WRN Inhibitor NDI-219216

**Semantic type:** Pharmacologic Substance

**Definition:** An orally bioavailable and selective inhibitor of the Werner syndrome ATP-dependent helicase (WRN), with potential antineoplastic activity. Upon oral administration, WRN inhibitor NDI-219216 non-covalently binds to WRN and inhibits the activity of WRN. This induces DNA damage, promotes cell cycle arrest and cell death in, and inhibits the growth of susceptible tumor cells, such as ones with high microsatellite instability (MSI-H). WRN, a multifunctional enzyme with both helicase and exonuclease activities, plays a key role in DNA replication and repair. It is overexpressed in a variety of cancer cells. NDI-219216 maintains its efficacy in the presence of the cysteine 727 resistance mutation while covalent WRN inhibitors lose their efficacy.

**Synonyms:** - NDI 219216 - NDI-219216 - NDI219216 - NTX 452 - NTX-452 - NTX452 - Werner Syndrome Helicase Inhibitor NDI-219216