From Dynamic Combinatorial Chemistry to in Vivo Evaluation of Reversible and Irreversible Myeloperoxidase Inhibitors

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• 作者：Jalal Soubhye ; Michel Gelbcke ; Pierre Van Antwerpen ; François Dufrasne ; Mokhtaria Yasmina Boufadi ; Jean Nève ; Paul G. Furtmüller ; Christian Obinger ; Karim Zouaoui Boudjeltia ; Franck Meyer
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2017
• 出版时间：February 9, 2017
• 年：2017
• 卷：8
• 期：2
• 页码：206-210
• 全文大小：429K
• ISSN：1948-5875

文摘

The implementation of dynamic combinatorial libraries allowed the determination of highly active reversible and irreversible inhibitors of myeloperoxidase (MPO) at the nanomolar level. Docking experiments highlighted the interaction between the most active ligands and MPO, and further kinetic studies defined the mode of inhibition of these compounds. Finally, in vivo evaluation showed that one dose of irreversible inhibitors is able to suppress the activity of MPO after inducing inflammation.