AOH1996

Description: AOH1996 is an orally active ligand for the replicasome component PCNA (proliferating cell nuclear antigen), targeting the transcription-replication conflict (TRC). It interferes with the interaction of PCNA with its binding proteins, leading to DNA replication stress and apoptosis. AOH1996 causes proteasome-dependent rpb1 degradation and lethal DNA damage by stabilizing the interaction between PCNA and RNA polymerase II, and acts synergistically with DNA damaging agents to inhibit tumor cell growth. Target: Apoptosis, DNA/RNA Synthesis. Smiles: C(NCC(NC1=C(OC2=CC(OC)=CC=C2)C=CC=C1)=O)(=O)C=3C4=C(C=CC3)C=CC=C4. References: Gu L, et al. Pharmacological targeting of transcription-replication conflict leads to anti-cancer efficacy with minimal side effects in preclinical models. Cancer Research. 2021, 81(13_Supplement): 1269-1269.