title: Nonacidic inhibitors of human microsomal prostaglandin synthase 1 (mPGES 1) identified by a multistep virtual screening protocol.
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.
authors.affiliation: Institute of Organic Chemistry and Chemical Biology, Johann Wolfgang Goethe University, LiFF/ZAFES, Siesmayer Strasse 70 B, D-60323 Frankfurt/Main, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Rörsch
authors.forename: Ivonne
authors.initials: I
authors.lastname: Wobst
authors.forename: Heiko
authors.initials: H
authors.lastname: Zettl
authors.forename: Manfred
authors.initials: M
authors.lastname: Schubert-Zsilavecz
authors.forename: Sabine
authors.initials: S
authors.lastname: Grösch
authors.forename: Gerd
authors.initials: G
authors.lastname: Geisslinger
authors.forename: Gisbert
authors.initials: G
authors.lastname: Schneider
authors.forename: Ewgenij
authors.initials: E
authors.lastname: Proschak
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003198:Computer Simulation; D051545:Cyclooxygenase 1 / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000187:drug effects; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors*; D008861:Microsomes / Q000201:enzymology; D000071876:Prostaglandin-E Synthases
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases