Stemcell, 74032, Geldanamycin

Geldanamycin is a benzoquinone ansamycin antibiotic that selectively inhibits heat shock protein 90 (Hsp90) (Schulte et al.; Whitesell et al.). It inhibits the ATPase activity of Hsp90 by binding with high affinity to the N-terminal ATP-binding site (Kd = 1.2 µM; Roe et al.). Geldanamycin also binds to the glucose-regulated protein GRP94, an endoplasmic reticulum protein with homology to Hsp90. This interaction destabilizes its complex with p185-ERBB2 leading to degradation of ERBB2 protein, which is overexpressed in aggressive breast cancers (Chavany et al.; Castagnola et al.).

CANCER RESEARCH

· Inhibits growth of 60 human tumor cell lines (Supko et al.).

DISEASE MODELING

· Regulates innate immune response as demonstrated by inhibition of inflammasome activity in a mouse gout model (Mayor et al.).

· Inhibits replication of HSV-1 and HSV-2 (Li et al.).