3 with IC50 values of 25-45 nM. ^[2] In addition to inducing apoptosis of Ba/F3 cells transformed with wild-type BCR-ABL with an IC50 of 5.2 μM, 17-AAG has the ability to induce apoptosis of cells transformed with T315I and E255K BCR-ABL mutants with IC50 values of 2.3 μM and 1.0 μM, respectively, by inducing the degradation of both wild-type BCR-ABL protein and mutants. ^[3]
Kinase Assay	Hsp90 binding assays
Kinase Assay	Purified native Hsp90 protein or cell lysates from HER-2-overexpressing cancer cells (BT474, N87, SKOV3 and SKBR3) or BT474 breast carcinoma cells in lysis buffer (20 mM HEPES, pH 7.3, 1 mM EDTA, 5 mM MgCl₂, 100 mM KCl) are incubated with various concentrations of 17-AAG for 30 minutes at 4 °C, and then incubated with biotin-GM linked to BioMag streptavidin magnetic beads for 1 hour at 4 °C. Tubes are placed on a magnetic rack, and the unbound supernatant removed. The magnetic beads are washed three times in lysis buffer and heated for 5 minutes at 95 °C in SDS–PAGE sample buffer. Samples are analysed on SDS protein gels, and western blots done using indicated antibodies. Bands in the western blots are quantified using the Bio-rad Fluor-S MultiImager, and the percentage inhibition of binding of Hsp90 to the biotin-GM is calculated. The IC50 reported is the concentration of 17-AAG needed to cause half-maximal inhibition of binding.
細胞実験	細胞株	BT474, SKBR3, N87, SKOV3, MCF7, MDA468, Hs578T, Hs578Bst, A549, HT29, U87, SKMG3, HT1080, RPTEC, NDF, HMVEC, HMEC, HUVEC, and PBMC cells
	濃度	Dissolved in DMSO, final concentrations ~10 μM
	反応時間	5 days
	実験の流れ	Cells are seeded in 96-well plates at 2,000 cells per well in a final culture volume of 100 μL for 24 hours before the addition of increasing concentrations of 17-AAG that is incubated for 5 days. Viable cell number is determined using the Celltiter 96 AQueous Nonradioactive Cell Proliferation Assay. The value of the background absorbance at 490 nm (A₄₉₀) of wells not containing cells is subtracted. Percentage of viable cells = (A₄₉₀ of 17-AAG treated sample/A₄₉₀ untreated cells) × 100. The IC50 is defined as the concentration that gave rise to 50% viable cell number.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	α-Synuclein / HSP90 / HSP70 / HSP32 / αB-Crystallin EGFR / PDGFR / AKT / MAPK / c-RAS pAKT / pMAPK / pRb Cleaved PARP / Survivin LATS1 / p-LATS1 / YAP / CTGF		20090920
	Immunofluorescence	STAT3 YAP / TAZ β-catenin / E-cadherin		27279418
	Growth inhibition assay	Cell viability		18682579

In Vivo
In Vivo	17-AAG displays significantly higher binding affinity for Hsp90 from 3T3-src, B16 or CT26 xenografts in nude mice with IC50 values of 8-35 nM as compared with that from the normal tissues with IC50 values of 200-600 nM. ^[1] Administration of 17-AAG (~50 mg/kg) causes significant decline in AR, HER2, HER3, and Akt expression in a dose-dependent manner with >50% decline at dose of 50 mg/kg, resulting in the dose-dependent inhibition of androgen-dependent (CWR22) and -independent (CWR22R and CWRSA6) prostate cancer xenografts growth by 67%, 80% and 68% at dose of 50 mg/kg, respectively. ^[2]
動物実験	動物モデル	Male nu/nu athymic mice inoculated s.c. with androgen-dependent CWR22 xenograft, and female nu/nu athymic mice inoculated s.c. with androgen-independent xenografts CWR22R and CWRSA6
	投与量	~50 mg/kg
	投与経路	Injection i.p.

