5-Lipoxygenase (5-LO) initiates the synthesis of leukotrienes (LTs) from arachidonic acid, primarily in certain leukocyte populations. CAY10606 is a potent, reversible inhibitor of 5-LO, both in cell-free assays (IC50 = 86 nM) and in intact neutrophils (IC50 = 230 nM). It prevents the production of LTs in whole blood, whether 5-LO is activated with the calcium ionophore A23187 (IC50 = 1.6 μM) or formyl peptide (fMLP) following priming with lipopolysaccharide (IC50 = 830 nM). In rats subjected to carrageenan-induced pleurisy, CAY10606 significantly reduces both LT biosynthesis and the inflammatory reaction.
