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Chemical Structure| 117048-59-6 Chemical Structure| 117048-59-6

Structure of Combretastatin A4
CAS No.: 117048-59-6

Chemical Structure| 117048-59-6

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Combretastatin A4 is a tubulin polymerization inhibitor with Kd value of 0.4 μM for binding to β-tubulin.

Synonyms: CRC 87-09; Combrestatin A4; CA4

4.5 *For Research Use Only !

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Product Details of Combretastatin A4

CAS No. :117048-59-6
Formula : C18H20O5
M.W : 316.35
SMILES Code : OC1=CC(/C=C\C2=CC(OC)=C(OC)C(OC)=C2)=CC=C1OC
Synonyms :
CRC 87-09; Combrestatin A4; CA4
MDL No. :MFCD03453309
InChI Key :HVXBOLULGPECHP-WAYWQWQTSA-N
Pubchem ID :5351344

Safety of Combretastatin A4

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H301+H311+H331-H318
Precautionary Statements:P261-P264-P270-P271-P280-P301+P310+P330-P302+P352+P312-P304+P340+P311-P305+P351+P338+P310-P403+P233-P405-P501
Class:6.1
UN#:2811
Packing Group:

Related Pathways of Combretastatin A4

cytoskeleton

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
HUVECs cocultured with SMCs 10 nM 48 hours To evaluate whether SMCs protect HUVECs from CA4P-induced cell death. Results showed that HUVECs cocultured with SMCs were resistant to CA4P. PMC1253622
Smooth muscle cells (SMCs) 50 nM 48 hours To assess the effect of CA4P on smooth muscle cells. Results showed that SMCs were not sensitive to CA4P, even at high concentrations. PMC1253622
Human umbilical vein endothelial cells (HUVECs) 1, 5, 10, 20, 30, 40, 50 nM 12, 24, 36, 48 hours To evaluate the effect of R-2-HG on endothelial cell migration, results showed that R-2-HG significantly enhanced the migration ability of HUVECs. PMC1253622
Human colon cancer cell line LS174-T 10 μM 72 hours To evaluate the cytotoxicity and apoptosis-inducing effects of SQ-gem/isoCA-4 nanocomposites on LS174-T cells, showing comparable effects to free drugs. PMC4060170
Human umbilical vein endothelial cells (HUVECs) 10 μM 72 hours To evaluate the effect of R-2-HG on endothelial cell migration, results showed that R-2-HG significantly enhanced the migration ability of HUVECs. PMC4060170
HER2-CAR-T cells 10 ng/mL CA4P inhibits the proliferation of HER2-CAR-T cells PMC6953963
HT-29 (colon cancer cell line) 0.1 ng/mL or higher CA4P inhibits the proliferation of HT-29 cells PMC6953963
SKOV3 (ovarian cancer cell line) 0.1 ng/mL or higher CA4P inhibits the proliferation of SKOV3 cells PMC6953963
LO2 cells 0.0025–25 μM 48 hours PMC8088584
HepG2 cells 0.0025–25 μM 48 hours Evaluate the effect of SR9009 on BMAL1 mRNA expression PMC8088584
Human umbilical vascular endothelial cells (HUVECs) 0.001 ng/mL 18 hours IDF-11774 inhibited capillary network formation of HUVECs on Matrigel, indicating anti-angiogenic effects. PMC6953963
Human umbilical vascular endothelial cells (HUVECs) 0.01 mg/mL 24 hours IDF-11774 inhibited capillary network formation of HUVECs on Matrigel, indicating anti-angiogenic effects. PMC6953963
Human umbilical vascular endothelial cells (HUVECs) 0.1 ng/mL or higher IDF-11774 inhibited capillary network formation of HUVECs on Matrigel, indicating anti-angiogenic effects. PMC6953963
Primary hepatocytes 0.0025–25 μM 48 hours To evaluate the effect of ethanol on hepatocyte death, it was found that ethanol increased the sensitivity of hepatocytes to TNF α-induced cell death, which was attenuated by the necroptosis inhibitor necrostatin-1 but not by caspase inhibitors. Induction of HO-1 or treatment with CORM-3 normalized the sensitivity of hepatocytes to TNF α-induced cell death. PMC8088584
Hepa1-6 cells 0.0025–25 μM 48 hours Evaluate the cytotoxicity of CA4-NPs on Hepa1-6 cells, results showed that CA4-NPs had lower cytotoxicity than CA4 in limited time due to incomplete drug release. PMC8088584

