Alvespimycin (17-DMAG) HCl

Alvespimycin (17-DMAG, NSC 707545, BMS 826476, KOS 1022) HCl is a potent HSP90 inhibitor with IC50 of 62 nM in a cell-free assay. Phase 2.

CAS No. 467214-21-7

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 55500	国内在庫あり
100mg	JPY 119500	国内在庫あり
200mg	JPY 200500	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（66）

製品安全説明書

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Alvespimycin (17-DMAG) HCl関連製品

関連ターゲット	HSP40 HSP70 HSP90 HSP105 HSF1	もっと見る
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	Concentration	Incubation Time	活性情報	PMID
NCI-H526	Function assay	1 uM	96 hrs	Inhibition of HSP90-mediated proliferation of human NCI-H526 cells at 1 uM after 96 hrs by sulforhodamine B assay	17603540
NCI-H526	Function assay	1 uM	24 hrs	Binding affinity to HSP90 in human NCI-H526 cells at 1 uM after 24 hrs by fluorescence polarization assay	17603540
LN229-Lux	Function assay	2.5 to 10 uM	1 hr	Inhibition of luciferase activity in human LN229-Lux cells at 2.5 to 10 uM incubated for 1 hr under normoxia followed by 24 hrs under hypoxia by reporter gene assay	22746274
HeLa	Function assay	10 uM	6 hrs	Inhibition of HSP90 in human HeLa cells assessed as induction of chk1 degradation at 10 uM after 6 hrs by Western blot method	28816449
HeLa	Function assay	10 uM	6 hrs	Inhibition of HSP90 in human HeLa cells assessed as induction of Akt degradation at 10 uM after 6 hrs by Western blot method	28816449
HeLa	Function assay	10 uM	6 hrs	Inhibition of HSP90 in human HeLa cells assessed as induction of HSP70 protein expression at 10 uM after 6 hrs by Western blot method	28816449
PC3	Function assay	10 uM	6 hrs	Inhibition of HSP90 in human PC3 cells assessed as induction of chk1 degradation at 10 uM after 6 hrs by Western blot method	28816449
PC3	Function assay	10 uM	6 hrs	Inhibition of HSP90 in human PC3 cells assessed as induction of Akt degradation at 10 uM after 6 hrs by Western blot method	28816449
PC3	Function assay	10 uM	6 hrs	Inhibition of HSP90 in human PC3 cells assessed as induction of HSP70 protein expression at 10 uM after 6 hrs by Western blot method	28816449
AGS	Function assay		24 hrs	Viability of human AGS cells under normoxic conditions after 24 hrs by MTT assay, IC50=16μM.	17583950
Hep3B	Function assay		16 hrs	Inhibition of HIF1 activation in human Hep3B cells assessed as inhibition of hypoxia-induced luciferase expression after 16 hrs by reporter assay, IC50=0.061μM.	17583950
AGS	Function assay		16 hrs	Inhibition of HIF1 activation in human AGS cells assessed as inhibition of hypoxia-induced luciferase expression after 16 hrs by reporter assay, IC50=0.036μM.	17583950
HuH7	Antiviral assay		3 days	Antiviral activity against Hepatitis C virus genotype 1b Con1 infected in human HuH7 cells assessed as GAPDH RNA or 18S rRNA level after 3 days by qRT-PCR analysis, EC50=0.0012μM.	18936191
HuH7	Antiviral assay		3 days	Antiviral activity against Hepatitis C virus genotype 1b Con1 infected in human HuH7 cells assessed as GAPDH RNA or 18S rRNA level after 3 days selected with 40 nM HCV-796 and 800 nM boceprevir by qRT-PCR analysis, EC50=0.0031μM.	18936191
