VVD-214 is a synthetic lethal allosteric inhibitor of WRN helicase with an IC50 of 0.1316 μM. VVD-214 covalently binds to cysteine 727 of WRN and inhibits ATP hydrolysis and helicase activity. VVD-214 is potent in causing double-stranded DNA breaks, nuclear swelling, and cell death in high microsatellite instability (MSI) cancers[1][2].
[1] Kikuchi S, et al. Abstract ND11: Chemoproteomic-enabled discovery of VVD-214, a synthetic lethal allosteric inhibitor of WRN helicase[J]. Cancer Research, 2024, 84(7_Supplement): ND11-ND11.
[2] Kikuchi S, et al., Pharmaceutical compositions comprising wrn helicase inhibitors. WO2024010782.
