The discovery of carboline analogs as potent MAPKAP-K2 inhibitors

Bioorg Med Chem Lett. 2007 Aug 15;17(16):4664-9. doi: 10.1016/j.bmcl.2007.05.101. Epub 2007 Jun 7.

Abstract

The discovery of a series of potent, carboline-based MK2 inhibitors is described. These compounds inhibit MK2 with IC50s as low as 10 nM, as measured in a DELFIA assay. An X-ray crystal structure reveals that they bind in a region near the p-loop and the hinge region of MK2a.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Carbolines / chemistry*
  • Carbolines / pharmacology*
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors*
  • Models, Molecular
  • Molecular Structure
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Carbolines
  • Intracellular Signaling Peptides and Proteins
  • MAP-kinase-activated kinase 2
  • Protein Serine-Threonine Kinases

Associated data

  • PDB/2PZY