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Pure and Applied Chemistry

The Scientific Journal of IUPAC

Ed. by Burrows, Hugh / Stohner, Jürgen

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Volume 80, Issue 8


Personalizing protein-drug interactions

Natasha Beeton-Kempen
  • Corresponding author
  • Department of Molecular and Cell Biology, University of Cape Town, Rondebosch 7701, Cape Town, South Africa
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/ Aubrey Shoko
  • Corresponding author
  • Department of Molecular and Cell Biology, University of Cape Town, Rondebosch 7701, Cape Town, South Africa
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/ Jonathan Blackburn
  • Corresponding author
  • Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, Cape Town, South Africa
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Published Online: 2009-01-01 | DOI: https://doi.org/10.1351/pac200880081811

The development of new drugs today is a hugely expensive process, with estimated costs of up to $1 billion to take a drug through to market. However, despite this seemingly massive expenditure, statistics show that the great majority of prescription drugs on the market today are only effective for around 40 % of the patients to whom they are administered. Worse still, recently there have been a series of high-profile instances where potentially block-busting FDA-approved drugs have subsequently been withdrawn due to unanticipated side effects that were only revealed when the drug entered use in the general population. A variety of factors are at play in underpinning such statistics, but at the heart of the problem is the fact that, despite the extensive knowledge being generated in the postgenomic era about the genetic differences between individuals, Western medicine still today largely ignores such differences. The hope therefore is that by gaining a greater understanding of the individual nature of disease progression and of drug response, we might move toward a new era of personalized medicine in which the right drug is prescribed at the right dose to treat the precise disease afflicting the specific patient. As a step along this road, this review will discuss new approaches in the pharmacogenomics field to understanding in a quantitative manner the molecular consequence of polymorphic variation and mutation, both on encoded protein function and on protein-drug interactions.

Keywords: kinase; P450; p53; polymorphic variation; protein-drug interactions; proteomics


CHEM-BIO-TECH-2007, a joint meeting of the IUPAC 1st Symposium on Chemical Biotechnology (ISCB-1) and the 8th Symposium on Bioorganic Chemistry (ISBOC-8), International Symposium on Bioorganic Chemistry, ISBOC, Bioorganic Chemistry, Turin, Italy, 2007-08-08–2007-08-11


  • 1.

    J. Woodcock. Making Medical Products Better, Faster and Cheaper (<http://www.fda.gov/consumer/updates/criticalpath091007.html>) (2007).Google Scholar

  • 2.

    , C. T. Caskey. Annu. Rev. Med. 58, 1 (2007).CrossrefGoogle Scholar

  • 3.

    , L. J. Lesko, J. Woodcock. Nat. Rev. Drug Discov. 3, 763 (2004).CrossrefGoogle Scholar

  • 4.

    , J. R. Senior. Clin. Liver Dis. 11, 507 (2007).CrossrefGoogle Scholar

  • 5.

    , W. Sadee, Z. Dai. Hum. Mol. Genet. 14, R207 (2005).CrossrefGoogle Scholar

  • 6.

    , J. A. DiMasi, R. W. Hansen, H. G. Grabowski. J. Health Econ. 22, 151 (2003).CrossrefGoogle Scholar

  • 7.

    , J. F. Blake. Med. Chem. 1, 649 (2005).CrossrefGoogle Scholar

  • 8.

    Pharmaceutical Industry Profile 2005: <http://www.phrma.org>.Google Scholar

  • 9.

    C. Hodges. Paper for the 2nd Annual Cambridge Conference on Regulation, Inspection, and Improvement, Cambridge (2007).Google Scholar

  • 10.

    , R. W. Peck. Drug Discov. Today 12, 289 (2007).CrossrefGoogle Scholar

  • 11.

    FDA Critical Path Initiative Fact Sheet: <http://www.fda.gov/oc/initiatives/criticalpath/factsheet.html> (2007).Google Scholar

  • 12.

