Progesterone receptor chaperone complex-based high-throughput screening assay: identification of capsaicin as an inhibitor of the Hsp90 machine.

ABSTRACT: Hsp90 and its co-chaperones are known to be important for cancer cell survival. The N-terminal inhibitors of Hsp90 that are in ongoing clinical trials as antitumor agents have unfortunately shown disappointing efficacies in the clinic. Thus, novel inhibitors of the Hsp90 machine with a different mechanism of action are urgently needed. We report here the development of a novel high-throughput screening assay platform to identify small-molecule inhibitors of Hsp90 and its co-chaperones. This assay quantitatively measures the ability of Hsp90 and its co-chaperones to refold/protect the progesterone receptor, a physiological client of Hsp90, in a 96-well plate format. We screened the National Institutes of Health clinical collection drug library and identified capsaicin as a hit molecule. Cap

SUBMITTER: Patwardhan CA 

PROVIDER: S-EPMC4836055 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature