Nonsteroidal anti-inflammatory drugs (NSAIDs), including traditional NSAIDs and selective cyclooxygenase (COX)-2 inhibitors are widely prescribed medications for inflammatory indications, despite well-known side effects.
Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible enzyme downstream of the COX enzymes and is upregulated by inflammatory stimuli. It is therefore a superior target for the treatment of various conditions where inflammation is a component.
In-house research has revealed novel uses for mPGES-1 inhibitors in the treatment of conditions with an inflammatory component and represents an opportunity for development of new medicines for certain indications.
While NSAIDs have been associated with dose-limiting safety issues, including serious cardiovascular (CV) and gastrointestinal (GI) side effect, mPGES-1 inhibitors may in contrast exert a beneficial effect on vascular function.
Preclinical data support that the CV and GI side effects of the NSAIDs may be attributed to the suppression of COX-2-mediated prostacyclin (PGI2) synthesis. Therefore, agents that suppress synthesis of pro-inflammatory prostaglandin E2 without inhibition of PGI2 synthesis may achieve the efficacy of NSAIDs without the increased risk of complications. Inhibition of mPGES-1 may therefore represent a novel treatment option for inflammatory conditions, without the undesirable toxicities from the classical NSAIDs.