| Identification | Back Directory | [Name]
SC 57461A | [CAS]
423169-68-0 | [Synonyms]
SC 57461
SC 57461A
SC-57461 Hydrochloride
N-methyl-N-[3-[4-(phenylmethyl)phenoxy]propyl]-β-alaninehydrochloride | [Molecular Formula]
C20H25NO3.ClH | [MDL Number]
MFCD00951253 | [MOL File]
423169-68-0.mol | [Molecular Weight]
363.882 |
| Hazard Information | Back Directory | [Description]
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. | [Chemical Properties]
White Solid | [Uses]
A potent and selective orally active leukotriene A4 hydrolase inhibitor. | [Biological Activity]
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. | [in vivo]
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. |
| [References]
[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 |
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Alfa Chemistry
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1-516-6625404 |
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https://www.alfa-chemistry.com |
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