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dc.contributor.authorSalla, Men_US
dc.contributor.authorAguayo-Ortiz, Ren_US
dc.contributor.authorDanmaliki, GIen_US
dc.contributor.authorZare, Aen_US
dc.contributor.authorSaid, Aen_US
dc.contributor.authorMoore, Jen_US
dc.contributor.authorPandya, Ven_US
dc.contributor.authorManaloor, Ren_US
dc.contributor.authorFong, Sen_US
dc.contributor.authorBlankstein, ARen_US
dc.contributor.authorGibson, SBen_US
dc.contributor.authorGarcia, LRen_US
dc.contributor.authorMeier, Pen_US
dc.contributor.authorBhullar, KSen_US
dc.contributor.authorHubbard, BPen_US
dc.contributor.authorFiteh, Yen_US
dc.contributor.authorVliagoftis, Hen_US
dc.contributor.authorGoping, ISen_US
dc.contributor.authorBrocks, Den_US
dc.contributor.authorHwang, Pen_US
dc.contributor.authorVelázquez-Martínez, CAen_US
dc.contributor.authorBaksh, Sen_US
dc.coverage.spatialUnited Statesen_US
dc.date.accessioned2019-03-05T10:51:47Z
dc.date.issued2018-05en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/29555876en_US
dc.identifierjpet.117.247163en_US
dc.identifier.citationJ Pharmacol Exp Ther, 2018, 365 (2), pp. 354 - 367en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3133
dc.identifier.eissn1521-0103en_US
dc.identifier.doi10.1124/jpet.117.247163en_US
dc.description.abstractReceptor-interacting protein kinase 2 (RIP2 or RICK, herein referred to as RIPK2) is linked to the pathogen pathway that activates nuclear factor κ-light-chain-enhancer of activated B cells (NFκB) and autophagic activation. Using molecular modeling (docking) and chemoinformatics analyses, we used the RIPK2/ponatinib crystal structure and searched in chemical databases for small molecules exerting binding interactions similar to those exerted by ponatinib. The identified RIPK2 inhibitors potently inhibited the proliferation of cancer cells by > 70% and also inhibited NFκB activity. More importantly, in vivo inhibition of intestinal and lung inflammation rodent models suggests effectiveness to resolve inflammation with low toxicity to the animals. Thus, our identified RIPK2 inhibitor may offer possible therapeutic control of inflammation in diseases such as inflammatory bowel disease, asthma, cystic fibrosis, primary sclerosing cholangitis, and pancreatitis.en_US
dc.format.extent354 - 367en_US
dc.languageengen_US
dc.language.isoengen_US
dc.subjectApoptosisen_US
dc.subjectCatalytic Domainen_US
dc.subjectCell Cycle Checkpointsen_US
dc.subjectCell Line, Tumoren_US
dc.subjectCell Proliferationen_US
dc.subjectColitis, Ulcerativeen_US
dc.subjectDrug Discoveryen_US
dc.subjectHumansen_US
dc.subjectMitochondriaen_US
dc.subjectMolecular Docking Simulationen_US
dc.subjectNF-kappa Ben_US
dc.subjectProtein Kinase Inhibitorsen_US
dc.subjectReceptor-Interacting Protein Serine-Threonine Kinase 2en_US
dc.titleIdentification and Characterization of Novel Receptor-Interacting Serine/Threonine-Protein Kinase 2 Inhibitors Using Structural Similarity Analysis.en_US
dc.typeJournal Article
dcterms.dateAccepted2018-02-26en_US
rioxxterms.versionofrecord10.1124/jpet.117.247163en_US
rioxxterms.licenseref.startdate2018-05en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfJ Pharmacol Exp Theren_US
pubs.issue2en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Cell Death and Inflammation
pubs.publication-statusPublisheden_US
pubs.volume365en_US
pubs.embargo.termsNot knownen_US
icr.researchteamCell Death and Inflammationen_US
dc.contributor.icrauthorMeier, Pascalen_US


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