Fluorescence polarization assay for identification of Hsp90 Inhibitors
Principal Investigator/Assay Provider:
Gabriela Chiosis, PhD, Sloan-Kettering Institute for Cancer Research
Discovery of novel Hsp90 inhibitors for potential development as anti-cancer therapies.
Hsp90 is a chaperone with important roles in maintaining transformation and in elevating the survival and growth potential of cancer cells. Recent evidence suggests additional applications of Hsp90 inhibitors in neurodegenerative diseases, nerve injuries, inflammation and infection. Several natural products that inactivate Hsp90 function have anti-tumor effects in in vitro and in vivo models of cancer. However, due to the role of Hsp90 in normal cellular homeostasis, it remained unclear whether Hsp90 inhibitors will be sufficiently specific for use as therapeutic agents. Early clinical results with 17AAG, the first Hsp90 inhibitor to enter clinical trials, suggest that these fears may be unfounded. These studies confirm that Hsp90 is a promising target for novel cancer therapeutics and pave the road for the introduction of Hsp90 inhibitors in the clinic. The potential of Hsp90 inhibitors as therapeutics in other diseases has been less explored due to limitations with the current inhibitors (i.e. 17AAG is not crossing the blood-brain barrier, BBB). There is thus increasing interest in developing novel inhibitors of this protein.
The FP assay for the Hsp90 in cell lysate is based on the competitive binding of fluorescently (Cy3B) labeled geldanamycin (cy3B-GM) to average Hsp90 population found in cancer cell lysates.