Florent Samain; Torun Ekblad; Gediminas Mikutis; Nan Zhong; Mauro Zimmermann; Angela Nauer; Davor Bajic; Willy Decurtins; Jörg Scheuermann; Peter J. Brown; Jonathan Hall; Susanne Gräslund; Herwig Schüler; Dario Neri; Raphael M. Franzini
J. Med. Chem., 2015, 58, 12, 5143-5149
https://doi.org/10.1021/acs.jmedchem.5b00432

Abstract

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.