« Back
Home /
Alvespimycin (17-DMAG) HCl

Alvespimycin (17-DMAG) HCl

Item no.	S1142-10mM
Manufacturer	Selleckchem
CASRN	467214-21-7
Amount	10 mM/1 mL
Quantity options	100 mg 1 g 10 g 10 mM/1 mL 2 mg 200 mg 25 mg 5 mg 5 g
Category	Oncology Neuroscience Neuroinflammation Protein Aggregation, Clearance & Misfolding Inhibitors & Compound Libraries Small Molecules By Organ Skin Cancer Colorectal Cancer Breast Cancer Heart & Blood Cancer Testicular & Prostate Cancer Lymphatic System Cancer
Type	Inhibitors
Specific against	other
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
ECLASS 10.1	32160490
ECLASS 11.0	32160490
UNSPSC	12000000
Alias	NSC 707545,BMS 826476 HCl,KOS 1022
Similar products	17-DMAG
Available
Storage Conditions	2 years -80 in solvent
Molecular Weight	653, 21
Administration	Intraperitoneal injection 5 times per week
Animal Models	SCID mice engrafted with TCL1 leukemia cells
Cell lines	Chronic lymphocytic leukemia (CLL)
Clinical Trials	A Phase I study of 17-DMAG in treating patients with an advanced solid tumor or lymphoma has been completed. A Phase I study of the combination of intravenous 17-DMAG, Trastuzumab with or without Paclitaxel in patients with advanced solid tumor malignancies or Her2 positive metastatic breast cancer who have previously failed frastuzumab therapy has been completed.
Concentrations	Dissolved in DMSO, final concentrations ca.1 uM
Dosages	10 mg/kg
Formulation	Dissolved in DMSO
IC50	62 nM [1], 62 nM [1], 62 nM [1], 62 nM [1], 62 nM [1], 62 nM [1]
In vitro	17-DMAG displays ca.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 IKKbeta in chronic lymphocytic leukemia (CLL) cells, 17-DMAG treatment effectively leads to depletion of the Hsp90 client protein, resulting in diminished NF-kappaB p50/p65 DNA binding, decreased NF-kappaB target gene transcription, and caspase-dependent apoptosis. By targeting the NF-kappaB 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]
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]
Incubation Time	24, or 48 hours
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 (alpha + beta 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 gamma-globulin (BGG), 1.0 mM fresh DTT, and protease inhibitor from stock solution in DMSO. Competition curves are obtained by mixing 10 uL 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 uM), and <=0.25% DMSO in a 384-well microplate. After 3 hours incubation at 30 C, fluorescence anisotropy (gammaEx = 485 nm, gammaEm = 535 nm) is measured on an EnVision 2100 multilabel plate reader. IC50 value of 17-DMAG is obtained from the competition curves.
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 V-fluorescein isothiocyanate and propidium iodide (PI).
Solubility (25C)	DMSO 131 mg/mL, Water <1 mg/mL, Ethanol <1 mg/mL
Information	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.
Chemical Name	Geldanamycin, 17-demethoxy-17-[[2-(dimethylamino)ethyl]amino]-, monohydrochloride
Features	17-DMAG is a synthetic derivative of the antibiotic Geldanamycin with lower hepatotoxicity than the parent antibiotic and higher potency and availability than the similar derivative 17-AAG.

Note: The presented information and documents (Manual, Product Datasheet, Safety Datasheet and Certificate of Analysis) correspond to our latest update and should serve for orientational purpose only. We do not guarantee the topicality. We would kindly ask you to make a request for specific requirements, if necessary.

All products are intended for research use only (RUO). Not for human, veterinary or therapeutic use.

Request Data Sheet

S1142-10mM-datasheet.pdf

S1142-10mM-safety-datasheet.pdf