AI Article Synopsis
- Werner Syndrome RecQ helicase (WRN) is an important target for treating cancers with microsatellite instability (MSI).
- Initial attempts to find WRN inhibitors faced difficulties due to false positives caused by non-specific interactions with other proteins.
- Existing WRN helicase inhibitors were tested and found to be non-specific, highlighting the need for new screening methods to discover more effective, specific inhibitors.
Article Abstract
The Werner Syndrome RecQ helicase (WRN) is a synthetic lethal target of interest for the treatment of cancers with microsatellite instability (MSI). Different hit finding approaches were initially tested. The identification of WRN inhibitors proved challenging due to a high propensity for artefacts via protein interference, i. e., hits inhibiting WRN enzymatic activities through multiple, unspecific mechanisms. Previously published WRN Helicase inhibitors (ML216, NSC19630 or NSC617145) were characterized in an extensive set of biochemical and biophysical assays and could be ruled out as specific WRN helicase probes. More innovative screening strategies need to be developed for successful drug discovery of non-covalent WRN helicase inhibitors.
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Article Synopsis
- Werner syndrome is linked to mutations in the WRN helicase, which plays a critical role in DNA functions and is associated with premature aging.
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