Home Cytoskeletal Signaling HSP (HSP90) inhibitor Alvespimycin (17-DMAG) HCl For research use only.

Alvespimycin (17-DMAG) HCl

Synonyms: NSC 707545,BMS 826476 HCl,KOS 1022

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.

Alvespimycin (17-DMAG) HCl Chemical Structure

Alvespimycin (17-DMAG) HCl Chemical Structure

CAS No. 467214-21-7

Purity & Quality Control

Alvespimycin (17-DMAG) HCl Related Products

Signaling Pathway

HSP (HSP90) Signaling Pathways

HSP (HSP90) Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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
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
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
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
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
SKBR3 Function assay Binding affinity to Hsp90 in human SKBR3 cells, IC50=0.024μM. 19017562
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
HCT116 Cytotoxicity assay Cytotoxicity against human HCT116 cells by Alamar blue assay, IC50=0.05μM. 20662534
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
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
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
SKBR3 Function assay Inhibition of Hsp90 in human SKBR3 cells, IC50=0.024μM. 26844689
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
Click to View More Cell Line Experimental Data

Biological Activity

Description 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.
Features 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
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 (γEx = 485 nm, γEm = 535 nm) is measured on an EnVision 2100 multilabel plate reader. IC50 value of 17-DMAG is obtained from the competition curves.
Cell Research Cell lines Chronic lymphocytic leukemia (CLL)
Concentrations Dissolved in DMSO, final concentrations ~1 μM
Incubation Time 24, or 48 hours
Method

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 isothiocyanate and propidium iodide (PI).
Experimental Result Images Methods Biomarkers Images 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]
Animal Research Animal Models SCID mice engrafted with TCL1 leukemia cells
Dosages 10 mg/kg
Administration Intraperitoneal injection 5 times per week
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
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

Chemical Information & Solubility

Molecular Weight 653.21 Formula

C32H48N4O8•HCl
CAS No. 467214-21-7 SDF Download Alvespimycin (17-DMAG) HCl SDF
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
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 100 mg/mL ( (153.09 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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