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 在浓度为1.25-5 μM、孵育时间为48小时时，显示出对HGC-27细胞增殖和迁移的浓度依赖性抑制作用[1]。当浓度为1.25-5 μM并孵育24小时时，TOPOI/PARP-1-IN-1表现出对HGC-27细胞的剂量依赖性诱导凋亡效果[1]。此外，TOPOI/PARP-1-IN-1在HGC-27细胞中引起了DNA损伤并抑制了TOPOI蛋白的表达[1]。这一化合物展示了抗肿瘤活性，其对HeLa、A549、HepG-2和HGC-27细胞的IC50分别为7.21 μM、9.48 μM、3.80 μM和2.49 μM[1]。在Cell Proliferation Assay中，1.25, 2.5, 5 μM的TOPOI/PARP-1-IN-1对HGC-27细胞的集落形成能力显示了剂量依赖性的抑制效果[1]。Apoptosis Analysis显示，当浓度为1.25, 2.5, 5 μM时，分别诱导了15.5%，43.1%及76.0%的HGC-27细胞凋亡[1]。

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].