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dc.contributor.authorBenek, Ondrej
dc.contributor.authorHroch, Lukas
dc.contributor.authorAitken, Laura
dc.contributor.authorGunn-Moore, Frank
dc.contributor.authorVinklarova, Lucie
dc.contributor.authorKuca, Kamil
dc.contributor.authorPerez, Daniel I.
dc.contributor.authorPerez, Concepcion
dc.contributor.authorMartinez, Ana
dc.contributor.authorFisar, Zdenek
dc.contributor.authorMusilek, Kamil
dc.date.accessioned2018-03-15T15:30:06Z
dc.date.available2018-03-15T15:30:06Z
dc.date.issued2018
dc.identifier.citationBenek , O , Hroch , L , Aitken , L , Gunn-Moore , F , Vinklarova , L , Kuca , K , Perez , D I , Perez , C , Martinez , A , Fisar , Z & Musilek , K 2018 , ' 1-(Benzo[ d ]thiazol-2-yl)-3-phenylureas as dual inhibitors of casein kinase 1 and ABAD enzymes for treatment of neurodegenerative disorders ' , Journal of Enzyme Inhibition and Medicinal Chemistry , vol. 33 , no. 1 , pp. 665-670 . https://doi.org/10.1080/14756366.2018.1445736en
dc.identifier.issn1475-6374
dc.identifier.otherPURE: 252361017
dc.identifier.otherPURE UUID: 12905e86-7042-4e1a-b5a4-4c77d180fa46
dc.identifier.otherScopus: 85044043186
dc.identifier.otherORCID: /0000-0003-3422-3387/work/42734886
dc.identifier.otherORCID: /0000-0001-7259-4491/work/42734893
dc.identifier.otherWOS: 000427559700001
dc.identifier.urihttp://hdl.handle.net/10023/12954
dc.descriptionThis work was supported by the Ministry of Health of the Czech Republic [no. NV15-28967 A], Specific Research Project of Faculty of Science, University of Hradec Kralove [no. 2103-2017], National Institute of Mental Health [NIMH CZ; no. ED2.1.00/03.0078] from the European Regional Development Fund, COST CA15135, The Alzheimer’s Society (specifically The Barcopel Foundation), The Rosetrees trust and The Biotechnology and Biological Sciences Research Council (BBSRC) [no. BB/J01446X/1]. Funding from Ministry of Economy and competitiveness, Spain [no. SAF2012-37979-C03-01] is also acknowledged.en
dc.description.abstractSeveral neurodegenerative disorders including Alzheimer’s disease (AD) have been connected with deregulation of casein kinase 1 (CK1) activity. Inhibition of CK1 therefore presents a potential therapeutic strategy against such pathologies. Recently, novel class of CK1-specific inhibitors with N-(benzo[d]thiazol-2-yl)-2-phenylacetamide structural scaffold has been discovered. 1-(benzo[d]thiazol-2-yl)-3-phenylureas, on the other hand, are known inhibitors amyloid-beta binding alcohol dehydrogenase (ABAD), an enzyme also involved in pathophysiology of AD. Based on their tight structural similarity, we decided to evaluate series of previously published benzothiazolylphenylureas, originally designed as ABAD inhibitors, for their inhibitory activity towards CK1. Several compounds were found to be submicromolar CK1 inhibitors. Moreover, two compounds were found to inhibit both, ABAD and CK1. Such dual-activity could be of advantage for AD treatment, as it would simultaneously target two distinct pathological processes involved in disease’s progression. Based on PAMPA testing both compounds were suggested to permeate the blood-brain barrier, which makes them, together with their unique dual activity, interesting lead compounds for further development.
dc.format.extent6
dc.language.isoeng
dc.relation.ispartofJournal of Enzyme Inhibition and Medicinal Chemistryen
dc.rights© 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en
dc.subjectAlzheimer's diseaseen
dc.subjectAmyloid-beta binding alcohol dehydrogenase (ABAD)en
dc.subjectBenzothiazoleen
dc.subjectCasein kinase 1 (CK1)en
dc.subjectNeurodegenerationen
dc.subjectRC0321 Neuroscience. Biological psychiatry. Neuropsychiatryen
dc.subjectQD Chemistryen
dc.subjectQH301 Biologyen
dc.subjectNDASen
dc.subject.lccRC0321en
dc.subject.lccQDen
dc.subject.lccQH301en
dc.title1-(Benzo[d]thiazol-2-yl)-3-phenylureas as dual inhibitors of casein kinase 1 and ABAD enzymes for treatment of neurodegenerative disordersen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Biologyen
dc.contributor.institutionUniversity of St Andrews.Institute of Behavioural and Neural Sciencesen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.identifier.doihttps://doi.org/10.1080/14756366.2018.1445736
dc.description.statusPeer revieweden


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