| Identification | Back Directory | [Name]
17-DMAG | [CAS]
467214-21-7 | [Synonyms]
KOS 1022
BMS 826476
BMS 826476 HCl
AlvespiMycin HCl
17-DMAG USP/EP/BP
KOS-1022 hydrochloride
Alvespimycin hydrochloride
Alvespimycin (17-DMAG) HCl
17-DMAG HCl (AlvespiMycin)
17-DMAG (AlvespiMycin) HCl
17-DIMETHYLAMINOGELDANAMYCIN
NSC 707545,BMS 826476 HCl,KOS 1022
17-DMAG hydrochloride (Alvespimycin)
Alvespimycin (17-DMAG) hydrochloride
17-DMAG - CAS 467214-21-7 - Calbiochem
AlvespiMycin hydrochloride(17-DMAG,BMS 826476
Geldanamycin 17-N-(2-Dimethylaminoethylamino)
Alvespimycin Hydrochloride (17-DMAG Hydrochloride
17-DIMETHYLAMINOETHYLAMINO-17-DEMETHOXY-GELDANAMYCIN
17DMAG; NSC 707545; KOS-1022; BMS 826476 HCL;KOS 1022
Geldanamycin, 17-demethoxy-17-[[2-(dimethylamino)ethyl]amino]-, monohydrochloride | [Molecular Formula]
C32H48N4O8 | [MDL Number]
MFCD08457919 | [MOL File]
467214-21-7.mol | [Molecular Weight]
616.75 |
| Chemical Properties | Back Directory | [storage temp. ]
Store at -20 | [solubility ]
≥26.2 mg/mL in DMSO; insoluble in EtOH; ≥3.04 mg/mL in H2O | [form ]
Purple solid | [color ]
Purple to purplish red | [Water Solubility ]
water: 10mg/mL
DMSO: 5mg/mL | [InChIKey]
KUFRQPKVAWMTJO-LMZWQJSESA-N | [SMILES]
N(C1C(C=C2NC(C(=CC=C[C@H](OC)[C@@H](OC(=O)N)C(C)=C[C@H](C)[C@@H](O)[C@@H](OC)C[C@H](C)CC=1C2=O)C)=O)=O)CCN(C)C.Cl |t:7,9,20,&1:11,14,22,24,26,30,r| |
| Hazard Information | Back Directory | [Uses]
Treatment of solid and hematological tumors. | [Biological Activity]
17-dmag is an inhibitor of hsp90 with ic50 value of 62±29nm [1].17-dmag can bind to the atp-binding motif of hsp90 and inhibit the protein chaperoning activity of hsp90. it will cause misfolding and subsequent degradation of hsp90’s client proteins, such as egfr, akt, mutant p53, and ikk. since there is more specific conformation hsp90 required for 17-dmag binding in tumor cells and many client proteins of hsp90 contribute to tumor cell growth, 17-dmag is usually more toxic to tumor cells than to normal cells [2].17-dmag is reported as an antitumor agent with more broadly exploitable activity and more pharmaceutically tractable characteristics in the in vitro and initial in vivo assay. 17-dmag can effect cell growth when treating the nci 60 cell lines with it, the mean gi50 is 0.053mm. the in vivo activity of 17-dmag is tested in four melanoma models using the freiburg human tumor xenograft panel and two lung xenografts. it shows that 17-dmag has high activity in the two lung xenografts and two of the four melanoma models, but not in another two, mexf 462 and mexf 514 [3]. | [Enzyme inhibitor]
This potent Hsp90 inhibitor (FWHCl-Salt = 653.21 g/mol; CAS 467214-21-7), also named 17-DMAG and 17-demethoxy-17-[[2-(dimethylamino) ethyl]amino]geldanamycin, targets Heat Shock Protein-90 (IC50 = 62 nM in a cell-free assay). (See also Ansamycin; Deguelin; Derrubone; Ganetespib; Geldanamycin; Herbimycin; Macbecin; Radicicol; Tanespimycin; and the nonansamycin Hsp90 inhibitor KW-2478) | [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 17-DMAG. Despite sample heterogeneity, the HSP90 inhibitor-treated animals have significantly lower tumour volumes than the vehicle control-treated animals. HSP90 inhibitors have been shown to cause liver toxicity in an animal model of gastrointestinal cancer. Nevertheless, the reduction in tumor size using dipalmitoyl-radicicol is statistically significant at 100 mg/kg, while 17-DMAG at either 10 or 20 mg/kg elicited a significant reduction in tumor size[3]. | [IC 50]
HSP90: 62 nM (EC50); GRP94: 65 nM (EC50) | [storage]
Store at -20°C | [References]
[1] jie ge, emmanuel normant, james r. porter, janid a. ali, marlene s. dembski, yun gao, asimina t. georges, louis grenier, roger h. pak, jon patterson, jens r. sydor, thomas t. tibbitts, jeffrey k. tong, julian adams, and vito j. palombella. design, synthesis and biological evaluation of hydroquinone derivatives of 17-amino-17-demethoxygeldanamycin as potent, water-soluble inhibitors of hsp90. j. med. chem. 2006, 49, 4606-4615.
[2] xiaoping sun, jillian a. bristol, satoko iwahori, stacy r. hagemeier, qiao meng, elizabeth a. barlow, joyce d. fingeroth, vera l. tarakanova, robert f. kalejta, shannon c. kenney. hsp90 inhibitor 17-dmag decreases expression of conserved herpesvirus protein kinases and reduces virus production inepstein-barr virus-infected cells. journal of virology. 2013, 87 (18): 10126–10138.
[3] melinda hollingshead, michael alley, angelika m. burger, suzanne borgel,christine pacula-cox, heinz-herbert fiebig, edward a. sausville. in vivo antitumor efficacy of 17-dmag (17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride), a water-soluble geldanamycin derivative. cancer chemother pharmacol. 2005, 56: 115–125. |
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