Benzothiophene inhibitors of MK2. Part 2: improvements in kinase selectivity and cell potency

Bioorg Med Chem Lett. 2009 Aug 15;19(16):4882-4. doi: 10.1016/j.bmcl.2009.02.017. Epub 2009 Feb 8.

Abstract

Optimization of kinase selectivity for a set of benzothiophene MK2 inhibitors provided analogs with potencies of less than 500 nM in a cell based assay. The selectivity of the inhibitors can be rationalized by examination of X-ray crystal structures of inhibitors bound to MK2.

MeSH terms

  • Binding Sites
  • Cell Line, Tumor
  • Crystallography, X-Ray
  • Cyclin-Dependent Kinase 2 / antagonists & inhibitors
  • Cyclin-Dependent Kinase 2 / metabolism
  • Drug Design
  • Humans
  • MAP Kinase Kinase 2 / antagonists & inhibitors*
  • MAP Kinase Kinase 2 / metabolism
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology
  • Thiophenes / chemical synthesis
  • Thiophenes / chemistry*
  • Thiophenes / pharmacology

Substances

  • Protein Kinase Inhibitors
  • Thiophenes
  • benzothiophene
  • Cyclin-Dependent Kinase 2
  • MAP Kinase Kinase 2