Stephane Ferretti, Jacques Hamon, Ruben de Kanter, Clemens Scheufler, Rita Andraos-Rey, Stephanie Barbe, Elisabeth Bechter, Jutta Blank, Vincent Bordas, Ernesta Dammassa, Andrea Decker, Noemi Di Nanni, Marion Dourdoigne, Elena Gavioli, Marc Hattenberger, Alisa Heuser, Christelle Hemmerlin, Jürgen Hinrichs, Grainne Kerr, Laurent Laborde, Isabel Jaco, Eloísa Jiménez Núñez, Hans-Joerg Martus, Cornelia Quadt, Markus Reschke, Vincent Romanet, Fanny Schaeffer, Joseph Schoepfer, Maxime Schrapp, Ross Strang, Hans Voshol, Markus Wartmann, Sarah Welly, Frédéric Zécri, Francesco Hofmann, Henrik Möbitz, Marta Cortés-Cros
The Werner syndrome RecQ helicase WRN was identified as a synthetic lethal target in cancer cells with microsatellite instability (MSI) by several genetic screens1-6 . Despite advances in treatment with immune checkpoint inhibitors7-10 , there is an unmet need in the treatment of MSI cancers11-14 . Here we report the structural, biochemical, cellular and pharmacological characterization of the clinical-stage WRN helicase inhibitor HRO761, which was identified through an innovative hit-finding and lead-optimization strategy...
April 24, 2024: Nature