Réactifs et instruments pour l'immunologie, la biologie cellulaire et la biologie moléculaire.

Alvespimycin [467214-20-6]

Imprimer

Référence HY-10389-1mg

Conditionnement : 1mg

Marque : MedChemExpress

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Description

Alvespimycin (17-DMAG) is a potent inhibitor of Hsp90, binding to Hsp90 with an EC₅₀ of 62 nM.

IC₅₀ & Target^[1]

HSP90

62 nM (EC₅₀)

GRP94

65 nM (EC₅₀)

Cellular Effect

Cell Line	Type	Value	Description	References
A2058	EC₅₀	7.9 nM Compound: 17-DMAG	Inhibition of Hsp90 in human A2058 cells Inhibition of Hsp90 in human A2058 cells	[PMID: 18929486]
A2058	IC₅₀	2.1 nM Compound: 17-DMAG	Cytotoxicity against human A2058 cells by MTT assay Cytotoxicity against human A2058 cells by MTT assay	[PMID: 18929486]
A2058	IC₅₀	24.3 nM Compound: 17-DMAG	Inhibition of Hsp90 in human A2058 cells assessed as Akt degradation Inhibition of Hsp90 in human A2058 cells assessed as Akt degradation	[PMID: 18929486]
A549	IC₅₀	68 nM Compound: 1e, 17-DMAG	Cytotoxicity against human A549 cells after 72 hrs by celltiter-glo assay Cytotoxicity against human A549 cells after 72 hrs by celltiter-glo assay	[PMID: 19405528]
AGS	IC₅₀	0.0036 μM Compound: page 2621, table 2 footnote	Inhibition of hypoxia-induced HIF1 activation in human AGS cells by reporter gene assay Inhibition of hypoxia-induced HIF1 activation in human AGS cells by reporter gene assay	[PMID: 18359631]
AGS	IC₅₀	0.036 μM Compound: 17-DMAG	Inhibition of HIF1 activation in human AGS cells assessed as inhibition of hypoxia-induced luciferase expression after 16 hrs by reporter assay Inhibition of HIF1 activation in human AGS cells assessed as inhibition of hypoxia-induced luciferase expression after 16 hrs by reporter assay	[PMID: 17583950]
AGS	IC₅₀	16 μM Compound: 17-DMAG	Viability of human AGS cells under normoxic conditions after 24 hrs by MTT assay Viability of human AGS cells under normoxic conditions after 24 hrs by MTT assay	[PMID: 17583950]
AGS	IC₅₀	16 μM Compound: page 2621, table 2 footnote	Cytotoxicity against human AGS cells by MTT assay Cytotoxicity against human AGS cells by MTT assay	[PMID: 18359631]
BT-549	IC₅₀	17.1 μM Compound: 47; 17-DMAG	Anticancer activity against human BT-549 cells assessed as cell growth inhibition incubated for 72 hrs by CCK-8 assay Anticancer activity against human BT-549 cells assessed as cell growth inhibition incubated for 72 hrs by CCK-8 assay	[PMID: 33650861]
CCRF-CEM	IC₅₀	2500 nM Compound: 1e, 17-DMAG	Cytotoxicity against human paclitaxel-resistant CCRF-CEM cells after 72 hrs by celltiter-96 aqueous one solution assay Cytotoxicity against human paclitaxel-resistant CCRF-CEM cells after 72 hrs by celltiter-96 aqueous one solution assay	[PMID: 19405528]
CCRF-CEM	IC₅₀	540 nM Compound: 1e, 17-DMAG	Cytotoxicity against human CCRF-CEM cells after 72 hrs by celltiter-96 aqueous one solution assay Cytotoxicity against human CCRF-CEM cells after 72 hrs by celltiter-96 aqueous one solution assay	[PMID: 19405528]
HCT-116	IC₅₀	0.05 μM Compound: 36, 17-DMAG	Cytotoxicity against human HCT116 cells by Alamar blue assay Cytotoxicity against human HCT116 cells by Alamar blue assay	[PMID: 20662534]