    , G. R. Wilkinson. N. Engl. J. Med. 352, 2211 (2005).CrossrefGoogle Scholar

  • 13.

    , C. Guzey, O. Spigset. Curr. Top. Med. Chem. 4, 1409 (2004).CrossrefGoogle Scholar

  • 14.

    , W. H. Koch. Nat. Rev. Drug Discov. 3, 749 (2004).CrossrefGoogle Scholar

  • 15.

    , H. L. McLeod. Clin. Infect. Dis. 41, S449 (2005).CrossrefGoogle Scholar

  • 16.

    dbSNP Database: <http://www.ncbi.nlm.nih.gov/projects/SNP/index.html>.Google Scholar

  • 17.

    , Biomarkers Definitions Working Group. Clin. Pharmacol. Ther. 69, 89 (2001).CrossrefGoogle Scholar

  • 18.

    European Union's Innovative Medicines Initiative: <http://www.imi-europe.org>.Google Scholar

  • 19.

    , J. M. Boutell, D. J. Hart, B. L. J Godber, R. Z. Kozlowski, J. M. Blackburn. Proteomics 4, 1950 (2004).CrossrefGoogle Scholar

  • 20.

    , J. M. Blackburn, D. J. Hart. "Fabrication of protein function microarrays for systems-oriented proteomic analysis", in Chemical Genomics: Reviews and Protocols, E. Zanders (Ed.), Chap. 14, Humana Press, Totowa, NJ (2005).CrossrefGoogle Scholar

  • 21.

    , G. Manning, D. B. White, R. Martinez, T. Hunter, S. Sudarsanam. Science 298, 1912 (2002).CrossrefGoogle Scholar

  • 22.

    , P. Cohen. Nat. Rev. Drug. Discov. 1, 309 (2002).CrossrefGoogle Scholar

  • 23.

    , M. A. Fabian, W. H. Biggs, D. K. Treiber, C. E. Atteridge, M. D. Azimioara, M. G. Benedetti, T. A. Carter, P. Ciceri, P. T. Edeen, M. Floyd, J. M. Ford, M. Galvin, J. L. Gerlach, R. M. Grotzfeld, S. Herrgard, D. E. Insko, M. A. Insko, A. G. Lai, J.-M. Lelias, S. A. Mehta, Z. V. Milanov, A. M. Velasco, L. M. Wodicka, H. K. Patel, P. P. Zarrinkar, D. J. Lockhart. Nat. Biotechnol. 23, 329 (2005).CrossrefGoogle Scholar

  • 24.

    S. Joyce, C. Wheeler, J. Blackburn, R. Fallon. Unpublished data.Google Scholar

  • 25.

    , M. Bantscheff, D. Eberhard, Y. Abraham, S. Bastuck, M. Boesche, S. Hobson, T. Mathieson, J. Perrin, M. Raida, C. Rau, V. Reader, G. Sweetman, A. Bauer, T. Bouwmeeester, C. Hopf, U. Kruse, G. Neubauer, N. Ramsden, J. Rick, B. Kuster, G. Drewes. Nat. Biotechnol. 25, 1035 (2007).CrossrefGoogle Scholar

  • 26.

    , C. B. Gambacorti-Passerini, R. H. Rosalind, R. Piazza, A. Galietta, R. Rostagno, L. Scapozza. Lancet Oncol. 4, 75 (2003).CrossrefGoogle Scholar

  • 27.

    , J. G. Paez, P. A. Janne, J. C. Lee, S. Tracy, H. Greulich, S. Gabriel, P. Herman, F. J. Kaye, N. Lindeman, T. J. Boggon, K. Naoki, H. Sasaki, Y. Fujii, M. J. Eck, W. R. Sellers, B. E. Johnson, M. Meyerson. Science 304, 1497 (2004).CrossrefGoogle Scholar

  • 28.

