AOH1160

AOH1160 is a **first-in-class, orally available small-molecule anticancer agent** that targets the cancer-associated isoform of proliferating cell nuclear antigen. Developed initially at **Beckman Research Institute of the City of Hope**, it was designed to bind the **L126-Y133 region of PCNA** and selectively disrupt DNA replication and homologous recombination-mediated DNA repair in malignant cells, leading to cell-cycle arrest and apoptosis. Preclinical studies reported broad cancer-cell killing at nanomolar concentrations with relative sparing of non-malignant cells and tumor suppression in mouse models including neuroblastoma, breast cancer, and small-cell lung cancer. However, AOH1160 showed inadequate metabolic stability for clinical development, including instability in rodent plasma attributed to carboxyl esterase ES-1 cleavage, and development was discontinued in favor of the more metabolically stable analog AOH1996.