17-AAG

Glendanamycin (GA), a benzoquinone ansamycin antibiotic, interferes with the action of Hsp90 leading to degradation of Hsp90 client proteins. GA itself however has undesirable properties such as poor aqueous solubility and liver toxicity; therefore, numerous analogs have been synthesized, such as 17-AAG(1). 17-AAG is an HSP-90 inhibitor that displays a 100-fold higher affinity for HSP-90 derived from tumor cells compared to HSP-90 from normal cells(2). 17-AAG inhibits Akt activation and expression in tumors and synergizes with a number of antitumor agents such as taxol(3), cisplatin(4) and UCN-01 (400 nM 17-AAG, U937 cells)(5). It has also been found that 17-AAG is alo an effective inducer fo the autophagic pathway by which alpha synuclein can be removed. It may provide a means to modulate autophagy in neural cells (6).

17- (Allylamino) -17-demethoxygeldanamycin, 17- (Allylamino) geldanamycin, 17-Demethoxy-17-allylamino geldanamycin, 17-AAG, CP 127374, Geldanamycin,17-demethoxy-17- (2-propenylamino) -, NSC 330507, Tanespimycin

1. Neckers L. (2002) Trends Mol Med. 84: S55-61. 2. Kamal A., et al.(2003) Nature. 425: 407. 3. Solit D.B., et al.(2003) Cancer Res. 63: 2139. 4. Vasilevskaya I.A., et al. (2003) Mol.Pharmacol. 65: 235. 5. Jia W., et al.(2003) Blood. 102: 1824. 6. Riedel M., Goldbaum O., Schwarz L., Schmitt S., Richter-Landsberg C. (2010) PLOS ONE. 5(1): e8753. https://doi.org/10.1371/journal.pone.0008754