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.

  • Timeline
  • Published:

A brief history of novel drug discovery technologies

Abstract

Laypersons, researchers and clinicians alike speak of the biotechnology revolution with excitement. Media coverage of new breakthroughs in medicine often have the public and the investment community on the edge of their seats, eager for the next blockbuster drug to cure everything from high cholesterol levels to cancer. In this perspective, we examine some of the more popularized and influential new technologies in drug discovery and assess their relative impact on the actual attainment of new therapeutics.

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

Access options

Buy this article

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

Figure 1: Virtual drug discovery.
Figure 2: Emerging technologies and their developers.

References

  1. Merrifield, R. B. Solid-phase syntheses (Nobel lecture). Angew. Chem. 97, 801–812 (1985).

    CAS  Google Scholar 

  2. Elmblad, A. et al. Synthesis of mixed oligodeoxyribonucleotides following the solid phase method. Nucleic. Acids Res. 10, 3291–3301 (1982).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Bunin, B. A. & Ellman, J. A. A general and expedient method for the solid-phase synthesis of 1,4-benzodiazepine derivatives. J. Am. Chem. Soc. 114, 10997–10998 (1992).

    CAS  Google Scholar 

  4. Day, K. Testing a combination punch against disease. The Washington Post (Washington) (April 14, 1996).

    Google Scholar 

  5. Dolle, R. E. Comprehensive survey of combinatorial library synthesis: 2000. J. Comb. Chem. 3, 477–517 (2001).

    CAS  PubMed  Google Scholar 

  6. Arya, P. et al. Toward high-throughput synthesis of complex natural product-like compounds in the genomics and proteomics age. Chem. Biol. 9, 145–156 (2002).

    CAS  PubMed  Google Scholar 

  7. Sears, P. & Wong, C. -H. Toward automated synthesis of oligosaccharides and glycoproteins. Science 291, 2344–2350 (2001).

    CAS  PubMed  Google Scholar 

  8. Wess, G. How to escape the bottleneck of medicinal chemistry. Drug Discov. Today 7, 533–535 (2002).

    PubMed  Google Scholar 

  9. Auld, D. S. et al. Targeting signal transduction with large scale combinatorial collections. Drug Discov. Today 7, 1206–1213 (2002).

    CAS  PubMed  Google Scholar 

  10. Hughes, D. Therapeutic antibodies make a comeback. Drug Discov. Today 3, 439–442 (1998).

    Google Scholar 

  11. Kohler, G. & Milstein, C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256, 495–497 (1975).

    CAS  PubMed  Google Scholar 

  12. To, A. et al. Monoclonal antibodies: present and future. Credit Suisse First Boston Corporation (2000).

    Google Scholar 

  13. Schmeck, Jr, H. M. Gene studies emerging as key engine of science. The New York Times (September 6, 1988).

    Google Scholar 

  14. Debouck, C. & Metcalf, C. The impact of genomics on drug discovery. Annu. Rev. Pharmacol. Toxicol. 40, 193–208 (2000).

    CAS  PubMed  Google Scholar 

  15. Zambrowicz, B. P. & Sands, A. T. Knockouts model the 100 best-selling drugs — will they model the next 100? Nature Rev. Drug. Discov. 2, 38–51 (2003).

    CAS  Google Scholar 

  16. Schmitt, C. A. & Lowe, S. W. Apoptosis and chemoresistance in transgenic animal models. J. Mol. Med. 80, 137–146 (2002).

    CAS  PubMed  Google Scholar 

  17. De Angelis, F. G. et al. Chimeric snRNA molecules carrying antisense sequences against the splice junctions of exon 51 of the dystrophin pre-mRNA induce exon skipping and restoration of a dystrophin synthesis in Δ 48–50 DMD cells. Proc. Natl Acad. Sci. USA 99, 9456–9461 (2002).

    PubMed  PubMed Central  Google Scholar 

  18. Specter, M. Computer is drug design's new mortar and pestle. Washington Post (December 17, 1988).

    Google Scholar 

  19. Whittaker, M. et al. Design and therapeutic application of matrix metalloproteinase inhibitors. Chem. Rev. 99, 2735–2776 (1999).

