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编 号:F307051
分子式:C18H18Na4O12P2
分子量:580.23
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生物活性:
Combretastatin A-1 phosphate (OXi-4503) tetrasodium, a proagent of Combretastatin A-1, is a microtubule polymerization inhibitor that binds to the colchicine-binding site of tubulin. Combretastatin A-1 phosphate tetrasodium inhibits the Wnt/β-catenin pathway through tubulin depolymerization mediated AKT deactivation. Combretastatin A-1 phosphate tetrasodium exhibits anti-tumor and anti-vascular effects.

体内研究:
Combretastatin A-1 phosphate (1-4?mg/kg; i.v. every other day for 4 weeks) significantly reduces the tumor volume in HepG2 subcutaneous xenograft model.Combretastatin A-1 phosphate (2 mg/kg; every other day for 21 days) shows enhanced apoptosis in orthotopic hepatocellular carcinoma mouse model.Animal Model:Male athymic BALB/c nu/nu mice (16-18 g; 4-6 weeks old) were inoculated with HepG2 cells
Dosage:1, 2, 4?mg/kg
Administration:I.v. every other day for 4 weeks
Result:Resulted in a significant tumor volume reduction at the dose of 2?mg/kg or 4?mg/kg.

体外研究:
Combretastatin A-1 phosphate (72 h) inhibits the growth of various tumor cell lines in vitro, including HepG2, SMMC-7721, Hepa 1-6, LM-3, Bel-7402, Huh7, BGC-803, MDA-MB-231, MCF-7, A375, NCI-1975, CT-26, HT-29, A549 cells (IC50=9.2, 12.8, 32.9, 33.8, 38.4, 728.2, 12.2, 17.6, 46.0, 61.0, 256.3, 1075.0, 2082.0, 2247.0 nM, respectively).Combretastatin A-1 phosphate (1-10 nM; 24 h) induces apoptosis by microtubule depolymerization-induced AKT inactivation and the removal of GSK-3β inhibition in HepG2 cells.Combretastatin A-1 phosphate (1-50?nM; 6 h) decreases the mitochondrial membrane potential (MMP) of HepG2 cells. Combretastatin A-1 shows dose-dependently ROS accumulation in HepG2 cells.
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