Identifying inhibitors of ER retrotranslocation/dislocation

National Center For Advancing Translational Sciences

Investigators

Abstract

To date, small molecules that target most of the major proteins involved in this process have not been identified. The collaborative team aims to identify small molecule inhibitors of ER dislocation. Prior to this period, a high-content imaging assay to study ER dislocation was successfully adapted to high-throughput format and approximately 50,000 compounds were screened. Several compounds that showed favorable activity profiles were re-synthesized and one chemotype has reconfirmed as a bonafide inhibitor of ER dislocation. During this period, the collaborative team has expanded screening to include an additional 50,000 compounds and continued a structure activity relationship (SAR) study and medicinal chemistry campaign to improve upon potency and physicochemical/ADME properties. In addition, confirmed chemotypes are being used for quantitative structure activity relationship (QSAR) studies to identify additional active compounds.