|Geldanamycin: A novel antibiotic with potent anti-cancer activity.
Novel antibiotics are important tools both in research and medicine and are increasingly becoming better characterized as more is being discovered about their mechanisms. Geldanamycin is one such antibiotic. Produced by the Actinomycete Streptomyces hygroscopicus var. geldanus, it is structurally a benzoquinone ansamycin antibiotic. It has been shown to possess weak broad-spectrum antibiotic activity and potent anticancer activity.
Geldanamycin is useful in the study of the action of Heat Shock Proteins. It binds to Heat Shock Protein 90 (Hsp90) and alters its function. HSP90 client proteins are involved in the regulation of the cell cycle, cell growth, cell survival, apoptosis, angiogenesis and oncogenesis. Hsp90 plays a major role in the folding and activation of several signaling proteins that promote the growth and survival of tumor cells. Geldanamycin, induces the degradation of these signaling proteins and, consequently, the death of malignant cells.
Antitumor effects of geldanamycin can be partly explained by the inhibition of oncoproteins such as v-Src, mutant p53 proteins, Raf-1, p185erbB2 proteins, and EGFR. Geldanamycin downregulates such target proteins as tyrosine kinases, steroid receptors, transcription factors and cell cycle regulatory kinases1,2. It induces the inactivation, destabilization and eventual degradation of HIF-1a. It also represents a potent inhibitor of p60src tyrosine kinase and of c-myc gene expression in murine lymphoblastoma cells.
1) DeBoer, C., et al. (1970) J. Antibiot. 23, 442
(2) Stebbins C.E.et al. (1997) Cell 89, 239-250.
Geldanamycin: G2024-50.1 1mg, G2024-50.5 5 mg
G2024-51A.250 250 mg
17-AAG (17-allylamino-17-demethoxygeldanamycin, Telatinib, Tanespimycin, NSC-330507, CNF-101, KOS-953, GLD-36, CP 127374)
A0001-85.250 250 mg
17-DMAG Hydrochloride (17-(Dimethylaminoethylamino)-17-demethoxygeldanamycin Hydrochloride, 17-DMAG Hydrochloride, NSC-707545, Alvespimycin)
D8072-60.250 250 mg
Hsp 90 products ...