288847-34-7
288847-34-7 structure
- Name: OXi4503
- Chemical Name: tetrasodium,[3-methoxy-2-phosphonooxy-6-[(Z)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenyl] dihydrogen phosphate
- CAS Number: 288847-34-7
- Molecular Formula: C18H18Na4O12P2
- Molecular Weight: 580.23500
- Catalog: Signaling Pathways Cell Cycle/DNA Damage Microtubule/Tubulin
- Create Date: 2017-10-25 22:45:09
- Modify Date: 2024-01-01 22:25:44
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Combretastatin A-1 phosphate (OXi-4503) tetrasodium, a prodrug 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[1][2][3].
| Name | tetrasodium,[3-methoxy-2-phosphonooxy-6-[(Z)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenyl] dihydrogen phosphate |
|---|---|
| Synonyms |
Combretastatin A1 disodium phosphate
OXi4503 1,2-Benzenediol, 3-methoxy-6-[(Z)-2-(3,4,5-trimethoxyphenyl)ethenyl]-, bis(dihydrogen phosphate), sodium salt (1:4) tetrasodium 3-methoxy-6-[(Z)-2-(3,4,5-trimethoxyphenyl)ethenyl]benzene-1,2-diyl bis(phosphate) 1,2-Benzenediol,3-methoxy-6-((1Z)-2-(3,4,5-trimethoxyphenyl)ethenyl)-,bis(dihydrogen phosphate),tetrasodium salt Combretastatin A-1 phosphate Tetrasodium 3-methoxy-6-[(Z)-2-(3,4,5-trimethoxyphenyl)vinyl]-1,2-phenylene bis(phosphate) |
| Description | Combretastatin A-1 phosphate (OXi-4503) tetrasodium, a prodrug 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[1][2][3]. |
|---|---|
| Related Catalog | |
| Target |
Microtubule/Tubulin[1] |
| In Vitro | 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)[2]. 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[2]. 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[2]. Western Blot Analysis[2] Cell Line: HepG2 cells Concentration: 1, 5, 10 nM Incubation Time: 24 hours Result: Significantly decreased Mcl-1 expression, but the Bcl-2 level was unchanged. Reduced p-GSK 3β (Ser9) without altering total GSK-3β protein levels, indicating an activation of GSK-3β. Reduced AKT phosphorylation on Ser473 without an obvious change in the total AKT protein levels. |
| In Vivo | 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[2]. Combretastatin A-1 phosphate (2 mg/kg; every other day for 21 days) shows enhanced apoptosis in orthotopic hepatocellular carcinoma mouse model[2]. Animal Model: Male athymic BALB/c nu/nu mice (16-18 g; 4-6 weeks old) were inoculated with HepG2 cells[2] 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. |
| References |
| Boiling Point | 766.4ºC at 760 mmHg |
|---|---|
| Molecular Formula | C18H18Na4O12P2 |
| Molecular Weight | 580.23500 |
| Flash Point | 417.3ºC |
| Exact Mass | 579.98600 |
| PSA | 201.38000 |
| LogP | 4.58720 |
| Vapour Pressure | 1.06E-24mmHg at 25°C |