423169-68-0

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 F_1α production . Oral or topical pretreatment with SC-57461A before challenge with arachidonic acid blocks ear edema in mice.

White Solid

A potent and selective orally active leukotriene A4 hydrolase inhibitor.

Potent and selective inhibitor of LTA 4 hydrolase. Does not inhibit other enzymes of the arachidonic acid cascade including COX-1, COX-2, LTC 4 synthase and 5-lipoxygenase. Potently inhibits LTB 4 production in whole blood (IC 50 = 49 nM). Orally active.

[1] THOMAS D. PENNING. Synthesis of Potent Leukotriene A4 Hydrolase Inhibitors. Identification of 3-[Methyl[3-[4-(phenylmethyl)phenoxy]propyl]amino]propanoic Acid[J]. Journal of Medicinal Chemistry, 2002, 45 16: 3482-3490. DOI: 10.1021/jm0200916
[2] KACHUR J, ASKONAS L J, VILLANI-PRICE D, et al. Pharmacological characterization of SC-57461A (3-[methyl[3-[4-(phenylmethyl)phenoxy]propyl]amino]propanoic acid HCl), a potent and selective inhibitor of leukotriene A(4) hydrolase II: in vivo studies.[J]. The Journal of Pharmacology and Experimental Therapeutics, 2002, 20 1: 0. DOI: 10.1124/jpet.300.2.583
[3] KACHUR J, ASKONAS L J, VILLANI-PRICE D, et al. Pharmacological characterization of SC-57461A (3-[methyl[3-[4-(phenylmethyl)phenoxy]propyl]amino]propanoic acid HCl), a potent and selective inhibitor of leukotriene A(4) hydrolase II: in vivo studies.[J]. The Journal of Pharmacology and Experimental Therapeutics, 2002, 20 1: 0. DOI: 10.1124/jpet.300.2.583