Compounds > 1-(2-chlorobenzyl)-2-(1-(4-isobutylphenyl)ethyl)-1h-benzimidazole

1-(2-chlorobenzyl)-2-(1-(4-isobutylphenyl)ethyl)-1h-benzimidazole and Pleurisy

1-(2-chlorobenzyl)-2-(1-(4-isobutylphenyl)ethyl)-1h-benzimidazole has been researched along with Pleurisy* in 1 studies

Other Studies

1 other study(ies) available for 1-(2-chlorobenzyl)-2-(1-(4-isobutylphenyl)ethyl)-1h-benzimidazole and Pleurisy

Article	Year
The novel benzimidazole derivative BRP-7 inhibits leukotriene biosynthesis in vitro and in vivo by targeting 5-lipoxygenase-activating protein (FLAP). British journal of pharmacology, 2014, Volume: 171, Issue:12 Leukotrienes (LTs) are inflammatory mediators produced via the 5-lipoxygenase (5-LOX) pathway and are linked to diverse disorders, including asthma, allergic rhinitis and cardiovascular diseases. We recently identified the benzimidazole derivative BRP-7 as chemotype for anti-LT agents by virtual screening targeting 5-LOX-activating protein (FLAP). Here, we aimed to reveal the in vitro and in vivo pharmacology of BRP-7 as an inhibitor of LT biosynthesis.. We analysed LT formation and performed mechanistic studies in human neutrophils and monocytes, in human whole blood (HWB) and in cell-free assays. The effectiveness of BRP-7 in vivo was evaluated in rat carrageenan-induced pleurisy and mouse zymosan-induced peritonitis.. BRP-7 potently suppressed LT formation in neutrophils and monocytes and this was accompanied by impaired 5-LOX co-localization with FLAP. Neither the cellular viability nor the activity of 5-LOX in cell-free assays was affected by BRP-7, indicating that a functional FLAP is needed for BRP-7 to inhibit LTs, and FLAP bound to BRP-7 linked to a solid matrix. Compared with the FLAP inhibitor MK-886, BRP-7 did not significantly inhibit COX-1 or microsomal prostaglandin E2 synthase-1, implying the selectivity of BRP-7 for FLAP. Finally, BRP-7 was effective in HWB and impaired inflammation in vivo, in rat pleurisy and mouse peritonitis, along with reducing LT levels.. BRP-7 potently suppresses LT biosynthesis by interacting with FLAP and exhibits anti-inflammatory effectiveness in vivo, with promising potential for further development. Topics: 5-Lipoxygenase-Activating Protein Inhibitors; 5-Lipoxygenase-Activating Proteins; Animals; Anti-Inflammatory Agents; Arachidonate 5-Lipoxygenase; Benzimidazoles; Carrageenan; Cells, Cultured; Disease Models, Animal; Dose-Response Relationship, Drug; Down-Regulation; Humans; Leukotriene Antagonists; Leukotrienes; Male; Mice; Monocytes; Neutrophils; Peritonitis; Pleurisy; Rats, Wistar; Zymosan	2014

Article

Year

The novel benzimidazole derivative BRP-7 inhibits leukotriene biosynthesis in vitro and in vivo by targeting 5-lipoxygenase-activating protein (FLAP).

British journal of pharmacology, 2014, Volume: 171, Issue:12

Leukotrienes (LTs) are inflammatory mediators produced via the 5-lipoxygenase (5-LOX) pathway and are linked to diverse disorders, including asthma, allergic rhinitis and cardiovascular diseases. We recently identified the benzimidazole derivative BRP-7 as chemotype for anti-LT agents by virtual screening targeting 5-LOX-activating protein (FLAP). Here, we aimed to reveal the in vitro and in vivo pharmacology of BRP-7 as an inhibitor of LT biosynthesis.. We analysed LT formation and performed mechanistic studies in human neutrophils and monocytes, in human whole blood (HWB) and in cell-free assays. The effectiveness of BRP-7 in vivo was evaluated in rat carrageenan-induced pleurisy and mouse zymosan-induced peritonitis.. BRP-7 potently suppressed LT formation in neutrophils and monocytes and this was accompanied by impaired 5-LOX co-localization with FLAP. Neither the cellular viability nor the activity of 5-LOX in cell-free assays was affected by BRP-7, indicating that a functional FLAP is needed for BRP-7 to inhibit LTs, and FLAP bound to BRP-7 linked to a solid matrix. Compared with the FLAP inhibitor MK-886, BRP-7 did not significantly inhibit COX-1 or microsomal prostaglandin E2 synthase-1, implying the selectivity of BRP-7 for FLAP. Finally, BRP-7 was effective in HWB and impaired inflammation in vivo, in rat pleurisy and mouse peritonitis, along with reducing LT levels.. BRP-7 potently suppresses LT biosynthesis by interacting with FLAP and exhibits anti-inflammatory effectiveness in vivo, with promising potential for further development.

Topics: 5-Lipoxygenase-Activating Protein Inhibitors; 5-Lipoxygenase-Activating Proteins; Animals; Anti-Inflammatory Agents; Arachidonate 5-Lipoxygenase; Benzimidazoles; Carrageenan; Cells, Cultured; Disease Models, Animal; Dose-Response Relationship, Drug; Down-Regulation; Humans; Leukotriene Antagonists; Leukotrienes; Male; Mice; Monocytes; Neutrophils; Peritonitis; Pleurisy; Rats, Wistar; Zymosan

2014