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). Looking for more information on HSP90? Visit our new HSP90 Scientific Resource Guide at http://www.HSP90.ca.
