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Discovery of a Novel, Isothiazolonaphthoquinone-Based Small Molecule Activator of FOXO Nuclear-Cytoplasmic Shuttling

dc.contributor.authorCautain, Bastien
dc.contributor.authorCastillo, Francisco
dc.contributor.authorMusso, Loana
dc.contributor.authorFerreira, Bibiana I.
dc.contributor.authorde Pedro, Nuria
dc.contributor.authorQuesada, Lorena Rodriguez
dc.contributor.authorMachado, Susana
dc.contributor.authorVicente, Francisca
dc.contributor.authorDallavalle, Sabrina
dc.contributor.authorLink, Wolfgang
dc.contributor.authoraffiliation[Cautain, Bastien] Fdn MEDINA, Parque Tecnol Ciencias Salud, Granada, Spain
dc.contributor.authoraffiliation[Castillo, Francisco] Fdn MEDINA, Parque Tecnol Ciencias Salud, Granada, Spain
dc.contributor.authoraffiliation[de Pedro, Nuria] Fdn MEDINA, Parque Tecnol Ciencias Salud, Granada, Spain
dc.contributor.authoraffiliation[Quesada, Lorena Rodriguez] Fdn MEDINA, Parque Tecnol Ciencias Salud, Granada, Spain
dc.contributor.authoraffiliation[Vicente, Francisca] Fdn MEDINA, Parque Tecnol Ciencias Salud, Granada, Spain
dc.contributor.authoraffiliation[Musso, Loana] Univ Milan, DeFENS Dept Food Environm & Nutr Sci, I-20122 Milan, Italy
dc.contributor.authoraffiliation[Dallavalle, Sabrina] Univ Milan, DeFENS Dept Food Environm & Nutr Sci, I-20122 Milan, Italy
dc.contributor.authoraffiliation[Ferreira, Bibiana I.] Ctr Biomed Res CBMR, Gambelas Campus, Faro, Portugal
dc.contributor.authoraffiliation[Machado, Susana] Ctr Biomed Res CBMR, Gambelas Campus, Faro, Portugal
dc.contributor.authoraffiliation[Link, Wolfgang] Ctr Biomed Res CBMR, Gambelas Campus, Faro, Portugal
dc.contributor.authoraffiliation[Ferreira, Bibiana I.] Univ Algarve, Dept Biomed Sci & Med, Regenerat Med Program, Campus Gambelas, Faro, Portugal
dc.contributor.authoraffiliation[Link, Wolfgang] Univ Algarve, Dept Biomed Sci & Med, Regenerat Med Program, Campus Gambelas, Faro, Portugal
dc.contributor.funderFundacao para a Ciencia e a Tecnologia (FCT) Research Center
dc.contributor.funderFCT
dc.contributor.funderProRegem grant
dc.date.accessioned2023-02-12T02:22:21Z
dc.date.available2023-02-12T02:22:21Z
dc.date.issued2016-12-09
dc.description.abstractFOXO factors are tumour suppressor proteins commonly inactivated in human tumours by posttranslational modifications. Furthermore, genetic variation within the FOXO3a gene is consistently associated with human longevity. Therefore, the pharmacological activation of FOXO proteins is considered as an attractive therapeutic approach to treat cancer and age-related diseases. In order to identify agents capable of activating FOXOs, we tested a collection of small chemical compounds using image-based high content screening technology. Here, we report the discovery of LOM612 (compound 1a), a newly synthesized isothiazolonaphthoquinone as a potent FOXO relocator. Compound 1a induces nuclear translocation of a FOXO3a reporter protein as well as endogenous FOXO3a and FOXO1 in U2OS cells in a dose-dependent manner. This activity does not affect the subcellular localization of other cellular proteins including NFkB or inhibit CRM1-mediated nuclear export. Furthermore, compound 1a shows a potent antiproliferative effect in human cancer cell lines.
dc.identifier.doi10.1371/journal.pone.0167491
dc.identifier.issn1932-6203
dc.identifier.unpaywallURLhttps://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0167491&type=printable
dc.identifier.urihttp://hdl.handle.net/10668/19166
dc.identifier.wosID389587100109
dc.issue.number12
dc.journal.titlePlos one
dc.journal.titleabbreviationPlos one
dc.language.isoen
dc.organizationFundación MEDINA (Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía)
dc.organizationFundación MEDINA
dc.publisherPublic library science
dc.rightsAttribution 4.0 International
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectForkhead transcription factor
dc.subjectDual-specificity phosphatase
dc.subjectCycloaddition reactions
dc.subjectNitrile sulfides
dc.subjectInhibitors
dc.subjectCancer
dc.subjectTranslocation
dc.subjectScreen
dc.subjectPotent
dc.subjectCells
dc.titleDiscovery of a Novel, Isothiazolonaphthoquinone-Based Small Molecule Activator of FOXO Nuclear-Cytoplasmic Shuttling
dc.typeresearch article
dc.type.hasVersionVoR
dc.volume.number11
dc.wostypeArticle
dspace.entity.typePublication

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