aoh1996

AOH1996 is an experimental, orally bioavailable small molecule anticancer drug that acts as a selective inhibitor of proliferating cell nuclear antigen (PCNA), specifically targeting a cancer-associated isoform known as caPCNA[1][2][7]. PCNA is essential for DNA replication and repair in all dividing cells, but the caPCNA isoform is preferentially expressed in cancer cells. By binding to this isoform, AOH1996 disrupts the interaction between PCNA and RNA polymerase II (RPB1), leading to dissociation of PCNA from actively transcribed chromatin regions and inducing double-stranded DNA breaks in a transcription-dependent manner[5][8]. This mechanism selectively kills cancer cells while sparing normal cells. Preclinical studies have shown efficacy across multiple solid tumor types with minimal toxicity in animal models[1][4][8]. Developed at City of Hope, AOH1996 entered Phase I clinical trials for refractory solid tumors as of 2023[1][3].