Pharmacological Characterization of the Microsomal Prostaglandin E₂ Synthase-1 Inhibitor AF3485 In Vitro and In Vivo.

ABSTRACT:

Rationale

The development of inhibitors of microsomal prostaglandin (PG)E₂ synthase-1 (mPGES-1) was driven by the promise of attaining antiinflammatory agents with a safe cardiovascular profile because of the possible diversion of the accumulated substrate, PGH₂, towards prostacyclin (PGI₂).

Objectives

We studied the effect of the human mPGES-1 inhibitor, AF3485 (a benzamide derivative) on prostanoid biosynthesis in human whole blood in vitro. To characterize possible off-target effects of the compound, we evaluated: i)the impact of its administration on the systemic biosynthesis of prostanoids in a model of complete Freund's adjuvant (CFA)-induced monoarthritis in rats; ii) the effects on cyclooxygenase (COX)-2 expression and the bios

SUBMITTER: Di Francesco L 

PROVIDER: S-EPMC7147323 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature