Abstract
A series of aminothiazoles that are potent inhibitors of LIM kinases 1 and 2 is described. Appropriate choice of substituents led to molecules with good selectivity for either enzyme. An advanced member of the series was shown to effectively interfere with the phosphorylation of the LIM kinases substrate cofilin. Consistent with the important role of the LIM kinases in regulating cytoskeletal structure, treated cells displayed dramatically reduced F-actin content.
Published by Elsevier Ltd.
MeSH terms
-
Actin Depolymerizing Factors / metabolism*
-
Cell Line
-
Crystallography, X-Ray
-
Dose-Response Relationship, Drug
-
Humans
-
Lim Kinases / antagonists & inhibitors*
-
Lim Kinases / metabolism
-
Models, Molecular
-
Molecular Structure
-
Phosphorylation / drug effects
-
Protein Kinase Inhibitors / chemical synthesis
-
Protein Kinase Inhibitors / chemistry
-
Protein Kinase Inhibitors / pharmacology*
-
Structure-Activity Relationship
-
Thiazoles / chemical synthesis
-
Thiazoles / chemistry
-
Thiazoles / pharmacology*
Substances
-
Actin Depolymerizing Factors
-
Protein Kinase Inhibitors
-
Thiazoles
-
LIMK1 protein, human
-
LIMK2 protein, human
-
Lim Kinases