The impact of genomics on drug discovery

High-throughput gene sequencing has revolutionized the process used to iden tify novel molecular targets for drug discovery. Thousands of new gene sequ ences have been generated but only a limited number of these can be convert ed into validated targets likely to be involved in disease. We describe her e some of the approaches used at SmithKline Beecham to select and validate novel targets. These include the identification of selective tissue gene pr oduct expression, such as for cathepsin K, a novel osteoclast-specific cyst eine protease. We also describe the discovery and functional characterizati on of novel members of the G-protein coupled receptor superfamily and their pairing with natural ligands. Lastly, we discuss the promises of gene micr oarrays and proteomics, developing technologies that allow the parallel ana lyses of tissue expression patterns of thousands of genes or proteins, resp ectively.