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:

Getting physical to fix pharma

Nature Chemistry volume 3, pages 692–695 (2011)Cite this article

Subjects

Powerful technologies allow the synthesis and testing of large numbers of new compounds, but the failure rate of pharmaceutical R&D remains very high. Greater understanding of the fundamental physical chemical behaviour of molecules could be the key to greatly enhancing the success rate of drug discovery.

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

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

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

References

  1. http://pubs.acs.org/cen/coverstory/83/8325/8325intro.html

  2. Kuljis, J., Paul, R. J. & Stergioulas, L. K in Proceedings of the 2007 Winter Simulation Conference, Washington, DC (eds Henderson, S. G., Biller, B., Hsieh, M.-H., Shortle, J., Tew, J. D. & Barton, R. R.) 1449–1453 (Winter Simulation Conference Foundation, 2007).

    Book  Google Scholar 

  3. Paul, S. M. et al. Nature Rev. Drug Discov. 9, 203–14 (2010).

    Article  CAS  Google Scholar 

  4. Wyman, J. Proc. Natl Acad. Sci. USA 72, 1464–1468 (1975).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Chodera, J. D. et al. Curr. Opin. Struct. Biol. 21, 150–160 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Southall, N. T., Dill, K. A. & Haymet, A. D. J. J. Phys. Chem. B 106, 521–533 (2002).

    Article  CAS  Google Scholar 

  7. Lafont, V. et al. Chem. Biol. Drug. Des. 69, 413–422 (2007).

    Article  CAS  PubMed  Google Scholar 

  8. Whitesides, G. M., Snyder, P. W., Moustakas, D. T. & Mirica, K. A. in Physical Biology: From Atoms to Medicine (Zewail, A. H. ed.) Ch. 9 (Imperial College Press, 2008).

    Google Scholar 

  9. Connelly, P. R. et al. Proc. Natl Acad. Sci. USA 91, 1964–1968 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Zhou, H. X., Rivas, G. & Minton, A. P. Annu. Rev. Biophys. 37, 375–397 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Gierasch, L. & Gershenson, A. Nature Chem. Biol. 5, 774–777 (2009).

    Article  CAS  Google Scholar 

  12. Parsegian, V. A., Rand, R. P. & Rau, D. C. Proc. Natl Acad. Sci. USA 97, 3987–3992 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Darling, P. J., Holt, J. M. & Ackers, G. K. J. Mol. Biol. 302, 625–638 (2000).

    Article  CAS  PubMed  Google Scholar 

  14. Catterall, W. A. Neuron 67, 915–28 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Potashman, M. H. & Duggan, M. E. J. Med. Chem. 52, 1231–1246 (2009).

    Article  CAS  PubMed  Google Scholar 

  16. Kenakin, T., Jenkinson, S. & Watson, C. J. Pharmacol. Exp. Ther. 319, 710–723 (2006).

    Article  CAS  PubMed  Google Scholar 

  17. Zhao, J.-H. Persp. Med. Chem. 1, 39–48 (2007).

    CAS  Google Scholar 

  18. Kim, M. W., Chelliah, Y., Kim, S. W., Otwinowski, Z. & Bezprozvanny, I. Structure 17, 1205–1212 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lewis, H. A. et al. J. Mol. Biol. 396, 406–430 (2010).

    Article  CAS  PubMed  Google Scholar 

  20. Thomas, J. M. & Daugherty, P. S. Protein Sci. 18, 2053–2059 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kratz, F., Abu, A. K. & Warnecke, A. Expert Opin. Investig. Drugs 16, 1037–58 (2007).

    Article  CAS  PubMed  Google Scholar 

  22. Lu, J., Liong, M., Zink, J. I. & Tamanoi, F. Small 3, 1341–1346 (2007).

    Article  CAS  PubMed  Google Scholar 

  23. Tang, B. C. et al. Proc. Natl Acad. Sci. USA 106, 19268–19273 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Farokhzad, O. C. et al. Proc. Natl Acad. Sci. USA 103, 6315–6320 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Fernandes, R., Roy, V., Wu, H. C. & Bentley, W. E. Nature Nanotech. 5, 213–217 (2010).

