PCNA-I1

PCNA-I1 is a selective small molecule inhibitor targeting proliferating cell nuclear antigen (PCNA) with anticancer activity. PCNA-I1 can stabilize the PCNA trimer structure (Kd=0.14-0.41μM), reduce its binding to chromatin, induce tumor cell cycle arrest, inhibit DNA replication and repair, and enhance the anti-tumor effect of DNA damaging agents. PCNA-I1 can be used in the study of targeted therapy for prostate cancer, lung cancer and other tumors^[1][2][3]. In Vitro:PCNA-I1 (0.05-10 μM; 72 h) inhibits the cell viability of human prostate cancer (PC-3, LNCaP), breast cancer (MCF-7), melanoma (A375) cell lines in a concentration-dependent manner, with an average IC₅₀ of 0.17 μM, which is significantly lower than that of normal cells^[1].
PCNA-I1 (1 μM; 24-48 h) induces cell cycle arrest in S and G₂/M phases and increases cell apoptosis^[1].
PCNA-I1 (1 μM; 48 h) reduces PCNA binding to chromatin in PC-3 cells (NP-R fragment decreased by 50%), accompanied by nuclear p21 aggregation^[1].
PCNA-I1 (1 μM; 24 h) increases the expression of γH2AX (a DNA damage marker) in PC-3 cells^[2].
In Vivo:PCNA-I1 (10 mg/kg; intravenous injection; 5 times a week; 2 weeks) significantly inhibits tumor growth in nude mouse xenograft models of human prostate cancer LNCaP cells without causing toxic reactions such as significant weight loss^[3].