Modelling of compound combination effects and applications to efficacy and toxicity: state-of-the-art, challenges and perspectives.

Autor: Bulusu KC; Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. Electronic address: kcb27@cam.ac.uk., Guha R; Division of Preclinical Innovation, National Institutes of Health Chemical Genomics Center, National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD 20580, USA., Mason DJ; Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK., Lewis RP; Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK., Muratov E; Laboratory for Molecular Modeling, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA., Kalantar Motamedi Y; Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK., Cokol M; Faculty of Engineering and Natural Sciences, Sabanci University, Tuzla, 34956 Istanbul, Turkey., Bender A; Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. Electronic address: ab454@cam.ac.uk.
Jazyk: angličtina
Zdroj: Drug discovery today [Drug Discov Today] 2016 Feb; Vol. 21 (2), pp. 225-38. Date of Electronic Publication: 2015 Sep 07.
DOI: 10.1016/j.drudis.2015.09.003
Abstrakt: The development of treatments involving combinations of drugs is a promising approach towards combating complex or multifactorial disorders. However, the large number of compound combinations that can be generated, even from small compound collections, means that exhaustive experimental testing is infeasible. The ability to predict the behaviour of compound combinations in biological systems, whittling down the number of combinations to be tested, is therefore crucial. Here, we review the current state-of-the-art in the field of compound combination modelling, with the aim to support the development of approaches that, as we hope, will finally lead to an integration of chemical with systems-level biological information for predicting the effect of chemical mixtures.
(Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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