4-Anilino-6-phenyl-quinoline inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK2)

Bioorg Med Chem Lett. 2010 Aug 15;20(16):4738-40. doi: 10.1016/j.bmcl.2010.06.107. Epub 2010 Jun 25.

Abstract

A class of inhibitors of mitogen activated protein kinase-activated kinase 2 (MK2) was discovered via high-throughput screening. This compound class demonstrates activity against the enzyme with sub-microM IC(50) values, and suppresses LPS-induced TNFalpha levels in THP-1 cells. MK2 inhibition kinetic measurements indicated mixed binding approaching non-ATP competitive inhibition.

MeSH terms

  • Aminoquinolines / chemical synthesis
  • Aminoquinolines / chemistry*
  • Aminoquinolines / pharmacology
  • Aniline Compounds / chemical synthesis
  • Aniline Compounds / chemistry*
  • Aniline Compounds / pharmacology
  • Cell Line
  • High-Throughput Screening Assays
  • Humans
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Kinetics
  • Lipopolysaccharides / pharmacology
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein Serine-Threonine Kinases / metabolism
  • Quinolines / chemical synthesis
  • Quinolines / chemistry*
  • Quinolines / pharmacology
  • Structure-Activity Relationship
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Aminoquinolines
  • Aniline Compounds
  • Intracellular Signaling Peptides and Proteins
  • Lipopolysaccharides
  • Protein Kinase Inhibitors
  • Quinolines
  • Tumor Necrosis Factor-alpha
  • quinoline
  • MAP-kinase-activated kinase 2
  • Protein Serine-Threonine Kinases