Alvespimycin (17-DMAG) HCl
Catalog No.S1142 Synonyms: NSC 707545,BMS 826476 HCl,KOS 1022
Molecular Weight(MW): 653.21
Alvespimycin (17-DMAG) HCl is a potent HSP90 inhibitor with IC50 of 62 nM in a cell-free assay. Phase 2.
6 Customer Reviews
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H2228/Vec or H2228/HGF cells were treated with or without alectinib (0.3 μmol/L) for 2 h or 17-DMAG (0.3 μmol/L) for 24 h and then stimulated with or without HGF (50 ng/mL) for 10 minutes. The resultant cells were lysed, and the indicated proteins were detected by immunoblotting.
Oncotarget, 2014, 5(13): 4920-28 . Alvespimycin (17-DMAG) HCl purchased from Selleck.
H2228 cells were treated with or without alectinib (0.3 μmol/L) for 2 h or 17-DMAG (0.3 μmol/L) for 24 h, and then stimulated with or without EGF (100 ng/mL), HB-EGF (10 ng/mL), and TGF-α (100 ng/mL) for 10 min. The resultant cells were lysed, and the indicated proteins were detected by immunoblotting.
Oncotarget, 2014, 5(13): 4920-28 . Alvespimycin (17-DMAG) HCl purchased from Selleck.
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17-DMAG suppresses EGF and Met protein expression and phosphorylation even in the presence of HGF. PC-9, Ma-1, Ma-1/Vec, and Ma-1/HGF tumor cells were treated with or without erlotinib (0.3 umol/l) or 17-DMAG (0.3 umol/l) for 24 hours, and then stimulated with or without HGF (20 ng/ml) for 10 minutes. The resultant cells were lysed, and the indicated proteins were detected by immunoblotting. EGF, epidermal growth factor; HGF, hepatocyte growth factor.
J Thorac Oncol 2012 7(7), 1078-85. Alvespimycin (17-DMAG) HCl purchased from Selleck.
17-DMAG overcomes HGF-induced erlotinib resistance in vivo. Ma-1/Vec or Ma-1/HGF cells (5 x 106 each) were inoculated subcutaneously into SCID mice on day 0. Mice received oral erlotinib (20 mg/kg/day) or intraperitoneal 17-DMAG (10 mg/kg/day), starting on day 7. Tumor size was measured twice a week and tumor volumes were calculated as described in Materials and Methods. Macroscopic appearances of representative tumors harvested on day 21. *p < 0.01 compared with the control group (Student’s t test). 17-DMAG, 17-Dimethylaminoethylamino-17-demethoxygeldanamycin; HGF, hepatocyte growth factor; SCID, severe combined immunodeficiency.
J Thorac Oncol 2012 7(7), 1078-85. Alvespimycin (17-DMAG) HCl purchased from Selleck.
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Mol Oncol 2013 7(6), 1093-102. Alvespimycin (17-DMAG) HCl purchased from Selleck.
(D) H&E staining and immunohistochemistry staining of CHIP and CD166 in consecutive sections of Cal27 xenografts in DMSO and 17-DMAG treated mice; bar=100 µm.
Experimental Cell Research, 2017, 353(1):46-53. Alvespimycin (17-DMAG) HCl purchased from Selleck.
Purity & Quality Control
Choose Selective HSP (e.g. HSP90) Inhibitors
Biological Activity
| Description | Alvespimycin (17-DMAG) HCl is a potent HSP90 inhibitor with IC50 of 62 nM in a cell-free assay. Phase 2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Features | A synthetic derivative Geldanamycin, with lower hepatotoxicity than parent antibiotic & higher potency and bioavailability than the similar derivative 17-AAG. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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] |
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| Cell Data |
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| 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] |
Protocol
| Kinase Assay:[1] |
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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. |
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| Cell Research:[5] |
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| Animal Research:[5] |
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Solubility (25°C)
| In vitro | DMSO | 131 mg/mL (200.54 mM) |
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| Water | Insoluble | |
| Ethanol | Insoluble | |
| In vivo | Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 1% DMSO+30% polyethylene glycol+1% Tween 80 For best results, use promptly after mixing. |
30 mg/mL |
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Information
| Molecular Weight | 653.21 |
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| Formula | C32H48N4O8•HCl |
| CAS No. | 467214-21-7 |
| Storage | powder |
| in solvent | |
| Synonyms | NSC 707545,BMS 826476 HCl,KOS 1022 |
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Clinical Trial Information
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT01126502 | Terminated | B-cell Chronic Lymphocytic Leukemia|Prolymphocytic Leukemia|Recurrent Small Lymphocytic Lymphoma|Refractory Chronic Lymphocytic Leukemia | National Cancer Institute (NCI) | May 2010 | Phase 1 |
| NCT00780000 | Terminated | Breast Cancer | Bristol-Myers Squibb | April 2008 | Phase 2 |
| NCT00803556 | Completed | Solid Tumor|Breast Cancer | Bristol-Myers Squibb | January 2006 | Phase 1 |
| NCT00248521 | Unknown status | Unspecified Adult Solid Tumor Protocol Specific | Institute of Cancer Research United Kingdom|National Cancer Institute (NCI) | October 2005 | Phase 1 |
