Voreloxin hydrochloride (SNS-595 hydrochloride) is a potent inhibitor of Topoisomerase II with broad-spectrum anti-tumor activity.

Voreloxin potentially inhibits the relaxation of topoisomerase II relaxation with IC50 of 3.2 μg /mL with no effect on topoisomerase II cleavage. Voreloxin has a cytotoxic activity against human tumor cell lines more potent than that of etoposide. [1] Voreloxin also has broad anti-proliferative activity in 15 cell lines, including 4 drug-resistant lines, with IC50 ranging from 0.04 to 1.155 μM. [2]

Voreloxin (50 mg/kg i.p.) shows potent antitumor activity in mice implanted with P388 leukemia cells. [1] Voreloxin (25 mg/kg i.v.) demonstrates strong tumor growth inhibition in 10 of 11 solid tumor (ovarian, breast, melanoma, gastric, colon, and lung) xenograft models, 2 hematologic tumor xenograft models, 3 multidrug resistant tumor models and 3 murine syngeneic tumor models (Colon 26, M5076 Ovarian Sarcoma, Lewis Lung carcinoma). [2]

Cell lines: P388 leukemia cells. Concentrations: about 10 μg/mL. Incubation Time: 72 hours. Method: Cells are seed in a 96-well microtiter plate (0.1 mL/well), preincubated for 24 h except for P388 cells, and incubated with various concentrations of a test compound in the 5% CO2 incubator at 37℃ for 72 h. Then, 0.02 mL MTT solution (5 mg/mL) is added in each well, and a further 4 h cells culturing is carried out. The medium is removed and 0.2 mL of DMSO is added in each well to dissolve the formed formazan. The absorbance is measured using Multiskan Bichromatic.

Animal Models: Mice implanted with P388 leukemia cells. Dosages: about 50 mg/kg. Administration: i.p.

DMSO: 1.09 mg/mL (2.49 mM), Sonication is recommended.