The promise of genomics to identify novel therapeutic targets.
The cataloguing of the human genome has provided an unprecedented prospectus for target identification and drug discovery. A current analysis indicates that slightly more than 3000 unique protein encoding loci are potentially amenable to pharmacological intervention (the 'druggable genome', which can be queried at http://function.gnf.org/druggable). However, the assessment of genome sequence data has not resulted in the anticipated acceleration of novel therapeutic developments. The basis for this shortfall lies in the significant attrition rates endemic to preclinical/clinical development, as well as the often underestimated complexity of gene function in higher order biological systems. To address the latter issue, a number of strategies have emerged to facilitate genomics-driven target identification and validation, including cellular profiling of gene function, in silico modelling of gene networks, and systematic analyses of protein complexes. The expectation is that the integration of these and other systems-based technologies may enable the conversion of potential genomic targets into functionally validated molecules, and result in practicable gene-based drug discovery pipelines.
Orth
Anthony P
AP
The Genomics Institute of the Novartis Research Foundation, 10675 John J. Hopkins Drive, San Diego, CA 92121, USA.
Batalov
Serge
S
Perrone
Mark
M
Chanda
Sumit K
SK
D000818:Animals; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D005544:Forecasting; D020869:Gene Expression Profiling; D018390:Gene Targeting; D015894:Genome, Human; D023281:Genomics; D006801:Humans; D007473:Ion Channels / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D005810:Multigene Family / Q000187:drug effects; D011480:Protease Inhibitors / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013329:Structure-Activity Relationship
D007473:Ion Channels; D011480:Protease Inhibitors; D047428:Protein Kinase Inhibitors