| NCT00089271 | Completed | Anaplastic Large Cell Lymphoma|Angioimmunoblastic T-cell Lymphoma|Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue|Intraocular Lymphoma|Nodal Marginal Zone B-cell Lymphoma|Recurrent Adult Burkitt Lymphoma|Recurrent Adult Diffuse Large Cell Lymphoma|Recurrent Adult Diffuse Mixed Cell Lymphoma|Recurrent Adult Diffuse Small Cleaved Cell Lymphoma|Recurrent Adult Hodgkin 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|Splenic Marginal Zone Lymphoma|Stage III Adult Burkitt Lymphoma|Stage III Adult Diffuse Large Cell Lymphoma|Stage III Adult Diffuse Mixed Cell Lymphoma|Stage III Adult Diffuse Small Cleaved Cell Lymphoma|Stage III Adult Hodgkin Lymphoma|Stage III Adult T-cell Leukemia/Lymphoma|Stage III Cutaneous T-cell Non-Hodgkin Lymphoma|Stage III Grade 1 Follicular Lymphoma|Stage III Grade 2 Follicular Lymphoma|Stage III Grade 3 Follicular Lymphoma|Stage III Mantle Cell Lymphoma|Stage III Marginal Zone Lymphoma|Stage III Mycosis Fungoides/Sezary Syndrome|Stage III Small Lymphocytic Lymphoma|Stage IV Adult Burkitt Lymphoma|Stage IV Adult Diffuse Large Cell Lymphoma|Stage IV Adult Diffuse Mixed Cell Lymphoma|Stage IV Adult Diffuse Small Cleaved Cell Lymphoma|Stage IV Adult Hodgkin Lymphoma|Stage IV Adult T-cell Leukemia/Lymphoma|Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma|Stage IV Grade 1 Follicular Lymphoma|Stage IV Grade 2 Follicular Lymphoma|Stage IV Grade 3 Follicular Lymphoma|Stage IV Mantle Cell Lymphoma|Stage IV Marginal Zone Lymphoma|Stage IV Mycosis Fungoides/Sezary Syndrome|Stage IV Small Lymphocytic Lymphoma|Unspecified Adult Solid Tumor Protocol Specific|Waldenström Macroglobulinemia | National Cancer Institute (NCI) | July 2004 | Phase 1 |
| NCT00089362 | Completed | Male Breast Cancer|Recurrent Adenoid Cystic Carcinoma of the Oral Cavity|Recurrent Basal Cell Carcinoma of the Lip|Recurrent Breast Cancer|Recurrent Colon Cancer|Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity|Recurrent Gastric Cancer|Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity|Recurrent Lymphoepithelioma of the Nasopharynx|Recurrent Lymphoepithelioma of the Oropharynx|Recurrent Melanoma|Recurrent Metastatic Squamous Neck Cancer With Occult Primary|Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity|Recurrent Mucoepidermoid Carcinoma of the Oral Cavity|Recurrent Ovarian Epithelial Cancer|Recurrent Prostate Cancer|Recurrent Renal Cell Cancer|Recurrent Salivary Gland Cancer|Recurrent Squamous Cell Carcinoma of the Hypopharynx|Recurrent Squamous Cell Carcinoma of the Larynx|Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity|Recurrent Squamous Cell Carcinoma of the Nasopharynx|Recurrent Squamous Cell Carcinoma of the Oropharynx|Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity|Recurrent Verrucous Carcinoma of the Larynx|Recurrent Verrucous Carcinoma of the Oral Cavity|Stage III Adenoid Cystic Carcinoma of the Oral Cavity|Stage III Basal Cell Carcinoma of the Lip|Stage III Colon Cancer|Stage III Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity|Stage III Gastric Cancer|Stage III Inverted Papilloma of the Paranasal Sinus and Nasal Cavity|Stage III Lymphoepithelioma of the Nasopharynx|Stage III Lymphoepithelioma of the Oropharynx|Stage III Melanoma|Stage III Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity|Stage III Mucoepidermoid Carcinoma of the Oral Cavity|Stage III Ovarian Epithelial Cancer|Stage III Renal Cell Cancer|Stage III Salivary Gland Cancer|Stage III Squamous Cell Carcinoma of the Hypopharynx|Stage III Squamous Cell Carcinoma of the Larynx|Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity|Stage III Squamous Cell Carcinoma of the Nasopharynx|Stage III Squamous Cell Carcinoma of the Oropharynx|Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity|Stage III Verrucous Carcinoma of the Larynx|Stage III Verrucous Carcinoma of the Oral Cavity|Stage IIIB Breast Cancer|Stage IIIC Breast Cancer|Stage IV Adenoid Cystic Carcinoma of the Oral Cavity|Stage IV Basal Cell Carcinoma of the Lip|Stage IV Breast Cancer|Stage IV Colon Cancer|Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity|Stage IV Gastric Cancer|Stage IV Inverted Papilloma of the Paranasal Sinus and Nasal Cavity|Stage IV Lymphoepithelioma of the Nasopharynx|Stage IV Lymphoepithelioma of the Oropharynx|Stage IV Melanoma|Stage IV Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity|Stage IV Mucoepidermoid Carcinoma of the Oral Cavity|Stage IV Ovarian Epithelial Cancer|Stage IV Prostate Cancer|Stage IV Renal Cell Cancer|Stage IV Salivary Gland Cancer|Stage IV Squamous Cell Carcinoma of the Hypopharynx|Stage IV Squamous Cell Carcinoma of the Larynx|Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity|Stage IV Squamous Cell Carcinoma of the Nasopharynx|Stage IV Squamous Cell Carcinoma of the Oropharynx|Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity|Stage IV Verrucous Carcinoma of the Larynx|Stage IV Verrucous Carcinoma of the Oral Cavity|Unspecified Adult Solid Tumor Protocol Specific|Untreated Metastatic Squamous Neck Cancer With Occult Primary | National Cancer Institute (NCI) | July 2004 | Phase 1 |
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