@article{c6f38a14d48f42208d0c20d12fdabdcd,
title = "Genome-wide assessment of the carriers involved in the cellular uptake of drugs: A model system in yeast",
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. {\textcopyright} 2011 Lanthaler et al; licensee BioMed Central Ltd.",
author = "Karin Lanthaler and Elizabeth Bilsland and Dobson, {Paul D.} and Moss, {Harry J.} and Pinar Pir and Kell, {Douglas B.} and Oliver, {Stephen G.}",
note = "The authors wish to thank Drs Phil Jeffrey and Scott Summerfield from GlaxoSmithKline (GSK) for many useful discussions; Mr Bharat Rash for the TAG4 hybridization; the Developmental Therapeutics Program Drug Discovery and Development Resources and National Institutes of Health Intramural Program (http://dtp.nci.nih.gov/about/irp.html) for providing the Mechanistic and Diversity drug sets; and the Biotechnology and BiologicalSciences Research Council (BBSRC; BB/D007747/1; BB/F008228/1) and GSK for funding. HJM thanks the BBSRC for a Research Experience Placement (REP/2011/44) in the Cambridge Laboratory. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This is a contribution from the Manchester Centre for Integrative Systems Biology (http://www.mcisb.org) and the Cambridge Systems Biology Centre (http:/www.sysbiol.cam.ac.uk).",
year = "2011",
month = oct,
day = "24",
doi = "10.1186/1741-7007-9-70",
language = "English",
volume = "9",
journal = "BMC Biology",
issn = "1741-7007",
publisher = "Springer Nature",
}
