解旋酶
沃纳综合征
基因组不稳定性
药物发现
药物靶点
计算生物学
遗传学
生物
DNA
生物信息学
生物化学
DNA损伤
基因
核糖核酸
作者
Arnd Heuser,Wassim Abdul Rahman,Elisabeth Bechter,Jutta Blank,Sylvia Buhr,Dirk Erdmann,Patrizia Fontana,Fanny Mermet‐Meillon,Marco Meyerhofer,Ross Strang,Maxime Schrapp,Catherine Zimmermann,Marta Cortés-Cros,Henrik Möbitz,Jacques Hamon
标识
DOI:10.1002/cmdc.202300613
摘要
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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