Novel E3 Ligase to Support Targeted Protein Degradation

Targeted protein degradation (TPD) continues to expand the possibilities for next-generation therapeutics, and identifying novel E3 ligases remains an important area of innovation in the field.

At AACR 2026, WuXi Biology and Testing presented a poster highlighting a discovery approach combining DNA-encoded library (DEL) screening and proteolysis-targeting chimera (PROTAC) design to explore new E3 ligase opportunities for TPD research.

In this work, our scientists identified and optimized proprietary binders for GID4, a substrate receptor within the CTLH complex, and demonstrated BRD4 degradation activity in cancer cell lines. The study also incorporated crystallography and direct-to-biology (D2B) high-throughput optimization approaches to further advance PROTAC development efforts. Together, these findings demonstrate how DEL-based strategies can help expand the E3 ligase toolbox and further enable TPD discovery programs.