    Article  CAS  Google Scholar 

  26. Gardner, C. R., Walsh, C. T. & Almarsson, O. Nature Rev. Drug Discov. 3, 926–934 (2004).

    Article  CAS  Google Scholar 

  27. Lu, J. & Rohani, S. Curr. Med. Chem. 16, 884–905 (2009).

    Article  CAS  PubMed  Google Scholar 

  28. Willart, J. F. & Descamps, M. Mol. Pharm. 5, 905–920 (2008).

    Article  CAS  PubMed  Google Scholar 

  29. Stark, W. J. Angew. Chem. Int. Ed. 50, 1242–1258 (2011).

    Article  CAS  Google Scholar 

  30. Angelova, A., Angelov, B., Mutafchieva, R., Lesieur, S. & Couvreur, P. Acc. Chem. Res. 44, 147–156 (2011).

    Article  CAS  PubMed  Google Scholar 

  31. Qian, F., Huang, J. & Hussain, M. A. J. Pharm. Sci. 99, 2941–2947 (2010).

    Article  CAS  PubMed  Google Scholar 

  32. Dobry, D. E. et al. J. Pharm. Innov. 4, 133–142 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  33. Bauer, J. et al. Pharm. Res. 18, 859–866

  34. Kaiser, J. Science 332, 523 (2011).

    Article  CAS  PubMed  Google Scholar 

  35. Connelly, P. R., Quinn, B. P., Hurter, P., Condon, J. & Mueller, P. Pharm. Outsourcing 11, 16 (2010).

    Google Scholar 

  36. Desiraju, G. R. Angew. Chem. Int. Ed. 46, 8342–8356 (2007).

    Article  CAS  Google Scholar 

  37. Andrew, J. P., DeRocco, E. S. & Taylor, A. The Innovation Imperative in Manufacturing (Boston Consulting Group, 2009); http://www.bcg.com/documents/file15445.pdf

    Google Scholar 

  38. Whitesides, G. M. Lab Chip 10, 2317–2318 (2010).

    Article  CAS  PubMed  Google Scholar 

  39. Armani, A. M., Kulkarni, R. P., Fraser, S. E., Flagan, R. C. & Vahala, K. J. Science 317, 783–787 (2007).

    Article  CAS  PubMed  Google Scholar 

  40. Mandal, S., Goddard, J. & Erickson, D. Lab Chip 9, 2924–2932 (2009).

    Article  CAS  PubMed  Google Scholar 

  41. Tian, R., Regonda, S., Gao, J., Liu, Y. & Hu, W. Lab Chip 11, 1952–1961 (2011).

    Article  CAS  PubMed  Google Scholar 

  42. Jin, M., Pully, V., Otto, C., van den Berg, A. & Carlen, E. T. J. Phys. Chem. C 114, 21953–21959 (2010).

    Article  CAS  Google Scholar 

  43. Chou, I. H. et al. Nano Lett. 8, 1729–1735 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  44. Choi, I., Huh, Y. S. & Erickson, D. Lab Chip 11, 632–638 (2011).

    Article  CAS  PubMed  Google Scholar 

  45. Ebbinghaus, S., Dhar, A., McDonald, D. & Gruebele, M. Nature Methods 7, 319–323 (2010).

    Article  CAS  PubMed  Google Scholar 

  46. Winslow, S. Georgetown Law Journal 98, 1891 (2010).

    Google Scholar 

  47. Zhou, W. et al. Nature 462, 1070–1074 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Mark Murcko is Chief Technology Officer at Vertex Pharmaceuticals, Cambridge, Massachusetts 02139, USA ,

    Mark A. Murcko

  2. Pat Connelly is Senior Director at Materials Discovery & Characterization, also at Vertex Pharmaceuticals, Cambridge, Massachusetts 02139, USA ,

    Patrick R. Connelly

  3. Minh Vuong is Senior Director, Instrumentation Research & Development, at Vertex Pharmaceuticals in San Diego, California, 92121, USA ,

    T. Minh Vuong

Authors
  1. Patrick R. Connelly
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. Minh Vuong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mark A. Murcko
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mark A. Murcko.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Connelly, P., Vuong, T. & Murcko, M. Getting physical to fix pharma. Nature Chem 3, 692–695 (2011). https://doi.org/10.1038/nchem.1121

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchem.1121

This article is cited by

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