The druggable genome

Abstract

An assessment of the number of molecular targets that represent an opportunity for therapeutic intervention is crucial to the development of post-genomic research strategies within the pharmaceutical industry. Now that we know the size of the human genome, it is interesting to consider just how many molecular targets this opportunity represents. We start from the position that we understand the properties that are required for a good drug, and therefore must be able to understand what makes a good drug target.

DIGE analysis of rat skeletal muscle proteins using nonionic detergent phase extraction of young adult versus aged gastrocnemius tissue

“…Integral proteins are both of fundamental biological importance and represent crucial therapeutic targets [35], giving central importance to the identification of their role in aging. However, to date skeletal muscle proteome studies have mostly investigated soluble proteins thereby underestimating altered expression levels of integral elements.…”

p53-dependent inhibition of mammalian cell survival by a genetically selected peptide aptamer that targets the regulatory subunit of protein kinase CK2

“…It is noteworthy that most drugs and leads achieve their activity by competing for structurally defined binding site on a protein with endogenous ligands (Hopkins and Groom, 2002). Interestingly, both the IE protein ICP27 of herpes simplex virus type I and the IE2 protein of herpes virus 6 (HHV-6), which have been implicated in the ethiology of a range of prominent diseases including cancers, are interacting with CK2b, suggesting that some functions of the herpes virus proteins may be regulated by CK2 binding (Wadd et al, 1999;Shimada et al, 2004).…”

Mission possible

“…This approach exploits both chemical (for example, protein structureactivity data and drug binding-site features) and genomic (DNA sequence) information about the pathogenic organism. Its power lies in the ability to relate targets in a parasite back to likely chemical starting points in silico, enabling potential targets to be selected before expensive and time-consuming drug-screening and optimization studies are undertaken 6 . Researchers can assign priority to the most promising mechanistic drug targets for further investigation, building up a portfolio of potential projects, which can then be ranked on the basis of 'drug-hunting' criteria.…”