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Chemical Structure| 168555-66-6 Chemical Structure| 168555-66-6

Structure of Fosbretabulin disodium
CAS No.: 168555-66-6

Chemical Structure| 168555-66-6

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Fosbretabulin 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.

Synonyms: Combretastatin A4 disodium phosphate; CA 4P; CRC 87-09

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Product Details of Fosbretabulin disodium

CAS No. :168555-66-6
Formula : C18H19Na2O8P
M.W : 440.29
SMILES Code : O=P([O-])([O-])OC1=CC(/C=C\C2=CC(OC)=C(OC)C(OC)=C2)=CC=C1OC.[Na+].[Na+]
Synonyms :
Combretastatin A4 disodium phosphate; CA 4P; CRC 87-09
MDL No. :MFCD00943911

Safety of Fosbretabulin disodium

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of Fosbretabulin disodium

cytoskeleton

Isoform Comparison

Biological Activity

Description
Fosbretabulin disodium (CA 4DP) is a tubulin destabilizing agent and is a proagent of Combretastatin A4, specifically targeting endothelial cells. It induces the regression of nascent tumor neovessels, diminishes tumor blood flow, and leads to central tumor necrosis[1].[3].

In Vitro:

Cell Line
Concentration Treated Time Description References
b3NULL endothelial cells 0.5 μM 15 h Test the effect of Fosbretabulin on random migration of b3NULL endothelial cells, results showed b3NULL cells were sensitive to Fosbretabulin. PMC6030693
b3HET endothelial cells 0.5 μM 15 h Test the effect of Fosbretabulin on random migration of b3HET endothelial cells, results showed b3HET cells were sensitive to Fosbretabulin. PMC6030693
b3WT endothelial cells 0.5 μM 15 h Test the effect of Fosbretabulin on random migration of b3WT endothelial cells, results showed b3WT cells were insensitive to Fosbretabulin. PMC6030693

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Nude mice DLD-1 and HT29 xenograft tumor models Intraperitoneal injection 250 mg/kg Once weekly for 5 weeks Evaluate the antitumor efficacy of Fosbretabulin on DLD-1 and HT29 xenograft tumors PMC8658273
Mice Subcutaneous tumor model Intraperitoneal injection 50 mg/kg Every 4 days for 21 days Test the effect of Fosbretabulin on tumor growth and angiogenesis, results showed Fosbretabulin reduced tumor growth and vascular density in Cre-positive animals. PMC6030693

