Abstract 6416: DEL-chemomics approach for the discovery of targeted protein degraders for cancer therapy

Abstract DNA-encoded chemical library (DEL) technology has become a powerful tool for hit identification, enabling the efficient screening of large collections of encoded compounds with advantages over traditional high-throughput screening in terms of library size, cost, and resource efficiency. The high chemical diversity and encoding fidelity of DELs yields extensive data that can support computational approaches such as machine learning (ML), 3D pharmacophore generation and structure-based discovery. This DEL-chemomics approach has been applied to the discovery of novel E3 ligase receptor ligands, expanding the repertoire of E3 ligands beyond the traditional CRBN and VHL for degradation of drug targets. A case study of the discovery of DCAF1 ligand and its application in PROTACs that targeted WDR5 for degradation will be presented. Citation Format: Ying Zhang, Anthony D. Keefe, Matthew A. Clark, Marie-Aude Guie, John Guilinger. DEL-chemomics approach for the discovery of targeted protein degraders for cancer therapy abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6416.