Pazopanib

Catalog No.S3012 Batch:S301204

Technical Data

Formula	C₂₁H₂₃N₇O₂S
Molecular Weight	437.52	CAS No.	444731-52-6
Solubility (25°C)*	In vitro	DMSO	88 mg/mL (201.13 mM)
		Water	Insoluble
		Ethanol	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

Pazopanib (GW786034) is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFR, FGFR, c-Kit and c-Fms/CSF1R with IC50 of 10 nM, 30 nM, 47 nM, 84 nM, 74 nM, 140 nM and 146 nM in cell-free assays, respectively. Pazopanib induces cathepsin B activation and autophagy.

Targets

VEGFR1 ^[1] (Cell-free assay)	VEGFR2 ^[1] (Cell-free assay)	VEGFR3 ^[1] (Cell-free assay)	c-Kit ^[1] (Cell-free assay)	PDGFR ^[1] (Cell-free assay)	View More
10 nM	30 nM	47 nM	74 nM	84 nM	View More

In vitro

Pazopanib potently inhibits VEGF-induced phosphorylation of VEGFR2 in HUVEC cells with IC50 of 8 nM. ^[1]

PPazopanib shows dose-dependent growth inhibition in all synovial sarcoma cell lines including SYO-1 and HS-SY-II cells. Proliferation of SYO-1 and HS-SY-II cells is inhibited even at 1 µg/mL of Pazopanib and is completely abolished at 5 µg/mL. Pazopanib induces G1 arrest, and thereby suppresses the growth of synovial sarcoma cells. Phosphorylation of Akts, GSK-3β, JNKs, p70 S6 Kinase, and mTOR is suppressed in Pazopanib-treated SYO-1 cells compared with that in the vehicle-treated cells. ^[2]

Pazopanib between 20 m g/mL and 22.5 m g/mL shows an increasing reduction of RPE cell viability. ^[3]

In vivo

The mice treated with 30 mg/kg or 100 mg/kg Pazopanib reveals a significant decrease in tumor burden compared with the mice treated with vehicle or 10 mg/kg Pazopanib. Treatment with Pazopanib is well-tolerated and there is no significant difference in the body weight among the mice in each group. ^[2]

Protocol (from reference)

Kinase Assay:^{^[1]}	Kinase enzyme assays VEGFR enzyme assays for VEGGR1, VEGFR2, and VEGFR3 are run in homogeneous time-resolved fluorescence (HTRF) format in 384-well microtiter plates using a purified, baculovirus-expressed glutathione-S-transferase (GST) fusion protein encoding the catalytic c-terminus of human VEGFR receptor kinases 1, 2, or 3. Reactions are initiated by the addition of 10 μL of activated VEGFR2 kinase solution [final concentration, 1 nM enzyme in 0.1 M HEPES, pH 7.5, containing 0.1 mg/mL bovine serum albumin (BSA), 300 μM dithiothreitol (DTT)] to 10 μL substrate solution [final concentration, 360 nM peptide, (biotin-aminohexyl-EEEEYFELVAKKKK-NH2), 75 μM ATP, 10 μM MgCl₂], and 1 μL of titrated Pazopanib in DMSO. Plates are incubated at room temperature for 60 min, and then the reaction is quenched by the addition of 20 μL of 100 mM ethylene diamine tetraacetic acid (EDTA). After quenching, 20 μL HTRF reagents (final concentration, 15 nM Streptavidin-linked allophycocyanin, 1 nM Europium-labeled antiphosphotyrosine antibody diluted in 0.1 mg/mL BSA, 0.1 M HEPES, pH 7.5) is added and the plates incubated for a minimum of 10 min. The fluorescence at 665 nM is measured with a Wallac Victor plate reader using a time delay of 50 μs.
Animal Study:^{^[2]}	Animal Models Immunodeficient mice bearing SYO-1 cells Dosages 0 mg/kg, 10 mg/kg, 30 mg/kg, or 100 mg/kg Administration Oral administration