HCT-116	IC₅₀	0.78 μM Compound: 17-DMAG	Antiproliferative activity against human HCT116 cells assessed as inhibition of cell viability after 48 hrs by MTT assay Antiproliferative activity against human HCT116 cells assessed as inhibition of cell viability after 48 hrs by MTT assay	[PMID: 24582477]
HCT-116	IC₅₀	1.21 μM Compound: 17-DMAG	Antiproliferative activity against human HCT116 cells after 48 hrs by MTT assay Antiproliferative activity against human HCT116 cells after 48 hrs by MTT assay	[PMID: 24763261]
HCT-116	IC₅₀	57 nM Compound: alvespimycin, 17-DMAG	Cytotoxicity against human HCT116 cells after 72 hrs Cytotoxicity against human HCT116 cells after 72 hrs	[PMID: 19231864]
HeLa	IC₅₀	0.15 μM Compound: page 2621, table 2 footnote	Inhibition of TNF-alpha-induced NF-kappaB activation in human HeLa cells Inhibition of TNF-alpha-induced NF-kappaB activation in human HeLa cells	[PMID: 18359631]
HeLa	IC₅₀	2.06 μM Compound: page 2621, table 2 footnote	Cytotoxicity against human HeLa cells by MTT assay Cytotoxicity against human HeLa cells by MTT assay	[PMID: 18359631]
Hep 3B2	IC₅₀	>30 μM Compound: 17-DMAG	Inhibition of hypoxia-induced HIF1 activation in human Hep3B cells by pGL3-HRE-luciferase reporter gene assay Inhibition of hypoxia-induced HIF1 activation in human Hep3B cells by pGL3-HRE-luciferase reporter gene assay	[PMID: 19072214]
Hep 3B2	IC₅₀	>50 μM Compound: 17-DMAG	Viability of human Hep3B cells under normoxic conditions after 24 hrs by MTT assay Viability of human Hep3B cells under normoxic conditions after 24 hrs by MTT assay	[PMID: 17583950]
Hep 3B2	IC₅₀	0.057 μM Compound: 17-DMAG	Inhibition of hypoxia-induced HIF1alpha protein accumulation in human Hep3B cells treated for 30 mins measured after 12 hrs by Western blot analysis Inhibition of hypoxia-induced HIF1alpha protein accumulation in human Hep3B cells treated for 30 mins measured after 12 hrs by Western blot analysis	[PMID: 20469887]
Hep 3B2	IC₅₀	0.061 μM Compound: 17-DMAG	Inhibition of HIF1 activation in human Hep3B cells assessed as inhibition of hypoxia-induced luciferase expression after 16 hrs by reporter assay Inhibition of HIF1 activation in human Hep3B cells assessed as inhibition of hypoxia-induced luciferase expression after 16 hrs by reporter assay	[PMID: 17583950]
Hep 3B2	IC₅₀	0.079 μM Compound: 17-DMAG	Inhibition of hypoxia-induced VEGF protein secretion in human Hep3B cells after 16 hrs by ELISA Inhibition of hypoxia-induced VEGF protein secretion in human Hep3B cells after 16 hrs by ELISA	[PMID: 20469887]
Hep 3B2	IC₅₀	57.2 nM Compound: 17-DMAG	Inhibition of hypoxia-induced HIF1alpha protein accumulation in human Hep3B cells treated for 30 mins measured after 12 hrs by Western blot analysis Inhibition of hypoxia-induced HIF1alpha protein accumulation in human Hep3B cells treated for 30 mins measured after 12 hrs by Western blot analysis	[PMID: 19072214]
Hep 3B2	IC₅₀	79.5 nM Compound: 17-DMAG	Inhibition of hypoxia-induced VEGF protein secretion in human Hep3B cells after 16 hrs by ELISA Inhibition of hypoxia-induced VEGF protein secretion in human Hep3B cells after 16 hrs by ELISA	[PMID: 19072214]
Hs-578T	IC₅₀	8.4 nM Compound: 47; 17-DMAG	Anticancer activity against human Hs-578T cells assessed as cell growth inhibition incubated for 72 hrs by CCK-8 assay Anticancer activity against human Hs-578T cells assessed as cell growth inhibition incubated for 72 hrs by CCK-8 assay	[PMID: 33650861]
