High-throughput gene sequencing has revolutionized the process used to identify novel molecular targets for drug discovery. Thousands of new gene sequences have been generated but only a limited number of these can be converted into validated targets likely to be involved in disease. We describe here some of the approaches used at SmithKline Beecham to select and validate novel targets. These include the identification of selective tissue gene product expression, such as for cathepsin K, a novel osteoclast-specific cysteine protease. We also describe the discovery and functional characterization of novel members of the G-protein coupled receptor superfamily and their pairing with natural ligands. Lastly, we discuss the promises of gene microarrays and proteomics, developing technologies that allow the parallel analyses of tissue expression patterns of thousands of genes or proteins, respectively.


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  • Article Type: Review Article
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