biostudies-literaturePatwardhan CANIGMS NIH HHS223-9https://www.ebi.ac.uk/biostudies/studies/S-EPMC4836055biostudies-literatureUnknown20(2)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. CapJournal of biomolecular screeningProgesterone receptor chaperone complex-based high-throughput screening assay: identification of capsaicin as an inhibitor of the Hsp90 machine.PMC4836055R01 GM102443GM102443-01Patwardhan CAChadli AAlfa ELu SfalseProgesterone receptor chaperone complex-based high-throughput screening assay: identification of capsaicin as an inhibitor of the Hsp90 machine.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. Cap2015-01-01T00:00:00Z2015 Feb2025-04-04T11:40:58.784Z2019-03-27T02:11:53ZS-EPMC48360552518451410.1177/1087057114549147