Voreloxin (Hydrochloride)

175519-16-1

C18H20ClN5O4S

DMSO : < 1 mg/mL (insoluble or slightly soluble)

Apoptosis; Cell Cycle/DNA Damage

Voreloxin Hydrochloride is a first-in-class topoisomerase II inhibitor that intercalates DNA and induces site-selective DNA DSB, G2 arrest, and apoptosis. IC50 & Target: Topoisomerase II^[1] In Vitro: Voreloxin Hydrochloride is a first-in-class topoisomerase II poison and inhibitor that intercalates DNA and induces site-selective DNA DSB, G2 arrest, and apoptosis. Voreloxin (0.1-20 uM) inhibits topoisomerase II activity and induces site-selective DNA DSB in CCRF-CEM cells. Voreloxin (0.11, 0.33, 1, 3 uM) induces G2 arrest partially through topoisomerase II in A549 lung cancer cell line. Voreloxin cytotoxic activity requires DNA intercalation. However, Voreloxin (1-9 uM) does not generate significant levels of ROS^[1]. Voreloxin has potent cytotoxic activity in AML cell lines MV4-11 and HL-60, with IC₅₀s of 95 +/- 8 nM and 884 +/- 114 nM, respectively. Voreloxin in combination with cytarabine shows additive or synergistic activity in acute leukemia cell lines^[2]. Voreloxin is active on the primary acute myeloid leukemia (AML) with a mean LD₅₀ of 2.3 uM. The LD₅₀ for voreloxin in myeloid cell lines NB4 and HL-60 is 0.59 uM +/- 0.25 uM. Voreloxin causes accumulation of cells in the S and G2 phases of the cell cycle and acts on topoisomerase II^[3]. In Vivo: Voreloxin (20 mg/kg, i.v.) alone results in 80% reduction in bone marrow cellularity of CD-1 mice by administration one dose every 4 days repeated twice (q4d x2). voreloxin at 10 mg/kg in combination with cytarabine causes ablation of the marrow, dilation of sinusoids, and infiltration of adipocytes in mice. Voreloxin (20 mg/kg, i.v.) combined with cytarabine causes a reversible decrease in myeloid and lymphoid cells in bone marrow and peripheral blood CD-1 mice. voreloxin (10 mg/kg, q4d x2) and cytarabine in combination causes reversible neutropenia with a more modest impact on platelets CD-1 mice^[2].