Discovery and structure activity relationship study of novel indazole amide inhibitors for extracellular signal-regulated kinase1/2 (ERK1/2)

Bioorg Med Chem Lett. 2016 Jun 1;26(11):2600-4. doi: 10.1016/j.bmcl.2016.04.029. Epub 2016 Apr 12.

Abstract

The discovery and optimization of a series of indazole amide based extracellular signal-regulated kinase inhibitors via structure/knowledge based drug design and kinase screen is reported. The optimized compounds demonstrate potent inhibition of ERK1/2 enzyme activity, growth of BRAF mutant HT29 cells and ERK signaling in HT29 cells.

Keywords: ERK1/2 kinase inhibitor; Indazole amide; Structure based drug design.

MeSH terms

  • Amides
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • HT29 Cells
  • Humans
  • Indazoles
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Models, Molecular
  • Molecular Structure
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Structure-Activity Relationship

Substances

  • Amides
  • Indazoles
  • Protein Kinase Inhibitors
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3