BRP-7: A Promising Benzimidazole Derivative Targeting FLAP to Inhibit Leukotriene Biosynthesis

The study focuses on leukotrienes, which are inflammatory mediators associated with various conditions such as asthma and cardiovascular diseases. The research identified a benzimidazole derivative, BRP-7, as a potential anti-leukotriene agent through virtual screening targeting the 5-lipoxygenase-activating protein (FLAP). The in vitro and in vivo pharmacology of BRP-7 was explored as an inhibitor of leukotriene biosynthesis.

Experiments were conducted to analyze leukotriene formation in human cells and blood, as well as in cell-free assays. The in vivo effectiveness of BRP-7 was evaluated in animal models of inflammatory conditions.

Key findings indicate that BRP-7 significantly inhibits leukotriene formation in neutrophils and monocytes, with no impact on cell viability or 5-lipoxygenase activity in cell-free assays. The compound requires a functional FLAP for its inhibitory effect and is selective for FLAP over other enzymes like COX-1. BRP-7 demonstrated efficacy in human whole blood and reduced inflammation and leukotriene levels in animal models of pleurisy and peritonitis.

The conclusion highlights that BRP-7 is a potent inhibitor of leukotriene biosynthesis through interaction with FLAP and shows anti-inflammatory activity in vivo, suggesting its potential for further development as a therapeutic agent.