One of the main challenges in small molecule drug discovery is to identify suitable chemical starting points, or "hits", for further chemical optimization. For decades, high-throughput screening based on functional assays was the leading paradigm for identifying small molecule hits. However, more costedective technologies have recently emerged . One such technology involves the use of DNAencoded libraries (DELs), in which each compound's synthetic history and composition are encoded in an associated DNA sequence . DELs enable the rapid screening of billions of compounds at relatively low cost . During selection, putative binders interact with the immobilized protein target, while non-binding compounds are washed away. Binders are identified by sequencing the attached DNA tags using next-generation sequencing. In the most common iteration of this technology, putative binders are re-synthesized without DNA labels and tested in direct confirmatory binding assays to validate (or invalidate) DEL-identified hits .