Discovery of a new series of Aurora inhibitors through truncation of GSK1070916

Bioorg Med Chem Lett. 2010 Apr 15;20(8):2552-5. doi: 10.1016/j.bmcl.2010.02.091. Epub 2010 Mar 1.

Abstract

Novel Aurora inhibitors were identified truncating clinical candidate GSK1070916. Many of these truncated compounds retained potent activity against Aurora B with good antiproliferative activity. Mechanistic studies suggested that these compounds, depending on the substitution pattern, may or may not exert their antiproliferative effects via inhibition of Aurora B. The SAR results from this investigation will be presented with an emphasis on the impact structural changes have on the cellular phenotype.

MeSH terms

  • Aurora Kinase B
  • Aurora Kinases
  • Aza Compounds / chemistry*
  • Cell Line, Tumor
  • Drug Discovery
  • Flow Cytometry
  • Humans
  • Indoles / chemistry*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Aza Compounds
  • GSK 1070916
  • Indoles
  • Protein Kinase Inhibitors
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein Serine-Threonine Kinases