Modulation of cofilin phosphorylation by inhibition of the Lim family kinases

  • Bioorg Med Chem Lett. 2012 Sep 15;22(18):5995-8. doi: 10.1016/j.bmcl.2012.07.002.
Liqi He  1 ,  Steven P Seitz ,  George L Trainor ,  David Tortolani ,  Wayne Vaccaro ,  Michael Poss ,  Christine M Tarby ,  John S Tokarski ,  Becky Penhallow ,  Chen-Yi Hung ,  Ricardo Attar ,  Tai-An Lin
Affiliations
  • 1. Oncology Chemistry, Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, USA. [email protected]
PMID: 22902653 DOI: 10.1016/j.bmcl.2012.07.002
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.