Compound B6, also known as TOPOI/PARP-1-IN-1, is a dual inhibitor targeting TOPOI and PARP, exhibiting low cytotoxicity and oral activity with a PARP1 IC 50 of 0.09 μM. This compound effectively inhibits cancer cell proliferation and migration, induces cell cycle arrest at the G0/G1 phase, and triggers apoptosis. In murine models, TOPOI/PARP-1-IN-1 demonstrated a tumor growth inhibition rate (TGI) of 75.4% [1].

TOPOI/PARP-1-IN-1, at concentrations of 1.25-5 μM over 48 hours, inhibits the proliferation and migration of HGC-27 cells in a concentration-dependent manner. Within 24 hours and at the same concentration range, it induces apoptosis in a dose-dependent way in HGC-27 cells. It also causes DNA damage and suppresses TOPOI protein expression in these cells. Demonstrating antitumor activity, TOPOI/PARP-1-IN-1 shows IC50 values of 7.21 μM, 9.48 μM, 3.80 μM, and 2.49 μM against HeLa, A549, HepG-2, and HGC-27 cells, respectively. In a cell proliferation assay, HGC-27 cells treated with 1.25, 2.5, and 5 μM concentrations over 48 hours showed a dose-dependent inhibition of clonogenicity. Apoptosis analysis of HGC-27 cells revealed apoptosis induction rates of 15.5%, 43.1%, and 76.0% for the same concentrations over 24 hours.

TOPOI/PARP-1-IN-1, administered orally at 40 mg/kg every two days for 17 days, inhibited the growth of HGC-27 tumors in a xenograft model using female BALB/c nude mice, resulting in a tumor growth inhibition (TGI) rate of 75.4% [1].