Structure-based lead identification of ATP-competitive MK2 inhibitors

Bioorg Med Chem Lett. 2011 Jun 15;21(12):3818-22. doi: 10.1016/j.bmcl.2011.04.018. Epub 2011 Apr 16.

Abstract

MK2 kinase is a promising drug discovery target for the treatment of inflammatory diseases. Here, we describe the discovery of novel MK2 inhibitors using X-ray crystallography and structure-based drug design. The lead has in vivo efficacy in a short-term preclinical model.

MeSH terms

  • Adenosine Triphosphate* / chemistry
  • Animals
  • Binding, Competitive
  • Caco-2 Cells
  • Crystallography, X-Ray
  • Disease Models, Animal
  • Drug Design*
  • Humans
  • Inhibitory Concentration 50
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors*
  • Intracellular Signaling Peptides and Proteins / chemistry
  • Models, Molecular
  • Molecular Structure
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein Serine-Threonine Kinases / chemistry
  • Rats
  • Structure-Activity Relationship

Substances

  • Intracellular Signaling Peptides and Proteins
  • Protein Kinase Inhibitors
  • Adenosine Triphosphate
  • MAP-kinase-activated kinase 2
  • Protein Serine-Threonine Kinases