Tankyrase 1 Inhibitors with Drug-like Properties Identified by Screening a DNA-Encoded Chemical Library

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• 作者：Florent Samain ; Torun Ekblad ; Gediminas Mikutis ; Nan Zhong ; Mauro Zimmermann ; Angela Nauer ; Davor Bajic ; Willy Decurtins ; J枚rg Scheuermann ; Peter J. Brown ; Jonathan Hall ; Susanne Gr盲slund ; Herwig Sch眉ler ; Dario Neri ; Raphael M. Franzini
• 刊名：Journal of Medicinal Chemistry
• 出版年：2015
• 出版时间：June 25, 2015
• 年：2015
• 卷：58
• 期：12
• 页码：5143-5149
• 全文大小：312K
• ISSN：1520-4804

文摘

We describe the synthesis and screening of a DNA-encoded chemical library containing 76230 compounds. In this library, sets of amines and carboxylic acids are directly linked producing encoded compounds with compact structures and drug-like properties. Affinity screening of this library yielded inhibitors of the potential pharmaceutical target tankyrase 1, a poly(ADP-ribose) polymerase. These compounds have drug-like characteristics, and the most potent hit compound (X066/Y469) inhibited tankyrase 1 with an IC₅₀ value of 250 nM.