zinc-95605533

T2AA (4-[4-[(2S)-2-amino-3-hydroxypropyl]-2,6-diiodophenoxy]phenol) is an inhibitor of proliferating cell nuclear antigen (PCNA) with IC50 of 1 μM for PCNA PIP-box peptide interaction. T2AA suppresses cancer cell growth and causes DNA replication stress by stalling DNA replication forks and inhibiting PCNA interaction with DNA polymerase δ.

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.