PARP1-IN-49 is a selective inhibitor of PARP1 with an IC50 value of 23.56 nM and a Kd of 17.78 nM. It exhibits higher selectivity for PARP1 over PARP2. By inhibiting PARP1, PARP1-IN-49 induces DNA damage, cell cycle arrest, and apoptosis (apoptosis). Additionally, it increases intracellular reactive oxygen species (ROS) levels and inhibits cell migration. This compound is applicable in breast and ovarian cancer research.

PARP1:23.56 nM

PARP1-IN-49 (compound 9a) at concentrations of 0.5-2 μM for 48 hours inhibits proliferation and migration of MDA-MB-231 cells. It upregulates apoptosis-related protein levels while decreasing Bcl-2 expression. This compound induces DNA damage and double-strand breaks in MDA-MB-231 cells, increases apoptosis, causes S-phase cell cycle arrest, and triggers apoptosis through ROS generation and mitochondrial membrane potential alteration at concentrations of 0.5-4 μM. Additionally, at 2 μM, it enhances the thermal stability of PARP1, suggesting a direct interaction.

PARP1-IN-49 (compound 9a), administered via intraperitoneal injection at doses of 20 or 40 mg/kg over 22 days, significantly inhibits the growth of tumors derived from subcutaneously implanted MDA-MB-231 cells in BALB/c mice.