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dc.contributor.authorAitken, Laura
dc.contributor.authorBaillie, Gemma
dc.contributor.authorPannifer, Andrew
dc.contributor.authorMorrison, Angus
dc.contributor.authorJones, Philip S.
dc.contributor.authorSmith, Terry K.
dc.contributor.authorMcElroy, Stuart P.
dc.contributor.authorGunn-Moore, Frank J.
dc.date.accessioned2017-03-20T09:30:11Z
dc.date.available2017-03-20T09:30:11Z
dc.date.issued2017-07
dc.identifier.citationAitken , L , Baillie , G , Pannifer , A , Morrison , A , Jones , P S , Smith , T K , McElroy , S P & Gunn-Moore , F J 2017 , ' In vitro assay development and HTS of small molecule human ABAD/17β-HSD10 inhibitors as therapeutics in Alzheimer’s Disease ' SLAS Discovery , vol. 22 , no. 6 , pp. 676-685 . DOI: 10.1177/247255521769796en
dc.identifier.issn2472-5552
dc.identifier.otherPURE: 249348383
dc.identifier.otherPURE UUID: f45fb1de-6b41-4946-a0c2-881c536f6648
dc.identifier.urihttp://hdl.handle.net/10023/10493
dc.identifier.urihttp://journals.sagepub.com/doi/suppl/10.1177/2472555217697964en
dc.descriptionThis research was funded by the Scottish Universities Life Science Alliance (SULSA) assay development fund. This research was also kindly supported by The Rosetrees Trust and The Alzheimer’s Society, specifically The Barcopel Foundation, and partly funded by the MSD Scottish Life Sciences fund. As part of an ongoing contribution to Scottish life sciences, MSD Limited, a global health care leader, has given substantial monetary funding to the Scottish Funding Council for distribution via SULSA to develop and deliver a high-quality drug discovery research and training program.en
dc.description.abstractA major hallmark of Alzheimer’s disease (AD) is the formation of neurotoxic aggregates composed of the amyloid-β peptide (Aβ). Aβ has been recognized to interact with numerous proteins, resulting in pathological changes to the metabolism of patients with AD. One such mitochondrial metabolic enzyme is amyloid-binding alcohol dehydrogenase (ABAD), where altered enzyme function caused by the Aβ-ABAD interaction is known to cause mitochondrial distress and cytotoxic effects, providing a feasible therapeutic target for AD drug development. Here we have established a high-throughput screening platform for the identification of modulators to the ABAD enzyme. A pilot screen with a total of 6759 compounds from the NIH Clinical Collections (NCC) and SelleckChem libraries and a selection of compounds from the BioAscent diversity collection have allowed validation and robustness to be optimized. The pilot screen revealed 16 potential inhibitors in the low µM range against ABAD with favorable physicochemical properties for blood-brain barrier penetration.en
dc.format.extent11en
dc.language.isoeng
dc.relation.ispartofSLAS Discoveryen
dc.rights© 2017 Society for Laboratory Automation and Screening. 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 may differ slightly from the final published version. The final published version of this work is available at: https://doi.org/10.1177/247255521769796en
dc.subjectEnzyme assays or enzyme kineticsen
dc.subjectNeurodegenerative diseasesen
dc.subjectPharmacology: ligand bindingen
dc.subjectReceptor bindingen
dc.subjectUltra-high throughput screeningen
dc.subjectQH301 Biologyen
dc.subjectRC0321 Neuroscience. Biological psychiatry. Neuropsychiatryen
dc.subjectRM Therapeutics. Pharmacologyen
dc.subjectNDASen
dc.subject.lccQH301en
dc.subject.lccRC0321en
dc.subject.lccRMen
dc.titleIn vitro assay development and HTS of small molecule human ABAD/17β-HSD10 inhibitors as therapeutics in Alzheimer’s Diseaseen
dc.typeJournal articleen
dc.description.versionPostprinten
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews. Institute of Behavioural and Neural Sciencesen
dc.identifier.doihttps://doi.org/10.1177/247255521769796
dc.description.statusPeer revieweden


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