Identification of Ikaros oncoprotein destabilizers

National Center For Advancing Translational Sciences

Investigators

Abstract

This study aims to identify small molecules with similar activity to thalidomide and to determine if other oncogenes expressed as luciferase fusion proteins can be used to find novel mechanisms of protein degradation. Prior to this period, the collaborative team optimized and miniaturized a cell-based assay to enable primary screening. During this period, a comprehensive screen of the NCATS small molecule libraries was conducted using this cell-based expression system to monitor target degradation. Compounds demonstrating modulation of target protein steady-state levels have been cherry-picked for validation using non-transformed and transformed cell lines to eliminate non-specific and/or toxic compounds prior to further testing.