Inhibitors of Heat Shock Protein 90

Hsp90 inhibitors are exciting intense interest as potential therapies in cancer, inflammatory diseases and neurodegenerative conditions – exemplified by Pfizer’s acquisition of Serenex Inc. in 2008.

Recently it was reported that the Hsp90 inhibitor, geldanamycin, has weak cytotoxic activity as a single agent, but it dramatically intensifies the cytotoxicity of doxorubicin and ICRF-193 in Jurkat and HL-60 cells.  These results suggest that abrogation of G2 checkpoint by geldanamycin may play a central role in sensitizing p53-negative tumor cells to DNA-damaging and decatenation-inhibiting agents (Sugimoto K. et al. Oncogene (2008) 27, 3091–3101).  Geldanamycin is also reported to augment the cytopathic effect of the measles virus in MDA-MB-231 (breast), SKOV3.IP (ovarian) and TE671 (rhabdomyosarcoma) cancer cell lines (Liu C. et al. Gene Therapy (2008) 15, 1024-1034).

Hsp90 inhibitors:

• Geldanamycin       BIA-G1101
• Herbimycin A         BIA-H1036
• Herbimycin C         BIA-H1144

Other ansamacrolides sold by BioAustralis

• Ansatrienin A BIA-A1004
• Ansatrienin B BIA-A1005
• Antibiotic TAN 420C BIA-H1039
• Antibiotic TAN 420E BIA-H1037