PCNA-I1 is an inhibitor of proliferating cell nuclear antigen (PCNA) that binds to PCNA trimers (Kd = 0.41 μM) and dose-dependently reduces the level of PCNA associated with chromatin in PC3 cells. It preferentially inhibits growth of a variety of human and mouse cancer cell lines (IC50s = 0.05-0.3 μM) over non-transformed cells (IC50s = 0.99-2 μM). PCNA-I1 leads to an accumulation of cells in the G1 phase during the first 24 hours of incubation and halts the cell cycle in the S and G2/M phases by 72 hours following treatment. It also reduces tumor growth in an LNCaP prostate cancer mouse xenograft model when administered at a dose of 10 mg/kg, five days per week, for two weeks.
