SC-57461A

SC-57461A is a potent, orally active, nonpeptide, and selective inhibitor of Leukotriene A4 (LTA4) hydrolase with IC50s of 2.5 nM, 3 nM, and 23 nM for recombinant human, mouse, and rat LTA4 hydrolase, respectively[1].

Signaling Pathways >> Metabolic Enzyme/Protease >> Aminopeptidase

Research Areas >> Inflammation/Immunology

SC-57461A inhibits ionophore-stimulated LTB4 production in whole blood with IC50s of 49, 166, and 466 nM in human mouse and rat, respectively[1].SC-57461A demonstrates excellent potency against LTA4 hydrolase (IC50=2.5 nM) and in whole cells (IC50=49 nM)[2]<

SC-57461A also shows excellent potency in the mouse ex vivo assay, inhibiting the production of LTB4 with an ED50=0.2 mg/kg and an ED90=1 mg/kg. SC-57461A also inhibits the production of LTB4 in the rat peritoneal model with an ED50=1 mg/kg[2]. SC-57461A is a potent, selective, and competitive inhibitor of LTA4 hydrolase with excellent activity in whole animals. SC-57461A demonstrates good oral activity in both the mouse and the rat[3]. Animal Model: Fasted CD rats[3] Dosage: 0.01, 0.1, 1, and 10 mg/kg Administration: Orally administered Result: The ED50 values were 0.2 mg/kg at 1.0 h and 0.8 mg/kg at 3.0 h. A single dose of 10 mg/kg blocked LTB4 production 79% at 6 h, 67% at 18 h, and 44% at 24 h.

[1]. Leslie J Askonas, 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 I: in vitro studies. J Pharmacol Exp Ther. 2002 Feb;300(2):577-82.

[2]. T D Penning. Inhibitors of leukotriene A4 (LTA4) hydrolase as potential anti-inflammatory agents. Curr Pharm Des. 2001 Feb;7(3):163-79.

[3]. James F Kachur, 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 Pharmacol Exp Ther. 2002 Feb;300(2):583-7.