– T2AA, a proliferating cell nuclear antigen (PCNA) inhibitor, disrupts protein-protein interactions between PCNA and both a PIP-box-containing peptide (IC50= 1 μM) and full-length p21, reducing cellular colocalization of PCNA with DNA polymerase δ. This compound effectively inhibits DNA replication and cell proliferation in U2OS and HeLa cells in a concentration-dependent manner, additionally inducing S phase cell cycle arrest at a 20 μM concentration. Furthermore, T2AA enhances DNA double strand break formation alongside cisplatin in a neutral comet assay and augments cisplatin-induced reductions in clonogenic survival in HeLa and U2OS cells.