Selective inhibitors of human mPGES-1 from structure-based computational screening

Bioorg Med Chem Lett. 2017 Aug 15;27(16):3739-3743. doi: 10.1016/j.bmcl.2017.06.075. Epub 2017 Jun 29.

Abstract

Human mPGES-1 is recognized as a promising target for next generation of anti-inflammatory drugs. Although various mPGES-1 inhibitors have been reported in literature, few have entered clinical trials and none has been proven clinically useful so far. It is highly desired for developing the next generation of therapeutics for inflammation-related diseases to design and discover novel inhibitors of mPGES-1 with new scaffolds. Here, we report the identification of a series of new, potent and selective inhibitors of human mPGES-1 with diverse scaffolds through combined computational and experimental studies. The computationally modeled binding structures of these new inhibitors of mPGES-1 provide some interesting clues for rational design of modified structures of the inhibitors to more favorably bind with mPGES-1.

Keywords: Inflammation; Inhibitor identification; Prostaglandin; Selective inhibitor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Prostaglandin-E Synthases / antagonists & inhibitors*
  • Prostaglandin-E Synthases / metabolism
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • PTGES protein, human
  • Prostaglandin-E Synthases