Topoisomerase I inhibitor 2

Topoisomerase I inhibitor 2 (ZML-8) is a highly selective inhibitor of DNA topoisomerase I (Top1). Topoisomerase I inhibitor 2 inhibits Top1 activity and results DNA damage. Topoisomerase I inhibitor 2 blocks G2/M phase and induces apoptosis, exhibits anti-tumor effect[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> Topoisomerase

Signaling Pathways >> Apoptosis >> Caspase

Topoisomerase I:0.58 μM (IC50)

Topoisomerase I inhibitor 2 (24 hours) exhibits strong inhibition with an IC50 value of 0.58 μM towards HepG2 and selective activity with SI values (selectivity index) of 55.70% between HepG2 and normal human liver cell line L-02[1]. Topoisomerase I inhibitor 2 (1.25, 2.5 μM, 48 hours) inhibits tumor cells proliferation by decreasing anti-apoptotic expression of Bcl-2 and enhancing caspase-dependent apoptosis[1]. Topoisomerase I inhibitor 2 (1.25, 2.5 μM, 48 hours) decreases Top1 specific activity and results in DNA damage by causing supercoiled DNA[1]. Cell Cycle Analysis[1] Cell Line: HepG2 cells Concentration: 2.5 μM Incubation Time: 24 hours Result: Arrested the cell cycle in G2/M phase in a dose-dependent manner. Cell Proliferation Assay[1] Cell Line: HepG2 cells Concentration: 0.625, 1.25, 2.5 μM Incubation Time: 48 hours Result: Inhibited tumor cells proliferation by inducing cell apoptosis in a dose-dependent manner, the apoptosis rate was 65.0% and 77.6%, respectively. Western Blot Analysis[1] Cell Line: HepG2 cells Concentration: 0.625, 1.25, 2.5 μM Incubation Time: 48 hours Result: Decreased anti-apoptotic expression of Bcl-2 at 2.5 μM significantly and increased the expression of pro-apoptotic protein Bax, Bad, and p53. And also significantly enhanced caspase- dependent apoptosis and activated Cleaved caspase-3 in a dose-dependent manner.

[1]. Zhou Y, et al. Design and synthesis of Aza-boeravinone derivatives as potential novel topoisomerase I inhibitors. Bioorg Chem. 2022 May. 122:105747.