Identification and characterization of potent, selective and metabolically stable IKKß inhibitor.
Bioorg Med Chem Lett
; 26(4): 1120-3, 2016 Feb 15.
Article
in En
| MEDLINE
| ID: mdl-26826731
ABSTRACT
We have previously reported the identification of a rhodanine compound (1) with well-balanced inhibitory activity against IKKß and collagen-induced TNFα activated cells. However, we need more optimized compounds because of its instability over plasma and microsome. As part of a program directed toward the optimization of IKKß inhibitor, we modified a substituent of parent compound to a series of functional groups. Among substituted compounds, fluorine substituent (12) on the para position of phenyl ring restored the stability toward plasma and microsome while retaining inhibitory potency and selectivity against IKKß over other kinases. Also, we have demonstrated that compound 12 is an ATP non-competitive inhibitor and safe enough to apply to animal experiment from an acute toxicity test.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Protein Kinase Inhibitors
/
I-kappa B Kinase
Type of study:
Diagnostic_studies
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
En
Year:
2016
Type:
Article