Front Cover: Challenges for the Discovery of Non‐Covalent WRN Helicase Inhibitors (ChemMedChem 8/2024)

Graphical Abstract The Front Cover shows the initial screening strategy for hit identification on WRN helicase. The main challenge was to understand the type of false positives which came out of standard DNA unwinding or ATPase assays. Beyond DNA binders, direct interferences of compounds with WRN protein were the major source of artefacts as illustrated by the extensive characterization of inhibitors (ML216 and NSC617145) wrongly considered as WRN probes. Some learnings on how to minimize and triage out those in vitro artefacts are shared for best hit discovery on WRN helicase. More information can be found in the Research Article by Alisia Heuser, Henrik Möbitz, Jacques Hamon et al.