Huh-7	EC₅₀	1.2 nM Compound: 17-DMAG	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 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	[PMID: 18936191]
Huh-7	EC₅₀	3.1 nM Compound: 17-DMAG	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 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	[PMID: 18936191]
MCF7	IC₅₀	0.39 μM Compound: 17-DMAG	Antiproliferative activity against human MCF7 cells assessed as inhibition of cell viability after 48 hrs by MTT assay Antiproliferative activity against human MCF7 cells assessed as inhibition of cell viability after 48 hrs by MTT assay	[PMID: 24582477]
MCF7	IC₅₀	0.5 μM Compound: 17-DMAG	Anti-cancer activity against human MCF7 cells assessed as inhibition of cell viability incubated for 72 hrs by MTS assay Anti-cancer activity against human MCF7 cells assessed as inhibition of cell viability incubated for 72 hrs by MTS assay	[PMID: 39042910]
MCF7	IC₅₀	0.8 μM Compound: 17-DMAG	Antiproliferative activity against human MCF7 cells after 48 hrs by MTT assay Antiproliferative activity against human MCF7 cells after 48 hrs by MTT assay	[PMID: 24763261]
MCF7	IC₅₀	230 nM Compound: 1e, 17-DMAG	Cytotoxicity against human MCF7 cells after 72 hrs by celltiter-glo assay Cytotoxicity against human MCF7 cells after 72 hrs by celltiter-glo assay	[PMID: 19405528]
MCF7	IC₅₀	71 nM Compound: alvespimycin, 17-DMAG	Cytotoxicity against human MCF7 cells after 72 hrs Cytotoxicity against human MCF7 cells after 72 hrs	[PMID: 19231864]
MCF7	IC₅₀	862 nM Compound: alvespimycin, 17-DMAG	Cytotoxicity against human MCF7 cells after 72 hrs in presence of NQO1 inhibitor dicoumarol Cytotoxicity against human MCF7 cells after 72 hrs in presence of NQO1 inhibitor dicoumarol	[PMID: 19231864]
MDA-MB-231	IC₅₀	17.6 nM Compound: 17-DMAG	Inhibition of Hsp90 in human MDA-MB-231 cells assessed as Akt degradation Inhibition of Hsp90 in human MDA-MB-231 cells assessed as Akt degradation	[PMID: 18929486]
MDA-MB-231	IC₅₀	4.5 nM Compound: 17-DMAG	Inhibition of Hsp90 in human MDA-MB-231 cells assessed as her2 degradation Inhibition of Hsp90 in human MDA-MB-231 cells assessed as her2 degradation	[PMID: 18929486]
MDA-MB-231	IC₅₀	45.7 μM Compound: 47; 17-DMAG	Anticancer activity against human MDA-MB-231 cells assessed as cell growth inhibition incubated for 72 hrs by CCK-8 assay Anticancer activity against human MDA-MB-231 cells assessed as cell growth inhibition incubated for 72 hrs by CCK-8 assay	[PMID: 33650861]
MDA-MB-231	IC₅₀	5.8 nM Compound: 17-DMAG	Cytotoxicity against human MDA-MB-231 cells by MTT assay Cytotoxicity against human MDA-MB-231 cells by MTT assay	[PMID: 18929486]
MDA-MB-468	IC₅₀	1600 nM Compound: alvespimycin, 17-DMAG	Cytotoxicity against NQ01-deficient human MDA468 cells after 72 hrs Cytotoxicity against NQ01-deficient human MDA468 cells after 72 hrs	[PMID: 19231864]
NCI-H1299	IC₅₀	0.1 μM Compound: 1c, DMAG	Inhibition of human HSP90 in human NCI-H1299 cells assessed as Akt degradation after 24 hrs by luminex assay Inhibition of human HSP90 in human NCI-H1299 cells assessed as Akt degradation after 24 hrs by luminex assay	[PMID: 21438541]
