Geldanamycin

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.

(4E,6Z,8S,9S,10E,12S,13R,14S,16R) -13-hydroxy-8,14,19-trimethoxy-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

1. Whitesell L., et al. (1994) Proc. Natl. Acad. Sci. USA 91:8324. 2. Neckers L. (2002) Trends Mol. Med. 8: S55. 3. Mabjeesh N.J., et al. (2002) Cancer Res. 62: 2478. 4. Chavany C., et al. 1996) Amer. Society Biochem Mol Bio. 9: 4974-4977. 5. Villa R., et al. (2003) Carcinogenesis. 24(5): 851-9. 6. Yamaki H., Iguchi-Ariga S.M., and Ariga H. (1989) J Antibiot (Tokyo). 42(4): 604-10.