Geldanamycin

Geldanamycin, a benzoquinone ansamycin, has been found to revert tyrosine kinase-induced oncogenic transformation. In the same study it was reported that Geldanamycin was able to bind elements of Hsp90 (heat shock protein 90) clients, such as HIF-1α (Hypoxia-inducible factor-1-α), and inhibit them. Geldanamycin binds in a specific and stable manner and as a result inhibits new protein maturation. Geldanamycin binds with high affinity into the ATP binding pocket of Hsp90. These heat shock proteins might positively impact cell proliferation by being a chaperone required for the assembly and activation of telomerase in cells. By binding them, Geldanamycin is thought to reduce new protein maturation and their downstream transcriptional activity. Geldanamycin has also displayed a capacity to bind to the endoplasmic reticulum homologue of the heat-shock protein, GP-96 and thus interferes with the cellular stress response. In addition, Geldanamycin has been reported as a potent inhibitor of the nuclear hormone receptor family. Other research has demonstrated Geldanamycin to be a protective agent against α-synuclein toxicity to dopaminergic neurons in Drosophila. Geldanamycin is an inhibitor of c-Src.