Determining direct binders of the Androgen Receptor using a high-throughput Cellular Thermal Shift Assay.

ABSTRACT: Androgen Receptor (AR) is a key driver in prostate cancer. Direct targeting of AR has valuable therapeutic potential. However, the lack of disease relevant cellular methodologies capable of discriminating between inhibitors that directly bind AR and those that instead act on AR co-regulators has made identification of novel antagonists challenging. The Cellular Thermal Shift Assay (CETSA) is a technology enabling confirmation of direct target engagement with label-free, endogenous protein in living cells. We report the development of the first high-throughput CETSA assay (CETSA HT) to identify direct AR binders in a prostate cancer cell line endogenously expressing AR. Using this approach, we screened a pharmacology library containing both compounds reported to directly engage AR, and comp

SUBMITTER: Shaw J 

PROVIDER: S-EPMC5760633 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature