PARP1-IN-44 is a derivative of Olaparib and functions as an orally active PARP1 inhibitor with an IC50 of 0.6 nM. It also inhibits PARP2 (IC50 = 1.0 nM) and PARP7 (IC50 = 7.5 nM). PARP1-IN-44 demonstrates selective antiproliferative activity against BRCA-deficient cancer cells with minimal toxicity to normal cells. It induces G2/M phase arrest, promotes apoptosis, increases reactive oxygen species (ROS) levels, and disrupts mitochondrial membrane potential. Additionally, PARP1-IN-44 inhibits PARylation and leads to the accumulation of γH2AX. It activates the cGAS-STING pathway, enhancing the expression of IFN-β and CXCL10. In a CT26 tumor mouse model, PARP1-IN-44 enhances CD8+ T cell infiltration, showcasing significant in vivo antitumor activity.

PARP1:0.6 nM