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dc.contributor.authorHughes, Rebecca E.
dc.contributor.authorNikolic, Katarina
dc.contributor.authorRamsay, Rona Ruth
dc.date.accessioned2016-04-26T10:30:03Z
dc.date.available2016-04-26T10:30:03Z
dc.date.issued2016-04-25
dc.identifier.citationHughes , R E , Nikolic , K & Ramsay , R R 2016 , ' One For All? Hitting multiple Alzheimer’s Disease targets with one drug ' , Frontiers in Neuroscience , vol. 10 , 177 . https://doi.org/10.3389/fnins.2016.00177en
dc.identifier.issn1662-453X
dc.identifier.otherPURE: 241962569
dc.identifier.otherPURE UUID: c944ecd6-e5a9-4abe-8dfa-3b22ffdfba38
dc.identifier.otherScopus: 84966377266
dc.identifier.otherWOS: 000374817000002
dc.identifier.urihttp://hdl.handle.net/10023/8677
dc.descriptionThe authors thank the participants in COST Action CM1103 “Structure-based drug design for diagnosis and treatment of neurological diseases: dissecting and modulating complex function in the monoaminergic systems of the brain” for productive collaborations and COST for funding open access publication.en
dc.description.abstractAlzheimer’s Disease is a complex and multifactorial disease for which the mechanism is still not fully understood. As new insights into disease progression are discovered, new drugs must be designed to target those aspects of the disease that cause neuronal damage rather than just the symptoms currently addressed by single target drugs. It is becoming possible to target several aspects of the disease pathology at once using multi-target drugs. Intended as a introduction for non-experts, this review describes the key multi-target drug design approaches, namely structure-based, in silico, and data-mining, to evaluate what is preventing compounds progressing through the clinic to the market. Repurposing current drugs using their off-target effects reduces the cost of development, time to launch, and the uncertainty associated with safety and pharmacokinetics. The most promising drugs currently being investigated for repurposing to Alzheimer’s Disease are rasagiline, originally developed for the treatment of Parkinson’s Disease, and liraglutide, an antidiabetic. Rational drug design can combine pharmacophores of multiple drugs, systematically change functional groups, and rank them by virtual screening. Hits confirmed experimentally are rationally modified to generate an effective multi-potent lead compound. Examples from this approach are ASS234 with properties similar to rasagiline, and donecopride, a hybrid of an acetylcholinesterase inhibitor and a 5-HT4 receptor agonist with pro-cognitive effects. Exploiting these interdisciplinary approaches, public-private collaborative lead factories promise faster delivery of new drugs to the clinic.
dc.format.extent10
dc.language.isoeng
dc.relation.ispartofFrontiers in Neuroscienceen
dc.rightsCopyright © 2016 Hughes, Nikolic and Ramsay. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.en
dc.subjectMulti-target drugsen
dc.subjectAlzheimer’s Diseaseen
dc.subjectIn silicoen
dc.subjectDataminingen
dc.subjectRational drug designen
dc.subjectRepurposingen
dc.subjectRB Pathologyen
dc.subjectRM Therapeutics. Pharmacologyen
dc.subjectChemistry (miscellaneous)en
dc.subject.lccRBen
dc.subject.lccRMen
dc.titleOne For All? Hitting multiple Alzheimer’s Disease targets with one drugen
dc.typeJournal itemen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Biologyen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.identifier.doihttps://doi.org/10.3389/fnins.2016.00177
dc.description.statusPeer revieweden


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