Geldanamycin

Geldanamycin is a benzoquinone ansamycin antibiotic that binds to Hsp90 (Heat Shock Protein 90) and alters its function. Geldanamycin induces the degradation of proteins that are mutated in tumor cells such as v-Src, Bcr-Abl and p53 preferentially over their normal cellular counterparts. This effect is mediated via HSP90. Despite its potent antitumor potential, geldanamycin presents several major drawbacks as a drug candidate (namely, hepatotoxicity) that have led to the development of geldanamycin analogues, in particular analogues containing a derivatisation at the 17 position:17-AAG,17-DMAG.