https://doi.org/10.1146/annurev-cancerbio-071124-011719

Abstract

This review describes recent developments in DNA-encoded library (DEL) technology, which has enabled transformative discoveries in cancer research. Successful DEL screening campaigns for cancer-relevant targets are described in detail to highlight the unique advantages of this technology compared to other hit-generation strategies. Moreover, recent developments in screening methods that have helped expand the DEL-addressable target space are described, and their implications for cancer research are emphasized. DEL screening campaigns targeting RNA and transcription factors are discussed, and various cell-based DEL evaluation methods for membrane proteins are compared and put into context. Finally, the use of DEL technology for the discovery of novel bifunctional degraders is presented. Overall, this article provides a comprehensive overview of key DEL discoveries that are expected to be of significant interest to cancer researchers and medicinal chemists working in the field of oncology.