Identification of Myc translation inhibitors

National Center For Advancing Translational Sciences

Investigators

Abstract

In our ongoing efforts to develop small molecule probes targeting Myc translation, our team conducted extensive structure-activity relationship (SAR) studies on a promising chemotype. During this period, the collaborative team expanded screening and synthesized over 150 analogs, including photoaffinity-labeled compounds, to identify the molecular target. All compounds were evaluated in our internal Myc translation assay, with active compounds undergoing further testing in advanced assays at a collaborator's lab. We also established a new bromodomain assay to assess potential off-target effects. This collaborative effort has expanded our medicinal chemistry efforts and analog testing, successfully leading to the identification of a lead molecule.