The design of screening libraries targeted at G-protein coupled receptors

The screening of large libraries in order to obtain hits for receptors of interest has been the mainstay of drug research for some time now. It is increasingly being recognised that this is a relatively inefficient way to achieve this end and the screening of libraries either designed or selected to hit particular targets is rapidly becoming the method of choice. The advantages in terms of success rate to achieve viable lead series are magnified by the cost and time savings achieved by screening more carefully selected groups of compounds. A number of approaches have been used for the design and production of such libraries or methods for selection of such focused sets from larger diverse collections. These range from combinatorially produced ligand-mimetic approaches through pharmacophore-based design to those methods based on statistical selection techniques. Most recently, progress in chemogenomic approaches has thrown new light on the relationship between receptor sequence and compounds that interact at particular receptors and this is also having an impact on the design of targeted libraries.