Fosbretabulin (Combretastatin A4 Phosphate (CA4P)) Disodium
Catalog No.S7204
Molecular Weight(MW): 440.29
Fosbretabulin (Combretastatin A4 Phosphate (CA4P)) Disodium is the water-soluble prodrug of Combretastatin A4 (CA4), which is a microtubule-targeting agent that binds β-tubulin with Kd of 0.4 μM in a cell-free assay. Fosbretabulin Disodium inhibits the polymerization of tubulin with IC50 of 2.4 μM, and also disrupts tumor vasculature. Phase 3.
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Real-time hemodynamic changes in the tumor upon administration of CA4P. Panel A shows the MRI anatomical reference of the tumor, followed by sO2 maps of a slice of brain showing the largest cross section of the tumor at time points 0, 1, 4 and 6 h. post CA4P administration. Panel B shows the real-time sO2 changes in the tumor and contralateral brain occurring immediately post CA4P administration over 1 hour in a representative animal. SD is represented by lighter shades on the graph. Panel C shows the real-time sO2 changes in the tumor and contralateral brain occurring immediately post CA4P administration (n = 4). Panel D shows the quantification of hypoxia in tumors using CAIX as a marker at times 0 (n = 3), 1 (n = 4) and 6 h. (n = 3) post CA4P administration. Unpaired t-test showed statistically significant difference in CAIX staining at 1 hour post CA4P administration compared to 0 and 6 hours. ** ‐ P > 0.01. Black dotted circle and Red full circle denote the ROIs drawn at the tumor and contralateral brain respectively to compute the sO2.
Transl Oncol, 2018, 11(5):1251-1258. Fosbretabulin (Combretastatin A4 Phosphate (CA4P)) Disodium purchased from Selleck.
Immunofluorescence analysis of the effects of CA4P on NECs using confocal microscopy. The effects of CA4P (100 nM) on tubulin (pseudo-color green) and actin (pseudo-color red) were evaluated in subconfluent and 100% confluent NECs. Nuclei are shown in pseudo-color blue. CA4P (100 nM) disrupted tubulin on both subconfluent and 100% confluent NECs in a time-dependent manner. In subconfluent NECs, cell morphology was gradually changed from a spindle shape to a round shape, and actin reorganization was observed by adding 100 nM CA4P for 3 h. However, CA4P did not affect cell morphology or actin in 100% confluent NECs. Scale bar = 20 μm. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Res Vet Sci, 2017, 112:222-228. Fosbretabulin (Combretastatin A4 Phosphate (CA4P)) Disodium purchased from Selleck.
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Representative images of Dylight 488-tomato lectin (pseudo-colored green) and Alexa-fluor 555-CD31 (pseudo-colored red) immuno-stained frozen sections from xenografted canine osteosarcoma tumors in the different treatment groups: control; combretastatin A-4 phosphate (CA4P, 30 mg/kg); VE-cadherin neutralizing antibody (VEC NAb, 40 μg/mouse); combination treatment (30 mg/kg CA4P 21 h after 40 μg VEC NAb); and CA4P (100 mg/kg). The upper half of this figure shows the image of the whole tumor and the lower half shows a magnified image. Tumors were excised 3 h after CA4P treatment or 24 h after VEC NAb treatment. Scale bars represent 1 mm or 100 μm.
Res Vet Sci, 2018, 122:1-6. Fosbretabulin (Combretastatin A4 Phosphate (CA4P)) Disodium purchased from Selleck.
Purity & Quality Control
Choose Selective Microtubule Associated Inhibitors
Biological Activity
| Description | Fosbretabulin (Combretastatin A4 Phosphate (CA4P)) Disodium is the water-soluble prodrug of Combretastatin A4 (CA4), which is a microtubule-targeting agent that binds β-tubulin with Kd of 0.4 μM in a cell-free assay. Fosbretabulin Disodium inhibits the polymerization of tubulin with IC50 of 2.4 μM, and also disrupts tumor vasculature. Phase 3. | ||||||||||||||||||||||||||||||
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| Features | A microtubule associated inhibitor with higher affinity to β-tubulin vs. Colchicine. Best for advanced solid tumors, anaplastic thyroid cancer, & choroidal neovascularization. | ||||||||||||||||||||||||||||||
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| In vitro |
Fosbretabulin disodium (Combretastatin A-4 phosphate disodium, CA4P disodium) is the water-soluble prodrug of combretastatin A4 (CA4), which is originally isolated from African tree Combretum caffrum. CA4 is a tubulin-binding agent that binds at or near the colchicine binding site of β-tubulin (Kd = 0.40 μM), inhibits tubulin assembly with IC50 of 2.4 μM. [1] CA4 is cytotoxic towards proliferating but not quiescent endothelial cells, has potent and selective toxicity towards tumor vasculature. [2] CA4P (1 mM, 30 minutes) disrupts the endothelial microtubule cytoskeleton and mediates changes in endothelial cell morphology. CA4P stimulates actin stress fiber formation and membrane blebbing and increases monolayer permeability via Rho/Rho-kinase. [3] CA4P increases endothelial cell permeability, while inhibiting endothelial cell migration and capillary tube formation predominantly through disruption of VE-cadherin/β-catenin/Akt signaling pathway, thereby leading to rapid vascular collapse and tumor necrosis. [4] |
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| In vivo | CA4P causes rapid, extensive and irreversible vascular shutdown in experimental tumor models following the administration of a single dose at 10% of the maximum tolerated dose (MTD). CA4P causes a 93% reduction in vascular volume 6 h following drug administration. [2] CA4P(100 mg/kg, 6 h following administration) reduces tumor blood by approximately 100-fold, compared with approximately 7-fold in the spleen. [5] |
Protocol
| Kinase Assay: |
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Tubulin assembly-disassembly: The assembly of microtubules from isolated tubulin is carried out spectrophotometrically at 350 nm and utilises the increase in turbidity which is associated with microtubule formation. Assembly is initiated by temperature increase from 10 to 35 °C. The effect of drugs on the increase in light absorption is carried. Drugs are dissolved in DMSO (<4%), which does not affect control assembly |
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Solubility (25°C)
| In vitro | Water | 28 mg/mL (63.59 mM) |
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| DMSO | Insoluble | |
| Ethanol | Insoluble | |
| In vivo | Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): Saline with a few drops of 5% Na2CO3 For best results, use promptly after mixing. |
30 mg/mL |
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Information
| Molecular Weight | 440.29 |
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| Formula | C18H19O8P.2Na |
| CAS No. | 168555-66-6 |
| Storage | powder |
| in solvent | |
| Synonyms | N/A |
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Clinical Trial Information
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
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| NCT02641639 | Terminated | Drug: Fosbretabulin tromethamine|Drug: Placebo | Platinum Resistant Ovarian Cancer | Mateon Therapeutics | June 2016 | Phase 2|Phase 3 |
| NCT02055690 | Terminated | Drug: Pazopanib|Drug: Fosbretabulin | Ovarian Neoplasms|Neoplasms Ovarian|Ovarian Cancer | Heather Driscoll|Novartis|Mateon Therapeutics|East and North Hertfordshire NHS Trust|The Christie NHS Foundation Trust | September 2014 | Phase 1|Phase 2 |
| NCT01023295 | Completed | Drug: fosbretabulin|Drug: Saline | Polypoidal Choroidal Vasculopathy | Mateon Therapeutics | July 2009 | Phase 2 |
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