Benzimidazole FLAP inhibitors gain a second, antiproliferative action
- A benzimidazole FLAP inhibitor lead was remodeled at two positions, with the library tested in intact human neutrophils.
- SAR showed the address region accepts polar, bulky aliphatic groups instead of aromatics, whereas the core bioisostere region tolerates only neutral, non-basic changes.
- Lipid profiling showed selective leukotriene suppression, and the scaffold separately displayed antiproliferative effects in cancer cell lines.
💡 Points Based on the abstract
The dual-action label needs a control it doesn't yet have: a FLAP-inactive analog or a 5-LO-null cell line, to show the antiproliferative effect isn't plain scaffold cytotoxicity. The polar aliphatic address groups are the interesting part. It's worth checking whether they lower lipophilicity compared with earlier FLAP chemotypes, so solubility and clearance are the sensible next measurements.