Inhibitors of the inducible microsomal prostaglandin E2 synthase (mPGES-1) derived from MK-886

Bioorg Med Chem Lett. 2005 Jul 15;15(14):3352-5. doi: 10.1016/j.bmcl.2005.05.027.


A series of potent and selective inhibitors of the inducible microsomal PGE2 synthase (mPGES-1) has been developed based on the indole FLAP inhibitor MK-886. Compounds 23 and 30 inhibit mPGES-1 with potencies in the low nanomolar range and with selectivities of at least 100-fold compared to their inhibition of mPGES-2, thromboxane synthase and binding affinity to FLAP. They also block the production of PGE2 in cell based assays but with a decreased potency and more limited selectivity compared to the enzyme assays.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclooxygenase Inhibitors / chemical synthesis*
  • Cyclooxygenase Inhibitors / chemistry
  • Cyclooxygenase Inhibitors / pharmacology*
  • Humans
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Intramolecular Oxidoreductases / antagonists & inhibitors*
  • Microsomes / enzymology
  • Prostaglandin-E Synthases
  • Structure-Activity Relationship


  • Cyclooxygenase Inhibitors
  • Indoles
  • MK-886
  • Intramolecular Oxidoreductases
  • PTGES protein, human
  • PTGES2 protein, human
  • Prostaglandin-E Synthases