Deciphering Therapeutic Targets

The recent publication of human genome maps by the International Human Genome Sequencing Consortium (10) and Celera Genomics (20) provides a milestone toward the continuing emergence of a “genes-to-drugs” paradigm for drug discovery. These studies estimate that approximately 30 000 human genes exist—equivalent to about 1% of the human genome. Genes provide the molecular template for the human proteome—the complete set of proteins encoded by the genome. It is also important not to exclude noncoding regions of the genome because these sequences contain regulatory elements for gene transcription and related functions that are manifest, for example, in alternative start and stop sites for transcription. The mapping of the human genome represents a major milestone for the drug discovery effort as it moves toward the implementation of sophisticated genomic technologies, which include functional genomics, proteomics, and informatics. These technologies complement the armamentarium of existing core competencies, such as high-throughput screening and mechanism-based assays, medicinal and combinatorial chemistry, structural biology and drug design, cell biology and pharmacology, in vivo disease models, pharmacokinetics and drug metabolism, and preclinical toxicology, as tools for the development of new medicines.