The goal of this project is to identify small molecule modulators of the SCFTrCP complex. SCF E3 ubiquitin ligases are a family of proteins which promote the proteasome-mediated degradation of almost 80% of cellular proteins and play a crucial role in cellular physiology, signaling, and transformation. SCFTrCP is a particularly important member of this family, as it is often deregulated in many types of cancers as well as other diseases. During the reporting period, the project team optimized a cell-based assay that employs a nanoluciferase degron to monitor specific cellular activity of the SCFTrCP complex. Initial screening of drug repurposing libraries has been completed and contributed to a publication. High-throughput screening efforts have been expanded to additional libraries, and a SCF counter assay is under development to support hit triage.