Chapter 14: Encoded Compound Libraries to Accelerate Small-molecule Therapeutic Discovery

DNA encoded library generation and screening techniques evolved out of a need within the drug discovery community for rapid and cost effective access to large numbers of novel chemical compounds. High throughput screening (HTS) has been developed within large pharmaceutical companies and select service providers to rapidly evaluate large compound collections for novel chemical matter that affects a therapeutically relevant process. The desire to efficiently and rapidly expand the number and diversity of chemical compounds available to feed into the HTS process led to the development of combinatorial chemistry. Methods to create encoded combinatorial compounds substantially improved the efficiency of synthesis and the ability to confirm a compound's identity, but still leveraged the relatively expensive HTS infrastructure to evaluate the compounds. The DNA encoding of compounds generated by combinatorial methods facilitates efficient and rapid synthesis of large numbers of diverse chemical compounds that can be screened as a complex mixture in a single affinity based process. As techniques to generate and screen DNA encoded compounds continue to evolve and become more accessible, they will serve both to complement established HTS approaches as well as a stand-alone discovery platform.