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Discovery and characterization of a novel WRN inhibitor

ABSTRACT: Discovery and characterization of a novel WRN inhibitor

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Hans Voshol

LAB HEAD: Johannes Voshol

PROVIDER: PXD044202 | Pride | 2024-01-31

REPOSITORIES: Pride

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Discovery of WRN inhibitor HRO761 with synthetic lethality in MSI cancers.

Ferretti Stephane S Hamon Jacques J de Kanter Ruben R Scheufler Clemens C Andraos-Rey Rita R Barbe Stephanie S Bechter Elisabeth E Blank Jutta J Bordas Vincent V Dammassa Ernesta E Decker Andrea A Di Nanni Noemi N Dourdoigne Marion M Gavioli Elena E Hattenberger Marc M Heuser Alisa A Hemmerlin Christelle C Hinrichs Jürgen J Kerr Grainne G Laborde Laurent L Jaco Isabel I Núñez Eloísa Jiménez EJ Martus Hans-Joerg HJ Quadt Cornelia C Reschke Markus M Romanet Vincent V Schaeffer Fanny F Schoepfer Joseph J Schrapp Maxime M Strang Ross R Voshol Hans H Wartmann Markus M Welly Sarah S Zécri Frédéric F Hofmann Francesco F Möbitz Henrik H Cortés-Cros Marta M

Nature 20240424 8011

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 throug ...[more]

PMID: 38658754

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Opposing actions of IL-2 and IL-21 on Th9 differentiation correlate with their differential regulation of BCL6 expression

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