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Chemical Structure| 635702-64-6 Chemical Structure| 635702-64-6

Structure of Pazopanib HCl
CAS No.: 635702-64-6

Chemical Structure| 635702-64-6

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Pazopanib Hydrochloride (GW786034 Hydrochloride) is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFRβ, c-Kit, FGFR1, and c-Fms with IC50 values of 10 nM, 30 nM, 47 nM, 84 nM, 74 nM, 140 nM, and 146 nM, respectively.

Synonyms: GW786034 Hydrochloride; GW786034 HCl; Pazopanib(Hydrochloride)

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Product Citations

Product Citations

James A. Kaduk ; Amy M. Gindhart ; Thomas N. Blanton ;

Abstract: The crystal structure of pazopanib hydrochloride Form 1 has been refined using synchrotron X-ray powder diffraction data and optimized using density functional theory techniques. Pazopanib hydrochloride crystallizes in space group P-1 (#2) with a = 8.45008(6), b = 8.71310(12), c = 16.05489(35) Å, α = 79.5996(9), β = 86.4784(5), γ = 87.3764(3)°, V = 1159.724(9) Å3, and Z = 2. The crystal structure is essentially identical to that of CSD Refcode CEVYEK. There are four strong N–H⋯Cl hydrogen bonds to the chloride anion. Several additional weaker N–H⋯Cl and C–H⋯Cl hydrogen bonds are also present. A variety of C–H⋯O, C–H⋯N, and N–H⋯S hydrogen bonds also contribute to the lattice energy. The powder pattern has been submitted to ICDD® for inclusion in the Powder Diffraction File™.

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Product Details of Pazopanib HCl

CAS No. :635702-64-6
Formula : C21H24ClN7O2S
M.W : 473.98
SMILES Code : O=S(C1=CC(NC2=NC=CC(N(C3=CC4=NN(C)C(C)=C4C=C3)C)=N2)=CC=C1C)(N)=O.[H]Cl
Synonyms :
GW786034 Hydrochloride; GW786034 HCl; Pazopanib(Hydrochloride)
MDL No. :MFCD12546138
InChI Key :MQHIQUBXFFAOMK-UHFFFAOYSA-N
Pubchem ID :11525740

Safety of Pazopanib HCl

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Related Pathways of Pazopanib HCl

RTK

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
Human brain microvascular endothelial cells (HBMEC) 2 μM (48h), 1 μM (72h) 48h, 72h To confirm the anti-angiogenic activity of pazopanib, it inhibited the growth and tube formation of HBMEC. PMC3059742
231-BR-HER2 breast cancer cells 5 μM 96h Pazopanib inhibited the growth of 231-BR-HER2 cells and suppressed MEK and ERK activation. PMC3059742
ATC cell lines 3 to 18 µM Pazopanib inhibited colony formation in ATC cell lines with IC50 values ranging from 3 to 18 µM. PMC3905331
KTC2 ATC cells 2.5 µM 24 hours Pazopanib enhanced the inhibitory effect of paclitaxel on colony formation in KTC2 ATC cells, demonstrating synergy. PMC3905331
BV2 cells 1, 5, 10 μM 4 hours Inhibited LPS-induced BV2 cell activation by suppressing the transcription of proinflaμMatory factors iNOS, COX2, Il-1β, and Il-6 through the MEK4-JNK-AP-1 pathway PMC10203146
Primary anaplastic thyroid cancer cells (pATC) 1, 10, 25, 50 µM 24 hours To evaluate the antineoplastic effect of Pazopanib on pATC cells, the results showed that Pazopanib significantly inhibited cell proliferation. PMC9916618

