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dc.contributor.authorTulloch, Lindsay B.
dc.contributor.authorMenzies, Stefanie K.
dc.contributor.authorCoron, Ross P.
dc.contributor.authorRoberts, Matthew D.
dc.contributor.authorFlorence, Gordon J.
dc.contributor.authorSmith, Terry K.
dc.date.accessioned2018-12-06T00:48:28Z
dc.date.available2018-12-06T00:48:28Z
dc.date.issued2018-01
dc.identifier.citationTulloch , L B , Menzies , S K , Coron , R P , Roberts , M D , Florence , G J & Smith , T K 2018 , ' Direct and indirect approaches to identify drug modes of action ' , IUBMB Life , vol. 70 , no. 1 , pp. 9-22 . https://doi.org/10.1002/iub.1697en
dc.identifier.issn1521-6543
dc.identifier.otherPURE: 251715513
dc.identifier.otherPURE UUID: bf16bbe6-c295-406f-a178-f6ac36c78ce3
dc.identifier.otherPubMed: 29210173
dc.identifier.otherScopus: 85037659292
dc.identifier.otherWOS: 000418829100001
dc.identifier.urihttps://hdl.handle.net/10023/16633
dc.description© 2017 International Union of Biochemistry and Molecular Biology.en
dc.description.abstractPhenotypic assays are becoming increasingly more common among drug discovery practices, expanding drug target diversity as lead compounds identified through such screens are not limited to known targets. While increasing diversity is beneficial to the drug discovery process and the fight against disease, the unknown modes of action of new lead compounds can hamper drug discovery as, in most cases, the process of lead compound optimization is made difficult due to the unknown nature of the target; blindly changing substituents can prove fruitless due to the inexhaustible number of potential combinations, and it is therefore desirable to rapidly identify the targets of lead compounds developed through phenotypic screening. In addition, leads identified through target-based screening often have off-target effects that contribute towards drug toxicity, and by identifying those secondary targets, the drugs can be improved. However, the identification of a leads mode of action is far from trivial and now represents a major bottleneck in the drug discovery pipeline. This review looks at some of the recent developments in the identification of drug modes of action, focusing on phenotype-based methods using metabolomics, proteomics, transcriptomics, and genomics to detect changes in phenotype in response to the presence of the drug, and affinity-based methods using modified/unmodified drug as bait to capture and identify targets.
dc.language.isoeng
dc.relation.ispartofIUBMB Lifeen
dc.rights© 2017 International Union of Biochemistry and Molecular Biology. This work has been made available online in accordance with the publisher’s policies. This is the author created accepted version manuscript following peer review and as such may differ slightly from the final published version. The final published version of this work is available at https://doi.org/10.1002/iub.1697en
dc.subjectDrug mode of actionen
dc.subjectTarget IDen
dc.subjectGenomicsen
dc.subjectTranscriptomicsen
dc.subjectProteomicsen
dc.subjectMetabolomicsen
dc.subjectAffinity chromatographyen
dc.subjectPhoto-affinity labellingen
dc.subjectQH301 Biologyen
dc.subjectQD Chemistryen
dc.subjectRM Therapeutics. Pharmacologyen
dc.subject.lccQH301en
dc.subject.lccQDen
dc.subject.lccRMen
dc.titleDirect and indirect approaches to identify drug modes of actionen
dc.typeJournal itemen
dc.contributor.sponsorMedical Research Councilen
dc.description.versionPostprinten
dc.contributor.institutionUniversity of St Andrews. School of Chemistryen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews. EaSTCHEMen
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.identifier.doihttps://doi.org/10.1002/iub.1697
dc.description.statusPeer revieweden
dc.date.embargoedUntil2018-12-06
dc.identifier.grantnumberMR/M020118/1en


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