Abstract
Two relatively recent trends have become apparent in current early stage drug discovery settings: firstly, a revival of phenotypic screening strategies and secondly, the increasing acceptance that some drugs work by modulating multiple targets in parallel (‘multi-target drugs’).
Highlights
Two trends are apparent in current early-stage drug discovery settings, firstly a revival of phenotypic screening strategies [1], and secondly the increasing acceptance that drugs modulate multiple targets in parallel (‘multi-target drugs’) [2].The work presented here combines those aspects by integrating experimental phenotypic screening for cytotoxic compounds with an experimental validation of individual protein targets modulated by the compounds
In silico target predictions for a dataset comprising cytotoxic compounds showed an enrichment of crucial enzymes for the cell cycle and for the defense against xenobiotics
* Correspondence: ab454@cam.ac.uk; adrianvc@unizar.es 1Institute of Biocomputation and Physics of Complex Systems (BIFI), Unidad Asociada IQFR-CSIC-BIFI, and Department of Biochemistry and Molecular and Cellular Biology, Universidad de Zaragoza, Zaragoza, Spain 2Unilever Centre for Molecular Science Informatics, Chemistry Department, University of Cambridge, Cambridge CB2 1EW, UK Full list of author information is available at the end of the article
Summary
Two trends are apparent in current early-stage drug discovery settings, firstly a revival of phenotypic screening strategies [1], and secondly the increasing acceptance that drugs modulate multiple targets in parallel (‘multi-target drugs’) [2].The work presented here combines those aspects by integrating experimental phenotypic screening for cytotoxic compounds with an experimental validation of individual protein targets modulated by the compounds. In silico target predictions for a dataset comprising cytotoxic compounds showed an enrichment of crucial enzymes for the cell cycle (such as Topoisomerase I, Bcl-X and protein kinase C alpha) and for the defense against xenobiotics (such as P-gp 1 and CYP450 enzymes).
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