Kinase Assay:^{^[1]}

Kinase enzyme assays
VEGFR enzyme assays for VEGGR1, VEGFR2, and VEGFR3 are run in homogeneous time-resolved fluorescence (HTRF) format in 384-well microtiter plates using a purified, baculovirus-expressed glutathione-S-transferase (GST) fusion protein encoding the catalytic c-terminus of human VEGFR receptor kinases 1, 2, or 3. Reactions are initiated by the addition of 10 μL of activated VEGFR2 kinase solution [final concentration, 1 nM enzyme in 0.1 M HEPES, pH 7.5, containing 0.1 mg/mL bovine serum albumin (BSA), 300 μM dithiothreitol (DTT)] to 10 μL substrate solution [final concentration, 360 nM peptide, (biotin-aminohexyl-EEEEYFELVAKKKK-NH2), 75 μM ATP, 10 μM MgCl₂], and 1 μL of titrated Pazopanib in DMSO. Plates are incubated at room temperature for 60 min, and then the reaction is quenched by the addition of 20 μL of 100 mM ethylene diamine tetraacetic acid (EDTA). After quenching, 20 μL HTRF reagents (final concentration, 15 nM Streptavidin-linked allophycocyanin, 1 nM Europium-labeled antiphosphotyrosine antibody diluted in 0.1 mg/mL BSA, 0.1 M HEPES, pH 7.5) is added and the plates incubated for a minimum of 10 min. The fluorescence at 665 nM is measured with a Wallac Victor plate reader using a time delay of 50 μs.

Animal Study:^{^[2]}

Animal Models
Immunodeficient mice bearing SYO-1 cells
Dosages
0 mg/kg, 10 mg/kg, 30 mg/kg, or 100 mg/kg
Administration
Oral administration

References

Customer Product Validation

: Data from [Data independently produced by Expert Opin Pharmacother, 2014, 15(11), 1489-99]

: Data from [J Virol, 2011, 85(5), 2296-303]

: Data from [Data independently produced by , , Arch Toxicol, 2018, 92(4):1435-1451]

: Data from [Data independently produced by , , Sci Rep, 2016, 6:31589]

Selleck's Pazopanib has been cited by 77 publications

Melatonin alleviates chronic stress-induced hippocampal microglia pyroptosis and subsequent depression-like behaviors by inhibiting Cathepsin B/NLRP3 signaling pathway in rats [ Transl Psychiatry, 2024, 14(1):166]	PubMed: 38538614
Extensive analysis of 59 sarcoma-related fusion genes identified pazopanib as a potential inhibitor to COL1A1-PDGFB fusion gene [ Cancer Sci, 2023, 114(10):4089-4100]	PubMed: 37592448
Extensive analysis of 59 sarcoma-related fusion genes identified pazopanib as a potential inhibitor to COL1A1-PDGFB fusion gene [ Cancer Sci, 2023, 10.1111/cas.15915]	PubMed: 37592448
Immune suppressive signaling regulated by latent transforming growth factor beta binding protein 1 promotes metastasis in cervical cancer [ Braz J Med Biol Res, 2023, 55:e12206]	PubMed: 36629522
miRNA-381 regulates renal cancer stem cell properties and sunitinib resistance via targeting SOX4 [ Biochem Biophys Rep, 2023, 10.1016/j.bbrep.2023.101566]	PubMed: 37965067
RECOVER identifies synergistic drug combinations in vitro through sequential model optimization [ Cell Rep Methods, 2023, 3(10):100599]	PubMed: 37797618
Therapeutic and immunomodulatory potential of pazopanib in malignant phyllodes tumor [ NPJ Breast Cancer, 2022, 8(1):44]	PubMed: 35365682
Comprehensive analysis to identify the RP11-478C19.2/ E2F7 axis as a novel biomarker for treatment decisions in clear cell renal cell carcinoma [ Transl Oncol, 2022, 25:101525]	PubMed: 36054996
Preclinical Evaluation of Ixabepilone in Combination with VEGF Receptor and PARP Inhibitors in Taxane-Sensitive and Taxane-Resistant MDA-MB-231 Breast Cancer Cells [ J Pharm Sci, 2022, 111(8):2180-2190]	PubMed: 35700798
Novel Bile Acid-Dependent Mechanisms of Hepatotoxicity Associated with Tyrosine Kinase Inhibitors [ J Pharmacol Exp Ther, 2022, 380(2):114-125]	PubMed: 34794962

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