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT00103272	Terminated	Adult Acute Basophilic Leukemia\|Adult Acute Eosinophilic Leukemia\|Adult Acute Megakaryoblastic Leukemia (M7)\|Adult Acute Minimally Differentiated Myeloid Leukemia (M0)\|Adult Acute Monoblastic Leukemia (M5a)\|Adult Acute Monocytic Leukemia (M5b)\|Adult Acute Myeloblastic Leukemia With Maturation (M2)\|Adult Acute Myeloblastic Leukemia Without Maturation (M1)\|Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities\|Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)\|Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)\|Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)\|Adult Acute Myelomonocytic Leukemia (M4)\|Adult Erythroleukemia (M6a)\|Adult Pure Erythroid Leukemia (M6b)\|Anaplastic Large Cell Lymphoma\|Angioimmunoblastic T-cell Lymphoma\|Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue\|Nodal Marginal Zone B-cell Lymphoma\|Recurrent Adult Acute Lymphoblastic Leukemia\|Recurrent Adult Acute Myeloid Leukemia\|Recurrent Adult Diffuse Large Cell Lymphoma\|Recurrent Adult T-cell Leukemia/Lymphoma\|Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma\|Recurrent Grade 1 Follicular Lymphoma\|Recurrent Grade 2 Follicular Lymphoma\|Recurrent Grade 3 Follicular Lymphoma\|Recurrent Mantle Cell Lymphoma\|Recurrent Marginal Zone Lymphoma\|Recurrent Mycosis Fungoides/Sezary Syndrome\|Recurrent Small Lymphocytic Lymphoma\|Refractory Chronic Lymphocytic Leukemia\|Small Intestine Lymphoma\|Splenic Marginal Zone Lymphoma\|Waldenström Macroglobulinemia	National Cancer Institute (NCI)	April 2005	Phase 1
NCT00098488	Terminated	B-cell Chronic Lymphocytic Leukemia\|Prolymphocytic Leukemia\|Refractory Chronic Lymphocytic Leukemia	National Cancer Institute (NCI)	April 2005	Phase 1
NCT00118248	Completed	Recurrent Thyroid Cancer\|Stage IV Follicular Thyroid Cancer\|Stage IV Papillary Thyroid Cancer\|Thyroid Gland Medullary Carcinoma	National Cancer Institute (NCI)	December 2004	Phase 2
NCT00098423	Completed	Accelerated Phase Chronic Myelogenous Leukemia\|Adult Acute Basophilic Leukemia\|Adult Acute Eosinophilic Leukemia\|Adult Acute Megakaryoblastic Leukemia (M7)\|Adult Acute Minimally Differentiated Myeloid Leukemia (M0)\|Adult Acute Monoblastic Leukemia (M5a)\|Adult Acute Monocytic Leukemia (M5b)\|Adult Acute Myeloblastic Leukemia With Maturation (M2)\|Adult Acute Myeloblastic Leukemia Without Maturation (M1)\|Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities\|Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)\|Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)\|Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)\|Adult Acute Myelomonocytic Leukemia (M4)\|Adult Erythroleukemia (M6a)\|Adult Pure Erythroid Leukemia (M6b)\|Blastic Phase Chronic Myelogenous Leukemia\|Chronic Myelomonocytic Leukemia\|de Novo Myelodysplastic Syndromes\|Previously Treated Myelodysplastic Syndromes\|Recurrent Adult Acute Lymphoblastic Leukemia\|Recurrent Adult Acute Myeloid Leukemia\|Refractory Anemia With Excess Blasts in Transformation\|Relapsing Chronic Myelogenous Leukemia\|Secondary Acute Myeloid Leukemia\|Secondary Myelodysplastic Syndromes	National Cancer Institute (NCI)	November 2004	Phase 1

参考
[1] Kamal A, et al. Nature, 2003, 425(6956), 407-410. [2] Solit DB, et al. Clin Cancer Res, 2002, 8(5), 986-993. [3] Gorre ME, et al. Blood, 2002, 100(8), 3041-3044.

参考

化学情報

分子量	585.69	化学式	C₃₁H₄₃N₃O₈
CAS No.	75747-14-7	SDF	Download Tanespimycin (17-AAG) SDFをダウンロードする
Smiles	CC1CC(C(C(C=C(C(C(C=CC=C(C(=O)NC2=CC(=O)C(=C(C1)C2=O)NCC=C)C)OC)OC(=O)N)C)C)O)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 ( (170.73 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 : 33 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 Corn oil

10.0mg/ml (17.07mM)

Taking the 1 mL working solution as an example, add 50 μL of 200 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

6.0mg/ml (10.24mM)

Taking the 1 mL working solution as an example, add 50 μL of 120 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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よくある質問（FAQ）

質問1:
What kind of subtypes does this compound inhibit? HSP90α or HSP90β ?

回答
17-AAG can inhibit both HSP90α and HSP90β, but it is unclear how much are they affected respectively. You should note that Hsp90 derived from tumor cells has a 100-fold higher binding affinity for 17-AAG than that from normal cells according to this paper. http://www.nature.com.ezp-prod1.hul.harvard.edu/nature/journal/v425/n6956/full/nature01913.html

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