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Nude mice 231-BR-HER2 breast cancer brain metastasis model Oral 200 mg/kg Once daily for 7 days Pazopanib significantly reduced the number of large and micrometastases of 231-BR-HER2 breast cancer cells in the brain. PMC3059742
Mice KTC2 ATC xenograft model Oral 1-30 mg/kg Twice daily for 14 days Combination of pazopanib and paclitaxel significantly reduced tumor volumes in the KTC2 ATC xenograft model, demonstrating synergy. PMC3905331
C57BL/6J mice LPS-stimulated Parkinson's disease model Intraperitoneal injection 30 mg/kg, 100 mg/kg Twice daily for 21 days Pazopanib significantly inhibited neuroinflammation, protected dopaminergic neurons, and improved motor abilities impaired by LPS in mice PMC10203146
Wistar albino rats D-galactose/ovariectomized Alzheimer’s rat model Intraperitoneal injection 287.5 mg/kg To investigate the impact of Pazopanib on cognitive impairment in D-galactose/ovariectomized rats and the underlying signaling pathways. Results showed that Pazopanib improved cognitive function, reversed histological abnormalities, significantly reduced p-Tau and Aβ plaques, and suppressed neuroinflammation and the RIPK1/RIPK3/MLKL necroptosis signaling pathway. PMC10518286

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT01027598 Non Small Cell Lung Cancer Phase 2 Completed - United States, Florida ... More >> Florida Cancer Specialists Fort Myers, Florida, United States, 33901 United States, Georgia Suburban Hem Onc Lawrenceville, Georgia, United States, 30045 United States, Ohio Oncology Hematology Care Cincinnati, Ohio, United States, 45242 United States, South Carolina South Carolina Oncology Associates, PA Columbia, South Carolina, United States, 29210 United States, Tennessee Chattanooga Oncology Hematology Associates Chattanooga, Tennessee, United States, 37404 Family Cancer Center Collerville, Tennessee, United States, 38119 Tennessee Oncology, PLLC Nashville, Tennessee, United States, 37023 United States, Virginia Virginia Cancer Institute Richmond, Virginia, United States, 23235 Less <<
NCT00788580 Unspecified Adult Solid Tumor,... More >> Protocol Specific Less << Phase 1 Withdrawn(Study was discontinu... More >>ed.) Less << - -
NCT01027598 - Completed - -
NCT01716416 Squamous Cell Carcinoma of the... More >> Head and Neck Less << Phase 1 Active, not recruiting December 31, 2018 United States, Missouri ... More >> Washington University School of Medicine Saint Louis, Missouri, United States, 63110 Less <<
NCT01472081 Renal Cell Carcinoma ... More >> Clear-cell Metastatic Renal Cell Carcinoma Less << Phase 1 Active, not recruiting June 2018 United States, California ... More >> City Of Hope Duarte, California, United States, 91010 United States, Maryland Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins Baltimore, Maryland, United States, 21231 United States, Massachusetts Beth Israel Deaconess Medical Center Boston, Massachusetts, United States, 02215 United States, New Hampshire Dartmouth-Hitchcock Medical Center Lebanon, New Hampshire, United States, 03756 United States, New York Memorial Sloan Kettering Cancer Center New York, New York, United States, 10065 United States, North Carolina Levine Cancer Institute Charlotte, North Carolina, United States, 28204 United States, Ohio Cleveland Clinic Cleveland, Ohio, United States, 44195 United States, Pennsylvania Fox Chase Cancer Center Philadelphia, Pennsylvania, United States, 19111 United States, Tennessee Tennessee Oncology, Pllc Nashville, Tennessee, United States, 37203 United States, Texas The University Of Texas Md Anderson Cancer Center Houston, Texas, United States, 77030 Canada, Alberta Tom Baker Cancer Centre Calgary, Alberta, Canada, T2N 4N2 Cross Cancer Institute Edmonton, Alberta, Canada, T6G 1Z2 Canada, British Columbia Bc Cancer Agency - Vancouver Centre Vancouver, British Columbia, Canada, V5Z 4E6 Canada, Ontario Princess Margaret Hospital-Uhn Toronto, Ontario, Canada, M5G 2M9 Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.11mL

0.42mL

0.21mL

10.55mL

2.11mL

1.05mL

21.10mL

4.22mL

2.11mL

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

 

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