ARTS-051

ARTS-051 is a potent, selective, and non-covalent small molecule inhibitor of Werner helicase (WRN), specifically targeting its ATPase and helicase activities. It is designed for the treatment of microsatellite instability-high (MSI-H) cancers, such as colorectal, gastric, endometrial, and ovarian cancers, which exhibit a synthetic lethal dependency on WRN. ARTS-051 demonstrates high selectivity (>2000-fold) for WRN over the closely related BLM helicase and shows significant potency against MSI-H cell lines while sparing microsatellite stable (MSS) cells. Notably, it remains effective against WRN C727 mutations that confer resistance to other clinical-stage WRN inhibitors like HRO761. Developed by Artis Biopharma, the compound has shown tumor regression in various MSI-H mouse models and possesses favorable pharmacokinetic properties for oral administration.