COH005

COH005 is a novel small-molecule inhibitor of the proliferating cell nuclear antigen (PCNA), identified through an artificial intelligence-guided drug discovery workflow. It binds to the major PCNA-interacting-protein (PIP)-box binding pocket, a critical interface for PCNA-mediated protein-protein interactions essential for DNA replication, repair, and cell-cycle regulation. Developed by researchers at City of Hope, COH005 was discovered as a next-generation scaffold to expand therapeutic opportunities beyond the first-in-class inhibitor AOH1996. Preclinical characterization, including X-ray crystallography and cellular thermal shift assays (CETSA), has demonstrated its direct engagement with PCNA and its potential for the treatment of solid and liquid tumors.