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT00507429 Anaplastic Thyroid Cancer Phase 2 Phase 3 Terminated(Low rate of subject... More >> accrual) Less << - -
NCT00395434 Tumors Phase 1 Completed - United Kingdom ... More >> Mount Vernon Hospital Northwood, Middlesex, United Kingdom, HA6 2RN Royal Marsden Hospital Sutton, Surrey, United Kingdom, SM2 5PT Less <<
NCT00653939 Tumors Phase 2 Completed - United States, California ... More >> Southbay Oncology Hematology Campbell, California, United States, 95008 Pacific Coast Hematology and Oncology Medical Group Fountain Valley, California, United States, 92708 UCLA Division of Hematology and Oncology Los Angeles, California, United States, 90095 Bay Area Cancer Research Group, LLC Pleasant Hill, California, United States, 94523 United States, Florida Boca Raton Comprehensive Cancer Center Boca Raton, Florida, United States, 21020 United States, Kentucky Kentuckiana Cancer Institute Louisville, Kentucky, United States, 40202 United States, Massachusetts Lahey Clinic Medical Center Burlington, Massachusetts, United States, 01805 United States, New Jersey The Center for Cancer and Hematologic Disease Cherry Hill, New Jersey, United States, 08003 United States, New Mexico San Juan Oncology Associates Farmington, New Mexico, United States, 87401 United States, Ohio Gabrail Cancer Center Canton, Ohio, United States, 44718 The Mark H. Zangmeister Center Columbus, Ohio, United States, 43219 Signal Point Clinical Research Middletown, Ohio, United States, 45042 United States, Virginia Blueridge Cancer Care Salem, Virginia, United States, 24153 United States, Washington Northwest Medical Specialties Tacoma, Washington, United States, 98405 United States, West Virginia Mary Babb Randolph Cancer Center-Clinical Trials Unit Morgantown, West Virginia, United States, 26506 Less <<
NCT00507429 - Terminated(Low rate of subject... More >> accrual) Less << - -
NCT01052363 Central Nervous System Tumors Phase 1 Withdrawn(No funding) - United States, West Virginia ... More >> MBRCC, West Virginia University Morgantown, West Virginia, United States, 26506 Less <<
NCT00077103 Head and Neck Cancer Phase 1 Phase 2 Terminated(slow accrual) - United States, Michigan ... More >> Josephine Ford Cancer Center at Henry Ford Hospital Detroit, Michigan, United States, 48202 United States, Ohio Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center Cleveland, Ohio, United States, 44106-5065 United States, Pennsylvania Hillman Cancer Center at University of Pittsburgh Cancer Institute Pittsburgh, Pennsylvania, United States, 15232 Less <<
NCT00003768 Unspecified Adult Solid Tumor,... More >> Protocol Specific Less << Phase 1 Completed - United States, Ohio ... More >> Ireland Cancer Center Cleveland, Ohio, United States, 44106-5065 Less <<
NCT00003698 Unspecified Adult Solid Tumor,... More >> Protocol Specific Less << Phase 1 Completed - United Kingdom ... More >> Mount Vernon Hospital Northwood, England, United Kingdom, HA6 2RN Less <<
NCT02279602 Neuroendocrine Tumors Phase 2 Completed - United States, California ... More >> Stanford University School of Medicine Stanford, California, United States, 94305 United States, Kentucky Markey Cancer Center, Clinical Research Office Lexington, Kentucky, United States, 40356 United States, New York Montefiore Bronx, New York, United States, 10467 United States, North Carolina Duke University Medical Center Durham, North Carolina, United States, 27710 United States, Wisconsin Froedtert Hospital, Medicial College of Wisconsin Milwaukee, Wisconsin, United States, 53226 Less <<
NCT01305213 Recurrent Fallopian Tube Carci... More >>noma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma Less << Phase 2 Completed - -
NCT02132468 - Completed - -
NCT00653939 - Completed - -
NCT02132468 Neuroendocrine Tumors Phase 2 Completed - United States, California ... More >> Stanford University School of Medicine Stanford, California, United States, 94305 United States, Kentucky Markey Cancer Center, Clinical Research Office Lexington, Kentucky, United States, 40356 United States, New York Montefiore Bronx, New York, United States, 10467 United States, North Carolina Duke University Medical Center Durham, North Carolina, United States, 27710 United States, Wisconsin Froedtert Hospital, Medicial College of Wisconsin Milwaukee, Wisconsin, United States, 53226 Less <<
NCT00113438 Cancer Tumor Phase 2 Completed - United States, Utah ... More >> Huntsman Cancer Institute Salt Lake City, Utah, United States, 84112 Less <<
NCT01305213 - Completed - -
NCT01701349 Anaplastic Thyroid Cancer Phase 3 Withdrawn(Expected inability t... More >>o recruit study participants in a reasonable amount of time.) Less << December 2017 -
NCT01423149 Choroidal Neovascularization ... More >> Myopia, Degenerative Less << Phase 2 Completed - -
NCT00060242 Head and Neck Cancer Phase 2 Completed - United States, Michigan ... More >> Josephine Ford Cancer Center at Henry Ford Hospital Detroit, Michigan, United States, 48202 United States, Ohio Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center Cleveland, Ohio, United States, 44106-5065 United States, Pennsylvania Hillman Cancer Center at University of Pittsburgh Cancer Institute Pittsburgh, Pennsylvania, United States, 15232 Less <<
NCT02641639 Platinum Resistant Ovarian Can... More >>cer Less << Phase 2 Phase 3 Terminated(Interim analysis fa... More >>iled to show efficacy benefit) Less << - -
NCT01023295 Polypoidal Choroidal Vasculopa... More >>thy Less << Phase 2 Completed - United States, California ... More >> OXiGENE Investigational Site Los Angeles, California, United States Hong Kong OXiGENE Investigational Site Hong Kong, Hong Kong Korea, Republic of OXiGENE Investigational Site Seoul, Korea, Republic of Singapore OXiGENE Investigational Site Singapore, Singapore Taiwan OXiGENE Investigational Site Changhua, Taiwan Less <<
NCT01570790 Combretastatin A4 Phosphate ... More >> Age-related Macular Degeneration AMD CNV Choroidal Neovascularization Less << Phase 1 Phase 2 Completed - United States, Maryland ... More >> Wilmer Eye Institute Baltimore, Maryland, United States, 21287 Less <<
NCT03014297 Neuroendocrine Tumors ... More >> Everolimus Less << Phase 1 Active, not recruiting June 30, 2019 United States, Kentucky ... More >> University of Kentucky Markey Cancer Center Lexington, Kentucky, United States, 40502 Less <<
NCT02055690 Ovarian Neoplasms ... More >> Neoplasms, Ovarian Ovarian Cancer Less << Phase 1 Phase 2 Terminated(Safety) - United Kingdom ... More >> Royal United Hospital Bath NHS Trust Bath, United Kingdom, BA1 3NG City Hospital Birmingham, United Kingdom, B18 7GH University Hospitals Bristol NHS Foundation Trust Bristol, United Kingdom, BS1 3NU University Collage London Hospitals NHS Foundation Trust London, United Kingdom, NW1 2PG The Royal Marsden NHS Foundation Trust London, United Kingdom, SM2 5PT The Christie NHS Foundation Trust Manchester, United Kingdom, M20 4BX Clatterbridge Centre for Oncology NHS Foundation Trust Merseyside, United Kingdom, CH63 4JY Mount Vernon Cancer Centre (East and North Herts NHS Trust) Middlesex, United Kingdom, HA6 2RN Freeman Hospital (Newcastle-upon-Tyne Hospitals NHS Foundation Trust) Newcastle-upon-Tyne And Wear, United Kingdom, NE7 7DN Oxford Radcliffe Hospitals NHS Trust Oxford, United Kingdom, OX3 9DU Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.27mL

0.45mL

0.23mL

11.36mL

2.27mL

1.14mL

22.71mL

4.54mL

2.27mL

Dissolving Methods
The prepared working fluid is recommended to be prepared now and used up as soon as possible in a short period of time. The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1

References

 

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