Geldanamycin (Hsp90 Inhibitor)

Stressmarq Biosciences

Geldanamycin is a benzoquinoid ansamycin produced by Streptomyces hygroscopicus. It binds specifically to heat shock protein HSP90 and downregulates target proteins including tyrosine kinases, steroid receptors, transcription factors and cell cycle regulatory kinases (1,2). It induces the inactivation, destabilization and eventual degradation of HIF-1á (3). It is also an inhibitor of pp60src tyrosinekinase and of c-myc gene expression in murine lymphoblastoma cells. It inhibits the transforming activity of abl, erbB, fps, src, and yes (4).

Geldanamycin is capable of destabilizing several oncogene and proto-oncogene products; it is a potent inhibitor of the nuclear hormone receptor family (5). It protects against á-synuclein toxicity to dopaminergic neurons in Drosophila, and destabilizes mutant p53 protein from a number of breast, leukemic, and prostate cell lines (6). Inhibits basal and hypoxia-induced expression of c-Jun (IC50=75nM) and abolishes hypoxia-induced increase in c-Jun N-terminal kinase (JNK) activity. Inhibits telomerase activity through inhibition of HSP90, a chaperone required for the assembly and activation of telomerase in human cells (6). It is ~10- fold more potent than herbimycin A.

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