NCI-H596	IC₅₀	1100 nM Compound: alvespimycin, 17-DMAG	Cytotoxicity against NQ01-deficient human NCI-H596 cells after 72 hrs Cytotoxicity against NQ01-deficient human NCI-H596 cells after 72 hrs	[PMID: 19231864]
NCI-N87	EC₅₀	62 nM Compound: 17-DMAG	Antitumor activity against human NCI-N87 cells assessed as reduction in cell growth Antitumor activity against human NCI-N87 cells assessed as reduction in cell growth	[PMID: 38232464]
PC-9	IC₅₀	0.01 μM Compound: 3; 17-DMAG	Cytotoxicity against HGF-induced erlotinib-resistant human PC9 cells assessed as inhibition of cell growth after 72 hrs by MTT assay Cytotoxicity against HGF-induced erlotinib-resistant human PC9 cells assessed as inhibition of cell growth after 72 hrs by MTT assay	[PMID: 26844689]
SK-BR-3	EC₅₀	4 nM Compound: 4b, 17-DMAG	Upregulation of Hsp70 in SKBR3 cells Upregulation of Hsp70 in SKBR3 cells	[PMID: 16854066]
SK-BR-3	EC₅₀	8 nM Compound: 4b, 17-DMAG	Degradation of Her2 in SKBR3 cells Degradation of Her2 in SKBR3 cells	[PMID: 16854066]
SK-BR-3	GI₅₀	29 nM Compound: 4b, 17-DMAG	Inhibition of human SKBR3 cell growth Inhibition of human SKBR3 cell growth	[PMID: 16854066]
SK-BR-3	IC₅₀	1.34 μM Compound: 17-DMAG	Antiproliferative activity against human SKBR3 cells assessed as inhibition of cell viability after 48 hrs by MTT assay Antiproliferative activity against human SKBR3 cells assessed as inhibition of cell viability after 48 hrs by MTT assay	[PMID: 24582477]
SK-BR-3	IC₅₀	230 nM Compound: alvespimycin, 17-DMAG	Cytotoxicity against human SKBR3 cells after 72 hrs in presence of NQO1 inhibitor dicoumarol Cytotoxicity against human SKBR3 cells after 72 hrs in presence of NQO1 inhibitor dicoumarol	[PMID: 19231864]
SK-BR-3	IC₅₀	24 nM Compound: 1e, 17-DMAG	Cytotoxicity against human SKBR3 cells after 72 hrs by celltiter-glo assay Cytotoxicity against human SKBR3 cells after 72 hrs by celltiter-glo assay	[PMID: 19405528]
SK-BR-3	IC₅₀	24 nM Compound: 1	Cytotoxicity against SKBr3 cells Cytotoxicity against SKBr3 cells	[PMID: 16165354]
SK-BR-3	IC₅₀	24 nM Compound: 3, 17-DMAG	Binding affinity to Hsp90 in human SKBR3 cells Binding affinity to Hsp90 in human SKBR3 cells	[PMID: 19017562]
SK-BR-3	IC₅₀	3.11 μM Compound: 17-DMAG	Antiproliferative activity against human SKBR3 cells after 48 hrs by MTT assay Antiproliferative activity against human SKBR3 cells after 48 hrs by MTT assay	[PMID: 24763261]
SK-BR-3	IC₅₀	58 nM Compound: alvespimycin, 17-DMAG	Cytotoxicity against human SKBR3 cells after 72 hrs Cytotoxicity against human SKBR3 cells after 72 hrs	[PMID: 19231864]
SK-OV-3	EC₅₀	14 nM Compound: 4b, 17-DMAG	Upregulation of Hsp70 in SKOV3 cells Upregulation of Hsp70 in SKOV3 cells	[PMID: 16854066]
SK-OV-3	EC₅₀	46 nM Compound: 4b, 17-DMAG	Degradation of Her2 in SKOV3 cells Degradation of Her2 in SKOV3 cells	[PMID: 16854066]
SK-OV-3	GI₅₀	32 nM Compound: 4b, 17-DMAG	Inhibition of human SKOV3 cell growth Inhibition of human SKOV3 cell growth	[PMID: 16854066]
SK-OV-3	IC₅₀	122 nM Compound: alvespimycin, 17-DMAG	Cytotoxicity against human SKOV3 cells after 72 hrs Cytotoxicity against human SKOV3 cells after 72 hrs	[PMID: 19231864]
SK-OV-3	IC₅₀	220 nM Compound: 1e, 17-DMAG	Cytotoxicity against human SKOV3 cells after 72 hrs by celltiter-glo assay Cytotoxicity against human SKOV3 cells after 72 hrs by celltiter-glo assay	[PMID: 19405528]

