VVD-214 (RO7589831, VVD-133214) is a synthetic allosteric inhibitor of WRN helicase. VVD-214 binds irreversibly to cysteine 727 on WRN, suppressing ATP hydrolysis and helicase activity. VVD-214 exhibits potent efficacy in inducing double-stranded DNA breaks, nuclear enlargement, and cellular apoptosis in cancers with high microsatellite instability (MSI).