Definition

An orally bioavailable and small molecule inhibitor of Werner syndrome ATP-dependent helicase (WRN; RecQ protein-like 2; Werner syndrome protein), with potential antineoplastic activity. Upon oral administration, WRN inhibitor RO7589831 covalently binds to and inhibits the activity of WRN. This may inhibit the growth of cancers with high microsatellite instability (MSI-H). WRN, a multifunctional enzyme with helicase, ATPase, and exonuclease activities, plays an important role in maintaining genome stability. Its helicase activity is essential for the survival of certain cancers with genomic microsatellite instability associated with defective DNA mismatch repair.