Combinatorial chemistry and high-throughput screening in drug discovery and development

Abstract

Combinatorial chemistry is a synthesis strategy that enables the simultaneous production of large numbers of related compounds. It is coupled to high-throughput screening (HTS) and computational methods and has been integrated into the lead discovery and optimization process throughout the pharmaceutical industry. Innovations in combinatorial chemistry have enabled the synthesis of large collections of libraries, which have led to the current efforts in developing methods capable of screening these compounds. The general synthetic strategy used for combinatorial chemistry is similar to the more classical approach, that is, commercial synthons or building blocks are combined through a range of usually established methods to generate a new entity. The combinatorial approach differs in that the reactions are generalized for a range of building blocks, so that a related set of compounds are simultaneously produced. As computational and experimental procedures for absorption, distribution, metabolism, and excretion (ADME) improve, the identification of problematic leads earlier in the drug discovery process will be possible. Taken together, innovations in chemical synthesis and library design, coupled with screening and bioinformatics technology, will help greatly to decrease drug development times and costs.