    CAS  PubMed  Google Scholar 

  20. Lipinski, C. A. Drug-like properties and the causes of poor solubility and poor permeability. J. Pharmacol. Toxicol. Methods 44, 235–249 (2000).

    CAS  PubMed  Google Scholar 

  21. Bemis, G. W. & Murcko, M. A. Properties of known drugs. 1. Molecular frameworks. J. Med. Chem. 39, 2887–2893, (1996).

    CAS  PubMed  Google Scholar 

  22. Golub, T. R. et al. Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 286, 531–537 (1999).

    CAS  PubMed  Google Scholar 

  23. Scherf, U. et al. A gene expression database for the molecular pharmacology of cancer. Nature Genet. 24, 236–244 (2000).

    CAS  PubMed  Google Scholar 

  24. Kodadek, T. Protein microarrays: prospects and problems. Chem. Biol. 8, 105–115 (2001).

    CAS  PubMed  Google Scholar 

  25. Gerhold, D. L. et al. Better therapeutics through microarrays. Nature Genet. 32, 547–551 (2002).

    CAS  PubMed  Google Scholar 

  26. Hodgson, J. ADMET — turning chemicals into drugs. Nature Biotechnol. 19, 722–726 (2001).

    CAS  Google Scholar 

  27. Ekins, S. & Rose, J. In silico ADME/Tox: the state of the art. J. Mol. Graph. Model 20, 305–309 (2002).

    CAS  PubMed  Google Scholar 

  28. Schmitt, C. A. & Lowe, S. W. Apoptosis and chemoresistance in transgenic animal models. J. Mol. Med. 80, 137–146 (2002).

    CAS  PubMed  Google Scholar 

  29. Zhang, J. et al. Modulation of acetaminophen-induced hepatotoxicity by the xenobiotic receptor CAR. Science 298, 422–424 (2002).

    CAS  PubMed  Google Scholar 

  30. Tarbit, M. H. & Berman, J. High-throughput approaches for evaluating absorption, distribution, metabolism and excretion properties of lead compounds. Curr. Opin. Chem. Biol. 2, 411–416 (1998).

    CAS  PubMed  Google Scholar 

  31. Lipinski, C. A. et al. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 23, 3–25 (1997).

    CAS  Google Scholar 

  32. Beresford, A. P. et al. The emerging importance of predictive ADME simulation in drug discovery. Drug Discov. Today 7, 109–116 (2002).

    CAS  PubMed  Google Scholar 

  33. Craigie, R. HIV integrase, a brief overview from chemistry to therapeutics. J. Biol. Chem. 276, 23213–23216 (2001).

    CAS  PubMed  Google Scholar 

  34. Klapholz, M. Emerging therapies in heart failure. Cardiol. Spec. Ed. 7, 71–74 (2001).

    Google Scholar 

  35. Michels, D. A. et al. Fully automated two-dimensional capillary electrophoresis for high sensitivity protein analysis. Mol. Cell. Proteomics 1, 69–74 (2002).

    CAS  PubMed  Google Scholar 

  36. Perkel, J. M. Tissue microarrays: advancing clinical genomics. The Scientist 21, 39 (2002).

    Google Scholar 

  37. Cornish, V. & Tao, H. Y. Milestones in directed enzyme evolution. Curr. Opin. Chem. Biol. 6, 858–864 (2002).

    PubMed  Google Scholar 

  38. James, W. Nucleic acid and polypeptide aptamers: a powerful approach to ligand discovery. Curr. Opin. Pharmacol. 1, 540–546 (2001).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors wish to acknowledge helpful discussions with the associate consultants and advisors of AGW BioStrategy.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Leland J. Gershell.

Related links

Related links

DATABASES

Cancer.gov

Non-Hodgkin's lymphoma

LocusLink

P38 MAP kinase

Online Mendelian Inheritance in Man

Asthma

Congestive heart failure

FURTHER INFORMATION

5Z.com

Bio.com

The National health Museum

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gershell, L., Atkins, J. A brief history of novel drug discovery technologies. Nat Rev Drug Discov 2, 321–327 (2003). https://doi.org/10.1038/nrd1064

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrd1064

This article is cited by

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