Discovery and Optimization of 2-Arylquinazolin-4-ones into a Potent and Selective Tankyrase Inhibitor Modulating Wnt Pathway Activity.
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:
12 09 2019
12 09 2019
Historique:
pubmed:
6
8
2019
medline:
1
7
2020
entrez:
6
8
2019
Statut:
ppublish
Résumé
Tankyrases 1 and 2 (TNKS1/2) are promising pharmacological targets that recently gained interest for anticancer therapy in Wnt pathway dependent tumors. 2-Aryl-quinazolinones were identified and optimized into potent tankyrase inhibitors through SAR exploration around the quinazolinone core and the 4'-position of the phenyl residue. These efforts were supported by analysis of TNKS X-ray and WaterMap structures and resulted in compound
Identifiants
pubmed: 31381853
doi: 10.1021/acs.jmedchem.9b00656
doi:
Substances chimiques
Enzyme Inhibitors
0
Quinazolines
0
arylquinazolin-4-one
0
TNKS2 protein, human
EC 2.4.2.30
Tankyrases
EC 2.4.2.30
TNKS protein, human
EC 2.4.4.30
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM