# A highly selective mPGES-1 inhibitor to block abdominal aortic aneurysm progression in the angiotensin mouse model

## TL;DR

A new drug that blocks a specific enzyme can stop the growth of a deadly aortic artery condition in mice, offering hope for future treatments.

## Contribution

First demonstration that a highly selective mPGES-1 inhibitor can block AAA progression in a mouse model.

## Key findings

- UK4b, a selective mPGES-1 inhibitor, completely blocked AAA progression in ApoE−/− angiotensin II mice.
- The results suggest mPGES-1 inhibition could be a viable treatment for AAA.
- This study highlights the translational potential of targeting mPGES-1 in clinical settings.

## Abstract

Abdominal aortic aneurysm (AAA) is a deadly, permanent ballooning of the aortic artery. Pharmacological and genetic studies have pointed to multiple proteins, including microsomal prostaglandin E2 synthase-1 (mPGES-1), as potentially promising targets. However, it remains unknown whether administration of an mPGES-1 inhibitor can effectively attenuate AAA progression in animal models. There are still no FDA-approved pharmacological treatments for AAA. Current research stresses the importance of both anti-inflammatory drug targets and rigor of translatability. Notably, mPGES-1 is an inducible enzyme responsible for overproduction of prostaglandin E2 (PGE2)—a well-known principal pro-inflammatory prostanoid. Here we demonstrate for the first time that a highly selective mPGES-1 inhibitor (UK4b) can completely block further growth of AAA in the ApoE−/− angiotensin (Ang)II mouse model. Our findings show promise for the use of a mPGES-1 inhibitor like UK4b as interventional treatment of AAA and its potential translation into the clinical setting.