Antibodies
Fosbretabulin (Combretastatin A4 Phosphate (CA4P)) Disodium
- 貨號 Cat. No.
- S7204
- 規格 Size
- 10mgã€25mg
- 品牌 Brand
- Selleckchem
Description
Fosbretabulin (Combretastatin A4 Phosphate (CA4P)) Disodium
Catalog No.S7204
Fosbretabulin (Combretastatin A4 Phosphate (CA4P)) Disodium is the water-soluble prodrug of Combretastatin A4 (CA4), which is amicrotubule-targeting agent that binds β-tubulin with Kd of 0.4 μM. Fosbretabulin Disodium inhibits the polymerization of tubulin with IC50 of 2.4 μM, and also disrupts tumor vasculature. Phase 3.
| Size | Price | Stock | Quantity | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| |||||||||||
Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
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. Fosbretabulin Disodium inhibits the polymerization of tubulin with IC50 of 2.4 μM, and also disrupts tumor vasculature. Phase 3. | |||||
|---|---|---|---|---|---|---|
| Targets | β-tubulin | |||||
| IC50 | 2.4 μM [1] | |||||
| 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] | |||||
| 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] | |||||
| Features | A microtubule associated inhibitor with higher affinity to β-tubulin vs. Colchicine. Best for advanced solid tumors, anaplastic thyroid cancer, & choroidal neovascularization. | |||||
Protocol(Only for Reference)
Kinase Assay:
| 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 |
|---|
Cell Assay:
| Cell lines | HUVECs |
|---|---|
| Concentrations | ~50 nM |
| Incubation Time | 12-48 h |
| Method | For the proliferation assay, the minimal concentration of FBS (1%) diluted in X-VIVO medium is used to allow sufficient viability of endothelial cells. After detachment, the cells are seeded at a concentration of 2×104HUVECs in each well of 24-well plates, allowed to adhere overnight, and then incubated with or without cytokines (5 ng/ml FGF-2 or 5 ng/ml VEGF-A). CA4P is added at 0 – 50 nM. After incubation for 12, 24, 36, and 48 hours, cells are detached by trypsin/EDTA and manually counted using trypan blue exclusion. |
Animal Study:
| Animal Models | BD9 rats implanted with tumor |
|---|---|
| Dosages | 100 mg/kg, 3 ml/kg |
| Administration | i.p. |
| Solubility | Saline with a few drops of 5% Na2CO3 , 30 mg/mL |
References
Clinical Trial Information( data from http://clinicaltrials.gov)
| NCT Number | Recruitment | Conditions | Sponsor /Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT00003698 | Active, not recruiting | Unspecified Adult Solid Tumor, Protocol Specific | National Cancer Institute (NCI)|University of Glasgow | 1998-07 | Phase 1 |
| NCT00003768 | Active, not recruiting | Unspecified Adult Solid Tumor, Protocol Specific | National Cancer Institute (NCI)|University Hospitals Seidman Cancer Center | 1998-09 | Phase 1 |
| NCT00060242 | Completed | Head and Neck Cancer | Case Comprehensive Cancer Center|National Cancer Institute (NCI) | 2003-02 | Phase 2 |
| NCT01570790 | Completed | Combretastatin A4 Phosphate|Age-related Macular Degeneration|AMD|CNV|Choroidal Neovascularization | Johns Hopkins University | 2003-05 | Phase 1|Phase 2 |
| NCT00077103 | Terminated | Head and Neck Cancer | Case Comprehensive Cancer Center|National Cancer Institute (NCI) | 2003-11 | Phase 1|Phase 2 |
Chemical Information
Download Fosbretabulin (Combretastatin A4 Phosphate (CA4P)) Disodium SDF
| Molecular Weight (MW) | 440.29 |
|---|---|
| Formula | C18H19O8P.2Na |
| CAS No. | 168555-66-6 |
| Storage | 3 years -20℃Powder |
|---|---|
| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | <1 mg/mL (<1 mM) |
|---|---|---|---|
| Water | 28 mg/mL (63 mM) | ||
| Ethanol | <1 mg/mL (<1 mM) | ||
| In vivo | Saline with a few drops of 5% Na2CO3 , | 30 mg/mL | |
| * <1 mg/ml means slightly soluble or insoluble. * 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 Name | Phenol, 2-methoxy-5-[(1Z)-2-(3,4,5-trimethoxyphenyl)ethenyl]-, 1-(dihydrogen phosphate), sodium salt (1:2) |
|---|
