RT Journal Article SR Electronic T1 Pharmacological Characterization of SC-57461A (3-[Methyl[3-[4-(phenylmethyl)phenoxy]propyl]amino]propanoic Acid HCl), a Potent and Selective Inhibitor of Leukotriene A4Hydrolase I: In Vitro Studies JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 577 OP 582 DO 10.1124/jpet.300.2.577 VO 300 IS 2 A1 Leslie J. Askonas A1 James F. Kachur A1 Doreen Villani-Price A1 Chi-Dean D. Liang A1 Mark A. Russell A1 Walter G. Smith YR 2002 UL http://jpet.aspetjournals.org/content/300/2/577.abstract AB Leukotriene (LT) B4 is an inflammatory mediator that has been implicated in the pathogenesis of various diseases, including inflammatory bowel disease and psoriasis. As the rate-limiting step for LTB4 production, LTA4 hydrolase represents an attractive target for therapeutic agents that interfere with LTB4 production. In the present study we evaluated a chemically novel compound designated SC-57461A (3-[methyl[3-[4-(phenylmethyl)phenoxy]propyl]amino]propanoic acid HCl) as an inhibitor of LTA4 hydrolase. Pharmacological comparisons are made to its free acid SC-57461. SC-57461A is a potent competitive inhibitor of recombinant human LTA4 hydrolase when either LTA4(IC50 = 2.5 nM, Ki = 23 nM) or peptide substrates (IC50 = 27 nM) are used. In human whole blood, the IC50 for calcium ionophore-induced LTB4 production was 49 nM, indicative of good cell penetration. Whole blood production of the cyclooxygenase metabolite thromboxane B2 was not affected. SC-57461A was also active in several other species, including mouse, rat, dog, and rhesus monkey. The data indicate that SC-57461A is a potent and selective inhibitor of LTA4 hydrolase. The American Society for Pharmacology and Experimental Therapeutics