Screening for small molecule modulators of SCFbTrCP ubiquitin ligase complex

National Center For Advancing Translational Sciences

Investigators

Abstract

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. High-throughput screening efforts have been expanded to additional libraries, and a SCF counter assay is under development to support hit triage.