PT - JOURNAL ARTICLE AU - Leslie J. Askonas AU - James F. Kachur AU - Doreen Villani-Price AU - Chi-Dean D. Liang AU - Mark A. Russell AU - Walter G. Smith TI - Pharmacological Characterization of SC-57461A (3-[Methyl[3-[4-(phenylmethyl)phenoxy]propyl]amino]propanoic Acid HCl), a Potent and Selective Inhibitor of Leukotriene A<sub>4</sub>Hydrolase I: In Vitro Studies AID - 10.1124/jpet.300.2.577 DP - 2002 Feb 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 577--582 VI - 300 IP - 2 4099 - http://jpet.aspetjournals.org/content/300/2/577.short 4100 - http://jpet.aspetjournals.org/content/300/2/577.full SO - J Pharmacol Exp Ther2002 Feb 01; 300 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