title: Modelling of compound combination effects and applications to efficacy and toxicity: state-of-the-art, challenges and perspectives.
abstract: 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.
authors.affiliation: Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. Electronic address: kcb27@cam.ac.uk.
authors.forename: Krishna C
authors.initials: KC
authors.lastname: Bulusu
authors.affiliation: 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.
authors.forename: Rajarshi
authors.initials: R
authors.lastname: Guha
authors.affiliation: Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Mason
authors.affiliation: Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
authors.forename: Richard P I
authors.initials: RP
authors.lastname: Lewis
authors.affiliation: Laboratory for Molecular Modeling, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Muratov
authors.affiliation: Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
authors.forename: Yasaman
authors.initials: Y
authors.lastname: Kalantar Motamedi
authors.affiliation: Faculty of Engineering and Natural Sciences, Sabanci University, Tuzla, 34956 Istanbul, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Cokol
authors.affiliation: Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. Electronic address: ab454@cam.ac.uk.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bender
mesh_terms: D000818:Animals; D004338:Drug Combinations; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D015870:Gene Expression; D006801:Humans; D008954:Models, Biological; D012313:RNA / Q000235:genetics
chemical_list: D004338:Drug Combinations; D012313:RNA