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dc.contributor.authorLain, Sonia
dc.contributor.authorHollick, Jonathan J.
dc.contributor.authorCampbell, Johanna
dc.contributor.authorStaples, Oliver D.
dc.contributor.authorHiggins, Maureen
dc.contributor.authorAoubala, Mustapha
dc.contributor.authorMcCarthy, Anna
dc.contributor.authorAppleyard, Virginia
dc.contributor.authorMurray, Karen E.
dc.contributor.authorBaker, Lee
dc.contributor.authorThompson, Alastair
dc.contributor.authorMathers, Joanne
dc.contributor.authorHolland, Stephen J.
dc.contributor.authorStark, Michael J. R.
dc.contributor.authorPass, Georgia
dc.contributor.authorWoods, Julie
dc.contributor.authorLane, David P.
dc.contributor.authorWestwood, Nicholas J.
dc.date.accessioned2012-06-26T14:31:02Z
dc.date.available2012-06-26T14:31:02Z
dc.date.issued2008-05-06
dc.identifier.citationLain , S , Hollick , J J , Campbell , J , Staples , O D , Higgins , M , Aoubala , M , McCarthy , A , Appleyard , V , Murray , K E , Baker , L , Thompson , A , Mathers , J , Holland , S J , Stark , M J R , Pass , G , Woods , J , Lane , D P & Westwood , N J 2008 , ' Discovery, in vivo activity, and mechanism of action of a small-molecule p53 activator ' , Cancer Cell , vol. 13 , no. 5 , pp. 454-463 . https://doi.org/10.1016/j.ccr.2008.03.004en
dc.identifier.issn1535-6108
dc.identifier.otherPURE: 614308
dc.identifier.otherPURE UUID: 22ce04ad-78b2-4bf7-8d20-439473572cfe
dc.identifier.otherWOS: 000255569000011
dc.identifier.otherScopus: 42949114938
dc.identifier.otherORCID: /0000-0003-0630-0138/work/56424128
dc.identifier.urihttp://hdl.handle.net/10023/2845
dc.description.abstractWe have carried out a cell-based screen aimed at discovering small molecules that activate p53 and have the potential to decrease tumor growth. Here, we describe one of our hit compounds, tenovin-1, along with a more water-soluble analog, tenovin-6. Via a yeast genetic screen, biochemical assays, and target validation studies in mammalian cells, we show that tenovins act through inhibition of the protein-deacetylating activities of SirT1 and SirT2, two important members of the sirtuin family. Tenovins are active on mammalian cells at one-digit micromolar concentrations and decrease tumor growth in vivo as single agents. This underscores the utility of these compounds as biological tools for the study of sirtuin function as well as their potential therapeutic interest.
dc.format.extent10
dc.language.isoeng
dc.relation.ispartofCancer Cellen
dc.rightsThis is an electronic version of an open access article, published by Cell Press at http://dx.doi.org/10.1016/j.ccr.2008.03.004. Readers are permitted to read, download, print out, extract, reuse, archive, translate and distribute the article provided the appropriate credit is given to the authors and source of the work.en
dc.subjectDNA-damageen
dc.subjectImmunochemical analysisen
dc.subjectCell-survivalen
dc.subjectMDM2en
dc.subjectSirtuinsen
dc.subjectDeacetylasesen
dc.subjectAcetylationen
dc.subjectInhibitorsen
dc.subjectEnzymesen
dc.subjectDiseaseen
dc.subjectRC0254 Neoplasms. Tumors. Oncology (including Cancer)en
dc.subjectQR180 Immunologyen
dc.subject.lccRC0254en
dc.subject.lccQR180en
dc.titleDiscovery, in vivo activity, and mechanism of action of a small-molecule p53 activatoren
dc.typeJournal articleen
dc.description.versionPostprinten
dc.contributor.institutionUniversity of St Andrews.School of Chemistryen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews.EaSTCHEMen
dc.identifier.doihttps://doi.org/10.1016/j.ccr.2008.03.004
dc.description.statusPeer revieweden
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=42949114938&partnerID=8YFLogxKen
dc.identifier.urlhttp://ukpmc.ac.uk/abstract/MED/18455128en


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