geldanamycin

Geldanamycin is a naturally occurring 1,4-benzoquinone ansamycin antibiotic originally isolated from the bacterium Streptomyces hygroscopicus. It functions as a potent inhibitor of heat shock protein 90 (Hsp90), binding to its ADP/ATP-binding pocket and disrupting the chaperone's function. Hsp90 is essential for the folding, stability, and activity of many client proteins involved in cell cycle regulation, growth, survival, apoptosis, angiogenesis, and oncogenesis. By inhibiting Hsp90, geldanamycin induces degradation of several oncogenic proteins such as v-Src, Bcr-Abl, p53, and ERBB2 (HER2), leading to antiproliferative effects in tumor cells. Despite its strong antitumor potential demonstrated in preclinical studies and its role as a lead compound for several clinical analogs (e.g., 17-AAG/tanespimycin), geldanamycin itself has not advanced to clinical use due to significant hepatotoxicity and poor pharmacokinetic properties[6][7][3]. It also exhibits antibacterial activity but is primarily studied for its anticancer properties.

Other names

(+)-geldanamycin