31
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Genome-wide assessment of the carriers involved in the cellular uptake of drugs: a model system in yeast

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          The uptake of drugs into cells has traditionally been considered to be predominantly via passive diffusion through the bilayer portion of the cell membrane. The recent recognition that drug uptake is mostly carrier-mediated raises the question of which drugs use which carriers.

          Results

          To answer this, we have constructed a chemical genomics platform built upon the yeast gene deletion collection, using competition experiments in batch fermenters and robotic automation of cytotoxicity screens, including protection by 'natural' substrates. Using these, we tested 26 different drugs and identified the carriers required for 18 of the drugs to gain entry into yeast cells.

          Conclusions

          As well as providing a useful platform technology, these results further substantiate the notion that the cellular uptake of pharmaceutical drugs normally occurs via carrier-mediated transport and indicates that establishing the identity and tissue distribution of such carriers should be a major consideration in the design of safe and effective drugs.

          Related collections

          Author and article information

          Journal
          BMC Biol
          BMC Biology
          BioMed Central
          1741-7007
          2011
          24 October 2011
          : 9
          : 70
          Affiliations
          [1 ]School of Chemistry, University of Manchester, Oxford Road, Manchester, M13 9PL, UK
          [2 ]Manchester Interdisciplinary Biocentre, 131 Princess Street, Manchester, M1 7DN, UK
          [3 ]Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK
          [4 ]Cambridge Systems Biology Centre and Department of Biochemistry, University of Cambridge, Sanger Building, 80 Tennis Court Road, Cambridge, CB2 1GA, UK
          Article
          1741-7007-9-70
          10.1186/1741-7007-9-70
          3280192
          22023736
          3fac171c-3077-443c-ae61-7e5bf09e0c50
          Copyright ©2011 Lanthaler et al; licensee BioMed Central Ltd.

          This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

          History
          : 29 April 2011
          : 24 October 2011
          Categories
          Research Article

          Life sciences
          Life sciences

          Comments

          Comment on this article