Boosting Anti-Inflammatory Potency of Zafirlukast by Designed Polypharmacology

Multitarget design
offers access to bioactive small molecules with
potentially superior efficacy and safety. Particularly multifactorial
chronic inflammatory diseases demand multiple pharmacological interventions
for stable treatment. By minor structural changes, we have developed
a close analogue of the cysteinyl-leukotriene receptor antagonist
zafirlukast that simultaneously inhibits soluble epoxide hydrolase
and activates peroxisome proliferator-activated receptor γ.
The triple modulator exhibits robust anti-inflammatory activity in
vivo and highlights the therapeutic potential of designed multitarget
agents.