PARP1/EZH2-IN-1 is a selective dual inhibitor targeting both PARP1 and EZH2. It exhibits IC50 values of 28 nM for PARP1, 414 nM for PARP2, and 74 nM for EZH2. This compound inhibits the proliferation and migration of TNBC cells (triple-negative breast cancer cells). It can induce PANoptosis, a form of cell death that includes apoptosis, pyroptosis, and necroptosis, elevate reactive oxygen species (ROS) levels, and activate associated inflammatory pathways. PARP1/EZH2-IN-1 is applicable in research related to triple-negative breast cancer.

PARP1:28 nM

PARP1/EZH2-IN-1 (compound PE32) effectively inhibits the proliferation and growth of MDA-MB-231 and BT-549 cells at concentrations ranging from 0.5 to 2.0 μM over 48 hours. At 2.0 μM, it exacerbates DNA damage and disrupts homologous recombination repair pathways in BT-549 cells. At a concentration of 1.5 μM, it induces apoptosis and pyroptosis, leading to the death of BT-549 cells. Its antitumor effects are mainly achieved through ROS burst induction at concentrations of 0.625 to 10 μM. Additionally, PARP1/EZH2-IN-1 significantly enriches tumor-related death pathways, such as transcriptional dysregulation in cancer, ECM-receptor interaction, and TNF signaling pathway, while activating crucial inflammatory pathways like IL-17 and NF-κB. This activation leads to pyroptosis in tumor cells through these inflammatory signaling cascades.