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dc.contributor.authorBenek, O.es_ES
dc.contributor.authorPérez Fernández, Daniel Ignacioes_ES
dc.contributor.authorPérez, Concepciónes_ES
dc.contributor.authorMartínez, Anaes_ES
dc.contributor.authorMusilek, Kamiles_ES
dc.identifier.citationJ Enzyme Inhib Med Chem 33(1):665-670 (2018)es_ES
dc.description6 p.-2 fig.-2 tab. Benek, O. et al.es_ES
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.es_ES
dc.description.sponsorshipThis 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.es_ES
dc.publisherInforma Healthcarees_ES
dc.relation.isversionofPublisher's versiones_ES
dc.subjectAlzheimer’s diseasees_ES
dc.subjectAmyloid-beta binding alcohol dehydrogenase (ABAD)es_ES
dc.subjectCasein kinase 1 (CK1)es_ES
dc.title1-(Benzo[d]thiazol-2-yl)-3-phenylureas as dual inhibitors of casein kinase 1 and ABAD enzymes for treatment of neurodegenerative disorderses_ES
dc.description.peerreviewedPeer reviewedes_ES
dc.contributor.funderNational Institute of Mental Health (Czech Republic)es_ES
dc.contributor.funderUniversity of Hradec Královées_ES
dc.contributor.funderRosetrees Trustes_ES
dc.contributor.funderBiotechnology and Biological Sciences Research Council (UK)es_ES
dc.contributor.funderMinisterio de Economía y Competitividad (España)es_ES
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