17-Dimethylaminoethylamino-17-demethoxygeldanamycin (DMAG, alvespimycin) is a semi-synthetic derivative of the benzoquinone ansamycin antibiotic isolated from Streptomyces hygroscopicus in which the methoxy group attached to the benzoquinone moiety has been replaced by a 2-(N,N-dimethylamino)ethylamino group. DMAG acts by binding to the 90-kDa heat shock protein (Hsp90) essential to maintain the conformation, stability, activity and cellular localisation of several key oncogenic proteins such as ERBB2, C-RAF, CDK4, AKT/PKB, steroid hormone receptors, mutant p53, HIF-1α, survivin and telomerase hTERT. DMAG is more potent than geldanamycin and 17-allylamino-17-demethoxygeldanamycin (17AAG) as an inhibitor of Hsp90.
| Molecular Formula | C32H48N4O8 |
| References |
Schneider C et al (1996) Pharmacologic shifting of a balance between protein refolding and degradation mediated by Hsp90. Proc. Nat.l Acad Sci. 93:14536 Onuoha SC et al (2007) Mechanistic studies on Hsp90 inhibition by ansamycin derivatives. J. Mol. Biol. 372:287. Smith V et al (2005) Comparison of 17-dimethylaminoethylamino-17-demethoxy-geldanamycin (17DMAG) and 17-allylamino-17-demethoxygeldanamycin (17AAG) in vitro: Effects on Hsp90 and client proteins in melanoma models. Cancer Chemother Pharmacol. 56:126 |
