Structural Basis for Achieving GSK-3β Inhibition with High Potency, Selectivity, and Brain Exposure for Positron Emission Tomography Imaging and Drug Discovery.
Animals
Blood-Brain Barrier
/ metabolism
Brain
/ diagnostic imaging
Catalytic Domain
Drug Discovery
Glycogen Synthase Kinase 3 beta
/ antagonists & inhibitors
HEK293 Cells
Humans
Mice
Models, Molecular
Neuroimaging
Oxazoles
/ chemistry
Positron-Emission Tomography
/ methods
Protein Kinase Inhibitors
/ chemistry
Triazoles
/ chemistry
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
14 11 2019
14 11 2019
Historique:
pubmed:
20
9
2019
medline:
17
6
2020
entrez:
20
9
2019
Statut:
ppublish
Résumé
Using structure-guided design, several cell based assays, and microdosed positron emission tomography (PET) imaging, we identified a series of highly potent, selective, and brain-penetrant oxazole-4-carboxamide-based inhibitors of glycogen synthase kinase-3 (GSK-3). An isotopologue of our first-generation lead, [
Identifiants
pubmed: 31535859
doi: 10.1021/acs.jmedchem.9b01030
pmc: PMC6883410
mid: NIHMS1059284
doi:
Substances chimiques
Oxazoles
0
PF-04802367
0
Protein Kinase Inhibitors
0
Triazoles
0
Glycogen Synthase Kinase 3 beta
EC 2.7.11.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
9600-9617Subventions
Organisme : NIA NIH HHS
ID : R01 AG054473
Pays : United States
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