dc.contributor.author | Hudson, L | |
dc.contributor.author | Mui, J | |
dc.contributor.author | Vázquez, S | |
dc.contributor.author | Carvalho, DM | |
dc.contributor.author | Williams, E | |
dc.contributor.author | Jones, C | |
dc.contributor.author | Bullock, AN | |
dc.contributor.author | Hoelder, S | |
dc.date.accessioned | 2020-11-17T11:09:15Z | |
dc.date.issued | 2018-08-23 | |
dc.identifier.citation | Journal of medicinal chemistry, 2018, 61 (16), pp. 7261 - 7272 | |
dc.identifier.issn | 0022-2623 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4232 | |
dc.identifier.eissn | 1520-4804 | |
dc.identifier.doi | 10.1021/acs.jmedchem.8b00782 | |
dc.description.abstract | Structure-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. | |
dc.format | Print-Electronic | |
dc.format.extent | 7261 - 7272 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER CHEMICAL SOC | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Cell Line | |
dc.subject | Humans | |
dc.subject | Activin Receptors, Type I | |
dc.subject | Protein Kinase Inhibitors | |
dc.subject | Crystallography, X-Ray | |
dc.subject | Drug Evaluation, Preclinical | |
dc.subject | Structure-Activity Relationship | |
dc.subject | Dose-Response Relationship, Drug | |
dc.subject | Quinazolinones | |
dc.title | Novel Quinazolinone Inhibitors of ALK2 Flip between Alternate Binding Modes: Structure-Activity Relationship, Structural Characterization, Kinase Profiling, and Cellular Proof of Concept. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-08-07 | |
rioxxterms.versionofrecord | 10.1021/acs.jmedchem.8b00782 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2018-08-07 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Journal of medicinal chemistry | |
pubs.issue | 16 | |
pubs.notes | Not known | |
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.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-status | Published | |
pubs.volume | 61 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Medicinal Chemistry 4 (including Analytical Chemistry) | |
icr.researchteam | Glioma Team | |
dc.contributor.icrauthor | Jones, Chris | |
dc.contributor.icrauthor | Hoelder, Swen | |