Hep3B	Function assay		30 mins	Inhibition of hypoxia-induced HIF1alpha protein accumulation in human Hep3B cells treated for 30 mins measured after 12 hrs by Western blot analysis, IC50=0.0572μM.	19072214
Hep3B	Function assay		16 hrs	Inhibition of hypoxia-induced VEGF protein secretion in human Hep3B cells after 16 hrs by ELISA, IC50=0.0795μM.	19072214
HCT116	Cytotoxicity assay		72 hrs	Cytotoxicity against human HCT116 cells after 72 hrs, IC50=0.057μM.	19231864
SKBR3	Cytotoxicity assay		72 hrs	Cytotoxicity against human SKBR3 cells after 72 hrs, IC50=0.058μM.	19231864
MCF7	Cytotoxicity assay		72 hrs	Cytotoxicity against human MCF7 cells after 72 hrs, IC50=0.071μM.	19231864
SKOV3	Cytotoxicity assay		72 hrs	Cytotoxicity against human SKOV3 cells after 72 hrs, IC50=0.122μM.	19231864
SKBR3	Cytotoxicity assay		72 hrs	Cytotoxicity against human SKBR3 cells after 72 hrs in presence of NQO1 inhibitor dicoumarol, IC50=0.23μM.	19231864
MCF7	Cytotoxicity assay		72 hrs	Cytotoxicity against human MCF7 cells after 72 hrs in presence of NQO1 inhibitor dicoumarol, IC50=0.862μM.	19231864
NCI-H596	Cytotoxicity assay		72 hrs	Cytotoxicity against NQ01-deficient human NCI-H596 cells after 72 hrs, IC50=1.1μM.	19231864
MDA468	Cytotoxicity assay		72 hrs	Cytotoxicity against NQ01-deficient human MDA468 cells after 72 hrs, IC50=1.6μM.	19231864
SKBR3	Cytotoxicity assay		72 hrs	Cytotoxicity against human SKBR3 cells after 72 hrs by celltiter-glo assay, IC50=0.024μM.	19405528
A549	Cytotoxicity assay		72 hrs	Cytotoxicity against human A549 cells after 72 hrs by celltiter-glo assay, IC50=0.068μM.	19405528
SKOV3	Cytotoxicity assay		72 hrs	Cytotoxicity against human SKOV3 cells after 72 hrs by celltiter-glo assay, IC50=0.22μM.	19405528
MCF7	Cytotoxicity assay		72 hrs	Cytotoxicity against human MCF7 cells after 72 hrs by celltiter-glo assay, IC50=0.23μM.	19405528
CCRF-CEM	Cytotoxicity assay		72 hrs	Cytotoxicity against human CCRF-CEM cells after 72 hrs by celltiter-96 aqueous one solution assay, IC50=0.54μM.	19405528
CCRF-CEM	Cytotoxicity assay		72 hrs	Cytotoxicity against human paclitaxel-resistant CCRF-CEM cells after 72 hrs by celltiter-96 aqueous one solution assay, IC50=2.5μM.	19405528
Hep3B	Function assay		30 mins	Inhibition of hypoxia-induced HIF1alpha protein accumulation in human Hep3B cells treated for 30 mins measured after 12 hrs by Western blot analysis, IC50=0.057μM.	20469887
Hep3B	Function assay		16 hrs	Inhibition of hypoxia-induced VEGF protein secretion in human Hep3B cells after 16 hrs by ELISA, IC50=0.079μM.	20469887
NCI-H1299	Function assay		24 hrs	Inhibition of human HSP90 in human NCI-H1299 cells assessed as Akt degradation after 24 hrs by luminex assay, IC50=0.1μM.	21438541
MCF7	Antiproliferative assay		48 hrs	Antiproliferative activity against human MCF7 cells assessed as inhibition of cell viability after 48 hrs by MTT assay, IC50=0.39μM.	24582477
HCT116	Antiproliferative assay		48 hrs	Antiproliferative activity against human HCT116 cells assessed as inhibition of cell viability after 48 hrs by MTT assay, IC50=0.78μM.	24582477
