A-78773: a selective, potent 5-lipoxygenase inhibitor

• Published in: Journal of lipid mediators Vol. 6; no. 1-3; p. 259
• Main Authors: Bell, R L, Brooks, D W, Young, P R, Lanni, C, Stewart, A O, Bouska, J, Malo, P E, Carter, G W
• Format: Journal Article
• Language: English
• Published: Netherlands 01-03-1993
• Subjects: Administration, Oral; Animals; Dogs; Humans; Hydroxyurea - administration & dosage; Hydroxyurea - analogs & derivatives; Hydroxyurea - pharmacology; In Vitro Techniques; Leukotriene Antagonists; Leukotriene B4 - antagonists & inhibitors; Leukotriene B4 - biosynthesis; Leukotrienes - biosynthesis; Lipoxygenase Inhibitors; Neutrophils - drug effects; Neutrophils - enzymology; Rats; Tumor Cells, Cultured - drug effects; Tumor Cells, Cultured - enzymology
• ISSN: 0921-8319

The potency and selectivity of A-78773, a newly discovered 5-lipoxygenase inhibitor, were examined. The compound was significantly more potent than zileuton in inhibiting leukotriene formation in cell free lysates and in isolated human neutrophils. A-78773 inhibited a RBL cell lysate 5-lipoxygenase at concentrations 2 orders of magnitude lower than those required to inhibit rabbit reticulocyte 15-lipoxygenase or human platelet 12-lipoxygenase. The compound was also a potent, long lasting, orally active inhibitor of leukotriene formation ex vivo in dogs and in vivo in the rat. In experiments where leukotriene formation was completely inhibited, no increase in eicosanoids from other pathways was observed. A-78773 should prove to be a valuable clinical tool in treating leukotriene mediated diseases.