RBx 7796: A novel inhibitor of 5-lipoxygenase

Abstract

The results suggest that RBx 7,796, a novel chemotype, is an orally efficacious inhibitor of 5-lipoxygenase enzyme that is effective against both neutrophilic and eosinophilic airway inflammation and shows potent inhibition with once daily administration.

Pharmacodynamic and pharmacokinetic characterisation of RBx 7796: a novel 5-lipoxygenase inhibitor

“…RBx 7796 belongs to a chemotype distinct from N-hydroxyurea class, selective for 5-lipoxy genase in comparison to 12-lipoxygenase, indifferent to redox environment an exhibited anti-infl ammatory effect in experimental animal models of neutrophilic and eosinophilic airway infl ammation [19]. In this study, we report effi cacy of RBx 7796 in additional models of airway reactivity.…”

“…In our earlier study [19], we had used RBx 7796 as a sodium salt. In this study, we have compared effi cacy and pharmacokinetic properties of two different salt forms of RBx 7796 -sodium and tris.…”

“…Neutrophil lysate was used as enzyme source as described in Shirumalla et al [19]. Blood was collected from healthy human volunteers in sodium heparin containing vacutainers (Becton Dickinson, USA).…”

“…Washed neutrophils were prepared following standard technique [19] and whole blood from healthy human volunteers or anesthetized wistar rats, was added to dextran (5 %) in the ratio of 1 (dextran): 4 (whole blood) and kept undisturbed for about 1 h. Supernatant containing leukocytes was centrifuged at 3,000 rpm for 10 min, pellet was resuspended in 2 mL of phosphate-buffered saline pH 7.4(PBS) containing 1 mg/mL glucose (PG buffer). Suspension was laid over 5 mL of fi coll (Histopaque  -density 1.083, Sigma-Aldrich Co, USA) and centrifuged at 3,000 rpm for 30 min.…”

“…We have reported the discovery of RBx 7796, a 5-Lipoxygenase inhibitor [19]. RBx 7796 belongs to a chemotype distinct from N-hydroxyurea class, selective for 5-lipoxy genase in comparison to 12-lipoxygenase, indifferent to redox environment an exhibited anti-infl ammatory effect in experimental animal models of neutrophilic and eosinophilic airway infl ammation [19].…”