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dc.contributor.authorHudson, Len_US
dc.contributor.authorMui, Jen_US
dc.contributor.authorVázquez, Sen_US
dc.contributor.authorCarvalho, DMen_US
dc.contributor.authorWilliams, Een_US
dc.contributor.authorJones, Cen_US
dc.contributor.authorBullock, ANen_US
dc.contributor.authorHoelder, Sen_US
dc.date.accessioned2020-11-17T11:09:15Z
dc.date.issued2018-08-07en_US
dc.identifier.citationJournal of medicinal chemistry, 2018, 61 (16), pp. 7261 - 7272en_US
dc.identifier.issn0022-2623en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4232
dc.identifier.eissn1520-4804en_US
dc.identifier.doi10.1021/acs.jmedchem.8b00782en_US
dc.description.abstractStructure-activity relationship and crystallographic data revealed that quinazolinone-containing fragments flip between two distinct modes of binding to activin receptor-like kinase-2 (ALK2). We explored both binding modes to discover potent inhibitors and characterized the chemical modifications that triggered the flip in binding mode. We report kinase selectivity and demonstrate that compounds of this series modulate ALK2 in cancer cells. These inhibitors are attractive starting points for the discovery of more advanced ALK2 inhibitors.en_US
dc.formatPrint-Electronicen_US
dc.format.extent7261 - 7272en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectCell Lineen_US
dc.subjectHumansen_US
dc.subjectActivin Receptors, Type Ien_US
dc.subjectProtein Kinase Inhibitorsen_US
dc.subjectCrystallography, X-Rayen_US
dc.subjectDrug Evaluation, Preclinicalen_US
dc.subjectStructure-Activity Relationshipen_US
dc.subjectDose-Response Relationship, Drugen_US
dc.subjectQuinazolinonesen_US
dc.titleNovel Quinazolinone Inhibitors of ALK2 Flip between Alternate Binding Modes: Structure-Activity Relationship, Structural Characterization, Kinase Profiling, and Cellular Proof of Concept.en_US
dc.typeJournal Article
rioxxterms.versionofrecord10.1021/acs.jmedchem.8b00782en_US
rioxxterms.licenseref.startdate2018-08-07en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfJournal of medicinal chemistryen_US
pubs.issue16en_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/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Glioma Team
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicinal Chemistry 4 (including Analytical Chemistry)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Glioma Team
pubs.publication-statusPublisheden_US
pubs.volume61en_US
pubs.embargo.termsNot knownen_US
icr.researchteamMedicinal Chemistry 4 (including Analytical Chemistry)en_US
icr.researchteamGlioma Teamen_US
dc.contributor.icrauthorJones, Chrisen_US
dc.contributor.icrauthorHoelder, Swenen_US


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