SKBR3	Antiproliferative assay		48 hrs	Antiproliferative activity against human SKBR3 cells assessed as inhibition of cell viability after 48 hrs by MTT assay, IC50=1.34μM.	24582477
A231	Antiproliferative assay		48 hrs	Antiproliferative activity against human A231 cells after 48 hrs by MTT assay, IC50=0.17μM.	24763261
MCF7	Antiproliferative assay		48 hrs	Antiproliferative activity against human MCF7 cells after 48 hrs by MTT assay, IC50=0.8μM.	24763261
HCT116	Antiproliferative assay		48 hrs	Antiproliferative activity against human HCT116 cells after 48 hrs by MTT assay, IC50=1.21μM.	24763261
SKBR3	Antiproliferative assay		48 hrs	Antiproliferative activity against human SKBR3 cells after 48 hrs by MTT assay, IC50=3.11μM.	24763261
NCI-H1299	Function assay		12 hrs	Reduction in oxygen consumption rate in human NCI-H1299 cells incubated for 12 hrs	25383915
PC9	Cytotoxicity assay		72 hrs	Cytotoxicity against HGF-induced erlotinib-resistant human PC9 cells assessed as inhibition of cell growth after 72 hrs by MTT assay, IC50=0.01μM.	26844689
Ma1	Cytotoxicity assay		72 hrs	Cytotoxicity against HGF-induced erlotinib-resistant human Ma1 cells assessed as inhibition of cell growth after 72 hrs by MTT assay, IC50=0.01μM.	26844689
MDA-MB-231	Function assay			Inhibition of Hsp90 in human MDA-MB-231 cells assessed as her2 degradation, IC50=0.0045μM.	18929486
A2058	Cytotoxicity assay			Cytotoxicity against human A2058 cells by MTT assay, IC50=0.0021μM.	18929486
AGS	Cytotoxicity assay			Cytotoxicity against human AGS cells by MTT assay, IC50=16μM.	18359631
HeLa	Cytotoxicity assay			Cytotoxicity against human HeLa cells by MTT assay, IC50=2.06μM.	18359631
HeLa	Function assay			Inhibition of TNF-alpha-induced NF-kappaB activation in human HeLa cells, IC50=0.15μM.	18359631
AGS	Function assay			Inhibition of hypoxia-induced HIF1 activation in human AGS cells by reporter gene assay, IC50=0.0036μM.	18359631
SKOV3	Function assay			Degradation of Her2 in SKOV3 cells, EC50=0.046μM.	16854066
SKOV3	Function assay			Upregulation of Hsp70 in SKOV3 cells, EC50=0.014μM.	16854066
SKBR3	Function assay			Degradation of Her2 in SKBR3 cells, EC50=0.008μM.	16854066
SKBR3	Function assay			Upregulation of Hsp70 in SKBR3 cells, EC50=0.004μM.	16854066
SKBr3	Cytotoxicity assay			Cytotoxicity against SKBr3 cells, IC50=0.024μM.	16165354
MDA-MB-231	Cytotoxicity assay			Cytotoxicity against human MDA-MB-231 cells by MTT assay, IC50=0.0058μM.	18929486
A2058	Function assay			Inhibition of Hsp90 in human A2058 cells, EC50=0.0079μM.	18929486
MDA-MB-231	Function assay			Inhibition of Hsp90 in human MDA-MB-231 cells assessed as Akt degradation, IC50=0.0176μM.	18929486
A2058	Function assay			Inhibition of Hsp90 in human A2058 cells assessed as Akt degradation, IC50=0.0243μM.	18929486
SKBR3	Function assay			Binding affinity to Hsp90 in human SKBR3 cells, IC50=0.024μM.	19017562
HCT116	Cytotoxicity assay			Cytotoxicity against human HCT116 cells by Alamar blue assay, IC50=0.05μM.	20662534
SKBR3	Function assay			Inhibition of Hsp90 in human SKBR3 cells, IC50=0.024μM.	26844689
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生物活性