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
C57BL/6 mice B16 melanoma model Intravenous (CA4P), intraperitoneal (BV13 or E4G10) 5 mg/kg Every 2 days for 8 days To evaluate the effect of CA4P alone or in combination with anti–VE-cadherin antibodies on tumor growth and angiogenesis. Results showed that CA4P combined with anti–VE-cadherin antibodies significantly inhibited tumor growth and angiogenesis, and induced tumor necrosis. PMC1253622
Female athymic nude mice Human colon carcinoma xenograft model LS174-T Intravenous injections 20 μmol/kg Injections on days 0, 4, 8, and 12, lasting for 22 days To evaluate the antitumor efficacy of SQ-gem/isoCA-4 nanocomposites in the LS174-T xenograft model, showing 93% tumor inhibition and better tolerance than free drug treatments. PMC4060170
Female Balb/C mice 4T1 mammary tumor model Intravenous injection 35 mg/kg Once on day 12 and day 19 PLG-CA4 induces the polarization of tumor-associated macrophages (TAMs) toward the M2-like phenotype in 4T1 metastatic breast cancer. Compared to the monotherapy of PLG-CA4, inhibition of PI3Kγ attenuates the immunosuppressive effect of PLG-CA4 treatment by decreasing the number of M2-like TAMs and enhancing cytotoxic T lymphocytes (CTLs), significantly extending the mean survival time. PMC6662090
Mice MMTV-PyMT mammary tumor model Intraperitoneal injection 50 mg/kg Single injection, culled 24 hours later CA4P induced vessel narrowing, hypoxia, and hemorrhagic necrosis, accompanied by elevated tumor levels of CXCL12 and infiltration by TEMs. PMC3083764
Mice Myelosuppression model Intravenous injection 25 mg/kg Every other day CA4P delays platelet recovery and blocks rebound thrombocytosis PMC1679710
NOD-Prkdc scid IL-2rg null (NPG) mice SKOV3 cell-derived xenograft (CDX) model Intraperitoneal injection 100 mg/kg Single injection CA4P combined with HER2-CAR-T cells significantly inhibits SKOV3 tumor growth PMC6953963
C57BL/6 mice Subcutaneous Hepa1-6 hepatic tumor models Intravenous injection 20 mg/kg and 40 mg/kg Administered on day 1 and day 8 Evaluate the anti-tumor efficacy of CA4-NPs combined with aPD-L1 in Hepa1-6 hepatic tumor models, results showed significant reduction in tumor volume and weight, and prolonged survival time in the combination group. PMC8088584
Balb/c mice H22 subcutaneous tumor model Intravenous injection 45 mg/kg Single dose CA4-NPs effectively reduced the HCC tumor burden by disrupting tumor blood vessels, inhibiting tumor cell proliferation, and enhancing tumor cell necrosis. PMC8058708
Mice MeWo human melanoma nude mouse model Intraperitoneal injection 100 mg/kg Single dose, evaluated 4 hours post-treatment To evaluate the effect of OXi-4503 on plasma levels of G-CSF, VEGF, and SDF-1, showing significant increases in these factors PMC2758166
SCID mice Bilateral subcutaneous RIF-1 tumor xenografts Intravenous injection 10 mg/kg Single treatment with 24-hour interval To evaluate the therapeutic efficacy of SMSDTTS, including survival rate, tumor volume, and necrosis ratio. Results showed that the treatment group significantly prolonged survival, inhibited tumor growth, and increased tumor necrosis ratio compared to control groups. PMC3575593

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
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 <<
NCT00507429 Anaplastic Thyroid Cancer Phase 2 Phase 3 Terminated(Low rate of subject... More >> accrual) 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 <<
NCT00507429 - Terminated(Low rate of subject... More >> accrual) 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 <<
NCT01305213 - Completed - -
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 <<
NCT01305213 Recurrent Fallopian Tube Carci... More >>noma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma Less << Phase 2 Completed - -
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 <<
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 <<
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 <<
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 <<
NCT02132468 - Completed - -
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 <<
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 <<
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 <<
NCT00113438 Cancer Tumor Phase 2 Completed - United States, Utah ... More >> Huntsman Cancer Institute Salt Lake City, Utah, United States, 84112 Less <<
NCT01701349 Anaplastic Thyroid Cancer Phase 3 Withdrawn(Expected inability t... More >>o recruit study participants in a reasonable amount of time.) Less << December 2017 -
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 <<
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 <<
NCT01423149 Choroidal Neovascularization ... More >> Myopia, Degenerative Less << Phase 2 Completed - -
NCT02641639 Platinum Resistant Ovarian Can... More >>cer Less << Phase 2 Phase 3 Terminated(Interim analysis fa... More >>iled to show efficacy benefit) Less << - -

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

3.16mL

0.63mL

0.32mL

15.81mL

3.16mL

1.58mL

31.61mL

6.32mL

3.16mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

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
Protocol 2

References

 

Historical Records

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