Rational Design of Highly Potent, Selective, and Bioavailable SGK1 Protein Kinase Inhibitors for the Treatment of Osteoarthritis.
Animals
Arthritis, Experimental
/ drug therapy
Disease Models, Animal
Immediate-Early Proteins
/ antagonists & inhibitors
Ligands
Male
Mice
Mice, Inbred C57BL
Microsomes, Liver
/ drug effects
Osteoarthritis
/ drug therapy
Protein Kinase Inhibitors
/ chemistry
Protein Serine-Threonine Kinases
/ antagonists & inhibitors
Pyrimidines
/ chemistry
Rats
Rats, Sprague-Dawley
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:
27 01 2022
27 01 2022
Historique:
pubmed:
22
12
2021
medline:
9
2
2022
entrez:
21
12
2021
Statut:
ppublish
Résumé
The serine/threonine kinase SGK1 is an activator of the β-catenin pathway and a powerful stimulator of cartilage degradation that is found to be upregulated under genomic control in diseased osteoarthritic cartilage. Today, no oral disease-modifying treatments are available and chronic treatment in this indication sets high requirements for the drug selectivity, pharmacokinetic, and safety profile. We describe the identification of a highly selective druglike 1
Identifiants
pubmed: 34931844
doi: 10.1021/acs.jmedchem.1c01601
doi:
Substances chimiques
Immediate-Early Proteins
0
Ligands
0
Protein Kinase Inhibitors
0
Pyrimidines
0
Protein Serine-Threonine Kinases
EC 2.7.11.1
serum-glucocorticoid regulated kinase
EC 2.7.11.1
pyrimidine
K8CXK5Q32L
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM