Structure-based generation of viable leads from small combinatorial libraries.
Parallel synthesis and structure-aided design have begun to converge in the process of drug discovery. Virtual screening using X-ray crystal structures of therapeutic targets to front-load a high-throughput screen or to establish a tractable collection for lower throughput assays has become a standard practice in many lead generation settings. The application of similar techniques for increasing the likelihood of including active compounds in a focused combinatorial library is a natural progression that is beginning to be recognized. In this review, we will cover recent reports of small, focused libraries designed for specific therapeutic targets, and for which X-ray crystallographic data is available.
Laird
Ellen R
ER
Array BioPharma Inc, 3200 Walnut Street, Boulder, CO 80301, USA. ellen.laird@arraybiopharma.com
Blake
James F
JF
D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D015195:Drug Design; D008024:Ligands; D015394:Molecular Structure; D019151:Peptide Library; D013329:Structure-Activity Relationship
D008024:Ligands; D019151:Peptide Library