1. Boosting Anti-Inflammatory Potency of Zafirlukast by Designed Polypharmacology
- Author
-
Jurema Schmidt, Cathrin Flauaus, Pascal Heitel, G. Enrico Rovati, Mario Wurglics, Simone Schierle, Tamara Goebel, Achim Schmidtko, Astrid Kaiser, Ewgenij Proschak, Sabine Willems, Gerd Geisslinger, Lilia Weizel, Astrid S. Kahnt, Daniel Merk, Dieter Steinhilber, and Publica
- Subjects
0301 basic medicine ,Epoxide hydrolase 2 ,Indoles ,Polypharmacology ,medicine.drug_class ,Phenylcarbamates ,Pharmacology ,Anti-inflammatory ,Tosyl Compounds ,Mice ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,Catalytic Domain ,Drug Discovery ,medicine ,Animals ,Humans ,Potency ,Zafirlukast ,Receptor ,Epoxide Hydrolases ,Sulfonamides ,Chemistry ,Anti-Inflammatory Agents, Non-Steroidal ,3T3 Cells ,Hep G2 Cells ,Receptor antagonist ,Small molecule ,Molecular Docking Simulation ,PPAR gamma ,030104 developmental biology ,Drug Design ,030220 oncology & carcinogenesis ,Molecular Medicine ,medicine.drug - Abstract
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 g. The triple modulator exhibits robust anti-inflammatory activity in vivo and highlights the therapeutic potential of designed multitarget agents.
- Published
- 2018
- Full Text
- View/download PDF