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

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.