Biological characterization of new inhibitors of microsomal PGE synthase-1 in preclinical models of inflammation and vascular tone.

ABSTRACT:

Background and purpose

Microsomal PGE synthase-1 (mPGES-1), the inducible synthase that catalyses the terminal step in PGE₂ biosynthesis, is of high interest as therapeutic target to treat inflammation. Inhibition of mPGES-1 is suggested to be safer than traditional NSAIDs, and recent data demonstrate anti-constrictive effects on vascular tone, indicating new therapeutic opportunities. However, there is a lack of potent mPGES-1 inhibitors lacking interspecies differences for conducting in vivo studies in relevant preclinical disease models.

Experimental approach

Potency was determined based on the reduction of PGE₂ formation in recombinant enzyme assays, cellular assay, human whole blood assay, and air pouch mouse model. Anti-inflammatory properties wer

SUBMITTER: Larsson K 

PROVIDER: S-EPMC6965680 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature