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dc.creatorHughes, Rebecca E.
dc.creatorNikolić, Katarina
dc.creatorRamsay, Rona R.
dc.date.accessioned2019-09-02T11:52:04Z
dc.date.available2019-09-02T11:52:04Z
dc.date.issued2016
dc.identifier.issn1662-453X
dc.identifier.urihttp://farfar.pharmacy.bg.ac.rs/handle/123456789/2592
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 (MTDs). Intended as an introduction for non-experts, this review describes the key MID 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.en
dc.publisherFrontiers Media Sa, Lausanne
dc.relationEU COST Action CM 1103
dc.rightsopenAccess
dc.sourceFrontiers in Neuroscience
dc.titleOne for All? Hitting Multiple Alzheimer's Disease Targets with One Drugen
dc.typearticle
dc.rights.licenseBY
dcterms.abstractНиколић, Катарина; Рамсаy, Рона Р.; Хугхес, Ребецца Е.;
dc.citation.volume10
dc.citation.other10: -
dc.citation.rankM22
dc.identifier.wos000374817000002
dc.identifier.doi10.3389/fnins.2016.00177
dc.identifier.pmid27199640
dc.identifier.scopus2-s2.0-84966377266
dc.identifier.fulltexthttp://farfar.pharmacy.bg.ac.rs//bitstream/id/1269/2590.pdf
dc.identifier.rcubconv_3547
dc.type.versionpublishedVersion


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