Small Targeted Cytotoxics: Current State and Promises from DNA‐Encoded Chemical Libraries

The targeted delivery of potent cytotoxic agents has emerged as a promising strategy for the treatment of cancer and other serious conditions. Traditionally, antibodies against markers of disease have been used as drug‐delivery vehicles. More recently, lower molecular weight ligands have been proposed for the generation of a novel class of targeted cytotoxics with improved properties. Advances in this field crucially rely on efficient methods for the identification and optimization of organic molecules capable of high‐affinity binding and selective recognition of target proteins. The advent of DNA‐encoded chemical libraries allows the construction and screening of compound collections of unprecedented size. In this Review, we survey developments in the field of small ligand‐based targeted cytotoxics and show how innovative library technologies will help develop the drugs of the future.