Geldanamycin

Potent antitumor antibiotic. Inhibitor of pp60^src tyrosine kinase and of c-myc gene expression in murine lymphoblastoma cells. Inhibits the transforming activity of abl, erbB, fps, src, and yes. Binds specifically to heat shock protein 90 (HSP90) and to its endoplasmic reticulum homolog GP96 (GRP94). Capable of destabilizing several oncogene and proto-oncogene products. Potent inhibitor of the nuclear hormone receptor family. Protects against α-synuclein toxicity to dopaminergic neurons in Drosophila. Destabilizes mutant p53 protein from a number of breast, leukemic, and prostate cell lines. 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. Hsp90 inhibitors geldanamycin or 17-DMAG reduces the uptake of Chaperone Mediated Autophagy (CMA) substrates by isolated lysosomes.~10-fold more potent than herbimycin A (Prod. No. BML-EI227)