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

作者：Florent Samain, T. Ekblad, Gediminas Mikutis, Nan Zhong, Mauro Zimmermann, Angela Nauer, Davor Bajic, Willy Decurtins, Jörg Scheuermann, Peter J. Brown, Jonathan Hall, S. Gräslund, H. Schüler, Dario Neri, Raphael M. Franzini · 发表于：Journal of Medicinal Chemistry · 年份：2015 · DOI：10.1021/acs.jmedchem.5b00432 · 被引用次数：63 · 研究领域：Biochemical and Molecular Research、Enzyme Structure and Function、Signaling Pathways in Disease

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.