Choose Your Country or Region

Fosbretabulin (Combretastatin A4 Phosphate) Disodium

Name: Fosbretabulin (Combretastatin A4 Phosphate) Disodium
Brand: Selleck Chemicals
SKU: S7204
Rating: 5 (11 reviews)

Synonyms: CA 4DP

Catalog No.S7204 Purity:99.86%

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 K_d 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

CAS No. 168555-66-6

Purity & Quality Control

Batch: Purity: 99.86%

99.86

Fosbretabulin (Combretastatin A4 Phosphate) Disodium Related Products

Related Products	Nocodazole Patupilone (Epothilone B) Lexibulin (CYT997) CW069 Combretastatin A4 ABT-751 (E7010) Epothilone A Cucurbitacin B TAI-1 Vindoline iHAP1 4-Demethylepipodophyllotoxin(NSC-122819,VM-26) MMAF TRx0237 (LMTX) mesylate INH1 Indibulin	Click to Expand
Related Compound Libraries	Kinase Inhibitor Library Angiogenesis Related compound Library TGF-beta/Smad compound library Cytoskeletal Signaling Pathway Compound Library Anti-Cardiovascular Disease Compound Library	Click to Expand

Signaling Pathway

Microtubule Associated Signaling Pathway

Cell Data

Cell Lines	Assay Type	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
Click to View More Cell Line Experimental Data

Biological Activity

Description

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
Kinase Assay	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
Experimental Result Images	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
Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2024-05-22)
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

References

+ Expand

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)	3 years-20°Cpowder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years-20°Cpowder		1 month-20°Cin solvent

In vitro
Batch:

Water : 28 mg/mL

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

Ethanol : Insoluble

Molecular Weight Calculator

In vivo Batch: Add solvents to the product individually and in order.				In vivo Formulation Calculator
Clear solution	saline	28.000mg/ml (63.59mM)	Taking the 1 mL working solution as an example, add 28 mg of this product to 1 ml of physiological saline (0.9% NaCL solution), mix evenly to make it clear, The mixed solution should be used immediately for optimal results.
Clear solution	saline	88.000mg/ml (199.87mM)	Taking the 1 mL working solution as an example, add 88 mg of this product to 1 ml of physiological saline (0.9% NaCL solution), mix evenly to make it clear, The mixed solution should be used immediately for optimal results.
Clear solution	Saline with a few drops of 5%Na2CO3 Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	30.000mg/ml (68.14mM)	Taking the 1 mL working solution as an example, add 30 mg of this product to 1 ml of physiological saline (0.9% NaCL solution, containing a few drops of 5% Na2CO3), mix evenly to make it clear, The mixed solution should be used immediately for optimal results.
Clear solution	saline	88.000mg/ml (199.87mM)	Taking the 1 mL working solution as an example, add 88 mg of this product to 1 ml of physiological saline (0.9% NaCL solution), mix evenly to make it clear, The mixed solution should be used immediately for optimal results.
Clear solution	saline	49.000mg/ml (111.29mM)	Taking the 1 mL working solution as an example, add 49 mg of this product to 1 ml of physiological saline (0.9% NaCL solution), mix evenly to make it clear, The mixed solution should be used immediately for optimal results.

Preparing Stock Solutions

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

* Indicates a Required Field

Tags: buy Fosbretabulin (Combretastatin A4 Phosphate) Disodium | Fosbretabulin (Combretastatin A4 Phosphate) Disodium supplier | purchase Fosbretabulin (Combretastatin A4 Phosphate) Disodium | Fosbretabulin (Combretastatin A4 Phosphate) Disodium cost | Fosbretabulin (Combretastatin A4 Phosphate) Disodium manufacturer | order Fosbretabulin (Combretastatin A4 Phosphate) Disodium | Fosbretabulin (Combretastatin A4 Phosphate) Disodium distributor

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):