Modulation of cofilin phosphorylation by inhibition of the Lim family kinases

作者：He Liqi^*; Seitz Steven P; Trainor George L; Tortolani David; Vaccaro Wayne; Poss Michael; Tarby Christine M; Tokarski John S; Penhallow Becky; Hung Chen Yi; Attar Ricardo; Lin Tai An

来源：Bioorganic & Medicinal Chemistry Letters, 2012, 22(18): 5995-5998.

DOI：10.1016/j.bmcl.2012.07.002

• LIMK1
• LIMK2
• Cofilin phosphorylation
• Actin cytoskeleton

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.

• 出版日期2012-9-15