tcsc1498 Topotecan (Hydrochloride)

Topotecan Hydrochloride (SKF 104864A; NSC 609669) is a Topoisomerase I inhibitor with potent antineoplastic activities.

IC50 & Target: Topoisomerase I^[1]

In Vitro: Topotecan (SKF 104864A) obviously inhibits proliferation of not only human glioma cells but also glioma stem cells (GSCs) in a dose- and time-dependent manner. According to the IC₅₀ values at 24 h, 3 μM of Topotecan (SKF 104864A) is selected as the optimal administration concentration. In addition, Topotecan (SKF 104864A) induces cell cycle arrest in G0/G1 and S phases and promoted apoptosis. Results show that the cell viability is inhibited by Topotecan (SKF 104864A) in a dose-dependent manner. 2, 20 and 40 μM of Topotecan (SKF 104864A) obviously inhibits the cell viability compared with the control groups. The IC₅₀ values of Topotecan (SKF 104864A) at 24 h are 2.73±0.25 μM of U251 cells, 2.95±0.23 μM of U87 cells, 5.46±0.41 μM of GSCs-U251 and 5.95±0.24 μM of GSCs-U87. Thus 3 μM of Topotecan (SKF 104864A) is selected as the optimal administration concentration in the subsequent experiments^[1].

In Vivo: NUB-7 metastatic model, the animals belonging to all the 4 groups are sacrificed after 14 days treatment. Compared with the control, Low dose metronomic (LDM) Topotecan (SKF 104864A) and TP+Pazopanib (PZ) liver weights are significantly lower in TP+PZ-treated animals, compared with PZ. Microscopic tumors are visible in the livers of mice belonging to all the groups except TP+PZ confirming the ability of Topotecan (SKF 104864A)+PZ to control liver metastasis. In a previous dose-response study, the daily dose of oral metronomic Topotecan (SKF 104864A) (0.5, 1.0, and 1.5 mg/kg) causes greater reduction in microvascular density compared with weekly maximum-tolerated dose regimen (7.5 and 15 mg/kg) in an ovarian cancer model, but the mice treated with 1.5 mg/kg daily, oral Topotecan (SKF 104864A) show decreased food intake, and a lesser antitumor effect^[2].