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.

Boosting Anti-Inflammatory Potency of Zafirlukast by Designed Polypharmacology / S. Schierle, C. Flauaus, P. Heitel, S. Willems, J. Schmidt, A. Kaiser, L. Weizel, T. Goebel, A. Kahnt, G. Geisslinger, D. Steinhilber, M. Wurglics, G. Rovati, A. Schmidtko, E. Proschak, D. Merk. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 61:13(2018 Jun 12), pp. 5758-5764.

Boosting Anti-Inflammatory Potency of Zafirlukast by Designed Polypharmacology

G. Rovati;
2018-06-12

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 γ. The triple modulator exhibits robust anti-inflammatory activity in vivo and highlights the therapeutic potential of designed multitarget agents.
Molecular Medicine; Drug Discovery3003 Pharmaceutical Science
Settore BIO/14 - Farmacologia
Settore CHIM/08 - Chimica Farmaceutica
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/595447
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