Home Cytoskeletal Signaling Microtubule Associated inhibitor - Apoptosis related activator Fosbretabulin (Combretastatin A4 Phosphate) Disodium For research use only.

Fosbretabulin (Combretastatin A4 Phosphate) Disodium

Synonyms: CA 4DP

Fosbretabulin (Combretastatin A4 Phosphate) 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. Fosbretabulin disodium induces mitotic arrest and apoptosis in endothelial cells. Phase 3.

Fosbretabulin (Combretastatin A4 Phosphate) Disodium Chemical Structure

Fosbretabulin (Combretastatin A4 Phosphate) Disodium Chemical Structure

CAS No. 168555-66-6

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Fosbretabulin (Combretastatin A4 Phosphate) Disodium Related Products

Signaling Pathway

Microtubule Associated Signaling Pathways

Microtubule Associated Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
SKOV3 cells Proliferation assay Antiproliferative activity against human SKOV3 cells by sulforhodamine B assay, IC50=0.0045 μM 20973488
HeLa cells Proliferation assay Antiproliferative activity against human HeLa cells by sulforhodamine B assay, IC50=0.0047 μM 20973488
rat A10 cells Function assay Inhibition of microtubule depolymerization in rat A10 cells assessed as reorganization of interphase microtubule network by indirect immunofluorescence technique, EC50=0.007 μM 20973488
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Biological Activity

Description Fosbretabulin (Combretastatin A4 Phosphate) 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. Fosbretabulin disodium induces mitotic arrest and apoptosis in endothelial cells. Phase 3.
Features Best for advanced solid tumors, anaplastic thyroid cancer, & choroidal neovascularization.
Targets
Tubulin [1]
(Cell-free assay)
2.4 μM
In vitro
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 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]
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 Research 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 2×104 HUVECs 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.
Experimental Result Images Methods Biomarkers Images PMID
Immunofluorescence tubulin / VE-cadherin Actin / N-cadherin / CD31 29221156
In Vivo
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]
Animal Research Animal Models BD9 rats implanted with tumor
Dosages 100 mg/kg, 3 ml/kg
Administration i.p.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02641639 Terminated
Platinum Resistant Ovarian Cancer
Mateon Therapeutics
 June 2016 Phase 2|Phase 3
NCT02055690 Terminated
Ovarian Neoplasms|Neoplasms Ovarian|Ovarian Cancer
The Christie NHS Foundation Trust|Novartis|Mateon Therapeutics|East and North Hertfordshire NHS Trust
 September 2014 Phase 1|Phase 2
NCT01023295 Completed
Polypoidal Choroidal Vasculopathy
Mateon Therapeutics
 July 2009 Phase 2

Chemical Information & Solubility

Molecular Weight 440.29 Formula

C18H19O8P.2Na
CAS No. 168555-66-6 SDF Download Fosbretabulin (Combretastatin A4 Phosphate) Disodium SDF
Smiles COC1=C(C=C(C=C1)C=CC2=CC(=C(C(=C2)OC)OC)OC)OP(=O)([O-])[O-].[Na+].[Na+]
Storage (From the date of receipt)

In vitro
Batch:

Water : 28 mg/mL

DMSO : Insoluble ( Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : Insoluble


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