In Vitro

Alvespimycin (17-DMAG) inhibits the growth of the human cancer cell lines SKBR3 and SKOV3, which overexpress Hsp90 client protein Her2, and causes down-regulation of Her2 as well as induction of Hsp70 consistent with Hsp90 inhibition, for Her2 degradation with EC₅₀ of 8 nM and 46 nM in SKBR3 and SKOV3 cells, respectively; for Hsp70 induction with EC₅₀ of 4 nM and 14 nM in SKBR3 and SKOV3 cells, respectively^[1].
Compared with the vehicle control, Alvespimycin (17-DMAG) dose-dependent apoptosis (P<0.001 averaged across 24- and 48-hour time points) at concentrations of 50 nM to 500 nM, which represent pharmacologically attainable doses. Similar to many other agents, Alvespimycin (17-DMAG) also demonstrates time-dependent apoptosis (P <0.001, averaged across all doses) in chronic lymphocytic leukemia (CLL) cells with extended exposure from 24 to 48 hours. In addition,Alvespimycin (17-DMAG) is much more potent after 24 and 48 hours of treatment than 17-AAG^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

The tumors are grown for two months before the start of i.p. injections every four days over one month with 0, 50, 100 and 200 mg/kg dipalmitoyl-radicicol or 0, 5, 10 and 20 mg/kg Alvespimycin (17-DMAG). Despite sample heterogeneity, the HSP90 inhibitor-treated animals have significantly lower tumour volumes than the vehicle control-treated animals^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Masse moléculaire

616.75

Formule

C₃₂H₄₈N₄O₈

CAS No.

467214-20-6

Appearance

Solid

Color

Pale purple to purple

SMILES

C/C1=C\C=C/[C@@H]([C@H](/C(C)=C/[C@@H]([C@H]([C@H](C[C@@H](CC(C(C(NC1=O)=CC2=O)=O)=C2NCCN(C)C)C)OC)O21)C)OC(N)=O)OC

Livraison

Room temperature in continental US; may vary elsewhere.

Stockage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Solvant et solubilité

In Vitro:

DMSO : 100 mg/mL (162.14 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	1.6214 mL	8.1070 mL	16.2140 mL
5 mM	0.3243 mL	1.6214 mL	3.2428 mL
10 mM	0.1621 mL	0.8107 mL	1.6214 mL

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (4.05 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.

Pureté et documentation

Purity: 99.52%

Fiche technique (281 KB) SDS (393 KB)

COA (252 KB) HNMR (204 KB) RP-HPLC (248 KB) MS (68 KB)

Instruction de manipulation (2659 KB)

Références

[1]. Ge J, et al. Design, synthesis, and biological evaluation of hydroquinone derivatives of 17-amino-17-demethoxygeldanamycin as potent, water-soluble inhibitors of Hsp90. J Med Chem. 2006 Jul 27;49(15):4606-15. [Content Brief]

[2]. Hertlein E, et al. 17-DMAG targets the nuclear factor-kappaB family of proteins to induce apoptosis in chronic lymphocytic leukemia: clinical implications of HSP90 inhibition. Blood. 2010 Jul 8;116(1):45-53. [Content Brief]

[3]. Henke A, et al. Reduced Contractility and Motility of Prostatic Cancer-Associated Fibroblasts after Inhibition of Heat Shock Protein 90. Cancers (Basel). 2016 Aug 24;8(9). pii: E77. [Content Brief]

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