    , S. H. Yang, L. E. Mechanic, P. Yang, M. T Landi, E. D. Bowman, J. Wampfler, D. Meerzaman, K. M. Hong, F. Mann, T. Dracheva, J. Fukuoka, W. Travis, N. E. Caporaso, C. C. Harris, J. Jen. Clin. Cancer Res. 11, 2106 (2005).CrossrefGoogle Scholar

  • 29.

    , T. J. Lynch, D. W. Bell, R. Sordella, S. Gurubhagavatula, R. A. Okimoto, B. W. Brannigan, P. L. Harris, S. M. Haserlat, J. G. Supko, F. G. Haluska, D. N. Louis, D.C. Christiani, J. Settleman, D. A. Haber. N. Engl. J. Med. 351, 1260 (2004).CrossrefGoogle Scholar

  • 30.

    H. Shigematsu, L. Lin, T. Takahashi, M. Nomura, M. Suzuki, I. I. Wistuba, K. M. Fong, H. Lee, S. Toyooka, N. Shimizu, T. Fujisawa, Z. Feng, J. A. Roth, J. Herz, J. D. Minna, A. F. Gazdar. J. Natl. Cancer Inst. 97, 326 (2005).Google Scholar

  • 31.

    , P. B. Danielson. Curr. Drug Metab. 3, 561 (2002).CrossrefGoogle Scholar

  • 32.

    , F. P. Guengerich. Mol. Interv. 3, 194 (2003).CrossrefGoogle Scholar

  • 33.

    , M. Ingelman-Sundberg. Trends Pharmacol. Sci. 25, 193 (2004).CrossrefGoogle Scholar

  • 34.

    PharmGKB Database: <http://www.pharmgkb.org/>.Google Scholar

  • 35.

    , R. Delgoda, A. C. Westlake. Toxicol. Rev. 23, 239 (2004).CrossrefGoogle Scholar

  • 36.

    E. Mills, C. Cooper, D. Seely, I. Kanfer. Nutr. J. 31, 4 (2005).Google Scholar

  • 37.

    M. Ingelman-Sundberg. Drug Metab. Dispos. 29, 570 (2001).Google Scholar

  • 38.

    , T. Dervieux, B. Meshkin, B. Neri. Mutat. Res. 573, 180 (2005).CrossrefGoogle Scholar

  • 39.

    , F. J. Thomas, H. L. McLeod, J. W. Watters. Curr. Top. Med. Chem. 4, 1397 (2004).CrossrefGoogle Scholar

  • 40.

    , A. Fantuzzi, M. Fairhead, G. Gilardi. J. Am. Chem. Soc. 126, 5040 (2004).CrossrefGoogle Scholar

  • 41.

    M. Dyson, N. Bockett, D. J. Hart, B. Godber, R. Z. Kozlowski, J. M. Blackburn. PCT application no. PCT//IB03/05258, filed 16 September 2003.Google Scholar

  • 42.

    , M. Lee, C. B. Park, J. S. Dordick, D. S. Clark. Proc. Natl. Acad. Sci. USA 102, 983 (2005).CrossrefGoogle Scholar

  • 43.

    FDA Guidance for Industry: <http://www.fda.gov/cder/guidance/6400fnl.pdf> (2005).Google Scholar

  • 44.

    , A. Katnelson. Nat. Biotechnol. 23, 510 (2005).CrossrefGoogle Scholar

  • 45.

    FDA's critical path initiative-science enhancing the health and well-being of all Americans: <http://www.fda.gov/oc/initiatives/criticalpath/initiative.html> (2007).Google Scholar

About the article

Published Online: 2009-01-01

Published in Print: 2008-01-01

Citation Information: Pure and Applied Chemistry, Volume 80, Issue 8, Pages 1811–1820, ISSN (Online) 1365-3075, ISSN (Print) 0033-4545, DOI: https://doi.org/10.1351/pac200880081811.

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