Combinatorial drug discovery: which methods will produce the greatest value?
Combinatorial strategies are important new approaches to drug discovery, and it seems quite likely that they will result in the discovery of interesting potential pharmaceuticals. However, it is less clear whether combinatorial approaches will result in quantum advances in therapeutics. Nor is there general agreement about the factors most important in defining how combinatorial strategies will provide value to the discovery of lead and therapeutic compounds. In this review, we propose criteria that define the value of combinatorial strategies and categorize the various approaches by: (a) the type of chemical space to be searched, (b) the tactics employed to synthesize and screen libraries, and (c) the structures of individual molecules in libraries. We evaluate the strengths and weaknesses of the various strategies and suggest milestones that can help to track their success.
Ecker
D J
DJ
Isis Pharmaceuticals, Carlsbad, CA 92008, USA. decker@isisph.com
Crooke
S T
ST
D001709:Biotechnology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D046911:Macromolecular Substances; D019151:Peptide Library; D013329:Structure-Activity Relationship
D046911:Macromolecular Substances; D019151:Peptide Library