Accelerating drug discovery - PubMed (original) (raw)

Accelerating drug discovery

Sandra Kraljevic et al. EMBO Rep. 2004 Sep.

Abstract

Although the evolution of '-omics' methodologies is still in its infancy, both the pharmaceutical industry and patients could benefit from their implementation in the drug development process

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Figure 1

Figure 1

Current time-scale of drug approval process. New drugs are developed through several phases: synthesis and extraction of new compounds, biological screening and pharmacological testing, pharmaceutical dosage formulation and stability testing, toxicology and safety testing, phase I, II and III clinical evaluation process, development for manufacturing and quality control, bioavailability studies and post-approval research. Before testing in humans can start, a significant body of pre-clinical data must be compiled, and appropriate toxic doses should be found for further in vivo testing to ensure human safety. Toxicology, pharmacology, metabolism and pharmaceutical sciences represent the core of pre-clinical development.

Figure 2

Figure 2

The increasing availability of quantitative biological data from the human genome project, coupled with advances in instrumentation, reagents, methodologies, bioinformatics tools and software, are transforming the ways drug discovery and drug development are performed. The ability to combine high-throughput genomic, proteomic, metabolomic and other experimental approaches with drug discovery will speed up the development of safer, more effective and better-targeted therapeutic agents. Functional genomics approaches should be exploited throughout the entire drug development process. Particularly, combinatorial chemistry, in silico structure prediction, new scaffold-like molecular weight compounds targeting conserved regions of multiple protein family members, accompanied by high-throughput X-ray crystallography and proteomic-based drug target discovery, will reduce the time required for drug discovery. Large-scale (robotics) in vitro screening using cultured human cell lines and in vivo studies on 'humanized' mouse models combined with functional genomic analysis of different organs will speed up testing. Finally, pharmacogenomics-guided clinical trials, followed by toxicogenomics-based analyses should shorten the clinical phase of testing by as much as 3–4 years.

Figure 3

Figure 3

New chemical approaches and biological assays combined with bioinformatics provide a general ability to globally assess many classes of cellular and other molecules. Such attempts are likely to expand the repertoire of potential therapeutics directed towards a particular molecular target in the near future.

Figure 4

Figure 4

The advantages of '-omics' approaches in the drug development process

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