Nonacidic inhibitors of human microsomal prostaglandin synthase 1 (mPGES 1) identified by a multistep virtual screening protocol

  • J Med Chem. 2010 Jan 28;53(2):911-5. doi: 10.1021/jm9012505.
Florian Rörsch  1 ,  Ivonne Wobst ,  Heiko Zettl ,  Manfred Schubert-Zsilavecz ,  Sabine Grösch ,  Gerd Geisslinger ,  Gisbert Schneider ,  Ewgenij Proschak
Affiliations
  • 1. Institute of Organic Chemistry and Chemical Biology, Johann Wolfgang Goethe University, LiFF/ZAFES, Siesmayer Strasse 70 B, D-60323 Frankfurt/Main, Germany.
PMID: 20025212 DOI: 10.1021/jm9012505
Abstract

Microsomal prostaglandin E(2)-synthase (mPGES-1) is a target for future anti-inflammatory drugs. Inhibitors of mPGES-1 mimicking prostaglandin E(2) often interact with cyclooxygenases (COXs) 1 and 2, leading to unwanted side effects. Selective inhibitors of mPGES-1 can be obtained by deliberate abdication of the acidic groups, which are an important feature of COX inhibition. Here, we present a successful virtual screening study that results in a potent nonacidic mPGES-1 inhibitor lacking COX inhibition.