Pharmacophore modeling and virtual screening for novel acidic inhibitors of microsomal prostaglandin E₂ synthase-1 (mPGES-1).

ABSTRACT: Microsomal prostaglandin E(2) synthase-1 (mPGES-1) catalyzes prostaglandin E(2) formation and is considered as a potential anti-inflammatory pharmacological target. To identify novel chemical scaffolds active on this enzyme, two pharmacophore models for acidic mPGES-1 inhibitors were developed and theoretically validated using information on mPGES-1 inhibitors from literature. The models were used to screen chemical databases supplied from the National Cancer Institute (NCI) and the Specs. Out of 29 compounds selected for biological evaluation, nine chemically diverse compounds caused concentration-dependent inhibition of mPGES-1 activity in a cell-free assay with IC(50) values between 0.4 and 7.9 μM, respectively. Further pharmacological characterization revealed that also 5-lipoxygenase

SUBMITTER: Waltenberger B 

PROVIDER: S-EPMC3088311 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature