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.