17-DMAG hydrochloride
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| Category | Antibiotics |
| Catalog number | BBF-05796 |
| CAS | 467214-21-7 |
| Molecular Weight | 653.21 |
| Molecular Formula | C32H48N4O8.HCl |
| Purity | >98% |
Ordering Information
| Catalog Number | Size | Price | Stock | Quantity |
|---|---|---|---|---|
| BBF-05796 | 100 mg | $499 | In stock |
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Add to cartDescription
17-DMAG hydrochloride (Alvespimycin hydrochloride) is the hydrochloride salt of alvespimycin, an analogue of the antineoplastic benzoquinone antibiotic geldanamycin. Alvespimycin binds to Hsp90, a chaperone protein that aids in the assembly, maturation and folding of proteins. Subsequently, the function of Hsp90 is inhibited, leading to the degradation and depletion of its client proteins such as kinases and transcription factors involved with cell cycle regulation and signal transduction.
Specification
| Related CAS | 467214-20-6 (free base) |
| Synonyms | 17-DMAG HCl; Alvespimycin HCl; 17-Dimethylaminoethylamino-17-demethoxygeldanamycin Hydrochloride; 17-N-(2-Dimethylaminoethylamino)-17-demethoxy Geldanamycin Hydrochloride; 17-Demethoxy-17-[[2-(dimethylamino)ethyl]amino]geldanamycin Hydrochloride; 17-[2-(Dimethylamino)ethylamino]-17-desmethylgeldanamycin Hydrochloride; Alvespimycin Hydrochloride; DMAG Hydrochloride; NSC 707545 Hydrochloride; 17-DMAG Hydrochloride |
| Storage | Store at -20°C |
| IUPAC Name | [(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-19-[2-(dimethylamino)ethylamino]-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl] carbamate;hydrochloride |
| Canonical 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 |
| InChI | InChI=1S/C32H48N4O8.ClH/c1-18-14-22-27(34-12-13-36(5)6)24(37)17-23(29(22)39)35-31(40)19(2)10-9-11-25(42-7)30(44-32(33)41)21(4)16-20(3)28(38)26(15-18)43-8;/h9-11,16-18,20,25-26,28,30,34,38H,12-15H2,1-8H3,(H2,33,41)(H,35,40);1H/b11-9-,19-10+,21-16+;/t18-,20+,25+,26+,28-,30+;/m1./s1 |
| InChI Key | DFSYBWLNYPEFJK-IHLRWNDRSA-N |
Properties
| Appearance | Very Dark Purple Solid |
| Antibiotic Activity Spectrum | Neoplastics (Tumor) |
| Melting Point | 215-230°C |
| Solubility | Soluble in DMSO (Slightly), Methanol (Slightly), Ethanol |
Reference Reading
1. Ansamycin inhibitors of Hsp90: nature's prototype for anti-chaperone therapy
Kip West, Jie Ge, Emmanuel Normant, John Lee, James R Porter Curr Top Med Chem . 2009;9(15):1386-418. doi: 10.2174/156802609789895719.
The ansamycin class of natural products is well known for its anti-tumor effects and has been extensively studied by cancer researchers for nearly four decades. The first description of geldanamycin in the scientific literature appeared in 1970 and nearly thirty years later the semi-synthetic derivative 17-AAG, or tanespimycin, entered Phase 1 clinical trials. In the subsequent years, three additional geldanamycin derivatives have entered clinical evaluation. Kosan Biosciences developed 17-DMAG or alvespimycin hydrochloride for clinical evaluation as both an intravenous and oral product. Infinity Pharmaceuticals is developing IPI-504 or retaspimycin hydrochloride as an intravenous product, which is in several Phase 2 clinical trials; IPI-504 is the hydroquinone hydrochloride salt of 17-AAG. More recently, Infinity Pharmaceuticals initiated a Phase 1 clinical trial with an oral formulation of 17-AG (IPI-493), the major metabolite of 17-AAG and IPI-504. Since a vast amount of scientific literature exists regarding the ansamycin field and Hsp90 inhibition, this review will survey key milestones in the development of the natural product class as anti-cancer drugs including discovery of the compounds and their anti-tumor effects, identification of Hsp90 as their biological target, the structure-activity relationships that have been identified in this interesting class of compounds, and development of clinical candidates for the treatment of cancer patients. A brief overview of important pre-clinical development data from each clinical lead is also provided.
2. Optical imaging with her2-targeted affibody molecules can monitor hsp90 treatment response in a breast cancer xenograft mouse model
Sanjiv S Gambhir, Sjoerd G Elias, Zheng Miao, Zhen Cheng, Stephanie M W Y van de Ven, Abhijit De, Carmel T Chan Clin Cancer Res . 2012 Feb 15;18(4):1073-81. doi: 10.1158/1078-0432.CCR-10-3213.
Purpose:To determine whether optical imaging can be used for in vivo therapy response monitoring as an alternative to radionuclide techniques. For this, we evaluated the known Her2 response to 17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride (17-DMAG) treatment, an Hsp90 inhibitor.Experimental design:After in vitro 17-DMAG treatment response evaluation of MCF7 parental cells and 2 HER2-transfected clones (clone A medium, B high Her2 expression), we established human breast cancer xenografts in nude mice (only parental and clone B) for in vivo evaluation. Mice received 120 mg/kg of 17-DMAG in 4 doses at 12-hour intervals intraperitonially (n = 14) or PBS as carrier control (n = 9). Optical images were obtained both pretreatment (day 0) and posttreatment (day 3, 6, and 9), always 5 hours postinjection of 500 pmol of anti-Her2 Affibody-AlexaFluor680 via tail vein (with preinjection background subtraction). Days 3 and 9 in vivo optical imaging signal was further correlated with ex vivo Her2 levels by Western blot after sacrifice.Results:Her2 expression decreased with 17-DMAG dose in vitro. In vivo optical imaging signal was reduced by 22.5% in clone B (P = 0.003) and by 9% in MCF7 parental tumors (P = 0.23) 3 days after 17-DMAG treatment; optical imaging signal recovered in both tumor types at days 6 to 9. In the carrier group, no signal reduction was observed. Pearson correlation of in vivo optical imaging signal with ex vivo Her2 levels ranged from 0.73 to 0.89.Conclusions:Optical imaging with an affibody can be used to noninvasively monitor changes in Her2 expression in vivo as a response to treatment with an Hsp90 inhibitor, with results similar to response measurements in positron emission tomography imaging studies.
3. 17-Dimethylaminoethylamino-17-demethoxygeldanamycin attenuates inflammatory responses in experimental stroke
Jin Lian Zhang, Shu Hong Bo, Jia Qi, Hai Tao Liu, Xiao Tong Lu, Jian Zhang, Xiao Han, Ting Chen, Ping Yang Biol Pharm Bull . 2014;37(11):1713-8. doi: 10.1248/bpb.b14-00208.
Heat shock protein 90 (HSP90) is a ubiquitous molecular chaperone involved in the proper conformation of many proteins. HSP90 inhibitors (17-dimethyl aminoethylamino-17-demethoxygeldanamycin hydrochloride [17-DMAG]) bind to and inactivate HSP90, suppressing some key signaling pathways involved in the inflammatory process. Since considerable evidence suggests that inflammation accounts for the progression of cerebral ischemic injury, we investigated whether 17-DMAG can modulate inflammatory responses in middle cerebral artery occluded (MCAO) mice. Male C57/BL6 mice were pretreated with 17-DMAG or vehicle for 7 d before being subjected to transient occlusion of middle cerebral artery and reperfusion. Mice were evaluated at 24 h after MCAO for neurological deficit scoring. Moreover, the mechanism of the anti-inflammatory effect of 17-DMAG was investigated with a focus on nuclear factor kappa B (NF-κB) pathway. 17-DMAG significantly reduced cerebral infarction and improved neurological outcome. 17-DMAG suppressed activation of microglia and decreased phosphorylation of inhibitory (I)κB and subsequent nuclear translocation of p65, which eventually downregulated expression of NF-κB-regulated genes. These results suggest that 17-DMAG has a promising therapeutic effect in ischemic stroke treatment through an anti-inflammatory mechanism.
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