ETS variant 1 (ETV1) is an ETS transcription factor gene that undergoes chromosomal translocation in prostate cancers and Ewing sarcomas, amplification in melanomas, and lineage dysregulation in gastrointestinal stromal tumors. The small molecule BRD32048 binds ETV1 directly (SPR KD of 17.1 µM) and modulates ETV1-mediated transcription, as well as inhibits invasion of ETV1-dependent cancer cells. Mechanistically, BRD32048 disrupts ETV1-p300 interaction leading to reduced p300-dependent acetylation of ETV1 thereby preventing its stabilization and activation, promoting the proteasome-dependent degradation of ETV1 oncoprotein. Pop et al., Mol. Cancer Ther. 13, 1492-1502, 2014.

ETV1 BRD32048 model.jpg