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Voreloxin Hydrochloride
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Voreloxin Hydrochloride
CAS No. : 175519-16-1
MCE 站:Voreloxin Hydrochloride
产品活性:Voreloxin Hydrochloride 是一种新创的拓扑异构酶 II (topoisomerase II) 抑制剂,能够诱导 DNA 双链断裂,阻滞 G2 期,*终细胞凋亡。
研究领域:Cell Cycle/DNA Damage | Apoptosis
作用靶点:Topoisomerase | Apoptosis
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 ?M) inhibits topoisomerase II activity and induces site-selective DNA DSB in CCRF-CEM cells. Voreloxin (0.11, 0.33, 1, 3 ?M) induces G2 arrest partially through topoisomerase II in A549 lung cancer cell line. Voreloxin cytotoxic activity requires DNA intercalation. However, Voreloxin (1-9 ?M) does not generate significant levels of ROS. 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. Voreloxin is active on the primary acute myeloid leukemia (AML) with a mean LD50 of 2.3 μM. The LD50 for voreloxin in myeloid cell lines NB4 and HL-60 is 0.59 μM ± 0.25 μM. Voreloxin causes accumulation of cells in the S and G2 phases of the cell cycle and acts on topoisomerase II.
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 ×2). 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 ×2) and cytarabine in combination causes reversible neutropenia with a more modest impact on platelets CD-1 mice.
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热门标签:SNS-595 Hydrochloride