Discovery and optimization of a novel series of Dyrk1B kinase inhibitors to explore a MEK resistance hypothesis

J Med Chem. 2015 Mar 26;58(6):2834-44. doi: 10.1021/acs.jmedchem.5b00098. Epub 2015 Mar 12.

Abstract

Potent and selective inhibitors of Dyrk1B kinase were developed to explore the hypothesis, based on siRNA studies, that Dyrk1B may be a resistance mechanism in cells undergoing a stress response.

MeSH terms

  • Animals
  • COS Cells
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Drug Discovery
  • Drug Resistance
  • Dyrk Kinases
  • Humans
  • MAP Kinase Kinase Kinases / antagonists & inhibitors
  • MAP Kinase Kinase Kinases / metabolism
  • Models, Molecular
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein Serine-Threonine Kinases / chemistry
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / chemistry
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Rats, Wistar

Substances

  • Protein Kinase Inhibitors
  • RNA, Small Interfering
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
  • MAP Kinase Kinase Kinases