Leukotriene A4 (LTA4) hydrolase/aminopeptidase is a bifunctional zinc metalloenzyme that both catalyzes the synthesis of LTB4 from LTA4 and cleaves the chemotactic peptide Pro-Gly-Pro. SC-57461A is a potent, orally active inhibitor of LTA4 hydrolase that blocks ionophore-stimulated LTB4 synthesis in whole blood (IC50 = 49 nM). It blocks both the hydrolase and aminopeptidase activity in vitro. SC-57461A is without effect against other enzymes of the arachidonic acid cascade, including 5-lipoxygenase, LTC4 synthase, COX-1, and COX-2. In a rat model of ionophore-induced peritoneal eicosanoid production, SC-57461A inhibits LTB4 biosynthesis without affecting LTC4 or 6-keto prostaglandin F1α production . Oral or topical pretreatment with SC-57461A before challenge with arachidonic acid blocks ear edema in mice.
