From DNA-Encoded Chemistry to Tumor-Targeted Small Molecule Therapeutics.

Unlike conventional screening methods, which are limited by library size, DNA-encoded chemical library (DEL) technology enables the simultaneous interrogation of billions of compounds, each uniquely barcoded with DNA tags. These libraries can be screened through affinity-based capture and decoded using high-throughput sequencing. DEL-derived ligands can be conjugated to cytotoxic agents or radioactive isotopes, facilitating the creation of highly selective therapeutics that target diseased cells while minimizing off-target effects. This article explores the use of DELs for identifying high-affinity small organic ligands for the development of small molecule-radio conjugates (SMRCs) and small molecule-drug conjugates (SMDCs).