Diflapolin is a dual inhibitor of 5-lipoxygenase-activating protein (FLAP) and soluble epoxide hydrolase (sEH). It inhibits formation of the 5-lipoxygenase (5-LO) products leukotriene B4 and 5-HpETE in isolated human monocytes and neutrophils (IC50s = 30 and 170 nM, respectively) and inhibits the epoxide hydrolase activity of sEH with an IC50 value of 20 nM in a cell-free assay. It is selective for FLAP and sEH over other arachidonic acid metabolism enzymes, including 5-LO, LTC4 synthase, mPGES-1, COX-1, or COX-2 in cell-free assays, as well as 12- and 15-LO in neutrophils. Diflapolin (1, 3, and 10 mg/kg) decreases inflammation in a mouse model of peritonitis induced by zymosan, reducing the production of LTB4 and LTC4 and inhibiting leukocyte recruitment.

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