TARGETS最新文献

High throughput functional annotation of the proteome has emerged as a standard tool for target identification. In contrast, target validation, which requires detailed analysis of biological function, has until recently remained an essentially experimental low throughput activity. Currently, there is considerable interest in accelerating and improving the validation process to counter the declining number of small-molecule-based therapeutics being released onto the market. Progress in high throughput proteomics is a key technology in this respect. Uniquely, it offers the ability to rapidly identify and characterize networks of interacting proteins, which in turn presents new opportunities to develop alternative lead development strategies.

Patent Update is a regular column dedicated to the complex issues that affect patents in the genomics and proteomics field. In each issue, there are two sections compiled by patent attorneys. The first section, Patents – a Practical Perspective, is a commentary on current issues, landmark patents, useful patent resources and how to search them, and legislative changes that impact the pharma and biotech industries. The second section, Patent News, provides brief synopses of recently issued patents and other patent events, and their significance to drug discovery R&D.

Since its initiation 3–4 years ago, the emerging field of structural genomics has faced many technical obstacles on the path to high-throughput protein structure determination. Although attrition in the gene-to-structure process remains high, much has been achieved and the first genome-scale studies are appearing in the literature. In terms of drug discovery, high-throughput structure determination is leading to increases in productivity, and to new approaches to hit identification.

Mitochondria are the organelles responsible for energy production that ‘house’ many pathways of intermediary metabolism. It should not be surprising, therefore, that several human diseases involve mitochondrial dysfunction or dysregulation, although many of these diseases have complex etiologies that are not yet fully defined. For some of these diseases, there is evidence that ameliorating the mitochondrial dysfunction will provide clinical benefit. Several marketed or late-stage drugs are now known to act on mitochondrial targets, although this was not recognized when they were initially developed. The main requirements for progress in the area of mitochondrial drug development are a more systematic and comprehensive definition of the mitochondrial proteome and the identification of targets for drug development.

Apoptosis and metastasis are complex processes involving many gene products. Various biochemical, genetic and technological approaches are used to identify functional gene products, and are valuable for understanding basic biology and disease. However, now that sequence information is abundant and accessible through databases, there is a simpler, more definitive technology to identify genes that are the most relevant to biological phenomena of interest. A rapid screening system using libraries of randomized ribozymes has been developed that identifies key gene products involved in a defined phenotype using a functional gene ‘knock-down’ approach. Libraries of randomized ribozymes have been used to identify genes involved in pathways of apoptosis and metastasis, and there is great potential for this system to identify genes involved in other processes and diseases as well.