製品説明

Alvespimycin (17-DMAG, NSC 707545, BMS 826476, KOS 1022) HCl is a potent HSP90 inhibitor with IC50 of 62 nM in a cell-free assay. Phase 2.

特性

A synthetic derivative Geldanamycin, with lower hepatotoxicity than parent antibiotic & higher potency and bioavailability than the similar derivative 17-AAG.

Targets

HSP90 ^[1]
(Cell-free assay)

62 nM

In Vitro
In vitro	17-DMAG displays ~2 times potency against human Hsp90 than 17-AAG, with IC50 of 62 nM versus 119 nM. In SKBR3 and SKOV3 cells which over-express Hsp90 client protein Her2, 17-DMAG causes down-regulation of Her2 with EC50 of 8 nM and 46 nM, respectively, as well as induction of Hsp70 with EC50 of 4 nM and 14 nM, respectively, leading to significant cytotoxicity with GI50 of 29 nM and 32 nM, respectively, consistent with Hsp90 inhibition. ^[1] 17-DMAG in combination with vorinostat synergistically induces apoptosis of the cultured MCL cells as well as primary MCL cells, more potently than either agent alone, by markedly attenuating the levels of cyclin D1 and CDK4, as well as of c-Myc, c-RAF and Akt. ^[3] In contrast to 17-AAG which is only active for IKKβ in chronic lymphocytic leukemia (CLL) cells, 17-DMAG treatment effectively leads to depletion of the Hsp90 client protein, resulting in diminished NF-κB p50/p65 DNA binding, decreased NF-κB target gene transcription, and caspase-dependent apoptosis. By targeting the NF-κB family, 17-DMAG selectively mediates dose- and time-dependent cytotoxicity against CLL cells, but not normal T cells or NK cells important for immune surveillance. ^[5]
Kinase Assay	Fluorescence polarization (FP)-based competition binding assay
Kinase Assay	This assay utilizes a boron difluoride dipyrromethene (BODIPY) labeled geldanamycin analogue (BODIPY-AG) as a probe and measured fluorescence polarization upon binding of the probe to a protein. Native human Hsp90 protein (α + β isoforms) is isolated from HeLa cells. BODIPY-AG solution is freshly prepared in FP assay buffer (20 mM HEPES-KOH, pH 7.3, 1.0 mM EDTA, 100 mM KCl, 5.0 mM MgCl₂, 0.01% NP-40, 0.1 mg/mL fresh bovine γ-globulin (BGG), 1.0 mM fresh DTT, and protease inhibitor from stock solution in DMSO. Competition curves are obtained by mixing 10 μL each of a solution containing BODIPY-AG and Hsp90, and a serial dilution of 17-DMAG freshly prepared in FP assay buffer from stock solution in DMSO. Final concentrations are 10 nM BODIPY-AG, 40 or 60 nM Hsp90, varying concentration of 17-DMAG (0.10 nM-10 μM), and ≤0.25% DMSO in a 384-well microplate. After 3 hours incubation at 30 °C, fluorescence anisotropy (γ_Ex = 485 nm, γ_Em = 535 nm) is measured on an EnVision 2100 multilabel plate reader. IC50 value of 17-DMAG is obtained from the competition curves.
細胞実験	細胞株	Chronic lymphocytic leukemia (CLL)
	濃度	Dissolved in DMSO, final concentrations ~1 μM
	反応時間	24, or 48 hours
	実験の流れ	Cells are exposed to various concentrations of 17-DMAG for 24, or 48 hours. For the assessment of cytotoxicity, MTT reagent is then added, and plates are incubated for an additional 24 hours before spectrophotometric measurement. Apoptosis is determined by staining with annexin V-fluorescein isothiocyanate and propidium iodide (PI).
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	HSP90 / HSP70 p-Akt / Survivin / MMP2 PARP / Cleaved caspase-3 / Cleaved caspase-8 / Cleaved caspase-9 / PUMA p-ALK / ALK / p-Akt / Akt / p-ERK / ERK α-Tax / α-IKKα / α-IKKβ/ α-NEMO / α-TBK1 / α-p65 / α-p50		28915605
	Growth inhibition assay	Cell proliferation		28915605

In Vivo
In Vivo	17-DMAG treatment at 5 mg/kg or 25 mg/kg thrice per week significantly reduces tumor growth of TMK-1 xenografts, by significantly reducing vessel area and numbers of proliferating tumor cells in sections. ^[2] Consistent the inhibition of FAK signaling in vivo, 17-DMAG treatment at 25 mg/kg three times a week significantly suppresses tumor growth, and metastasis of ME180 and SiHa xenografts in mice. ^[4] Administration of 17-DMAG at 10 mg/kg for 16 days significantly decreases the white blood cell count and prolongs the survival in a TCL1-SCID transplant mouse model. ^[5]
動物実験	動物モデル	SCID mice engrafted with TCL1 leukemia cells
	投与量	10 mg/kg
	投与経路	Intraperitoneal injection 5 times per week

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT00780000	Terminated	Breast Cancer	Bristol-Myers Squibb	April 2008	Phase 2
NCT00248521	Unknown status	Unspecified Adult Solid Tumor Protocol Specific	Institute of Cancer Research United Kingdom\|National Cancer Institute (NCI)	October 2005	Phase 1

参考
[1] Ge J, et al. J Med Chem, 2006, 49(15), 4606-4615. [2] Lang SA, et al. Mol Cancer Ther, 2007, 6(3), 1123-1132. [3] Rao R, et al. Cancer Biol Ther, 2009, 8(13), 1273-1280. [4] Schwock J, et al. Cancer Res, 2009, 69(11), 4750-4759. [5] Hertlein E, et al. Blood, 2010, 116(1), 45-53. + 展開

参考

+ 展開

化学情報

分子量	653.21	化学式	C₃₂H₄₈N₄O₈•HCl
CAS No.	467214-21-7	SDF	Download Alvespimycin (17-DMAG) HCl 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)NCCN(C)C)C)OC)OC(=O)N)C)C)O)OC.Cl
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 ( (153.09 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。)

Water : Insoluble

Ethanol : 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。

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):