Journal Article

Chemogenomics: an emerging strategy for rapid target and drug discovery

Jacoby, Edgar, Bredel, Markus

2004

Overview

Key Points Chemogenomics is the study of the genomic and/or proteomic response of an intact biological system to chemical compounds, or the ability of isolated molecular targets to interact with such compounds. In chemogenomics, large collections of chemical compounds are screened for the parallel identification of biological targets and biologically active compounds. In reverse chemogenomics, gene sequences of interest are expressed as target proteins and screened in a high-throughput, 'target-based' manner by compound libraries. On the basis of the structure–activity relationship homology concept, particular emphasis is placed on the parallel exploration of gene and protein families. In forward chemogenomics, active compounds are identified on the basis of their conditional phenotypic effect on a whole biological system rather than on their inhibition of a specific protein target, followed by the subsequent study of the mechanistic basis of the phenotype. Predictive chemogenomics strategies primarily attempt to holistically characterize gene–compound response associations by concurrently considering the response profiles of thousands of drug responses, coupled with the secondary aim of identifying novel therapeutic molecules. Computational or in silico methods complement experimental chemogenomics strategies in the search for targets and drugs. Chemogenomics has garnered support from virtually all areas of medical research. Cancer research was particularly poised to take advantage of the high-throughput nature of chemogenomics, as the approach can help to identify treatment strategies that selectively target the multiple and complex molecular alterations that are observed in human tumours. Chemogenomics faces unique and mainly technical challenges, including the need for a more refined integration of bioinformatics and chemoinformatics data, a more rational approach to selecting designed compounds from an almost infinite number of synthetic possibilities and the ability to build more focused libraries for screening. A recent trend in chemogenomics focuses on data quality rather than on the number of data points that can be generated. Chemogenomics is an emerging discipline that combines the latest tools of genomics and chemistry and applies them to target and drug discovery. Its strength lies in eliminating the bottleneck that currently occurs in target identification by measuring the broad, conditional effects of chemical libraries on whole biological systems or by screening large chemical libraries quickly and efficiently against selected targets. The hope is that chemogenomics will concurrently identify and validate therapeutic targets and detect drug candidates to rapidly and effectively generate new treatments for many human diseases.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Agriculture / Animal Genetics and Genomics / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / Biotechnology / Cancer Research / Chemical compounds / Chemistry / Computational Biology / Databases, Factual / Disease / Drug Design / Fundamental and applied biological sciences. Psychology / Gene Function / Genes / Genomes / Genomics / Genomics - trends / Health. Pharmaceutical industry / Human Genetics / Humans / Industrial applications and implications. Economical aspects / Miscellaneous / Pharmaceuticals / Pharmacogenetics / R&D / Research & development / review-article