Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Commentary
  • Published:

Pharmacogenetics and drug metabolism

Nature Biotechnology volume 16, pages 4–5 (1998)Cite this article

The past 10 years or so have witnessed a dramatic change in the way in which drugs are discovered and developed. New target identification has been impacted by what has been termed the "genome rush"1. High-throughput screening of novel targets with many thousands of molecules, often from combinatorial chemistry–based synthetic approaches or vast chemical libraries, can yield large numbers of active molecules.

Now, a significant challenge within the industry is how to decide which of these active molecules should be advanced into preclinical development. The incorporation of screens that allow the rational selection and/or optimization of these molecules based on pivotal characteristics—such as the way in which a candidate is metabolized or is absorbed in models in vitro and in vivo—has been widely adopted. The theory is that they will enable major metabolic imperfections in these molecules to be identified early, and that these will then form the basis, along with pharmacologic and preliminary toxicologic data, for the decision to advance one candidate into development over another.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

References

  1. The genome rush of 1996 [Editorial]. Nature Biotechnology 14: 1516–1518 .

  2. Nebert, D.W. 1997. Polymorphisms in drug-metabolizing enzymes: What is their clinical relevance and why do they exist? Am. J. Hum. Genet. 60: 265–271.

    Google Scholar 

  3. Idle J.R. and Smith R.L. 1979. Polymorphisms of oxidation at carbon centers of drugs and their clinical significance. Drug Metab. Rev. 9: 301–317.

    Article  Google Scholar 

  4. Daly, A.K. 1995. Molecular basis of polymorphic drug metabolism. J. Mol. Med. 73: 539–553.

    Article  Google Scholar 

  5. Ball, S.E., Scatina, J.A., Sisenwine, S.F., and Fisher, G.L. 1995. The application of in vitro models of drug metabolism and toxicity in drug discovery and drug development. Drug Chem. Tox. 18: 1–28.

    Article  Google Scholar 

  6. Rendic, S. and Di Carlo, F. 1997. Human cytochromes P450 enzymes: A status report summarizing their reactions, substrates, inducers, and inhibitors. Drug Metab. Rev. 29: 413–580.

    Article  Google Scholar 

Download references

Acknowledgements

The authors would like to thank the pharmaceutical companies that responded to the survey. J.A. Scatina and J. Kao (Wyeth-Ayerst Research, Princeton, New Jersey) and Professor Roland Wolf (University of Dundee, Scotland) are acknowledged for helpful discussions.

Author information

Authors and Affiliations

  1. senior research scientist in drug metabolism at Wyeth-Ayerst Research, CN 8000,, Princeton,, 08543, NJ

    Simon Ball

  2. research scientist in general and experimental toxicology at Novartis Pharmaceuticals, 59 Route 10,, East Hanover,, 07936-1080., NJ

    Neil Borman

Authors
  1. Simon Ball
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Neil Borman
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ball, S., Borman, N. Pharmacogenetics and drug metabolism. Nat Biotechnol 16 (Suppl 2), 4–5 (1998). https://doi.org/10.1038/5135

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/5135

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing