Improving the efficacy-safety balance of polypharmacology in multi-target drug discovery

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dc.contributor.author Ravikumar, Balaguru
dc.contributor.author Aittokallio, Tero
dc.date.accessioned 2020-12-01T14:00:01Z
dc.date.available 2020-12-01T14:00:01Z
dc.date.issued 2018
dc.identifier.citation Ravikumar , B & Aittokallio , T 2018 , ' Improving the efficacy-safety balance of polypharmacology in multi-target drug discovery ' , Expert opinion on drug discovery , vol. 13 , no. 2 , pp. 179-192 . https://doi.org/10.1080/17460441.2018.1413089
dc.identifier.other PURE: 95142072
dc.identifier.other PURE UUID: f221930a-29f9-445a-a91d-4d3d725a0bcd
dc.identifier.other Bibtex: urn:456764bf1c9803eba166989d220e7dff
dc.identifier.other WOS: 000427055800007
dc.identifier.other Scopus: 85041192581
dc.identifier.other ORCID: /0000-0002-0886-9769/work/41626140
dc.identifier.other ORCID: /0000-0003-0500-533X/work/53827466
dc.identifier.uri http://hdl.handle.net/10138/322247
dc.description.abstract Introduction: Polypharmacology has emerged as an essential paradigm for modern drug discovery process. Multiple lines of evidence suggest that agents capable of modulating multiple targets in a selective manner may offer also improved balance between therapeutic efficacy and safety compared to single-targeted agents. Areas covered: Herein, the authors review the recent progress made in experimental and computational strategies for addressing the critical challenges with rational discovery of selective multi-targeted agents within the context of polypharmacological modelling. Specific focus is placed on multi-targeted mono-therapies, although examples of combinatorial polytherapies are also covered as an important part of the polypharmacology paradigm. The authors focus mainly on anti-cancer treatment applications, where polypharmacology is playing a key role in determining the efficacy-toxicity trade-off of multi-targeting strategies. Expert opinion: Even though it is widely appreciated that complex polypharmacological interactions can contribute both to therapeutic and adverse side-effects, systematic approaches for improving this balance by means of integrated experimental-computational strategies are still lacking. Future developments will be needed for comprehensive collection and harmonization of systems-wide target selectivity data, enabling better utilization and control for multi-targeted activities in the drug development process. Additional areas of future developments include model-based strategies for drug combination screening and improved pre-clinical validation options with animal models. en
dc.format.extent 14
dc.language.iso eng
dc.relation.ispartof Expert opinion on drug discovery
dc.rights unspecified
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject 317 Pharmacy
dc.subject 3111 Biomedicine
dc.subject Polypharmacology
dc.subject efficacy-toxicity ratio
dc.subject drug repositioning
dc.subject multi-target drug design
dc.subject profiling strategies
dc.subject screening libraries
dc.subject drug combination therapies
dc.subject computational models
dc.subject data resources
dc.subject web-tools
dc.subject TARGET INTERACTION NETWORKS
dc.subject PROTEIN INVERSE DOCKING
dc.subject LIGAND-BINDING-SITES
dc.subject SIDE-EFFECT TARGETS
dc.subject DE-NOVO DESIGN
dc.subject WEB SERVER
dc.subject COMPUTATIONAL METHODS
dc.subject KINASE INHIBITOR
dc.subject SMALL-MOLECULE
dc.subject CANCER-CELLS
dc.title Improving the efficacy-safety balance of polypharmacology in multi-target drug discovery en
dc.type Review Article
dc.contributor.organization Institute for Molecular Medicine Finland
dc.contributor.organization University of Helsinki
dc.contributor.organization Tero Aittokallio / Principal Investigator
dc.contributor.organization Bioinformatics
dc.contributor.organization Computational Systems Medicine
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1080/17460441.2018.1413089
dc.relation.issn 1746-0441
dc.rights.accesslevel openAccess
dc.type.version acceptedVersion

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